Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma.

BACKGROUND: This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach. METHODS: We used the Toray® 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers. RESULTS: (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P < 0.001, area under the receiver operating characteristic curve = 0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P = 0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P = 0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (ρ = 0.64, P = 0.005) between miR-210-3p expression in plasma and urine. CONCLUSIONS: Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC. TRIAL REGISTRATION: Not applicable.

Cancer-Derived Small Extracellular Vesicles Affect Vascular Endothelial Cells and Promote Adhesiveness of Pancreatic Cancer Cells.

OBJECTIVES: Pancreatic cancer (PC) is one of the most aggressive malignancies due to the high rate of metastasis. The mechanisms underlying metastasis need to be elucidated. Small extracellular vesicles (sEVs) mediate cell-to-cell communication, and cancer-derived sEVs contribute to the formation of premetastatic niches. The present study examined changes in adhesiveness by the internalization of PC-derived sEVs into vascular endothelial cells, and investigated the molecular mechanisms underlying metastasis. MATERIALS AND METHODS: Pancreatic cancer-derived sEVs were internalized into vascular endothelial cells, and changes in adhesiveness were evaluated. We evaluated the effects of sEVs on the formation of liver metastasis in vivo. We also assessed molecular changes in vascular endothelial cells by the internalization of PC-derived sEVs. RESULTS: The internalization of PC-derived sEVs into vascular endothelial cells promoted the adhesiveness of vascular endothelial cells and PC cells. Pancreatic cancer-derived sEVs contained high levels of transforming growth factor ß1 mRNA and acted as its transporter. Once PC-derived sEVs were internalized into vascular endothelial cells, the expression of fibronectin 1 increased on the cell surface, and the adhesiveness of vascular endothelial cells was enhanced. CONCLUSIONS: We investigated association between PC-derived sEVs and adhesiveness. Regulation of PC-derived sEVs has potential as a therapeutic modality to suppress the metastasis of PC.

Aberrant regulation of serine metabolism drives extracellular vesicle release and cancer progression.

Cancer cells secrete extracellular vesicles (EVs) to regulate cells in the tumor microenvironment to benefit their own growth and survive in the patient's body. Although emerging evidence has demonstrated the molecular mechanisms of EV release, regulating cancer-specific EV secretion remains challenging. In this study, we applied a microRNA library to reveal the universal mechanisms of EV secretion from cancer cells. Here, we identified miR-891b and its direct target gene, phosphoserine aminotransferase 1 (PSAT1), which promotes EV secretion through the serine-ceramide synthesis pathway. Inhibition of PSAT1 affected EV secretion in multiple types of cancer, suggesting that the miR-891b/PSAT1 axis shares a common mechanism of EV secretion from cancer cells. Interestingly, aberrant PSAT1 expression also regulated cancer metastasis via EV secretion. Our data link the PSAT1-controlled EV secretion mechanism and cancer metastasis and show the potential of this mechanism as a therapeutic target in multiple types of cancer.

Adult cardiomyocytes-derived EVs for the treatment of cardiac fibrosis.

Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM-derived EVs represent a promising cell-free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFß-activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte-specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFß, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM-derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo.

Unique presentation of acute neuro-Behçet's disease involving a cytotoxic edema core surrounded by vasogenic edema.

A 53-year-old woman with recurrent stomatitis, genital ulcers, and folliculitis was admitted to our hospital after experiencing visual disturbances for the past two weeks, and a non-throbbing headache for the past three days. She had also developed numbness in her left extremities. An ophthalmological examination revealed inflammatory changes in the eye. Cerebrospinal fluid analysis showed increased cell counts, protein, and interleukin-6 levels. Brain magnetic resonance imaging revealed multiple high signal intensities on T2-weighted (T2W)/fluid-attenuated inversion recovery (FLAIR) images of the pons and occipital and parietal lobes. The T2W/FLAIR high-signal-intensity lesion in the pons was hyperintense on diffusion-weighted imaging (DWI) and hypointense on apparent diffusion coefficient mapping (ADC), suggesting cytotoxic edema. Another high-signal-intensity lesion on T2W/FLAIR was isointense to hyperintense on DWI and hyperintense on ADC, indicating vasogenic edema. The vasogenic edema in the left occipital lobe contained a small core that was hyperintense on DWI and hypointense on ADC, suggesting cytotoxic edema. The patient was diagnosed with acute neuro-Behçet's disease (neuro-BD) and responded well to high-dose glucocorticoid and colchicine treatment. The present report emphasizes that patients with acute neuro-BD may present with cytotoxic edema in the pons and cerebral spheres. Further reports of similar cases would contribute to a better understanding of the role of cytotoxic edema in the pathophysiology of neuro-BD and help elucidate the mechanisms underlying a unique presentation characterized by a central cytotoxic edema core within vasogenic edema. (233 words).

Impact of biliary drainage method before pancreaticoduodenectomy on short- and long-term outcomes in patients with periampullary carcinoma and obstructive jaundice: A multicenter retrospective analysis.

BACKGROUND: The optima preoperative biliary drainage before pancreaticoduodenectomy in patients with biliary tract and pancreatic cancer remains controversial. METHODS: A total of 898 patients who underwent preoperative biliary drainage via endoscopic retrograde biliary drainage, endoscopic transnasal biliary drainage, or percutaneous transhepatic biliary drainage before pancreaticoduodenectomy for biliary tract and pancreatic cancer were included. Perioperative and long-term outcomes were analyzed. RESULTS: The Clavien-Dindo grade ≥3 morbidity rates after pancreaticoduodenectomy were higher in the endoscopic retrograde biliary drainage (21.9%; P = .001) or endoscopic transnasal biliary drainage (20.2%; P = .007) than in the percutaneous transhepatic biliary drainage (9.7%) groups. In biliary tract cancer, the frequency of dissemination after pancreaticoduodenectomy was higher in the percutaneous transhepatic biliary drainage (15.3%) than in the endoscopic retrograde biliary drainage (0.7%; P = .001) and endoscopic transnasal biliary drainage (4.1%; P = .037) groups; percutaneous transhepatic biliary drainage was an independent factor associated with worse disease-free survival (P = .04), whereas in pancreatic cancer the frequency of dissemination and survival was comparable among the 3 preoperative biliary drainage methods. Albumin <3.9 g/dL was independently associated with worse overall survival in patients with both pancreatic (P = .038) and biliary tract (P = .002) cancers, respectively. During biliary drainage, external drainage (P = .038) was independently associated with albumin <3.9 g/dL; albumin was higher in endoscopic retrograde biliary drainage group than in endoscopic transnasal biliary drainage or percutaneous transhepatic biliary drainage groups after 21 days from tube insertion. CONCLUSION: In biliary tract cancer, percutaneous transhepatic biliary drainage may carry the risk of increasing the incidence of disseminative recurrence. In pancreatic cancer, percutaneous transhepatic biliary drainage is preferable owing to fewer complications without influencing recurrence. However, if patients cannot undergo surgery immediately, endoscopic retrograde biliary drainage will be applicable to help the preservation of nutritional status, which can have an impact on survival.

Evaluation of ventral branches of segment VI portal vein relative to the right hepatic vein in laparoscopic right anterior sectionectomy.

INTRODUCTION: The right intersectional plane and the right hepatic hilum were noted too often exhibit anatomical variations, making difficult the laparoscopic right anterior sectionectomy (LRAS). METHODS: We analyzed the anatomical features employing 3D-CT images of 55 patients, and evaluated these features according to the course of ventral branches of segment VI of the portal vein (PV, P6a) relative to the right hepatic vein (RHV). RESULTS: P6a run on the dorsal side of RHV in 32 patients (58%, Dorsal-P6a) and the ventral side of RHV in 23 (42%, Ventral-P6a). Ventral-P6a had more patients with S6 partially drained by middle hepatic vein (MHV, 39% vs. 0%, P < 0001), the narrower angle between the anterior and posterior branches of PV (73.1° vs. 93.8°, P = 0.006), the wider angle between the RHV and inferior vena cava  (54.3° vs. 44.3°, P < 0.001), and more steeply pitched angle between S6 and S7 along the RHV (140.6° vs. 162.0°, P < 0.001) compared to Dorsal-P6a. CONCLUSION: In LRAS for Dorsal-P6a patients, the transection surface was relatively flat. In LRAS for Ventral-P6a patients, the narrow space between anterior and posterior glissons makes difficult the glissonean approach. The transection plane was steeply pitched, and RHV was partially exposed. S6 was often partially drained to MHV in 39% of the Ventral-P6a patients, which triggers congestion during liver transection of a right intersectional plane after first splitting the confluence of this branch.

Use of accelerometry to detect varus thrust of osteoarthritic knees before and one year after high tibial osteotomy.

BACKGROUND: The purpose of this study was to determine the effects of high tibial osteotomy (HTO) on varus thrust during gait in patients with medial compartment knee osteoarthritis (KOA), and to identify factors that influence thrust before and one year after surgery. METHODS: HTO was performed in 60 KOA patients (70 knees, including 56 knees by open wedge and 14 by closed wedge). The control group comprised 28 normal, control subjects. Several parameters were evaluated before surgery and one year thereafter. Varus thrust was defined as acceleration of the thigh relative to the lower leg in the coronal plane. Knee-injury-and-osteoarthritis-outcome scores (KOOSs), knee joint angles, radiography, and mediolateral knee acceleration during free speed gait were measured and analyzed. RESULTS: One-year after HTO, KOOSs, knee extension angles, and range of knee motion were improved (p < 0.001). The hip-knee-ankle angle and joint-line-convergent angle (JLCA) had decreased (p < 0.001), and walking speed had increased (p < 0.001). Preoperatively, patient acceleration was significantly (p < 0.05) higher than that of controls, and it did not change after HTO. However, it was reduced significantly (p < 0.05) after adjusting for walking speed. Walking speed correlated significantly with acceleration preoperatively, postoperatively, and among controls. Surgical methods (open-wedge/closed-wedge HTO) and correction angle did not affect postoperative acceleration. There was a low correlation between acceleration and KOOSs (KOOSa, KOOSp), knee joint angles, or JLCA postoperatively, but no relationship was found between acceleration and these parameters in the preoperative or the control group. CONCLUSIONS: Walking speed correlated significantly with acceleration preoperatively, postoperatively, and with those of controls. Mediolateral acceleration of the thigh relative to the lower leg in patients with KOA was significantly higher than that of normal controls before surgery, and it did not change after HTO. However, after surgery it was reduced significantly after adjusting for walking speed.

Risk factors for liver dysfunction and their clinical importance after gastric cancer surgery.

Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.

Suggestive answers strategy in human-chatbot interaction: a route to engaged critical decision making.

In this study, we proposed a novel chatbot interaction strategy based on the suggestive ending of answers. This strategy is inspired by the cliffhanger ending narrative technique, which ends a story without specifying conclusions to spark readers' curiosity as to what will happen next and is often used in television series. Common chatbots provide relevant and comprehensive answers to users' questions. In contrast, chatbots with our proposed strategy end their answers with hints potentially interest-triggering users. The suggestive ending strategy aims to stimulate users' inquisition for critical decision-making, relating to a psychological phenomenon where humans are often urged to finish the uncompleted tasks they have initiated. We demonstrated the implication of our strategy by conducting an online user study involving 300 participants, where they used chatbots to perform three decision-making tasks. We adopted a between-subjects factorial experimental design and compared between the following UIs: (1) plain chatbot-it provides a generated answer when participants issue a question; (2) expositive chatbot-it provides a generated answer for a question, adding short summaries of a positive and negative person's opinion for the answer; (3) suggestive chatbot-it provides a generated answer for a question, which ends with a suggestion of a positive and negative person for the answer. We found that users of the suggestive chatbot were inclined to ask more questions to the bot, engage in prolonged decision-making and information-seeking actions, and formulate their opinions from various perspectives. These findings vary with the users' experience with plain and expositive chatbots.

Lymphovascular invasion is associated with poor long-term outcomes in patients with pT1N0-3 or pT2-3N0 remnant gastric cancer: a retrospective cohort study.

BACKGROUND: Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. METHODS: We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. RESULTS: Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285-161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513-171.2). CONCLUSIONS: LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer.

OBJECTIVE: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy. METHODS: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients. RESULTS: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively. CONCLUSIONS: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients.

Assessing ulnar neuropathy at the elbow using magnetoneurography.

OBJECTIVE: To measure neuromagnetic fields of ulnar neuropathy patients at the elbow after electrical stimulation and evaluate ulnar nerve function at the elbow with high spatial resolution. METHODS: A superconducting quantum interference device magnetometer system recorded neuromagnetic fields of the ulnar nerve at the elbow after electrical stimulation at the wrist in 16 limbs of 16 healthy volunteers and 21 limbs of 20 patients with ulnar neuropathy at the elbow. After artifact removal, neuromagnetic field signals were processed into current distributions, which were superimposed onto X-ray images for visualization. RESULTS: Based on the results in healthy volunteers, conduction velocity of 30 m/s or 50% attenuation in current amplitude was set as the reference value for conduction disturbance. Of the 21 patient limbs, 15 were measurable and lesion sites were detected, whereas 6 limbs were unmeasurable due to weak neuromagnetic field signals. Seven limbs were deemed normal by nerve conduction study, but 5 showed conduction disturbances on magnetoneurography. CONCLUSIONS: Measuring the magnetic field after nerve stimulation enabled visualization of neurophysiological activity in patients with ulnar neuropathy at the elbow and evaluation of conduction disturbances. SIGNIFICANCE: Magnetoneurography may be useful for assessing lesion sites in patients with ulnar neuropathy at the elbow.

Impact of hypoglycemia after gastrectomy on Global Leader Initiative on Malnutrition-defined malnutrition: a retrospective study.

PURPOSE: The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. METHODS: We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1 month and 1 year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). RESULTS: One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70 mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). CONCLUSIONS: Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1 year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.

Uterine leiomyosarcoma cell-derived extracellular vesicles induce the formation of cancer-associated fibroblasts.

OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare malignant tumor, which is aggressive, and has a poor prognosis even during its early stages. Extracellular vesicles (EVs) carry cargo, such as microRNAs (miRNAs), which are involved in intercellular communication in the tumor microenvironment and other processes. Because there are no studies on EV-related miRNAs in ULMS, we identified EV-related miRNAs in ULMS and examined their function. METHODS: Small EVs (sEVs) and medium/large EVs (m/lEVs) were extracted from ULMS cells by ultracentrifugation and their basic characteristics were evaluated. Then, small RNA sequencing was done to obtain EV-related miRNA profiles. Next, miRNA expression levels in sera and tissues of ULMS patients were compared with those of myoma patients. RESULTS: miR-654-3p and miR-369-3p were indicated to be highly expressed in both sera and tissues of ULMS patients. These two miRNAs are also highly expressed in ULMS cell lines and ULMS-derived EVs. Some cancer-associated fibroblast (CAF) markers were increased when fibroblasts were treated with ULMS-derived EVs. Furthermore, fibroblasts took up EVs derived from ULMS as determined by confocal laser microscopy. In addition, the transfection of the two candidate miRNAs into fibroblasts significantly increased some CAF markers, particularly ACTA2. CONCLUSION: miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts.

Analysis of the responsiveness to antiandrogens in multiple breast cancer cell lines.

Antiandrogens were originally developed as therapeutic agents for prostate cancer but are also expected to be effective for breast cancer. However, the role of androgen signaling in breast cancer has long been controversial due to the limited number of experimental models. Our study aimed to comprehensively investigate the efficacy of antiandrogens on breast cancer. In the present study, a total of 18 breast cancer cell lines were treated with the agonist or antagonists of the androgen receptor (AR). Among the 18 cell lines tested, only T-47D cells proliferated in an androgen-dependent manner, while the other cell lines were almost irresponsive to AR stimulation. On the other hand, treatment with AR antagonists at relatively high doses suppressed the proliferation of not only T-47D cells but also some other cell lines including AR-low/negative cells. In addition, expression of the full-length AR and constitutively active AR splice variants, AR-V7 and ARV567es, was not correlated with sensitivity to AR antagonists. These data suggest that the antiproliferative effect of AR antagonists is AR-independent in some cases. Consistently, proliferation of AR-knockout BT-549 cells was inhibited by AR antagonists. Identification of biomarkers would be necessary to determine which breast cancer patients will benefit from these drugs.

A case of massive hemoptysis caused by lung cancer saved by V-V ECMO and hemostasis achieved by radiotherapy.

Massive hemoptysis is one of the fatal complications of lung cancer. There is no established standard treatment method for it, and it often causes sudden suffocation, and some cases may be difficult to save. A 63-year-old man was admitted to the hospital with dyspnea, and developed massive hemoptysis from lung cancer shortly after admission. The tumor had obstructed the right main bronchus and had invaded the right pulmonary artery. Surgery and interventional radiology were judged impossible. The patient was successfully saved by the introduction of Veno-Venous Extra Corporeal Membrane Oxygenation (V-V ECMO), and hemostasis was obtained by radiotherapy. Two months after completion of radiotherapy, he was weaned off the ventilator and discharged on his own. He died of increased peritoneal dissemination and other complications 1 year and 1 month later, but no recurrence of hemoptysis was noted until his death. We experienced a case of massive hemoptysis in which V-V ECMO and radiation therapy succeeded in saving life and stopping bleeding. The use of V-V ECMO by emergency care teams and multimodality therapy, including radiotherapy, were effective for massive hemoptysis from lung cancer.

Drug-induced lung injury in a patient treated with prior atezolizumab and subsequent sotorasib: A case report.

We report a case of drug-induced lung injury treated with prior atezolizumab and subsequent sotorasib. The patient was a 62-year-old woman with lung adenocarcinoma harbouring a KRAS G12C mutation that was resistant to chemotherapy, including immune checkpoint inhibitors. Cough and dyspnea appeared on day 80 after sotorasib was administered as second-line therapy, and chest computed tomography revealed ground glass opacities in all lung lobes. Bronchoalveolar lavage fluid showed an increased total cell count with lymphocyte predominance. The patient was considered to have lung injury caused by prior atezolizumab or sotorasib administration. Withdrawal of sotorasib did not improve symptoms and shadows in both lungs. We administered moderate-dose prednisolone and the lung disorder quickly resolved. Prednisolone tapering was completed in 2 months, followed by several months without relapse. Definitive identification of the responsible drug for the drug-induced lung injury proved challenging in the setting of exposure to multiple potential inciting agents. There is a need for high levels of clinical suspicion for timely evaluation and management.

Collagen induction of immune cells in the mammary glands during pregnancy.

The mammary glands are dynamic tissues affected by pregnancy-related hormones during the pregnancy-lactation cycle. Collagen production and its dynamics are essential to the remodeling of the mammary glands. Alterations of the mammary microenvironment and stromal cells during the pregnancy-lactation cycle are important for understanding the physiology of the mammary glands and the development of breast tumors. In this study, we performed an evaluation of collagen dynamics in the mammary fat pad during the pregnancy-lactation cycle. Reanalysis of single-cell RNA-sequencing (scRNA-Seq) data showed the ectopic collagen expression in the immune cells and cell-cell interactions for collagens with single-cell resolution. The scRNA-Seq data showed that type I and type III collagen were produced not only by stromal fibroblasts but also by lymphoid and myeloid cell types in the pregnancy phase. Furthermore, the total cell-cell interaction score for collagen interactions was dramatically increased in the pregnancy tissue. The data presented in this study provide evidence that immune cells contribute, at least in part, to mammary collagen dynamics. Our findings suggest that immune cells, including lymphoid and myeloid cells, might be supportive members of the extracellular matrix orchestration in the pregnancy-lactation cycle of the mammary glands.NEW & NOTEWORTHY Our study evaluated mammary gland collagen dynamics during the pregnancy-lactation cycle using single-cell RNA-sequencing data. We found ectopic collagen expression in immune cells and an increase in collagen interactions during pregnancy. Type I and type III collagen were produced by lymphoid, myeloid, and stromal fibroblast cells during pregnancy. These findings suggest that immune cells, including lymphoid and myeloid cells, play a crucial role in supporting the extracellular matrix in mammary glands during pregnancy-lactation cycles.