[Long-Term Survival after Resection of Two Lung Metastases That Appeared Five Years after Pancreatic Cancer Surgery-A Case Report].

A woman in her 70s was diagnosed with cancer of pancreatic head. She underwent subtotal stomach-preserving pancreatoduodenectomy. Moderately differentiated adenocarcinoma, positive peripancreatic exfoliation surface, and R1 resection was diagnosed by histopathological examination. She underwent adjuvant chemotherapy(S-1), but 5 years and 6 months after the operation, a single nodule(16×9 mm)appeared on anterior segment of left lung. She underwent thoracoscopic left upper lobectomy on suspicion of primary lung cancer. Adenocarcinoma consistent with pancreatic cancer metastasis was diagnosed by histopathological examination. She didn't choose chemotherapy after second operation. 1 year and 1 month after the left pneumonectomy, a single nodule(11×10 mm)reappeared in lateral basal segment of right lung. Although it was difficult to diagnose whether it was primary or metastatic, she decided to undergo thoracoscopic partial lung resection. Histopathological examination revealed that the histology was similar to that of the previous lung lesion and was consistent with pancreatic cancer metastasis. After that, she also didn't choose chemotherapy. She has been alive for 7 years and 7 months after her first pancreatic cancer surgery without any new obvious recurrence.

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis.

PURPOSE: Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO2) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF. METHODS: We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO2 and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation. RESULTS: Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO2 during sleep and total sleep time spent with SpO2 < 90% were associated with the sustained pattern, and apnea-hypopnea index was associated with the intermittent pattern. CONCLUSION: We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

Exacerbation of nontuberculous mycobacterial pulmonary disease in a patient with advanced non-small-cell lung cancer during treatment with PD-1 inhibitor and chemotherapy.

A 69-year-old man visited our hospital due to an abnormal shadow on a chest X-ray. Chest CT showed a mass shadow in his left lower lobe accompanied by an infiltrative shadow in the right upper lobe. Thorough examination led to a diagnosis of pulmonary squamous cell lung carcinoma, stage IIIB (T3N2M0). Combination treatment with chemotherapy and programmed cell death receptor 1 (PD-1) inhibitor was started, leading to a partial response. However, his pre-existing pulmonary infiltrative shadow progressed during the maintenance treatment with PD-1 inhibitor, and sputum culture revealed Mycobacterium abscessus infection. Thus, exacerbation of pre-existing nontuberculous mycobacterial pulmonary disease (NTM-PD) resulting from treatment with PD-1 inhibitor was suspected. Then, treatment with PD-1 inhibitor was discontinued, and he underwent pulmonary resection after antibiotic therapy against Mycobacterium abscessus infection. Recently, special attention has been paid to the association of Mycobacterium tuberculosis (TB) infection and treatment with immune checkpoint inhibitors (ICIs) in TB-endemic areas. This case also emphasizes the importance of realizing the risk of NTM infection when treating patients with ICIs, especially in NTM-endemic areas.

Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically.

Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62-year-old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic-type MPM. We re-examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.

Phase II study of adjuvant chemotherapy with pemetrexed and cisplatin with a short hydration method for completely resected nonsquamous non-small cell lung cancer.

BACKGROUND: Cisplatin (CDDP) and vinorelbine as an adjuvant chemotherapy improve the overall survival of patients with completely resected non-small cell lung cancer (NSCLC). However, the treatment completion rate is low due to severe adverse events (AEs). Pemetrexed (PEM) has been used in advanced NSCLC due to its high safety and efficacy. Additionally, the safety of a short hydration method for CDDP administration has been previously reported. Here, we investigated the feasibility of CDDP plus PEM with a short hydration method as adjuvant chemotherapy. METHODS: A total of 21 completely resected nonsquamous NSCLC patients with pathological stage IIA to IIIA disease were enrolled into the study. Adjuvant chemotherapy consisted of four cycles of CDDP (75 mg/m2 ) plus PEM (500 mg/m2 ) every three weeks with a short hydration method. The primary endpoint was the treatment completion rate, and the secondary endpoints included toxicity, the two-year relapse-free survival (RFS) rate, and the outpatient treatment rate. RESULTS: A total of 21 patients (median age: 66 years; 12 males) were enrolled in two centers. All cases were adenocarcinoma with PS0 (71.4%) or PS1 (28.6%). A total of 81.0% of the patients received four cycles of therapy as scheduled and the primary endpoint was met. The rate of outpatient chemotherapy completion after the second cycle was 90.5%. The grade 3 or higher toxicities were anorexia (n = 2) and pulmonary thromboembolism (n = 1). No grade 3/4 hematological toxicities or creatinine level elevations were observed. The two-year RFS rate was 57.3%. CONCLUSIONS: CDDP and PEM with a short hydration is well tolerated in the outpatient setting with limited toxicity. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: CDDP plus PEM adjuvant therapy with a short hydration method is well tolerated in the outpatient setting with limited toxicity. WHAT THIS STUDY ADDS: CDDP plus PEM with a short hydration method has the potential to be one of the options of adjuvant therapy in the future.

Successful crizotinib rechallenge after crizotinib-induced interstitial lung disease.

We report the case of a 70-year-old Japanese male diagnosed with advanced lung adenocarcinoma harboring the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene. As soon as crizotinib was administered, tumor shrank immediately. On Day 25, he developed interstitial lung disease. Bronchoalveolar lavage fluid analysis demonstrated elevated lymphocytes fractionation. A drug lymphocyte stimulating test for crizotinib with the bronchoalveolar lavage lymphocytes was negative. Crizotinib administration was discontinued, but a life-threatening flare of tumor growth occurred. Since there was no alternative treatment for the lung cancer, we restarted crizotinib in combination with prednisolone. The patient experienced neither disease progression nor recurrence of interstitial lung disease at 6 months. In cases in which no alternate treatment is known, crizotinib retreatment combined with steroid therapy after crizotinib-induced interstitial lung disease could be considered after a careful consideration of the potential risks and benefits.

Ewing's sarcoma family of tumors originating in the main bronchus.

Ewing's sarcoma family tumors (ESFT), which include Ewing's sarcoma and primitive neuroectodermal tumors (PNET), have been reported to originate in a variety of sites, mostly in the extremities. Previous reports have shown ESFT originating in the thoracic region, such as chest wall and peripheral lung. We herein report the first case of the ESFT that originated in the main bronchus. Endobronchial snare resection was followed by five courses of chemotherapy (VDC-IE; including vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide) and sequential radiation. After the treatment, the patient's condition has improved, and he has remained disease-free for the past year.

An open-label, prospective clinical study to evaluate the efficacy of prophylactic antibiotics after diagnostic bronchoscopy.

The aim of this study was to prospectively examine the effect of prophylactic antibiotic use on the development of respiratory infections and on the worsening of symptoms after diagnostic fiberoptic bronchoscopy procedures. This study was an open-label, multicenter, controlled, clinical trial. Patients were alternately assigned to a group given prophylactic antibiotics after bronchoscopy (prophylaxis(+) group) and a group not given antibiotic prophylaxis after bronchoscopy (prophylaxis(-) group), and they were followed-up for 1 week. 158 patients were assigned to the prophylaxis(-) group and 153 to the prophylaxis(+) group. Therapeutic antibiotic administration was needed in 3 patients (1.90%) in the prophylaxis(-) group and 5 patients (3.27%) in the prophylaxis(+) group (risk ratio 1.014, 95% confidence interval 0.978-1.052; p=0.446). Worsening of symptoms after bronchoscopy occurred in 57.6% of all patients by day 7, but no significant differences were observed between the 2 study groups. Prophylactic antibiotic use after bronchoscopy did not prevent the development of infectious events and worsening of symptoms, suggesting that prophylactic antibiotics might not be necessary for routine diagnostic bronchoscopic procedures.

Long-term outcome after multidisciplinary approach for leptomeningeal carcinomatosis in a non-small cell lung cancer patient with poor performance status.

The present study describes a case of a 60-year-old Japanese man who was histologically diagnosed with lung adenocarcinoma harboring L858R mutation of epidermal growth factor receptor. He was successfully treated with gefitinib, but eventually developed leptomeningeal carcinomatosis. He underwent ventriculoperitoneal shunting for hydrocephalus and received erlotinib in place of gefitinib with concurrent whole brain radiotherapy; this resulted in dramatic improvement in his symptoms and performance status from four to one and he survived for as long as 13.6 months after the initiation of erlotinib therapy. This multidisciplinary approach may be particularly useful in terms of increasing survival and improving quality of life.

Successful erlotinib treatment for a patient with gefitinib-related hepatotoxicity and lung adenocarcinoma refractory to intermittently administered gefitinib.

A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patient's enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity.

Chemotherapy improves thymoma-associated graft-versus-host-disease-like erythroderma.

Graft-versus-host-disease (GVHD) with erythroderma can rarely occur in the context of thymoma and is associated with a poor prognosis due to an increased risk of infection-related death. The present study describes a case of a 50-year-old man with malignant thymoma who developed sepsis in addition to skin manifestations similar to that seen in GVHD. This patient experienced marked improvement in skin lesions in response to steroids and combination chemotherapy with carboplatin and paclitaxel, with subsequent resolution of infection. The present study describes the clinical course of this patient, followed by a review of pertinent reports of thymoma associated with GVHD with particular focus on the efficacy of treatment strategies.

Randomized phase II study of two different schedules of gemcitabine and oral S-1 in chemo-naïve patients with advanced non-small cell lung cancer.

INTRODUCTION: This study was conducted to evaluate the efficacy and safety and to compare dosing schedules of gemcitabine combined with S-1 in chemo-naïve non-small cell lung cancer patients. METHODS: Patients with chemo-naïve stage IIIB/IV non-small cell lung cancer were randomized into two treatment arms. Patients were given oral S-1 (60 mg/m/d, twice a day) from days 1 to 14 with gemcitabine (1000 mg/m/d) on days 1 and 8 (arm A) or on days 8 and 15 (arm B). This cycle was repeated every 21 days. RESULTS: A total of 80 patients were entered in this trial. The primary end point of this study was response rate. The response rates of arm A and arm B were 22.0 and 28.9%, respectively (p = 0.606). Median time to treatment failure in arm A was 3.6 months and 4.8 months in arm B. Median time to progression in arm A was 4.1 months and 5.5 months in arm B. Median survival time in arm A and arm B was 15.5 months and 18.8 months, respectively. The toxicity profile was relatively mild and did not differ very much between two arms. CONCLUSION: The combination of gemcitabine and S-1 was determined to be feasible and effective for advanced non-small cell lung cancer. We selected arm B for further studies because of its higher response rate and survival data.

Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model.

The airway remodeling that occurs in asthma is characterized by an excess of extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of smooth muscle, goblet cell metaplasia, and accumulation of fibroblasts/myofibroblasts. The urokinase-type plasminogen activator (uPA)/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors. In a mouse ovalbumin (OVA) asthma model, we increased plasminogen activator activity in the lung by administering exogenous uPA or by using mice genetically deficient in the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) to assess the role of this system in asthma pathogenesis. After intraperitoneal OVA sensitization, mice inhaled OVA plus uPA (500 IU/mouse) or saline by ultrasonic nebulization for 3 wk. When studied 24 h after the final exposure, the groups with upregulated plasmin activity had significantly reduced subepithelial fibrosis within the airway walls and had decreased airway hyperresponsiveness (AHR) to methacholine. Morphometric analysis showed that subepithelial wall thickening of the bronchi (subepithelial area ratio) was also reduced, as were collagen and alpha-smooth muscle actin. Upregulation of plasmin activity also increased the level of hepatocyte growth factor activity in bronchoalveolar lavage fluid, whereas the release of transforming growth factor-beta was decreased. The administration of uPA 1 wk after the last OVA inhalation also significantly reduced lung hydroxyproline content and AHR. These results show that enhancing uPA/plasmin activity lessens the airway remodeling in a murine asthma model.

Diffuse periairway thickening in patients with Mikulicz disease.

A 70-year-old woman presented with dry mouth, bilateral swelling of the eyelids, and abnormal taste and smell sensations that had persisted for 3 years. She was diagnosed with Mikulicz disease and presented with dyspnea on exertion afterwards. Chest computed tomography and magnetic resonance imaging showed wall thickening of the trachea and bilateral bronchus. Transbronchial needle aspiration showed lymphoproliferative lesion in the tracheobronchus. The patient was treated with corticosteroid, which improved all of her clinical symptoms, computed tomography, and magnetic resonance findings. In this case, we presented a rare condition of coexistent Mikulicz disease with tracheobroncial wall thickening caused by lymphoproliferation without lesions in small airways or lung.

t(14;18)(q32;q21)-bearing pleural MALT lymphoma with IgM paraproteinemia: value of detection of specific cytogenetic abnormalities in the differential diagnosis of MALT lymphoma and lymphoplasmacytic lymphoma.

A 67-year-old woman presented with a pleural effusion and a tumor in the right pleural wall. Histological examination of thoracoscopic tumor and pleural biopsy specimens showed infiltration by medium sized cells, some of which showed plasmacytoid differentiation. In view of the presence of IgM paraproteinemia and bone marrow involvement by lymphoma cells, the patient was diagnosed tentatively as having lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the cells in the pleural fluid detected t(14;18)(q32;q21), while fluorescence in situ hybridization was positive for 11% of the MALT1 split signal. Because of the presence of characteristic genetic abnormalities and notable extranodal involvement, the patient was diagnosed as having MALT lymphoma. She was treated with three courses of cladribine and rituximab, and achieved complete regression of the tumor. In this case the detection of t(14;18)(q32;q21) involving IGH and MALT1 was useful for the differential diagnosis of LPL and MALT lymphoma.

Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis. CD40-CD40 ligand interaction promotes several proinflammatory mediators and plays a pivotal role in the various stages of atherosclerotic diseases. The present study examines whether CD40 ligation contributes to outcomes in patients with OSAS. METHODS: The study population comprised OSAS patients with an apnea hypopnea index (AHI) > or = 30 (n = 35) and control subjects (AHI < 5; n = 16). We measured serum levels of soluble CD40 ligand (sCD40L), tumor necrosis factor (TNF)-alpha, and hypersensitive C-reactive protein (hsCRP) before and after nasal continuous positive airway pressure (nCPAP) therapy for 3 months. RESULTS: Baseline levels of sCD40L were significantly higher in patients with OSAS (6.93 +/- 4.64 ng/mL) [mean +/- SD] than in control subjects (3.43 +/- 2.11 ng/mL, p < 0.01). Baseline levels of sCD40L positively correlated with TNF-alpha but not with hsCRP. The elevation of sCD40L was improved for 1 night after nCPAP therapy (3.83 +/- 2.78 ng/mL, p < 0.001). Even though patients with severe OSAS did not receive any other medication to control atherosclerotic risk factors for 3 months, nCPAP was continued to reduce the levels of sCD40L. CONCLUSION: The present study suggested that sCD40L is a key factor that links OSAS and atherosclerotic progression.