Computed tomographic characteristics of testicular teratoma in a cat.

A 5-year-old intact male mixed-breed cat weighing 4.5 kg was referred to our hospital with a left testicular mass. CT revealed mild heterogeneous contrast enhancement and calcification in the testicular mass. A well-defined, contrast-enhancing, multiloculated mass with fluid-filled areas was extended from the testicular mass in the scrotum to the caudal aspect of the left kidney. The abdominal mass extended to the right crus of the diaphragm, and the gastrointestinal tract was compressed dorsally. Histopathology was consistent with teratoma. Characteristic CT findings in a feline testicular teratoma may include calcification and cystic areas.

D-dimer cut-off value for predicting venous thromboembolism at the initial diagnosis in Japanese patients with advanced lung cancer.

OBJECTIVE: Cancer is a well-known risk factor for venous thromboembolism. The D-dimer level is used to predict venous thromboembolism; however, reports on an appropriate D-dimer cut-off value in Japanese patients with advanced lung cancer are lacking. Therefore, this study aimed to calculate the D-dimer cut-off value for venous thromboembolism at the time of lung cancer diagnosis. METHODS: The Rising-venous thromboembolism/NEJ037 study was a multicenter, prospective observational study. Patients with lung cancer who were contraindicated for radical resection or radiation were enrolled and followed up for 2 years. In the present study (jRCT no. 061180025), a receiver operating characteristic curve for D-dimer levels was created using the dataset of the Rising-venous thromboembolism/NEJ037 study. RESULTS: The Rising-venous thromboembolism/NEJ037 study included a total of 1008 patients, of whom 976, whose D-dimer levels had been measured at the time of cancer diagnosis, were included in the present study. At the time of lung cancer diagnosis, 62 (6.3%) and 914 (93.7%) patients presented with and without venous thromboembolism, respectively. The D-dimer values ranged from 0.1 to 180.1 µg/ml and from 0.1 to 257.2 µg/ml in patients with and without venous thromboembolism, respectively. The receiver operating characteristic curve was discriminative with a cut-off value of 3.3 µg/ml and an area under the curve of 0.794 (sensitivity, 0.742; specificity, 0.782; 95% confidence interval, 0.725-0.863). CONCLUSIONS: This is the first study to calculate the D-dimer cut-off value in Japanese patients with advanced lung cancer. Patients with D-dimer levels ≥3.3 µg/ml at the time of initial diagnosis may have coexisting venous thromboembolism.

Suspected renal interstitial cell tumor causing polycythemia in two dogs.

Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia. RICT is a rare tumor in dogs, originating from renal interstitial cells. While several renal tumors such as renal lymphoma, adenocarcinoma, carcinoma, sarcoma, fibrosarcoma and nephroblastoma may cause polycythemia, polycythemia caused by RICT has never been reported in dogs. The tumors in both dogs were solitary and lied within cortex or cortico-medullary junction. Histopathology revealed spindle-shaped cells suggesting mesenchymal origin, with no mitotic figures suggesting that the tumors in both dogs were benign. Following surgical removal of the affected kidney, serum erythropoietin level and polycythemia normalized in both dogs.

Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study.

PURPOSE: Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC. METHODS: We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003). RESULTS: A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046). CONCLUSION: ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.

Risk Factors for Bleeding Events in Japanese Patients with Advanced Lung Cancer: Data from the Rising-VTE/NEJ037 Study.

Despite the occurrence of various hemorrhagic events during advanced lung cancer treatment, few researchers have reported on their risk factors. Moreover, the development of cancer-related thromboembolism indicates anticoagulant use. However, adverse events such as bleeding should be monitored. In this study, we aimed to identify factors that influence the onset of hemorrhagic events in patients with lung cancer. The Rising-VTE/NEJ037 study was a multicenter, prospective, observational study. A total of 1008 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Multivariate analysis using a Cox proportional hazard model was performed to compare the outcomes of the time to the onset of hemorrhagic events for 2 years after registration. Hemorrhagic events occurred in 115 patients (11.4%), with 35 (30.4%) experiencing major bleeding. Significant risk factors included venous thromboembolism (VTE) (hazard ratio [HR]: 4.003, p < 0.001) and an Eastern Cooperative Oncology Group Performance Status score of 1 (HR: 2.476, p < 0.001). Factors that significantly reduced hemorrhagic event risk were female sex (HR: 0.454, p = 0.002) and M1a status (HR: 0.542, p = 0.038). VTE is a risk factor for hemorrhagic events in patients with advanced lung cancer, and risks associated with anticoagulant therapy should be considered.

Effects of Alfaxalone on the Induction and Maintenance of Total Intravenous Anesthesia in Gentoo Penguins (Pygoscelis papua).

Systemic anesthesia in penguins is often achieved using inhalation anesthetic agents alone, and information on injectable drugs for systemic anesthesia is limited. General anesthesia with a minimal effect on circulatory dynamics is necessary to perform noninvasive examinations and treatments in animals, including penguins. In this study, alfaxalone (ALFX), an injectable anesthetic agent, was examined to establish the optimal anesthetic method for gentoo penguins (Pygoscelis papua). Alfaxalone was administered intravenously through the metatarsal vein, and anesthesia was maintained by a constant rate infusion (CRI). A biological monitor was used to record numerous clinical indices, and the anesthetic depth was evaluated every 5 minutes during anesthesia; the CRI was adjusted until the optimal anesthetic depth was obtained. Anesthesia depth was assessed, and the CRI rate was adjusted. The CRI was stopped, and the time until recovery was recorded. Blood samples were collected to analyze plasma concentrations of ALFX. The mean total dose of ALFX required for anesthetic induction was 9 ± 1.9 mg/kg, the intubation time was 126 ± 21 seconds, and the maintenance infusion rate of ALFX was 0.3 ± 0.08 mg/kg/min. The time from discontinuation of anesthesia to extubation was 42 ± 23 minutes, and the time to recovery was 90 ± 33 minutes. Significant changes in the heart rate and blood pressure were not observed during the anesthetic events. The plasma concentration of ALFX under stable anesthesia was 6734 ± 4386 ng/mL (range, 3315-14 326 ng/mL). Although anesthesia using ALFX tended to result in a prolonged time to recovery in gentoo penguins, rapid induction of anesthesia and stable hemodynamics during anesthetic maintenance were achieved. Therefore, ALFX may be considered a suitable anesthetic method for noninvasive examinations and treatments in penguins.

Effects of Antibacterial Agents on Cancerous Cell Proliferation.

Myelosuppression, a side effect of anticancer drugs, makes people more susceptible to infectious diseases by compromising the immune system. When a cancer patient develops a contagious disease, treatment with an anticancer drug is suspended or postponed to treat the infectious disease. If there was a drug that suppresses the growth of cancer cells among antibacterial agents, it would be possible to treat both infectious diseases and cancer. Therefore, this study investigated the effect of antibacterial agents on cancer cell development. Vancomycin (VAN) had little effect on cell proliferation against the breast cancer cell, MCF-7, prostate cancer cell, PC-3, and gallbladder cancer cell, NOZ C-1. Alternatively, Teicoplanin (TEIC) and Daptomycin (DAP) promoted the growth of some cancer cells. In contrast, Linezolid (LZD) suppressed the proliferation of MCF-7, PC-3, and NOZ C-1 cells. Therefore, we found a drug that affects the growth of cancer cells among antibacterial agents. Next, when we examined the effects of the combined use of existing anticancer and antibacterial agents, we found VAN did not affect the growth suppression by anticancer agents. However, TEIC and DAP attenuated the growth suppression of anticancer agents. In contrast, LZD additively enhanced the growth suppression by Docetaxel in PC-3 cells. Furthermore, we showed that LZD inhibits cancer cell growth by mechanisms that involve phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway suppression. Therefore, LZD might simultaneously treat cancer and infectious diseases.

Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data.

BACKGROUND: Management of cancer-associated venous thromboembolism (VTE) is essential in cancer treatment selection and prognosis. However, currently, no method exists for assessing VTE risk associated with advanced lung cancer. Therefore, we assessed VTE risk, including driver gene mutation, in advanced lung cancer and performed a Khorana score validation. METHODS: The Rising-VTE/NEJ037 study was a multicenter prospective observational study that included patients with advanced lung cancer. In the Rising-VTE/NEJ037 study, the Khorana score was calculated for enrolled patients with available data on all Khorana score components. The modified Khorana score was based on the body mass index of ≥ 25 kg/m2, according to the Japanese obesity standard. A multivariate logistic regression analysis, including patient background characteristics, was performed to evaluate the presence of VTE 2 years after the lung cancer diagnosis. RESULTS: This study included 1008 patients with lung cancer, of whom 100 (9.9%) developed VTE. From the receiver operating characteristic curve analysis, VTE risk could not be determined because both the Khorana score (0.518) and modified Khorana score (0.516) showed very low areas under the curve. The risk factors for VTE in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2 and diastolic blood pressure. CONCLUSION: The Khorana score, which is widely used in cancer-VTE risk assessment, was less useful for Japanese patients with advanced lung cancer. Prothrombin fragment 1 + 2, a serum marker involved in coagulation, was more suitable for risk identification. CLINICAL TRIAL INFORMATION: jRCTs061180025.

Pre-Existing Interstitial Lung Abnormalities Are Independent Risk Factors for Interstitial Lung Disease during Durvalumab Treatment after Chemoradiotherapy in Patients with Locally Advanced Non-Small-Cell Lung Cancer.

Introduction/Background: Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments; however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients and Methods: Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. Results: A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70; 95% confidence interval, 1.69−7.72; p < 0.001). Conclusions: We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs.

Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study).

Background: Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors. Methods: The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation. Results: Data were available for 1008 patients. The median age was 70 years (range: 30-94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group. Conclusions: VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate. Trial registration: jRCTs061180025.

First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study.

PURPOSE: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. METHODS: We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). RESULTS: Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. CONCLUSION: In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.

A new risk-assessment tool for venous thromboembolism in advanced lung cancer: a prospective, observational study.

Management of cancer-associated venous thromboembolism (VTE) is essential in treatment selection and cancer prognosis. However, to date, there is no method to assess the risk of VTE specifically associated with advanced lung cancer. Our aim was to create a new risk assessment scoring system that can predict the concomitant or incidence of VTE in advanced lung cancer. We used the dataset of 1008 patients with lung cancer in the Rising-VTE/NEJ037 study, of which 100 (9.9%) developed VTE. The items extracted in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2, and diastolic blood pressure. This model had a maximum score of 8 points, with ≥ 5 points indicating a high risk of VTE. This simple risk-assessment model for VTE complications with advanced lung cancer could help identify cases that required monitoring for VTE.

Phase 2 study of first-line pembrolizumab monotherapy in elderly patients with non-small-cell lung cancer expressing high PD-L1.

BACKGROUND: Pembrolizumab is the recommended first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, its efficacy and safety for patients ≥75 years have not been prospectively investigated; this was the aim of this study. METHODS: This multicenter and open-label single-arm phase II study was conducted at 12 institutions. Chemotherapy-naïve patients with advanced NSCLC and a PD-L1 TPS of ≥50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression-free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life. RESULTS: Twenty-six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1-20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade ≥3 treatment-related adverse events was 15.4%. The quality of life score did not change significantly during treatment. CONCLUSION: While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE-024 study), the median PFS did not achieve the expected value.

Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study.

The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan-Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05-2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31-3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.

A splicing factor phosphorylated by protein kinase A is increased in HL60 cells treated with retinoic acid.

Retinoic acid (RA) induces the differentiation of human promyelocytic leukemia HL60 cells into granulocytic cells and inhibits proliferation. Certain of actions of RA are mediated by RA nuclear receptors that regulate gene expression. However, it is also known that direct protein modification by RA (retinoylation) can occur. One such retinoylated protein in HL60 cells is a regulatory subunit of protein kinase A (PKA), which is increased in the nucleus following RA treatment and which then increases phosphorylation of other nuclear proteins. However, a complete understanding of which nuclear proteins are phosphorylated is lacking. In the current study, we employed mass spectrometry to identify one of the PKA-phosphorylated proteins as a serine/arginine-rich splicing factor 1 (SF2, SRSF1). We found that RA treatment increased the level of PKA-phosphorylated SF2 but decreased the level of SF2. While SF2 regulates myelogenous cell leukemia-1 (Mcl-1, anti-apoptotic factor), RA treatment reduced the level of Mcl-1L (full-length Mcl-1 long) and increased the level of Mcl-1S (Mcl-1 short; a short splicing variant of the Mcl-1). Furthermore, treatment with a PKA inhibitor reversed these effects on Mcl-1 and inhibited RA-induced cell differentiation. In contrast, treatment with a Mcl-1L inhibitor enhanced RA-induced cell differentiation. These results indicate that RA activates PKA in the nucleus, increases phosphorylation of SF2, raises levels of Mcl-1S and lowers levels of Mcl-1L, resulting in the induction of differentiation. RA-modified PKA may play an important role in inducing cell differentiation and suppressing cell proliferation.

Comparison of vascular endothelial growth factor/vascular endothelial growth factor receptor 2 expression and its relationship to tumor cell proliferation in canine epithelial and mesenchymal tumors.

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway plays an important role in tumor angiogenesis. VEGFR2 is expressed not only in vascular endothelial cells but also in tumor cells; however, the relationship of VEGF/VEGFR2 expression and tumor proliferation has yet to be elucidated. In addition, since several studies have reported that VEGFR2 inhibitors are more effective against epithelial tumors than mesenchymal tumors, there may be a difference in VEGF/VEGFR2 expression between epithelial and mesenchymal tumors. The purpose of this study was to elucidate differences in VEGF/VEGFR2 expression between epithelial and mesenchymal tumors and the relationship of VEGF/VEGFR2 expression and proliferation in canine tumor cells. We assessed 29 epithelial and 21 mesenchymal canine tumors for microvessel density (MVD), mRNA transcription levels of von Willebrand Factor (vWF) and endoglin, expression of VEGF, VEGFR2, and phosphorylated VEGFR2 (pVEGFR2), and proliferation index (PI) using real-time reverse transcription polymerase chain reaction and immunohistochemistry. VEGFR2 expression on vascular endothelial cells, MVD, and mRNA transcription levels of vWF and endoglin were not significantly different between the two groups. However, expression of VEGF, VEGFR2, and pVEGFR2 was higher in epithelial tumors (P<0.01). Moreover, PI correlated with pVEGFR2 expression in only epithelial tumors (P<0.01, Rs=0.543). These results suggest that the activity of VEGF/VEGFR2 signaling in tumor cells is raised in epithelial tumors, and that this signaling pathway may be related to tumor cell proliferation in epithelial tumors.

Pulmonary Alveolar Proteinosis with Severe Respiratory Failure Improved by Segmental Lung Lavage with Fiberoptic Bronchoscopy under General Anesthesia.

Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous materials accumulate in the alveolar compartments. A 72-year-old man was diagnosed with autoimmune PAP with severe respiratory failure. We decided to perform segmental lung lavage (SLL) with fiberoptic bronchoscopy under general anesthesia. If improvement was not significant, whole-lung lavage (WLL) would be done. SLL improved the respiratory failure and computed tomography findings. This case showed improvement in not only the area where lavage was done but also the non-lavaged area. SLL with fiberoptic bronchoscopy under general anesthesia might be an appropriate treatment option for patients with severe PAP.

Vitamin A in health care: Suppression of growth and induction of differentiation in cancer cells by vitamin A and its derivatives and their mechanisms of action.

Vitamin A is an important micro-essential nutrient, whose primary dietary source is retinyl esters. In addition, ß-carotene (pro-vitamin A) is a precursor of vitamin A contained in green and yellow vegetables that is converted to retinol in the body after ingestion. Retinol is oxidized to produce visual retinal, which is further oxidized to retinoic acid (RA), which is used as a therapeutic agent for patients with promyelocytic leukemia. Thus, the effects of retinal and RA are well known. In this paper, we will introduce (1) vitamin A circulation in the body, (2) the actions and mechanisms of retinal and RA, (3) retinoylation: another RA mechanism not depending on RA receptors, (4) the relationship between cancer and actions of retinol or ß-carotene, whose roles in vivo are still unknown, and (5) anti-cancer actions of vitamin A derivatives derived from fenretinide (4-HPR). We propose that vitamin A nutritional management is effective in the prevention of cancer.

Pulmonary pleomorphic carcinoma in an elderly patient treated with pembrolizumab shows a marked response.

Pulmonary pleomorphic carcinoma, a relatively rare histopathological subtype of non-small cell lung cancer, is a malignant neoplasm with a poor prognosis. Despite the reports of a good response to immune-checkpoint inhibitor, only a few reports of pembrolizumab as the first-line treatment exist. We report the case of a 78-year-old male with right lung mass, mediastinal, right neck, and supraclavicular lymphadenopathies. He was diagnosed with pulmonary pleomorphic carcinoma, cT4N3M1c, Stage IVB. The tumor cells showed high programmed death-ligand 1 (PD-L1) expression but no microsatellite instability. After three cycles of pembrolizumab as the first-line therapy, chest computed tomography revealed marked reduction in tumor diameter. No remarkable adverse events occurred. The patient is alive with no complaints and no disease progression and has continued pembrolizumab for 8 months. Thus, first-line pembrolizumab therapy appears beneficial against pulmonary pleomorphic carcinoma, at least when PD-L1 expression is high. It is also effective in elderly patients.

Efficacy of erlotinib and its effects on the quality of life of older patients with epidermal growth factor receptor-mutant non-small cell lung cancer: A prospective, multicenter, dose-modification study.

AIM: Gefitinib and erlotinib are efficacious and safe for older patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, prolonged use of epidermal growth factor receptor-tyrosine kinase inhibitors in older patients is difficult, owing to potential adverse events. Hence, dose reduction or treatment discontinuation is often required. We investigated the efficacy of low-dose first-line erlotinib and its effects on the quality of life of older patients with lung cancer. METHODS: A prospective, multicenter, phase II clinical trial was carried out in patients aged ≥75 years with epidermal growth factor receptor-mutant non-small cell lung cancer. Initially, 100 mg/day erlotinib was administered orally; if well tolerated, it was increased to 150 mg/day. The primary end-point was progression-free survival, and secondary end-points were the response rate, overall survival and change in quality of life ("Care Notebook" questionnaire). RESULTS: The median progression-free survival was 17.8 months, response rate was 63.6% and median overall survival was 27.8 months. The change in the quality of life after 6 weeks was assessed in 72.7% of the patients. Fatigue, pain, anxiety and deterioration in daily activities were found in at least 40% of the patients. Despite the therapeutic effect of 100 mg/day erlotinib, many patients required dose reduction, and in some, the quality of life could not be maintained. CONCLUSIONS: Many older patients with epidermal growth factor receptor-mutant non-small cell lung cancer might require treatment dose reduction. Further studies are required to develop individualized treatments for older patients with lung cancer. Geriatr Gerontol Int 2021; 21: 881-886.