Clinical Features of Patients With Hematological Malignancies Treated at the Palliative Care Unit.

Background: In Japan, the number of patients with aggressive hematological malignancies (PHMs) admitted at the palliative care unit (PCU) in their end-of-life (EOL) stage was fewer than that of patients with solid tumors due to several reasons. The assessment of patient characteristics and the methods of survival prediction among PHMs in the EOL stage are warranted. Objectives: This study aimed to identify the current medical status and the method of survival prediction among PHMs treated at the PCU. Setting/Subjects/Measurements: We retrospectively analyzed the clinical data of 25 PHMs treated at our PCU between January 2017 and December 2020. The association between survival time and the palliative prognostic score (PAP) and palliative prognostic index (PPI) was analyzed. Results: The average age of the PHMs was higher than that of patients with lung cancer as a control. The median survival time of the PHMs was shorter than the control group. Most PHMs could not receive standard chemotherapy, and the most common cause of death was disease-related organ failure. Significant associations were observed between the survival time and each PAP/PPI value in patients with malignant lymphoma, but not in those with leukemia. Conclusion: The PHMs in the PCU had a lower median survival time than the control group. These results were induced by the result of patient selection to avoid treatment-related severe toxicity. The survival prediction using the PAP and PPI was less accurate in patients with leukemia.

A surgical case of pulmonary adenocarcinoma in the right upper lobe associated with a systemic artery-to-pulmonary artery fistula.

A 52-year-old female never-smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast-enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video-assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review.

The complexity of EGFR exon 19 deletion and L858R mutant cells as assessed by proteomics, transcriptomics, and metabolomics.

Most lung adenocarcinoma-associated EGFR tyrosine kinase mutations are either an exon 19 deletion (19Del) or L858R point mutation in exon 21. Although patients whose tumors contain either of these mutations exhibit increased sensitivity to tyrosine kinase inhibitors, progression-free and overall survival appear to be longer in patients with 19Del than in those with L858R. In mutant-transfected Ba/F3 cells, 19Del and L858R were compared by multi-omics analyses including proteomics, transcriptomics, and metabolomics. Proteome analysis identified increased plastin-2, TKT, PDIA5, and ENO1 expression in L858R cells, and increased EEF1G expression in 19Del cells. RNA sequencing showed significant differences between 19Del and L858R cells in 112 genes. Metabolome analysis showed that amino acids, adenylate, guanylate, NADPH, lactic acid, pyruvic acid glucose 6-phosphate, and ribose 5-phosphate were significantly different between the two mutant cells. Because GSH was increased with L858R, we combined osimertinib with the GSH inhibitor buthionine sulfoximine in L858R cells and observed synergistic effects. The complexity of EGFR 19Del and L858R mutant cells was demonstrated by proteomics, transcriptomics, and metabolomics analyses. Therapeutic strategies for lung cancer with different EGFR mutations could be considered because of their different metabolic phenotypes.

Herpes zoster in lung cancer patients treated with PD-1/PD-L1 inhibitors.

Background: Herpes zoster (HZ) occurs mostly in elderly and immunocompromised individuals. Immune reconstitution may be associated with the pathogenesis of HZ. As immune checkpoint inhibitor (ICI) treatment amplifies the immune response, use of ICI may increase the incidence of HZ. There have been few studies of HZ in lung cancer patients treated with ICI. This study was performed to investigate the frequency of HZ in lung cancer patients who received ICI or cytotoxic chemotherapeutic agents. Methods: We searched the electronic medical records for lung cancer patients receiving anticancer drug therapy at our hospital, who developed HZ between April 2011 and June 2020. Results: The review identified 80 patients with a history of ICI treatment (ICI group) and 356 who had been treated with cytotoxic chemotherapeutic agents alone (non-ICI group). Among the 20 patients who developed HZ, 4 (5.0%) belonged to the ICI group and 16 (4.5%) to the non-ICI group (P=0.782). After exclusion of patients aged 65 years and older, to avoid effects of advanced age on the results, the ICI and non-ICI groups consisted of 24 and 81 patients, respectively. In total, 3 of the 24 patients (12.5%) in the ICI group and 1 of the 81 (1.2%) patients in the non-ICI group developed HZ (P=0.0365). Conclusions: There was no significant difference in the rate of HZ between lung cancer patients treated with ICI and those treated with cytotoxic chemotherapy alone. However, patients younger than 65 years treated with ICI might be at increased risk of HZ. Because this is a retrospective small study, further prospective observational studies are needed.

Targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer cells.

Lung cancer that exhibits epidermal growth factor receptor (EGFR) gene mutation is sensitive to EGFR-tyrosine kinase inhibitors (TKIs), such as osimertinib. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) may be involved in overcoming EGFR-TKI resistance. Growth inhibition, colony formation, apoptosis, and mRNA/protein levels in four osimertinib-sensitive and resistant cell lines transfected with small interfering RNA (siRNA) targeting ROR1 (siROR1) were evaluated. Cell growth and colony formation were suppressed and apoptosis was increased in all cell lines treated with siROR1. Although EGFR, AKT, and ERK phosphorylation were not suppressed in all cell lines, TGF-ß2, AXL, CDH2, PARP1, PEG10, and TYMS mRNA expression levels were reduced. The combination of osimertinib with siROR1 was effective for the four cell lines, particularly in the two osimertinib-sensitive lines. In conclusion, targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer may be a novel therapeutic option.

IgA Vasculitis in a Lung Cancer Patient During Chemoradiotherapy.

A 72-year-old man with locally advanced lung squamous cell carcinoma experienced red purpura on the lower legs and hematuria when the disease progressed during definitive chemoradiotherapy. He had renal dysfunction and proteinuria. Biopsy specimens of the skin lesion and kidney revealed immunoglobulin A vasculitis. Potential causes such as paraneoplastic syndrome and cancer treatment have been proposed. The administration of steroids rapidly improved the symptoms. The presentation of immunoglobulin A vasculitis is accompanied by malignancies. Clinicians should keep this syndrome in mind, even during curative-intent treatment.

Lung cancer metastasis to the pancreas mimicking autoimmune pancreatitis.

The unique radiological manifestation mimicking autoimmune pancreatitis caused by lung cancer metastasis to the pancreas has not previously been reported. The incidence of pancreatic secondary tumors has previously been reported to be approximately 15% in autopsy cases of malignant tumors, and it is unusual for thoracic oncologists to find that the second common primary tumor site of metastatic pancreas tumor is the lung.

Do Elderly Lung Cancer Patients Aged ≥75 Years Benefit from Immune Checkpoint Inhibitors?

Lung cancer patients ≥75 years represent nearly 40% of all lung cancer patients and continue to increase. If elderly patients have a good performance status and adequate organ function, they can be treated the same as non-elderly patients. However, few comparative studies limited to elderly patients (≥75 years) have been conducted. We review the evidence on using immune check inhibitors for the treatment of elderly patients (≥75 years old) with advanced non-small cell lung cancer. Prospective randomized or non-randomized, retrospective, registrational, insurance-based, and community-based studies have shown that elderly (≥75 years) and non-elderly patients are similarly treated with immune check inhibitors effectively and safely. However, such analyses have not shown that immune check inhibitors are significantly more effective than chemotherapy alone. In addition, patient selection might be critically performed to administer immune check inhibitors in the elderly because they are more likely to have a poor performance status with comorbidities, which lead to little benefit, even in non-elderly patients. There is a need for more evidence showing the benefit of immune check inhibitors in non-small cell lung cancer patients ≥75 years.

Targeting ROR1 in combination with pemetrexed in malignant mesothelioma cells.

OBJECTIVE: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in a subset of malignant cells. However, it remains unknown whether ROR1 is targetable in malignant mesothelioma (MM). Therefore, in this study, we investigated the effects of ROR1 inhibition in mesothelioma cells. MATERIALS AND METHODS: Growth inhibition, colony formation, apoptosis, and mRNA/protein levels using siRNA-transfected MM cells were evaluated. Cluster analysis using Gene Expression Omnibus repository of transcriptomic information was also performed. RESULTS: Our results indicated that in three (H2052, H2452, and MESO-1) among four MM cell lines, ROR1 inhibition had anti-proliferative and apoptotic effects and suppressed the activation of AKT and STAT3. Although growth inhibition by siROR1 was minimal in another mesothelioma cell line (H28), colony formation was significantly suppressed. Microarray, quantitative polymerase chain reaction, and Western blot analyses showed that there were differences in the suppression of mRNA and proteins between H2452 and H28 cells transfected with siROR1 compared with those transfected with control siRNA. Cluster analysis further showed that MM tumors had relatively high ROR1 expression, although the cluster in them was different from that in MM cell lines. Thymidylate synthase, a target of pemetrexed, was downregulated in H2452 cells transfected with siROR1. Accordingly, a combination of pemetrexed with siROR1 was found to be effective in the three MM cell lines we studied. CONCLUSION: Our findings may provide novel therapeutic insight into the treatment of advanced MM.

Descending necrotizing mediastinitis in a healthy young adult.

A 26-year-old man with right lower mandibular and chest pain, fever, and respiratory distress was urgently transported to our hospital. CT images revealed gas collection and an abscess from the neck to the mediastinum with bilateral pleural effusion. Descending necrotizing mediastinitis (DNM) induced by an odontogenic infection of a right mandibular molar abscess was diagnosed. The cervical and mediastinal areas were drained, extensive debridement was performed, necrotic tissue was excised, and broad-spectrum antibiotics were administered immediately. Prompt diagnosis and intensive care were necessary for managing the DNM, and the patient was discharged with no comorbidities.

Drug-induced interstitial lung disease in the treatment of malignant lymphoma as a potential diagnostic marker: a comparison of serum Krebs von Lungen-6 and thymus and activation-regulated chemokine/CC chemokine ligand 17.

PURPOSE: Cure-oriented treatment of malignant lymphoma (ML) is possible even in an advanced stage; however, the progression of drug-induced interstitial lung disease (DILD) sometimes accounts for poor clinical outcomes. This study aims to assess the incidence and clinical characteristics of DILD among patients with ML and compares the serum level of Krebs von den Lungen-6 (KL-6) with that of circulating thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17) as a diagnostic biomarker for DILD. PATIENTS AND METHODS: Between July 2011 and August 2016, we enrolled 36 patients with ML who were undergoing systemic chemotherapy at our hospital. Then, we evaluated the serum concentration of KL-6 and TARC/CCL17 by a sandwich-type electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: DILD developed in 22.2% of patients with ML. All patients recovered immediately after the discontinuation of causative drug and/or glucocorticoid therapy. Although the sensitivity of both TARC/CCL17 and KL-6 was almost equal, the mean concentration of serum KL-6 after the progression of interstitial lung disease was significantly higher than that before progression. CONCLUSION: DILD developed in patients who were treated with first-line rituximab combined regimen. Remarkably, TARC/CCL17 and KL-6 seemed approximately equal as a predictive biomarkers for DILD; however, KL-6 was more specific than TARC/CCL17.

Publication of lung cancer clinical trials in the Japanese Clinical Trial Registry.

INTRODUCTION: Since June 2005, the University Hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR) has been an International Committee of Medical Journal Editors (ICMJE)-approved clinical trial registry in Japan. The number of clinical trials registered in the UMIN-CTR has increased annually. To date, no report exists regarding the publishing of clinical trials registered in the UMIN-CTR. Therefore, we evaluated the publication frequency of clinical trials registered in the UMIN-CTR in Japan. METHODS: We targeted trials that assessed the treatment effect of chemotherapy or molecular targeting drugs for lung cancer. We included trials registered between June 2005 and January 2010, and identified published trials through a computer-based search of MEDLINE and Google Scholar. The cumulative publication rate of the trials was calculated using Kaplan-Meier analysis. RESULTS: In our study, 179 trials met the inclusion criteria. Of these, 46.4% (83/179) trials were published by the end of the cut-off period. With regard to publication, differences existed between the information recorded in the UMIN-CTR database and the actual searched results. The publication rate between groups was insignificantly different; however, whether a clinical study group did or did not conduct a trial differed significantly (53.3% vs. 36.1%; P = 0.024). Phase II studies with positive results were more likely to be published (84.4%); however, the overall publication rate was low (41.8%), which may reflect publication bias. CONCLUSIONS: The UMIN-CTR fundamentally functions as the unique ICMJE-approved clinical trial registry in Japan. However, it seems insufficient to require it as the official clinical database.

Patients with osteosarcoma and soft tissue sarcoma might become "cancer refugees" in some Japanese regional cities.

PURPOSE: "Rare cancer" is defined as malignancy with a disease prevalence (age-adjusted incidence rate) of less than six per 100,000 population. Proper treatments which these patients need cannot always be performed unless they find dedicated facilities. Patients tend to be desperate, searching for advice and care. Thus, they are called "cancer refugees". Osteosarcoma and soft tissue sarcoma (OS/STS) are representative rare cancers in Japan. We conducted a retrospective analysis of patients with OS/STS to improve the current treatment modalities in a Japanese regional city. PATIENTS AND METHODS: Twenty-one patients with OS/STS who were hospitalized to receive standard chemotherapy or palliative treatment were enrolled between October 2011 and January 2017. Patients with non-Hodgkin's lymphoma (NHL) and advanced cancer who were treated in the palliative care unit (PCU) of the Kawasaki Medical School General Medical Center were recruited as the control groups. We analyzed the difference in residential area between patients with OS/STS and the control groups. RESULTS: Approximately one-third of patients with OS/STS were referred from hospitals outside of Okayama prefecture. The ratio of patients with OS/STS referred from Okayama city and/or the same medical administration area of Okayama prefecture was lower than that of patients with NHL and advanced cancer who were treated in the PCU. CONCLUSION: Because the medical environment of patients with OS/STS in Japanese local cities has not been consolidated, completing medical care within the patient's own medical administration area is difficult. Thus, some patients with OS/STS may become "cancer refugees" who are unable to receive standard therapy near their residence.

Ceftriaxone-associated pancreatitis captured on serial computed tomography scans.

A 74-year-old man was treated with ceftriaxone for 5 days and subsequently experienced epigastric pain. Computed tomography (CT) was performed 7 and 3 days before epigastralgia. Although the first CT image revealed no radiographic signs in his biliary system, the second CT image revealed dense radiopaque material in the gallbladder lumen. The third CT image, taken at symptom onset, showed high density in the common bile duct and enlargement of the pancreatic head. This is a very rare case of pseudolithiasis involving the common bile duct, as captured on a series of CT images.

High Uptake of FDG Along a Biliary Stent.

A 66-year-old woman presented with abdominal discomfort. Contrast-enhanced CT revealed a mass in the pancreas and multiple liver metastases. Pathological examination confirmed the mass to be primary pancreatic cancer. Endoscopic insertion of a biliary stent was performed to prevent common bile duct obstruction. Subsequently, she received combination chemotherapy, which resulted in a complete response. FDG-PET-CT after chemotherapy revealed a high uptake of FDG along the outline of the biliary stent, with complete disappearance of both the primary and metastatic tumors.