Monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma: an autopsy case and review of the literature.

A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jß2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.

CpG ODN (K3)-toll-like receptor 9 agonist-induces Th1-type immune response and enhances cytotoxic activity in advanced lung cancer patients: a phase I study.

BACKGROUND: Cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) (K3)-a novel synthetic single-stranded DNA immune adjuvant for cancer immunotherapy-induces a potential Th1-type immune response against cancer cells. We conducted a phase I study of CpG ODN (K3) in patients with lung cancer to assess its safety and patients' immune responses. METHODS: The primary endpoint was the proportion of dose-limiting toxicities (DLTs) at each dose level. Secondary endpoints included safety profile, an immune response, including dynamic changes in immune cell and cytokine production, and progression-free survival (PFS). In a 3 + 3 dose-escalation design, the dosage levels for CpG ODN (K3) were 5 or 10 mg/body via subcutaneous injection and 0.2 mg/kg via intravenous administration on days 1, 8, 15, and 29. RESULTS: Nine patients (eight non-small-cell lung cancer; one small-cell lung cancer) were enrolled. We found no DLTs at any dose level and observed no serious treatment-related adverse events. The median observation period after registration was 55 days (range: 46-181 days). Serum IFN-α2 levels, but not inflammatory cytokines, increased in six patients after the third administration of CpG ODN (K3) (mean value: from 2.67 pg/mL to 3.61 pg/mL after 24 hours). Serum IFN-γ (mean value, from 9.07 pg/mL to 12.7 pg/m after 24 hours) and CXCL10 levels (mean value, from 351 pg/mL to 676 pg/mL after 24 hours) also increased in eight patients after the third administration. During the treatment course, the percentage of T-bet-expressing CD8+ T cells gradually increased (mean, 49.8% at baseline and 59.1% at day 29, p = 0.0273). Interestingly, both T-bet-expressing effector memory (mean, 52.7% at baseline and 63.7% at day 29, p = 0.0195) and terminally differentiated effector memory (mean, 82.3% at baseline and 90.0% at day 29, p = 0.0039) CD8+ T cells significantly increased. The median PFS was 398 days. CONCLUSIONS: This is the first clinical study showing that CpG ODN (K3) activated innate immunity and elicited Th1-type adaptive immune response and cytotoxic activity in cancer patients. CpG ODN (K3) was well tolerated at the dose settings tested, although the maximum tolerated dose was not determined. TRIAL REGISTRATION: UMIN-CTR number 000023276. Registered 1 September 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000026649.

A lung abscess caused by secondary syphilis - the utility of polymerase chain reaction techniques in transbronchial biopsy: a case report.

BACKGROUND: In Japan and other countries, the number of patients with syphilis is increasing year by year. Recently, the cases of the pulmonary involvement in patients with secondary syphilis have been reported. However, it is still undetermined how to obtain a desirable specimen for a diagnosis of the pulmonary involvement, and how to treat it if not cured. CASE PRESENTATION: A 34-year-old man presented with cough and swelling of the right inguinal nodes. A physical examination revealed erythematous papular rash over the palms, soles and abdomen. A 4 cm mass in the right lower lobe of the lung was detected on computed tomography. He was diagnosed as having secondary syphilis, because he was tested positive for the rapid plasma reagin and Treponema pallidum hemagglutination assay. Amoxycillin and probenecid were orally administered for 2 weeks. Subsequently, rash and serological markers were improved, however, the lung mass remained unchanged in size. Transbronchial biopsy (TBB) confirmed the pulmonary involvement of syphilis using polymerase chain reaction techniques (tpp47- and polA-PCR). Furthermore, following surgical resection revealed the lung mass to be an abscess. CONCLUSIONS: To our knowledge, this is the first surgically treated case of a lung abscess caused by syphilis, which was diagnosed by PCR techniques in TBB. This report could propose a useful diagnostic method for the pulmonary involvement of syphilis.

[A Case of Mediastinal Small Cell Lung Cancer in a Patient Receiving Mechanical Ventilation Who Was Successfully Treated with Chemotherapy and Finally Extubated].

BACKGROUND: The efficacy and safety of chemotherapy for patients with lung cancer who are in need of intensive care, such as invasive mechanical ventilation, have not been established. CASE: A 59-year-old woman consulted a doctor with complaints of dyspnea.She was intubated because of acute respiratory failure and transferred to our hospital.Enhanced CT images revealed advanced stenosis of her trachea due to a bulky mediastinal tumor.Cervical lymph node biopsy was performed, and she was diagnosed with mediastinal small cell lung cancer.She received combination chemotherapy with carboplatin and etoposide along with invasive mechanical ventilation.Chemotherapy was effective, and extubation was performed under careful bronchoscopic observation.Her general condition improved gradually, and she was discharged from our hospital on foot with ambulatory chemotherapy. CONCLUSION: Even though patients with lung cancer develop respiratory failure and need invasive mechanical ventilation, they may be treated with effective chemotherapy and may be weaned from ventilation.

[Retrospective Analysis of the Afatinib Clinical Pathway during the 28-Day Introductory Period-The Japanese Style of Collaborative Drug Therapy Management(J-CDTM)].

Afatinib is a newly approved second-generation epidermal growth factor receptor-tyrosine kinase inhibito r(EGFR-TKI). Afatinib has been shown to prolongthe overall survival of patients with non-small cell lungcancer (NSCLC) with EGFR mutations compared with the standard chemotherapy. However, Grade 3 or 4 toxicities, includingdiarrhea, rash, paronychia, and stomatitis, have been observed more frequently in patients treated with afatinib than in those treated with first-generation EGFR-TKIs. Accordingly, our institution developed an afatinib clinical pathway (the afatinib pathway), which was designed by certified nurses, medical physicians, and certified pharmacists, with the goal of reducing the severity of diarrhea and rash that occur most frequently duringthe 28-day introductory period of afatinib treatment. Between May and October 2014, afatinib was administered accordingto the afatinib pathway to 14 patients with NSCLC and EGFR mutations. Of these patients, only one (7.1%) experienced Grade 3 diarrhea. No other patient experienced Grade 3 or 4 toxicity. The afatinib pathway was effective in reducingthe severities of the diarrhea and rash duringthe 28-day introductory period of the afatinib treatment. Our implementation of the afatinib pathway could be considered the Japanese style of collaborative drugtherapy management (J-CDTM).

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

Emergency department visits after hours by lung cancer patients in Japan.

PURPOSE: The aims of this study were to clarify frequency with which Japanese lung cancer patients visited an emergency department (ED) after hours and their final outcome. METHODS: This is a retrospective and single institutional study. We reviewed medical records of patients who died of lung cancer from January 2008 to June 2012 at Osaka Police Hospital who had been followed up since diagnosis of lung cancer until death. We compared patients who had visited the ED after hours on weekdays, weekends, or holidays over their lives with cancer (ED visitors) and patients who had never visited the ED (non-ED visitors). RESULTS: Overall, 245 patients met the inclusion criteria for analysis. There were 149 after hours ED visits by 106 lung cancer patients. Mean number of ED visits was 0.6 for all patients. Median interval from ED visit to death was 49 days. The most common chief compliant for these patients was respiratory problems (37.6%). Most patients visited the ED during chemotherapy (32.9%) or for best supportive care (42.3%). Directly after ED visits, 56.4% of ED visitors were finally hospitalized. In a multivariate analysis, performance status (PS) (odds ratio [OR]: 11.2, 95% confidence interval [CI]: 2.1-59.0, p = 0.004) and cancer stage (OR: 0.003, 95% CI: 0.0006-0.014, p < 0.001) at diagnosis were statistically associated with ED visits after hours. CONCLUSIONS: Japanese patients with lung cancer frequently visit ED after hours. An ED visit is itself an indicator of poor prognosis.

Streptococcal Toxic Shock Syndrome Due to Invasive Coloproctitis Caused by Group G Streptococcus: A Case Report and Literature Review.

Streptococcus dysgalactiae subsp. equisimillis (SDSE) is classified as a group G streptococcus (GGS). In systemic SDSE infection, septic shock is easily induced and has a high mortality of 44%. The case was a 78-year-old man presented with fever and chills of 20 hours duration. He was in shock at the presentation and developed melena on day nine. CT images showed bowel wall thickening with emphysema and bedside colonoscopy showed active bleeding in the descending colon and rectum. Blood cultures were positive for Streptococcus dysgalactiae and a diagnosis of streptococcal toxic shock syndrome (STSS) due to SDSE was made. Urgent Hartmann procedure with laparotomy for removal of descending and rectal colon was performed to relieve his shock status. His shock status was reversed after surgery. Surgical specimens confirmed the presence of SDSE on the intestinal mucosa. This is the first case of STSS due to SDSE infection of the intestinal wall. Resection of infected tissue in the setting of multiple organ dysfunction syndrome and necrotizing enterocolitis is indicated in such cases.

Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study.

BACKGROUND: Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. METHODS: A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m(2) of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2-16. RESULTS: Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48-78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. CONCLUSIONS: Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC.

Unexpected Complication of R-CHOP Chemotherapy: Rapidly Progressive Bronchiolitis Obliterans Syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the term used for the progressive obliteration of small airways before the patient has had a confirmatory lung biopsy. It is also recognized as a transplant-related complication. There have been no reports of BOS during initial standard chemotherapy. CASE PRESENTATION: A 50-year-old woman with newly diagnosed follicular lymphoma grade 2, stage 3A, presented with hypoxia and progressive dyspnoea after the fifth cycle of R-CHOP. High-resolution computed tomography showed air trapping enhanced at the end-expiratory phase. Pulmonary function testing revealed severe obstructive and restrictive failure without bronchodilator response. We diagnosed BOS based on current criteria and treated the patient with glucocorticoids and cyclosporin. She was discharged home on oxygen therapy. However, soon after discharge, her respiratory symptoms deteriorated and she was hospitalized in a palliative care unit. She died of respiratory failure within a year of symptom onset. CONCLUSIONS: This is the first case report to describe rapidly progressive BOS in a patient undergoing R-CHOP treatment, which strongly suggests the condition was caused by the chemotherapy. Although a pathological diagnosis was not obtained, the clinical diagnosis of BOS was important so that the patient could receive appropriate treatment and palliative care based on the prognosis of this incurable condition. LEARNING POINTS: R-CHOP chemotherapy may cause rapidly progressive bronchiolitis obliterans syndrome (BOS).When it is difficult to obtain a pathological diagnosis, a clinical diagnosis of BOS is important for early intervention and appropriate palliative care.

Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients.

BACKGROUND: The PD-1-blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events. METHODS: To define the duration of binding and residual efficacy of nivolumab after discontinuation, we developed a simplified strategy for T cell monitoring and used it to analyze T cells from peripheral blood from 11 non-small cell lung cancer patients previously treated with nivolumab. To determine the suitability of our method for other applications, we compared transcriptome profiles between nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell monitoring in 2 nivolumab-treated patients who developed progressive lung tumors during long-term follow-up. RESULTS: Prolonged nivolumab binding was detected more than 20 weeks after the last infusion, regardless of the total number of nivolumab infusions (2-15 doses) or type of subsequent treatment, in 9 of the 11 cases in which long-term monitoring was possible. Ki-67 positivity, a proliferation marker, in T cells decreased in patients with progressive disease. Transcriptome profiling identified the signals regulating activation of nivolumab-bound T cells, which may contribute to nivolumab resistance. In 2 patients who restarted nivolumab, T cell proliferation markers exhibited the opposite trend and correlated with clinical response. CONCLUSIONS: Although only a few samples were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T cells might help determine residual efficacy under various types of concurrent or subsequent treatment. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000024623. FUNDING: This work was supported by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282, and JP15K09220), Japan Agency for Medical Research and Development (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for Evolutional Science and Technology (JPMJCR16G2).

Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports.

RATIONALE: Most of nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations eventually acquire resistance to the first EGFR-tyrosine kinase inhibitors (TKIs) therapy after varying periods of treatment. Of note, approximately one-third of those patients develop brain metastases, which deteriorate their quality of life and survival. The effect of systemic chemotherapy on brain metastases after acquisition of EGFR-TKI resistance is limited, and thus far, whole-brain radiation therapy, which may cause the harmful effect on neurocognitive functions, has been the only established therapeutic option for especially symptomatic brain metastases. Osimertinib is a third-generation oral, potent, and irreversible EGFR-TKI. It can bind to EGFRs with high affinity even when the EGFR T790M mutation exists in addition to the sensitizing mutations. Its clinical efficacy for NSCLC patients harboring the T790M mutation has already been shown; however, the evidence of osimertinib on brain metastases has not been documented well, especially in terms of the appropriate timing for treatment and its response evaluation. PATIENT CONCERNS, DIAGNOSES, AND INTERVENTIONS: We experienced 2 NSCLC patients with the EGFR T790M mutation; a 67-year-old woman with symptomatic multiple brain metastases administered osimertinib as seventh-line chemotherapy, and a 76-year old man with an asymptomatic single brain metastasis administered osimertinib as fifth-line chemotherapy. OUTCOMES: These patients showed great response to osimertinib within 2 weeks without radiation therapy. LESSONS: These are the first reports to reveal the rapid response of the brain metastases to osimertinib within 2 weeks. These cases suggest the possibility that preemptive administration of osimertinib may help patients to postpone or avoid radiation exposures. In addition, rapid reassessment of the effect of osimertinib on brain metastases could prevent patients from being too late to receive essential radiotherapy.

Mandatory dexamethasone strictly monitored by pharmacists reduces the severity of pemetrexed-induced skin rash.

OBJECTIVE: The present study aimed to retrospectively examine the effectiveness of mandatory dexamethasone (m-DEX) strictly monitored by pharmacists collaborating with medical physicians and nurses for reducing pemetrexed (PEM)-induced skin rash in patients with non-squamous non-small-cell lung cancer (ns-NSCLC). METHODS: We compared the rash grades during the first cycle of PEM-containing regimens between patients who received m-DEX after February 2012 and those who received dexamethasone (DEX) at their physician's discretion (d-DEX) before January 2012. RESULTS: Of 163 patients with ns-NSCLC included in this study, 89 received d-DEX and 74 received m-DEX. The mean DEX doses the night before and the day after PEM administration were significantly higher in the m-DEX group than in the d-DEX group. The frequency of grade ≥2 skin rash was significantly lower in the m-DEX group than in the d-DEX group. CONCLUSIONS: The use of m-DEX strictly monitored by pharmacists might significantly reduce the severity of PEM-induced skin rash.

Efficacy of nanoparticle albumin-bound paclitaxel regimens for relapsed small cell lung cancer: A retrospective analysis.

Although small cell lung cancer (SCLC) is initially sensitive to chemotherapy, it recurs in most cases. Standard regimens for salvage chemotherapy have not been established, and the prognosis of relapsed SCLC remains poor. In the present study, we investigated the clinical efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) regimens for the treatment of relapsed SCLC.In this retrospective multicenter analysis, 14 patients (3 women and 11 men; median age 71 years) with relapsed SCLC received nab-paclitaxel alone or in combination with carboplatin between February 2013 and July 2014. The safety and efficacy of the regimens were evaluated.The response rates, disease control rates, and median overall survival for the total patient population were 36%, 64%, and 7.8 months, respectively. Response rates, disease control rates, and the median overall survival were 11%, 44%, and 4 months, respectively, in the monotherapy group; and 80%, 100%, and 10.6 months, respectively, in the combination therapy group. The most common adverse events were hematological toxicities such as neutropenia and anemia. Severe neutropenia appeared in some patients, although it was resolved by treatment in all. The most common nonhematological toxicity was anorexia (64%), followed by neurotoxicity and constipation. All nonhematological toxicities were mild and manageable.Our results suggest that chemotherapy with nab-paclitaxel regimens for relapsed SCLC exhibits moderate clinical efficacy and is well-tolerated. Further clinical trials in relapsed SCLC patients are warranted.

Effective Management of Persistent Pneumothorax Using a Thopaz® Digital Drainage System Combined with an Endobronchial Watanabe Spigot.

A 72-year-old man with salivary gland cancer and multiple pulmonary metastases suffering from intractable pneumothorax was transferred to our institution; he was inoperable because of a low pulmonary function. A chest tube had been placed more than a month prior to this admission. A digital drainage system was used for 24-h monitoring of air leaks (Thopaz®). Using the Thopaz® system, we performed endoscopic bronchial occlusion using an endobronchial Watanabe spigot (EWS) to reduce air leaks. Finally, the air leaks ceased, and the chest tube was removed five days after EWS placement. We herein report a case of persistent pneumothorax that was successfully treated by endoscopic bronchial EWS placement with the aid of a Thopaz® system.

Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion.

AIM: Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF. Therefore, this study evaluated whether plasma or pleural effusion VEGF might predict bevacizumab treatment outcome. PATIENTS AND METHODS: We enrolled 23 patients with NSCLC and MPE between September 2010 and June 2012. Plasma VEGF levels were measured in 19 patients and pleural VEGF levels were measured in 22 patients. RESULTS: Compared to patients with a low plasma VEGF level, patients with a high level exhibited significantly shorter overall survival (OS: 13.8 vs. 6.5 months, p=0.04), progression-free survival (PFS: 8.7 vs. 4.8 months, p<0.01), and period to re-accumulation of MPE (pPFS: 9.7 vs. 6.2 months, p=0.02). Compared to patients with a low VEGF level in pleural effusion, patients with a high VEGF level exhibited significantly shorter OS (19.6 vs. 6.9 months, p<0.01) and pPFS (9.6 vs. 6.7 months, p=0.04), although there was no significant difference in their PFS (6.6 vs. 5.9 months, p=0.18). CONCLUSION: VEGF levels in the plasma and pleural effusion may predict the outcome of bevacizumab treatment in patients with NSCLC and MPE.

A Rare Case of Pleomorphic Carcinoma of the Lung Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement.

Molecular testing for anomalies, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangement, is part of the current standard of care for non-small cell lung cancer, particularly adenocarcinoma. ALK rearrangement occurs most frequently in adenocarcinoma cells and rarely in non-adenocarcinoma cells. We herein report a rare case of pleomorphic lung carcinoma with ALK rearrangement in both its adenocarcinoma and spindle cell components. This case suggests the possibility of ALK rearrangement in pleomorphic carcinoma.

The alternatively spliced actinin-4 variant as a prognostic marker for metastasis in small-cell lung cancer.

BACKGROUND: The alternatively spliced actinin-4 variant (ACTN4va) is expressed in small-cell lung cancer (SCLC) and is thought to be a potential diagnostic marker. However, ACTN4va expression has not been examined in transbronchial biopsy specimens. MATERIALS AND METHODS: We retrospectively examined the relationship between ACTN4va expression, clinical factors and survival in 104 consecutive newly-diagnosed SCLC patients. RESULTS: Of the 104 screened cases, 83 (median age=69 years; transbronchial biopsy, 71) were included in our study. Survival was significantly different in the group with no distant metastasis (1996 vs. 422 days, respectively; p=0.000115) but was not significantly different with regard to ACTN4va expression in the group with distant metastasis (293 vs. 254 days, respectively; p=0.678). CONCLUSION: ACTN4va expression was identifiable in small biopsy samples. ACTN4va expression was also significantly related to distant metastasis and could stratify SCLC patients according to prognosis.

Ambulatory pulse oximetry monitoring in Japanese COPD outpatients not receiving oxygen therapy.

BACKGROUND: It remains unknown whether desaturation profiles during daily living are associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Point measurements of resting oxygen saturation by pulse oximetry (SpO2) and partial pressure of arterial oxygen (PaO2) are not sufficient for assessment of desaturation during activities of daily living. A small number of studies continuously monitored oxygen saturation throughout the day during activities of daily living in stable COPD patients. This study aims to analyse the frequency of desaturation in COPD outpatients, and investigate whether the desaturation profile predicts the risk of exacerbation. METHODS: We studied stable COPD outpatients not receiving supplemental oxygen therapy. Baseline assessments included clinical assessment, respiratory function testing, arterial blood gas analysis, body mass index, and the COPD Assessment Test (CAT). Patients underwent 24-hour ambulatory monitoring of SpO2 during activities of daily living. Exacerbations of COPD and death from any cause were recorded. RESULTS: Fifty-one patients were enrolled in the study, including 12 current smokers who were excluded from the analyses in case high serum carboxyhaemoglobin concentrations resulted in inaccurately high SpO2 readings. The mean percent predicted forced expiratory volume in one second (%FEV1) was 50.9%. The mean proportion of SpO2 values below 90% was 3.0% during the day and 7.4% during the night. There were no daytime desaturators, defined as ≥ 30% of daytime SpO2 values below 90%. Twenty-one exacerbations occurred in 13 patients during the mean follow-up period of 26.4 months. Univariate and multivariate Cox proportional hazards analyses did not detect any significant factors associated with exacerbation. CONCLUSIONS: Our 24-hour ambulatory oximetry monitoring provided precise data regarding the desaturation profiles of COPD outpatients. Both daytime and nighttime desaturations were infrequent. The proportion of ambulatory SpO2 values below 90% was not a significant predictor of exacerbation.

Phase II study of pemetrexed plus intermittent erlotinib combination therapy for pretreated advanced non-squamous non-small cell lung cancer with documentation of epidermal growth factor receptor mutation status.

INTRODUCTION: Erlotinib and pemetrexed have been approved for the second-line and maintenance treatment of non-small cell lung cancer (NSCLC). With the recommended doses determined by our previous phase I study, we conducted a phase II study to evaluate the efficacy and safety of combination of the two agents in pretreated non-squamous NSCLC patients. METHODS: This study was performed in patients with stage IIIB/IV or post-surgically recurrent non-squamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m(2) of intravenous pemetrexed every 21 days and 150 mg of oral erlotinib on days 2-16 until disease progression, unacceptable toxicity, or withdrawal of consent. The expected response rate and threshold were defined as 33.5% and 10%, respectively. Assuming a one-sided alpha of 5%, a power of 80%, the possible deviation from assessment, 26 patients were necessary. RESULTS: A total of 27 patients, 16 males and 11 females were recruited. Patients had the median age of 70 years (range, 48-80 years) and included 21 stage IV diseases, 22 adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations were examined in all patients. One patient had positive EGFR mutation, but the other 26 patients had wild-type EGFR. The median number of treatment courses was 3 (range, 1 to over 19). The best overall response rate and disease control rate were 11.1% and 63.0%, respectively. The median progression-free survival and overall survival were 2.8 months (95% confidence interval (CI); 1.9-7.5 months) and 15.8 months (95% CI; 9.3 months to not available), respectively. Dermal, hepatic, gastrointestinal and hematological disorders were the frequently observed adverse events. One patient experienced grade 3 drug-induced interstitial lung disease. CONCLUSIONS: We could not demonstrate the add-on effect of intermittent erlotinib on pemetrexed in a second-line setting for patients with non-squamous NSCLC without EGFR mutations.