Airway stenosis secondary to mediastinal lymph node metastasis of lung adenocarcinoma treated with AERO stent and osimertinib: A case report.

A woman in her mid-50s was admitted to our hospital with airway stenosis secondary to mediastinal lymph node enlargement. An AERO stent was placed under rigid bronchoscopy. Immediately after stent placement, tissue sampling was performed on the lymph nodes. Metastatic lesions were found to have an EGFR mutation (exon 19 deletion). Consequently, osimertinib treatment was initiated 15 days after stent placement. The tumour partially responded to osimertinib, and the airway stenosis improved. The patient underwent stent removal 66 days after stent placement. Our findings indicate that temporary oncological emergencies due to airway stenosis may be bridged by airway stenting.

Safety and efficacy of airway stent placement following bronchial artery embolization: A retrospective study at a single institute.

BACKGROUND: Airway stenting is an established procedure for treating oncological emergencies in patients with airway disorders. In patients with airway hemorrhage, respiratory conditions may worsen during stenting. Bronchial artery embolization (BAE) is useful to prevent bleeding from the bronchus. We aimed to evaluate the efficacy and safety of airway stenting after BAE in patients with malignant airway disorders. METHODS: The medical records of all patients who underwent airway stenting following BAE at the National Hospital Organization Okayama Medical Center between 2016 and 2023 were retrospectively reviewed. RESULTS: Thirteen procedures (11 silicone Y stents, one hybrid stent, and one self-expandable metallic stent) were performed. The median duration from BAE to airway stenting was one day (range: 1-5 days). Nine patients experienced tumor shrinkage, and none experienced severe bleeding after BAE during the stent procedure. No other major complications were associated with the stent placement. The median survival time after stenting was 169 days (range; 24-1086). No serious complications caused by BAE, such as spinal cord infarction, were observed. CONCLUSIONS: Airway stent placement was safely performed after BAE without severe bleeding or acute respiratory failure. BAE, followed by airway stenting, is useful.

Successful ultrathin bronchoscopy with cryobiopsy for diagnosing and removing mucus plugs in allergic bronchopulmonary mycosis mimicking lung cancer.

In patients presenting with abnormal pulmonary nodules, especially those with a history of asthma, allergic bronchopulmonary mycosis should be considered. Eosinophil counts and IgE levels should be checked in such patients.

Autopsy case of meningoencephalitis induced by nivolumab and ipilimumab in a patient being treated for non-small cell lung cancer.

A 75-year-old woman with stage IVB (cT2bN3M1b) lung adenocarcinoma was administered nivolumab, ipilimumab, carboplatin, and paclitaxel. Fourteen days after receiving chemotherapy, she experienced an impaired consciousness and a cerebrospinal fluid analysis revealed high protein levels and pleocytosis. She was diagnosed with nivolumab- and ipilimumab-induced encephalitis and was treated with corticosteroids which were tapered to 10 mg/day, with no symptom recurrence. She died 18 weeks after the initial presentation, as the cancer worsened. An autopsy showed encephalitis and CD8+ lymphocyte infiltration around the blood vessels. Thus, immune-related adverse events should be suspected and treatment should be initiated for patients presenting with an impaired consciousness when concurrently being treated with nivolumab and ipilimumab.

A Case of Pancreatic Neuroendocrine Tumor with Liver Metastases Demonstrating the Possibility of Enhanced ACTH Production by the SACI Test.

Objective: ACTH-producing pancreatic NETs have a propensity to metastasize, and in patients with metastases, there is no established method yet to precisely determine if the excess ACTH is produced by the primary or the metastatic tumors. Localizing the source of production of ACTH in such cases is important for devising suitable treatment strategies and evaluating the benefit of local therapies from the viewpoint of control of Cushing's syndrome. Methods: We performed the selective arterial calcium injection (SACI) test combined with selective portal and hepatic venous sampling in a 32-year-old female patient with ectopic ACTH-producing pancreatic NET and liver metastases. Results: The blood level of ACTH after Ca loading was significantly elevated only in the vessels thought to be directly feeding the pancreatic tumor, and Ca loading from any artery did not significantly increase ACTH concentrations in the hepatic veins compared to the main trunk of the portal vein. Conclusions: The present case demonstrates that there might be an ACTH-producing p-NET that responds to Ca loading. Further in vitro studies are required to validate this possibility.

Secondary Pulmonary Alveolar Proteinosis Development during the Treatment for Anti-aminoacyl-tRNA Synthetase Antibody-positive Interstitial Lung Disease.

A 70-year-old woman with anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease (ARS-ILD) received daily medications and regular cyclophosphamide cycles for recurring exacerbations. Approximately four years after immunosuppression initiation, the patient was admitted for progressive dyspnea on exertion. Chest computed tomography (CT) findings were suggestive of acute exacerbation. Despite intensified immunosuppressive treatment, the radiographic findings worsened, and serum Krebs von den Lungen-6 (KL-6) levels increased. A bronchoalveolar lavage fluid (BALF) examination revealed amorphous globules and alveolar macrophages with eosinophilic granules. Owing to negative anti-GM-CSF antibody tests, a diagnosis of secondary pulmonary alveolar proteinosis (PAP) was established.

Large-vessel vasculitis induced by pegfilgrastim and immune checkpoint inhibitor in a patient with small-cell lung cancer.

A 75-year-old woman with stage IVB (cT3N3M1c) extensive disease small-cell lung cancer was treated with carboplatin, etoposide, and atezolizumab. Ten days after pegfilgrastim initiation, during the second chemotherapy cycle, she experienced back pain. Contrast-enhanced computed tomography revealed soft tissue thickening around the descending aorta and brachiocephalic artery. She was diagnosed with atezolizumab and pegfilgrastim-induced large-vessel vasculitis (LVV) and was treated with prednisolone, which was tapered and discontinued after 14 weeks, with no symptom recurrence. LVV should be included in the differential diagnosis of patients with nonspecific body pain when pegfilgrastim and immune checkpoint inhibitors are used in combination.

Effectiveness of AERO Stent Placement for Malignant Airway Disorder in Patients with a Poor Performance Status.

Objective Airway stenting is an established procedure for treating various airway disorders. The AERO stent (Merit Medical Systems, South Jordan, UT, USA) is a fully covered self-expandable metallic stent approved for use in Japan in 2014. However, its effectiveness in treating malignant airway disorders in patients with a poor performance status remains unclear. Therefore, we investigated the safety and efficacy of the AERO stent in patients with malignant airway disorders and a poor performance status. Patients and Methods We retrospectively reviewed the medical records of all patients who underwent AERO stent placement at our institute between April 2016 and March 2022, and 21 patients underwent 25 procedures for malignant airway disorders. All AERO stenting procedures were performed using an over-the-wire delivery system with flexible and/or rigid bronchoscopy. Results Eighteen of the 21 patients (85.7%) had a poor general condition (Eastern Cooperative Oncology Group performance status 3 or 4). AERO stents were successfully placed in 23 of the 25 procedures and migrated in the remaining 2 cases. Complications occurred in 10 cases, with infection being the most common (3 cases). Fourteen patients (66.6%) showed an improvement in their performance status. In addition, 5 of the 6 intubated patients were extubated following AERO stenting, and 11 patients subsequently received anticancer treatment. Conclusion The placement of the AERO stent is useful in patients with a poor performance status, including those who are intubated and afflicted with malignant airway disorders.

Distinct development trajectories and symbiosis modes in vent shrimps.

Most animal species have a singular developmental pathway and adult ecology, but developmental plasticity is well-known in some such as honeybees where castes display profoundly different morphology and ecology. An intriguing case is the Atlantic deep-sea hydrothermal vent shrimp pair Rimicaris hybisae and R. chacei that share dominant COI haplotypes and could represent very recently diverging lineages or even morphs of the same species. Rimicaris hybisae is symbiont-reliant with a hypertrophied head chamber (in the Mid-Cayman Spreading Centre), while R. chacei is mixotrophic with a narrow head chamber (on the Mid-Atlantic Ridge). Here, we use X-ray micro-computed tomography and fluorescence in situ hybridization to show that key anatomical shifts in both occur during the juvenile-subadult transition, when R. hybisae has fully established symbiosis but not R. chacei. On the Mid-Atlantic Ridge, the diet of R. chacei has been hypothetically linked to competition with the obligatorily symbiotic congener R. exoculata, and we find anatomical evidence that R. exoculata is indeed better adapted for symbiosis. We speculate the possibility that the distinct development trajectories in R. hybisae and R. chacei may be determined by symbiont colonization at a "critical period" before subadulthood, though further genetic studies are warranted to test this hypothesis along with the true relationship between R. hybisae and R. chacei.

Genetic divergence and migration patterns of a galatheoid squat lobster highlight the need for deep-sea conservation.

Information on genetic divergence and migration patterns of vent- and seep-endemic macrobenthos can help delimit biogeographical provinces and provide scientific guidelines for deep-sea conservation under the growing threats of anthropogenic disturbances. Nevertheless, related studies are still scarce, impeding the informed conservation of these hotspots of deep-sea biodiversity. To bridge this knowledge gap, we conducted a population connectivity study on the galatheoid squat lobster Shinkaia crosnieri - a deep-sea foundation species widely distributed in vent and seep ecosystems in the Northwest Pacific. With the application of an interdisciplinary methodology involving population genomics and oceanographic approaches, we unveiled two semi-isolated lineages of S. crosnieri with limited and asymmetrical gene flow potentially shaped by the geographic settings, habitat types, and ocean currents - one comprising vent populations in the Okinawa Trough, with those inhabiting the southern trough area likely serving as the source; the other being the Jiaolong (JR) seep population in the South China Sea. The latter might have recently experienced a pronounced demographic contraction and exhibited genetic introgression from the Okinawa Trough lineage, potentially mediated by the intrusion of the North Pacific Intermediate Water. We then compared the biogeographic patterns between S. crosnieri and two other representative and co-occurring vent- and seep-endemic species using published data. Based on their biogeographical subdivisions and source-sink dynamics, we highlighted the southern Okinawa Trough vents and the JR seep warrant imperative conservation efforts to sustain the deep-sea biodiversity in the Northwest Pacific.

Discovery and Genetic Characterization of a Vestimentiferan, Lamellibrachia satsuma, from the Submarine Volcano Omuro Dashi in the Izu-Ogasawara Arc.

Vestimentiferan tube worms (Annelida: Siboglinidae) were discovered in a hydrothermal field at a depth of 195 m in the crater of the submarine volcano Omuro Dashi in the Izu-Ogasawara Arc. Based on the nucleotide sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene in individuals sampled in 2022, they were identified as Lamellibrachia satsuma Miura, Tsukahara & Hashimoto, 1997. STRUCTURE analysis and discriminant analysis of principal components (DAPC) based on 14 microsatellite markers showed a large genetic deviation of the population of Omuro Dashi from those of Kagoshima Bay and the north Mariana Arc (the Nikko and Daikoku Seamounts), whereas the population of Omuro Dashi did not show significant genetic deviation from that of the Nikko Seamount based on the COI gene. All analyses showed that individuals of a methane seep area on the Kanasu-No-Se Bank, the Nankai Trough, which were collected only in 1994, were more closely related to those of Omuro Dashi than to those of other habitats. These results suggest that the ancestors of the Omuro Dashi and Nankai Trough populations originated from migrants from the north Mariana Arc and that there might be undiscovered source population(s) of L. satsuma around the Nankai Trough.

Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer.

Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.

Successful Treatment with Mepolizumab for Coronary Spastic Angina Associated with Eosinophilic Granulomatosis with Polyangiitis.

A 46-year-old man with a history of bronchial asthma and chronic sinusitis presented to our hospital with chest pain. We suspected angina evoked by epicardial coronary spasm and performed an ergonovine provocation test to diagnose coronary spastic angina (CSA). The patient also met the diagnostic criteria for eosinophilic granulomatosis with polyangiitis (EGPA) and was treated with 60 mg prednisolone (PSL) for EGPA-associated CSA. After PSL administration, eosinophils decreased, and angina attacks disappeared. However, when PSL was tapered to 12.5 mg, chest pain recurred. We administered mepolizumab subcutaneously and chest pain disappeared. Additional mepolizumab may be effective for EGPA with CSA.

From commensalism to parasitism within a genus-level clade of barnacles.

Understanding how animals evolve to become parasites is key to unravelling how biodiversity is generated as a whole, as parasites could account for half of all species richness. Two significant impediments to this are that parasites fossilize poorly and that they retain few clear shared morphological features with non-parasitic relatives. Barnacles include some of the most astonishingly adapted parasites with the adult body reduced to just a network of tubes plus an external reproductive body, but how they originated from the sessile, filter-feeding form is still a mystery. Here, we present compelling molecular evidence that the exceedingly rare scale-worm parasite barnacle Rhizolepas is positioned within a clade comprising species currently assigned to Octolasmis, a genus exclusively commensal with at least six different phyla of animals. Our results imply that species in this genus-level clade represent an array of species at various transitional stages from free-living to parasitic in terms of plate reduction and host-parasite intimacy. Diverging only about 19.15 million years ago, the route to parasitism in Rhizolepas was associated with rapid modifications in anatomy, a pattern that was likely true for many other parasitic lineages.

PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer.

OBJECTIVES: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored. MATERIALS AND METHODS: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined. RESULTS: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity. CONCLUSION: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.

Lambert-Eaton Myasthenic Syndrome Recurrence Induced by Pembrolizumab in a Patient with Non-small-cell Lung Cancer.

A 73-year-old woman in complete remission from localized small-cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) 22 years earlier was referred to our hospital and diagnosed with non-small-cell lung cancer. After three courses of pembrolizumab, an immune checkpoint inhibitor, the patient complained of muscle weakness, fatigue, ptosis, and dysarthria. The anti-voltage-gated calcium channel antibody level was elevated, and waxing was observed on a high-frequency repetitive stimulation test using an electromyogram. We diagnosed her with recurrence of LEMS as an immune-related adverse event (irAE) induced by pembrolizumab. After intravenous immunoglobulin therapy, the patient's symptoms improved, and she was discharged.

Species assemblage networks identify regional connectivity pathways among hydrothermal vents in the Northwest Pacific.

The distribution of species among spatially isolated habitat patches supports regional biodiversity and stability, so understanding the underlying processes and structure is a key target of conservation. Although multivariate statistics can infer the connectivity processes driving species distribution, such as dispersal and habitat suitability, they rarely explore the structure. Methods from graph theory, applied to distribution data, give insights into both connectivity pathways and processes by intuitively formatting the data as a network of habitat patches. We apply these methods to empirical data from the hydrothermal vent habitats of the Northwest Pacific. Hydrothermal vents are "oases" of biological productivity and endemicity on the seafloor that are imminently threatened by anthropogenic disturbances with unknown consequences to biodiversity. Here, we describe the structure of species assemblage networks at hydrothermal vents, how local and regional parameters affect their structure, and the implications for conservation. Two complementary networks were formed from an extensive species assemblage dataset: a similarity network of vent site nodes linked by weighted edges based on their pairwise assemblage similarity and a bipartite network of species nodes linked to vent site nodes at which they are present. Using these networks, we assessed the role of individual vent sites in maintaining network connectivity and identified biogeographic sub-regions. The three sub-regions and two outlying sites are separated by their spatial arrangement and local environmental filters. Both networks detected vent sites that play a disproportionately important role in regional pathways, while the bipartite network also identified key vent sites maintaining the distinct species assemblages of their sub-regions. These regional connectivity pathways provide insights into historical colonization routes, while sub-regional connectivity pathways are of value when selecting sites for conservation and/or estimating the multivent impacts from proposed deep-sea mining.

COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma.

We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy.

Clinical utility of whole body diffusion-weighted imaging in an immunocompetent adult with atypical cat scratch disease.

BACKGROUND: Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae. CSD follows a typical course, characterized by regional lymphadenopathy. In atypical CSD, the lesions spread to systemic organs and can cause fever of unknown origin (FUO). A previous study showed the usefulness of whole-body magnetic resonance imaging (WB-MRI) with diffusion-weighted imaging (DWI) for limited areas in the diagnosis of FUO, but there are no studies on the clinical utility of whole-body DWI (WB-DWI). We herein report the case of an immunocompetent young man in whom contrast-enhanced CT-unidentifiable multiple liver abscess and osteomyelitis were successfully detected by WB-DWI. Follow-up with a liver biopsy helped confirm an atypical CSD diagnosis. CASE PRESENTATION: A 23-year-old previously healthy man was admitted for a 19-day history of high fever despite 3-day treatment by azithromycin. His physical examination was unremarkable and contrast-enhanced CT showed only a low attenuated area in the right lobe of the liver, indicating a cyst. WB-DWI revealed multiple nodular lesions of hypo-diffusion in the liver, spine, and pelvic region. The biopsy specimens of the liver abscess showed no evidence of tuberculosis/malignancy and the polymerase chain reaction (PCR) test of liver abscess aspirate showed positive findings for Bartonellahenselae, confirming the diagnosis of CSD. He completed minocycline monotherapy for a total of 60 days without any deterioration. CONCLUSIONS: WB-DWI can be useful for the diagnosis of atypical CSD with hepatic and bone involvement, which can cause FUO in young immunocompetent adults.