Concise synthesis of amino acid component of amicoumacins via dihydrooxazine formation through intramolecular conjugate addition.

Amicoumacins are a family of antibiotics with a variety of important bioactivities. A concise and efficient method was developed for synthesizing the amino acid component of amicoumacins via the corresponding dihydrooxazine intermediate. The dihydrooxazine ring was formed with complete stereoselectivity through an intramolecular conjugate addition of a δ-trichloroacetimidoyloxy-α,ß-unsaturated ester, which was obtained from a known 4,6-O-p-methoxybenzylidene-protected d-glucose. The synthesis developed in this study can be used to synthesize the building blocks of amicoumacins and can likely be adapted for the synthesis of other types of molecules possessing dihydrooxazine rings or amino alcohol moieties.

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.

Morphine May Contribute to Improving Respiratory Failure in Severe COVID-19: A Case Report.

At present, the world is undergoing successive waves of the COVID-19 pandemic. When COVID-19 becomes severe, it causes respiratory failure and symptoms of dyspnoea. The patient's dyspnoea worsens to the IPOS of 3. One COVID-19 patient admitted to our medical institution developed severe illness characterised by hypoxaemia and dyspnoea. In addition to disease-modifying treatments such as remdesivir and dexamethasone, we administered morphine to relieve his dyspnoea. Surprisingly, we observed an improvement in both hypoxaemia and dyspnoea.

Characteristics of the nocturnal desaturation waveform pattern of SpO2 in COPD patients: an observational study.

BACKGROUND: Nocturnal desaturation is common in patients with chronic obstructive pulmonary disease (COPD) and impacts disease exacerbation and prognosis. In our previous study, we developed a diagnostic algorithm to classify nocturnal desaturation from SpO2 waveform patterns based on data from patients receiving home oxygen therapy. In this study, we aimed to investigate nocturnal desaturation in patients with COPD based on SpO2 waveform patterns and the associations between the waveforms and clinical data. METHODS: We investigated patients diagnosed with COPD and measured SpO2 and nasal airflow with a type 4 portable long-term recordable pulse oximeter. Then, we classified the SpO2 waveforms with the algorithm and compared the clinical data. RESULTS: One hundred fifty-three patients (136 male and 17 female) were analysed. One hundred twenty-eight of the 153 (83.7%) patients had nocturnal desaturation, with an intermittent pattern (70.6%), sustained pattern (13.1%) and periodic pattern (68.0%). Intriguingly, desaturation with an intermittent pattern was associated with the apnoea-hypopnea index obtained with the portable monitor, and desaturation with a sustained pattern was associated with the cumulative percentage of time at a SpO2 below 90%. CONCLUSIONS: We found that nocturnal desaturation was frequently observed in patients with COPD and could be classified into 3 types of waveform patterns.

Adapalene Gel 0.1% Versus Placebo as Prophylaxis for Anti-Epidermal Growth Factor Receptor-Induced Acne-Like Rash: A Randomized Left-Right Comparative Evaluation (APPEARANCE).

LESSONS LEARNED: The results of the APPEARANCE trial indicate that adapalene does not prevent acne-like rash over placebo when added to topical moisturizer and oral minocycline but instead may have a detrimental effect. Therefore, adapalene is not recommended as prophylaxis against acne-like rash induced by anti-epidermal growth factor receptor therapies.Given that acne-like rash was completely controlled with placebo in approximately half of patients, predictive measures to identify patients needing intensive prophylaxis are required. BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapies are frequently associated with acne-like rash. To evaluate the prophylactic efficacy of adapalene, a topical retinoid used as first-line therapy for acne vulgaris, we conducted a randomized, placebo-controlled, evaluator-blinded, left-right comparative trial. METHODS: Patients with non-small cell lung, colorectal, or head and neck cancer scheduled to receive anti-EGFR therapies were randomly assigned to once-daily adapalene application on one side of the face, with placebo on the other side. All patients had topical moisturizer coapplied to both sides of the face, and received oral minocycline. The primary endpoint was the difference in total facial lesion count of acne-like rash at 4 weeks. Secondary endpoints included complete control rate (CCR) of acne-like rash (≤5 facial lesions) and global skin assessment (Investigator's Global Assessment [IGA] scale, grade 0-4) at 4 weeks. Two blinded dermatologists independently evaluated the endpoints from photographs. RESULTS: A total of 36 patients were enrolled, of whom 26 were evaluable. Adapalene treatment was associated with a greater lesion count than placebo at 4 weeks, although the difference was not statistically significant (mean, 12.6 vs. 9.8, p = .12). All four patients with a difference >10 in lesion count between face sides had a greater count on the adapalene-treated side. No significant differences were observed in CCR of acne-like rash (54% vs. 50%) or IGA scale (mean grade, 1.9 vs. 1.7) between the adapalene and placebo sides. CONCLUSION: Adapalene is not recommended as prophylaxis against acne-like rash induced by anti-EGFR therapies.

Overexpression of CD 133 and BCL-2 in non-small cell lung cancer with neuroendocrine differentiation after transformation in ALK rearrangement-positive adenocarcinoma.

Transformation to small cell lung cancer is one phenomenon of acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in ALK rearrangement-positive non-small cell lung cancer (NSCLC). Few case reports have focused on other types of histological transformation. We report a case of transformation of ALK rearrangement-positive adenocarcinoma to NSCLC with neuroendocrine differentiation during alectinib therapy. A 36-year-old woman presented with a tumor in the left lower lobe and bone metastases. She was diagnosed with ALK rearrangement-positive adenocarcinoma by histopathology of the primary tumor. Alectinib had been effective for 8 months before new lesions appeared. Histopathological re-examination of a recurrent tumor revealed poorly differentiated carcinoma with insulinoma-associated protein 1 (INSM1) expression, which remained ALK-positive. Expression of CD133, BCL-2, and SOX2 was positive in comparison to the initial tumor. Expression of SOX2 became more strongly positive than it was before treatment. The immunohistochemical findings of these markers associated with cancer stem-like cells and/or neuroendocrine differentiation suggest that cancer stem cells play a role in the mechanisms of histological transformation and acquired resistance of ALK rearrangement-positive cancer. To our knowledge, this is the first report to suggest an association between cancer stem-like cells and histological transformation in ALK rearrangement-positive lung cancer.

Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells.

BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine the contribution of the signaling of S1P and S1PRs expressed in airway epithelial cells (ECs) to asthma responses in mice. METHODS: Bronchial asthma was experimentally induced in BALB/c mice by ovalbumin (OVA) sensitization followed by an OVA inhalation challenge. The effects of S1PR antagonists on the development of asthma were analyzed 24 h after the OVA challenge. RESULTS: Immunohistological analysis revealed S1PR1-3 expression on mouse airway ECs. Quantitative real-time polymerase chain reaction demonstrated that S1P greatly stimulated the induction of CCL3 and TIMP2 mRNA in human airway ECs, i.e., BEAS-2B cells, in a dose-dependent manner. Pretreatment with the S1PR2 antagonist JTE013 inhibited the CCL3 gene expression in BEAS-2B cells. Immunohistological analysis also showed that the expression level of CCL3 was attenuated by JTE013 in asthmatic mice. Furthermore, JTE013 as well as anti-CCL3 antibody attenuated allergic responses. Intratracheal administration of JTE013 also attenuated eosinophilic reactions in bronchoalveolar lavage fluids. S1P induced transcription factor NFκB activation, while JTE013 greatly reduced the NFκB activation. CONCLUSIONS: JTE013 attenuated allergic airway reactions by regulating CCL3 production from bronchial ECs. The intratracheal administration of JTE013 may be a promising therapeutic strategy for bronchial asthma.

Diagnostic utility of additional conventional techniques after endobronchial ultrasonography guidance during transbronchial biopsy.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) has been used to diagnose peripheral pulmonary lesions (PPLs). In this study, we evaluated the diagnostic utility of conventional TBB after EBUS-GS TBB. METHODS: A retrospective analysis of patients who underwent conventional TBB after EBUS-GS TBB for PPL between August 1, 2012 and December 31, 2014. We performed multivariate analysis to examine the association of various clinical factors, including EBUS probe distance and sample size area, with diagnostic yield. RESULTS: Of 88 eligible patients, 57 (65%) were successfully diagnosed by EBUS-GS TBB. In 31 patients not diagnosed by EBUS-GS TBB, 15 (48%) were successfully diagnosed by additional conventional TBB. Ground glass opacity (GGO) was a significant factor associated with the diagnostic yield of additional conventional TBB following EBUS-GS TBB. Multivariate analysis and receiver operator curves revealed that distance between the PPL and the EBUS probe of less than 2.55 mm favored the utility of conventional TBB. CONCLUSION: Additional conventional TBB after EBUS-GS TBB could be a useful procedure for the diagnosis of ground glass opacity PPLs and in cases of a distance of less than 2.55 mm between the EBUS probe and the lesion.

Drug-induced interstitial lung disease after chemoimmunotherapy for extensive-stage small cell lung cancer.

Objectives: The combination of chemotherapy and immune checkpoint inhibitors (chemo-ICI) has become the new standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). Recently, slight changes in interstitial shadows, defined as interstitial lung abnormalities (ILA), have been identified. In patients with ES-SCLC who received chemo-ICI, there are limited data on the incidence of drug-induced interstitial lung disease (D-ILD) in daily practice and the association between the development of D-ILD and ILA in the baseline computed tomography (CT). Materials and methods: A multicenter, retrospective study was conducted to investigate the incidence of D-ILD, the risk factors for developing D-ILD, progression-free survival (PFS), and overall survival (OS) in patients with ES-SCLC who received chemo-ICI between August 2019 and November 2021. Results: This study enrolled 70 patients (median age, 71 years; including 58 men) from nine institutions in Japan. There were 62 patients (89%) treated with carboplatin/etoposide/atezolizumab and 8 patients treated with carboplatin or cisplatin/etoposide/durvalumab. Twenty-nine patients (41.4%) were found to have ILA at baseline CT. Eleven patients (15.7%) developed D-ILD. The proportion of patients with ILA was significantly higher in the group who developed D-ILD than in the group who did not (9/11 (81.8%) vs. 20/59 (33.9%), respectively, P = 0.0057). In addition, the frequency of ground glass attenuation (GGA) and reticulation was higher in patients who developed D-ILD. There was no significant difference in PFS and OS between patients who developed D-ILD and those who did not (median PFS, 8.0 (95% confidence interval (CI), 5.5-9.5) months vs. 5.0 (95% CI, 4.5-5.6) months, respectively, P = 0.11 and median OS, not reached (NR) (95% CI, 8.7-NR) vs. 18.2 (95% CI, 13.2-NR) months, respectively, P = 0.20). Conclusion: The incidence of D-ILD in patients with ES-SCLC who received chemo-ICI in clinical practice was higher than that in clinical trials. Patients with pre-existing ILA were more likely to develop D-ILD.

Re-expansion pulmonary edema after chest tube drainage of malignant pleural effusion.

A 62-year-old man presented with a 3-day history of dyspnea. Chest X-ray revealed a pleural effusion. We performed chest tube drainage, and then the patient experienced re-expansion pulmonary edema. His respiratory distress improved after the treatment of noninvasive positive pressure ventilation and intravenous methylprednisolone.

Usefulness Analysis of Fraction of Exhaled Nitric Oxide for the Differential Diagnosis of Acute Cough.

BACKGROUND/AIM: Measuring the fraction of exhaled nitric oxide (FeNO) is useful in the diagnosis of asthma and cough variant asthma. The aim of this study was to clarify the significance of measuring the FeNO in the differential diagnosis of acute cough. PATIENTS AND METHODS: We analyzed 80 patients who visited the clinic with the chief complaint of acute cough having experienced an asthma-like episode from January 2014 to July 2015. RESULTS: Infectious cough alone was present in 21% of patients, while 30% had asthmatic cough alone and 49% had a combination of infectious and asthmatic cough. The values of FeNO in those with asthmatic cough (30.4±24.7 ppb) and asthmatic/infectious cough (33.2±17.4 ppb) were significantly higher than those with just infectious cough (13.7±3.2 ppb) (p=0.0089 and p<0.0001, respectively). CONCLUSION: FeNO measurement is useful for distinguishing asthmatic diseases, even in the differential diagnosis of acute cough.

Hypersensitivity Pneumonitis Caused by Exposure to a Gray Parrot (Psittacus erithacus).

A 73-year-old woman complaining of cough and dyspnea was admitted to our hospital. High-resolution computed tomography chest revealed patchy ground-glass attenuation in the upper lung field. The patient suffered an asthma attack and was diagnosed with allergic pneumonitis; prednisolone was administered for treatment. Bird-related hypersensitivity pneumonitis was suspected, as she had a gray parrot (Psittacus erithacus) and a budgerigar (Melopsittacus undulatus) at home. An immunoblotting analysis with the patient's serum demonstrated IgG-binding fractions to the gray parrot's feathers only; no binding was noted with the budgerigar antigens. The patient was conclusively diagnosed with hypersensitivity pneumonitis related to exposure to a gray parrot.

Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells.

BACKGROUND: There have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs) in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. METHODS: In FcγRIIB deficient (KO) and C57BL/6 (WT) mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA). Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs) in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs) differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL). RESULTS: In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. CONCLUSION: Antigen-specific IgG ameliorates allergic airway inflammation via FcγRIIB on DCs.

Pulmonary lymphangitic carcinomatosis secondary to ureteral cancer.

BACKGROUND: Pulmonary lymphangitic carcinomatosis (PLC) is a metastatic lung disease of malignant tumors that spread through pulmonary lymphatic vessels. Although prompt diagnosis and specific treatment of PLC are required due to the poor prognosis associated with this disease, it is often challenging to determine the primary cancer site. CASE PRESENTATION: A 67-year-old Japanese woman presented to our hospital with a 10-day history of cough and dyspnea on exertion. Chest radiography and computed tomography (CT) revealed diffuse nodular opacities with interlobular septal thickening. Both bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) revealed carcinoma cells with unknown origin. Contrast-enhanced CT depicted a mass in the right ureter with hydronephrosis, and retrograde urography showed a narrowing of the right ureter. Urine cytology from her right ureter via ureteral catheter also revealed atypical cells, highly suggestive of malignancy. Immunohistochemical examination of lung specimens via TBLB showed results consistent with lung metastasis of ureteral cancer. Therefore, we arrived at a diagnosis of PLC secondary to ureteral cancer. CONCLUSIONS: This case encouraged multidisciplinary discussion and a whole-body examination, including TBLB with immunohistochemistry, to determine the origin of PLC.

Effect of Bronchial Thermoplasty on Air Trapping Assessed by Xenon Ventilation Computed Tomography.

Objective Bronchial thermoplasty (BT) is a bronchoscopic procedure for patients with severe asthma. Although it has been suggested that BT works by reducing airway smooth muscle, the detailed mechanism underlying its effects is still unknown. Methods We performed xenon ventilation computed tomography (Xe-CT) before each BT procedure and six weeks after the third treatment to assess the improvement in lung ventilation at each separate lung region. The air trapping index in each lobe was defined as the mean trapping value (0: none, 1: mild, 2: moderate, and 3: severe) of the included segments. Patients and Materials Four patients were included. Results Asthma symptoms were improved after BT. The comparison of the scores at baseline with those after the third treatment showed that the air trapping index was improved in both the treated and untreated regions. However, neither the pulmonary function nor the exhaled nitric oxide was improved. Conclusion Using Xe-CT, we successfully evaluated the air trapping in patients who underwent BT. The improvement in asthma symptoms by BT may be related to the amelioration of peripheral lung ventilation in both the treated and untreated regions.

Prospective Study of Nocturnal Desaturation in Patients Receiving Home Oxygen Therapy.

Objective Nocturnal desaturation is common in patients with chronic respiratory disease and often worsens the prognosis. Therefore, it should be diagnosed accurately and appropriately treated. The aim of this study was to clarify the diversity of nocturnal desaturation. Methods We prospectively enrolled 58 outpatients diagnosed with chronic respiratory disease receiving home oxygen therapy and measured nocturnal SpO2 using a portable oximeter. We classified nocturnal desaturation (3% decrease in SpO2 from baseline) into three patterns: periodic pattern (desaturation duration of <655 seconds), sustained pattern (desaturation duration of ≥655 seconds), and intermittent pattern (desaturation and recovery of SpO2 repeated with a cycle of several minutes). Results Nocturnal hypoxemia (SpO2≤88% for more than 5 minutes) was found in 23.8% of patients. The percentage of patients with chronic obstructive pulmonary disease (COPD) was significantly higher in the nocturnal hypoxemia group than in the non-hypoxemia group (80% vs. 40.6%, p=0.03). Desaturation with a periodic pattern was found in 81% of patients, desaturation with a sustained pattern was found in 40.5% of patients, and desaturation with an intermittent pattern was found in 59.5% of patients. In patients with COPD, desaturation with a periodic pattern was found in 85.7%, desaturation with a sustained pattern was found in 47.6%, and desaturation with an intermittent pattern was found in 57.1%. Conclusion The SpO2 waveform of nocturnal hypoxemia was able to be classified into three patterns. Suitable treatment for each pattern might improve the prognosis of these patients.

The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner.

Asthma is a chronic inflammatory airway disease characterized by airway hyperreactivity, increased mucus production, and reversible airway contraction. Asthma is a complex genetic trait caused by environmental factors in genetically predisposed individuals. The transportation of maternal antigen-specific IgG via amniotic fluid, placenta and breast milk plays an important role in passive immunity. First, to examine whether maternal passive immunity by the transportation of antigen-specific IgG via FcRn regulates allergic airway inflammation, ovalbumin-immunized FcRn(+/-) female mice were bred with FcRn(-/-) male mice to evaluate the degree of ovalbumin-induced allergic airway inflammation of FcRn(-/-) offspring. Maternal passive immunity regulated allergic airway inflammation in an FcRn-dependent manner. Second, to examine the role of maternal antigen-specific IgG1 injection into mothers, we intravenously injected ovalbumin-specific IgG1 into wild-type or FcRn(+/-) mice immediately after they gave birth. The offspring were sensitized and challenged with ovalbumin. Antigen-specific IgG1 administered to lactating mice reduced allergic airway inflammation in their offspring in an FcRn-dependent manner. Last, to exclude the factor of maternal passive immunity other than ovalbumin-specific IgG1, we administered ovalbumin-specific IgG1 orally to offspring after birth. Oral administration of ovalbumin-specific IgG1 to offspring during the lactating period prevented the development of allergic airway inflammation in an FcRn-dependent manner. These data show that the transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner.

Black bronchoscopy in a patient with pulmonary malignant melanoma: A case report.

A 47-year-old Japanese man was referred to our hospital with a one-week history of chest discomfort. Chest computed tomography (CT) revealed a mass in the right upper lobe suspected to be primary lung cancer. A biopsy of the mass using endobronchial ultrasonography (EBUS) with guide sheath (GS) was performed, and a black-colored mass was observed which occluded almost all of the right B2 b bronchus. Immunohistochemistry of lung specimens was compatible with a diagnosis of malignant melanoma which was confirmed to be BRAF wild-type. Furthermore, positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) of the head revealed multiple metastatic lesions in the brain, liver, and bones. The patient was referred to another hospital for specific treatment. After that, the patient's melanoma was confirmed to have the BRAF wild-type gene and PD-L1 expression was 80%. Then, combined therapy of nivolumab plus ipilimumab was subsequently administered.

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.