U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Differentiation Between Invasive Adenocarcinoma and Focal Interstitial Fibrosis among Persistent Pulmonary Part-solid Nodules: With Emphasis on the CT Morphologic Analysis.

PURPOSE: Focal interstitial fibrosis (FIF) manifesting as a persistent part-solid nodule (PSN) has been mistakenly treated surgically due to similar imaging features to invasive adenocarcinoma (ADC). The purpose of this study was to observe predictive imaging features correlated with FIF through CT morphologic analysis. MATERIALS AND METHODS: From January 2009 to December 2020, 44 patients with surgically proven FIF in a single institution were enrolled and compared with 88 ADC patients through propensity score matching. Patient characteristics and CT morphologic analysis of persistent PSNs were used to identify predictive imaging features of FIF. Receiver operating characteristic (ROC) curve analysis was used to quantify the performance of imaging features. RESULTS: A total of 132 patients with 132 PSNs (44 FIF, 88 ADC; mean age, 67.7±7.58; 75 females) were involved in our analysis. Multivariable analysis demonstrated that preserved peritumoral vascular margin (preserved vascular margin), preserved secondary pulmonary lobule margin (preserved lobular margin), and lower coronal to axial ratio (C/A ratio; cutoff: 1.005) were significant independent predictors of FIF (P<0.05). ROC curve analysis to evaluate the predictive value of the logistic model based on the imaging features of FIF, and the AUC value was 0.881. CONCLUSION: CT imaging features of preserved vascular margin, preserved lobular margin, and lower C/A ratio (cutoff, <1.005) might be helpful imaging features in discriminating FIF over ADC among persistent PSN in clinical practice.

Clinical utility of the Oncomine Dx Target Test multi-CDx system and the possibility of utilizing those original sequence data.

BACKGROUND: Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi-CDx System has emerged as a prominent companion diagnostic method. However, its efficacy in detecting driver gene mutations, particularly rare mutations, warrants investigation. AIMS: This study aimed to assess the performance of the ODxTT in detecting driver gene mutations in NSCLC patients. Specifically, we aimed to evaluate its sensitivity in detecting epidermal growth factor receptor (EGFR) mutations, a key determinant of treatment selection in NSCLC. MATERIALS AND METHODS: We conducted a retrospective analysis of NSCLC patients who underwent testing with the ODxTT at Keio University Hospital between May 2020 and March 2022. Patient samples were subjected to both DNA and RNA tests. Driver gene mutation status was assessed, and instances of missed mutations were meticulously examined. RESULTS: Of the 90 patients, five had nucleic acid quality problems, while 85 underwent both DNA and RNA tests. Driver gene mutations were detected in 56/90 (62.2%) patients. Of the 34 patient specimens, driver mutations were not detected using the ODxTT; however, epidermal growth factor receptor (EGFR) mutations were detected using polymerase chain reaction-based testing in two patients, and a KRAS mutation was detected by careful examination of the sequence data obtained using the ODxTT in one patient. For the above three cases, carefully examining the gene sequence information obtained using the ODxTT could identify driver mutations that were not mentioned in the returned test results. Additionally, we confirmed comparable instances of overlook results for EGFR mutations in the dataset from South Korea, implying that this type of oversight could occur in other countries using the ODxTT. EGFR mutation was missed in ODxTT in Japan (6.3%, 2/32), South Korea (2.0%, 1/49), and overall (3.7%, 3/81). CONCLUSION: Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Placental transmogrification of the lung: CT findings with pathologic correlation in six patients.

Background: Placental transmogrification of the lung is a very rare benign lung disease with a characteristic finding being alveoli resembling chorionic villi of the placenta. The purpose of this study was to assess the computed tomography (CT) findings of placental transmogrification of the lung in six patients and their relation to the histopathologic findings. Methods: Six patients with histopathologically proven placental transmogrification of the lung from 2004 to 2021 were included. Their CT findings were analyzed and their imaging features were compared with pathology specimens. Results: In four of six cases, CT showed variable sized cystic lesions confined to a unilateral lung. One case presented nodule and cystic lesion together. The other case showed solitary pulmonary nodule without cystic lesion. Moreover, nodular interlobular septal thickening and clustered interstitial nodules were observed in all six cases. In four of the six cases, these nodules merged into dense nodular consolidation. Three cases showed dilated pulmonary vasculatures of the involved lung. Conclusions: On CT, placental transmogrification of the lung typically presents as cystic lesion confined to a unilateral lung. Pulmonary nodule with or without associated cystic lesion can also be seen. Nodular interlobular septal thickening and clustered interstitial nodules were observed in all cases. This might be attributable to the proliferation of chorionic villi-like structures in interstitium which are found in histopathologic specimens.

Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer.

Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.

Intraoperative neurological pupil index and postoperative delirium and neurologic adverse events after cardiac surgery: an observational study.

Neurological pupil index (NPi) calculated by automated pupillometry predicts clinical outcomes in critically ill patients. However, there are few data on intraoperative NPi and postoperative outcome after cardiac surgery. We evaluated the relationships between intraoperative NPi and clinical outcomes, such as delirium, in cardiac surgery patients. NPi was measured at baseline, after anesthesia induction, at 30 min intervals after initiation of cardiopulmonary bypass or anastomosis of coronary artery bypass graft, and at skin closure. Abnormal NPi was defined as one or more measurements of NPi < 3.0 during surgery. The worst intraoperative NPi was recorded, then multivariate logistic regression analysis was performed to evaluate the relationship between abnormal NPi and postoperative delirium following cardiac surgery. Among 123 included patients, postoperative delirium developed in 19.5% (24/123) of patients. Intraoperative abnormal NPi was significantly associated with postoperative delirium (odds ratio 6.078; 95% confidence interval 1.845-20.025; P = 0.003) after adjustment for Society of Thoracic Surgeons Predicted Risk of Mortality score, coronary artery disease, and use of calcium channel blockers. In conclusion, abnormal intraoperative NPi independently predicted postoperative delirium following cardiac surgery. Intraoperative application of pupillometry may have prognostic value for development of postoperative delirium, thereby enabling close surveillance and early intervention in high-risk patients.Registry number: ClinicalTrials.gov (NCT04136210).

A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion.

A 58-year-old woman visited the hospital complaining of fatigue and indigestion lasting for more than 3 months. She had no medical history other than taking a calcium plus vitamin D supplement for osteopenia. The initial blood test showed a high calcium level of 14.0 mg/dL. Additional tests were performed to differentially diagnose hypercalcemia. The blood test results were as follows: serum parathyroid hormone (PTH)=247.0 pg/mL, PTH-related peptide <1.0 pg/mL, phosphorous=2.6 mg/dL, 25-hydroxy-vitamin D=14.5 pg/mL, creatinine=1.09 mg/dL, and 24 hr urine calcium=215 mg/dL. A 4.5 cm sized cystic lesion on the intra-thyroidal space was confirmed on neck sonography and 4-dimensional parathyroid computed tomography, but technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy showed equivocal results. After removal of the cystic lesion, serum calcium and PTH were normalized, and parathyroid lipoadenoma was confirmed in the postoperative pathology. Clinical features of parathyroid lipoadenoma are known to be similar to common parathyroid adenoma, but imaging studies often report negative findings. Therefore, it is necessary to better understand this rare disease for the differential diagnosis. For the final diagnosis and treatment of this disease, parathyroidectomy with intraoperative PTH measurement may be required.

Tract seeding in indwelling pleural catheter placement for the drainage of malignant pleural effusions: Incidence and related clinical and imaging factors.

BACKGROUND: The incidence of tract seeding after the placement of indwelling pleural catheter (IPC) for malignant pleural effusion drainage has been variable in the literature. RESEARCH QUESTION: To evaluate the incidence of IPC-related cancer tract seeding and find out related demographic, clinical or imaging factors to the tract seeding. STUDY DESIGN AND METHODS: This retrospective study included 124 consecutive patients seen between January 2011 and December 2021 who underwent IPC placement for malignant pleural effusion drainage. Chest radiographs before IPC placement and serial chest CT studies were obtained. One patient was diagnosed pathologically, and the other patients were diagnosed as tract seeding radiologically. The incidence of and related factors to tract seeding were assessed by reviewing medical records and imaging studies. RESULTS: The incidence of IPC tract seeding was 21.7% (27 of 124 malignant effusions). Of 27 patients, 15 had primary lung cancer and remaining 12 had extra-thoracic malignancy. Adenocarcinoma (19 of 27, 70.3%) either from the lung (N = 12) or extra-thoracic malignancy (N = 7) was the most common cell type. Mean time elapsed until tract seeding occurrence after IPC placement was 96 days (ranges; 28-306 days). The survival in seeding group after IPC placement was 185 days (ranges, 32-457 days). On odd ratio analysis, the presence of mediastinal pleural thickening (OR [95% CI]; 9.79 (2.67-35.84), p = 0.001) was significantly related to the occurrence of tract seeding. Neither tumor volume within pleural space (p = 0.168), duration of IPC indwelling (p = 0.142), days of survival after IPC placement (p = 0.26), nor pleural effusion amount (p = 0.481) was related to the tract seeding. INTERPRETATION: IPC tract seeding is seen in 27 (21.7%) of 124 malignant pleural effusion patients, particularly with adenocarcinoma cytology. CT features of mediastinal pleural thickening are related to the occurrence of tract seeding.

Five-year Progress of Gastric MALT Lymphoma Presenting as Gastric Outlet Obstruction.

This paper reports a 70-year-old female with gastric extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) as a rare case of gastric outlet obstruction. Five years earlier, she initially presented with weight loss and anemia. Esophagogastroduodenoscopy (EGD) revealed multiple gastric and duodenal ulcers with a pyloric deformity, while histology revealed chronic active inflammation and a Helicobacter pylori (H. pylori) infection. Three years earlier, she underwent EGD per the National Cancer Screening Program and was diagnosed with antral and duodenal ulcers. A forceps biopsy specimen from one of the ulcers showed the findings of gastric MALT lymphoma, but she did not visit the hospital for proper management. She visited complaining of a loss of appetite. EGD revealed a gastric outlet obstruction (GOO) caused by antral deformity and pyloric narrowing. A staged workup with CT and PET revealed full-layered, encircling antral wall thickening and several enlarged mesenteric lymph nodes. She was finally diagnosed with a gastric MALT lymphoma at Ann Arbor stage I1E with translocation t(11;18). She was treated with palliative surgery for GOO and systemic chemotherapy with a CHOP regimen. This paper reports a gastric MALT lymphoma that progressed from superficial mucosal lesions to an overt mass with regional lymph node metastasis for five years.

[Clinical Impact Assessment and Utilization Prospects of the t(11:18) Chromosomal Translocation in Gastric MALT Lymphoma in Koreans: A Single Center Retrospective Analysis].

Background/Aims: The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. Methods: The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. Results: Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value= 0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). Conclusions: H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.

Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015.

PURPOSE: This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015. MATERIALS AND METHODS: The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020. RESULTS: We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non-small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%). CONCLUSION: In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

Prognostic Implication of Exfoliative Airway Pathology in Cancer-Free Coal Workers' Pneumoconiosis.

BACKGROUND: The purpose of this study is to see if exfoliative pulmonary airway pathology in cancer-free coal workers' pneumoconiosis (CWP) can be used as a biomarker for predicting pulmonary morbidity. METHODS: We investigated persistent metaplastic changes in bronchoscopic washing cytology and differential cell counts in bronchoalveolar lavages (BAL) in 97 miners with CWP and 80 miners without CWP as the control. Clinicopathological parameters were examined including pulmonary function tests and the presence of progressive massive fibrosis. RESULTS: When compared to the control group, severe alveolitis, severe goblet cell hyperplasia (GCH), severe hyperplastic epithelial change, and severe squamous metaplasia were the distinguishing biomarkers in CWP. Multivariate analysis revealed that severe alveolitis and severe GCH, along with miner duration and current smoker, were independent predictors of pulmonary mortality. The survival analysis revealed a significantly different survival rate between the three groups: no evidence of severe alveolitis and severe GCH, presence of severe alveolitis or severe GCH but not both, and both severe alveolitis and severe GCH. CONCLUSIONS: The severities of alveolitis and goblet cell hyperplasia in the bronchoscopic study are independent prognostic factors for CWP. A pathologic grading system based on these two parameters could be used in the stratification and clinical management of CWP patients.

Solitary Pulmonary Capillary Hemangioma: CT and PET-CT Features with Clinicopathologic Correlation.

The aim of this study was to evaluate the CT and PET-CT features of solitary pulmonary capillary hemangioma (SPCH) with clinicopathologic correlations. This retrospective study included 17 patients with histologically proven SPCH from four tertiary institutions. The clinical, pathological and imaging findings of SPCH were reviewed. The CT features assessed included lesion location, size, density, contour, margin, enhancement, presence of air bronchogram, perivascular lucency and pleural retraction, and 18F-fluorodeoxyglucose uptake on PET-CT. Changes in the size during the follow-up period were also evaluated. Imaging features were correlated with the clinicopathologic findings. The mean age of the patients was 47 years (range 30-60 years). All SPCHs were incidentally detected during screening CT examinations (n = 13, 76%) or during cancer work-up (n = 4, 24%). Most SPCHs appeared as part-solid nodules (n = 15, 88%), the remaining appeared as a pure ground-glass nodule or a pure solid nodule, respectively. Most had smooth contours (n = 16, 94%), while one had a lobulated contour. Nine SPCHs (53%) showed ill-defined margins. Air bronchogram was present in ten (59%) SPCHs, and perivascular lucency in two (12%). All SPCHs exhibited hypoattenuation on contrast-enhanced CT and hypometabolism on PET-CT. During the follow-up period (mean 14.8 ± 17.7 months), the lesions showed no change in size or density in ten SPCHs (59%), decreased or fluctuation in size and density in three (18%). SPCH is often incidentally detected in young and middle-aged adults, commonly as an ill-defined part-solid nodule that may accompany air bronchogram, perivascular lucency, and fluctuation in size or density on CT and hypometabolism on PET-CT.

Therapeutic Applications of the CRISPR-Cas System.

The clustered regularly interspaced palindromic repeat (CRISPR)-Cas system has revolutionized genetic engineering due to its simplicity, stability, and precision since its discovery. This technology is utilized in a variety of fields, from basic research in medicine and biology to medical diagnosis and treatment, and its potential is unbounded as new methods are developed. The review focused on medical applications and discussed the most recent treatment trends and limitations, with an emphasis on CRISPR-based therapeutics for infectious disease, oncology, and genetic disease, as well as CRISPR-based diagnostics, screening, immunotherapy, and cell therapy. Given its promising results, the successful implementation of the CRISPR-Cas system in clinical practice will require further investigation into its therapeutic applications.

Comprehensive Comparison of 22C3 and SP263 PD-L1 Expression in Non-Small-Cell Lung Cancer Using Routine Clinical and Conditioned Archives.

PD-L1 harmonization studies revealed a strong correlation between the 22C3 and SP263 assays in non-small-cell lung cancer (NSCLC). However, the assays' characteristics have yet to be validated in a variety of clinical and analytical settings. The results of 431 NSCLC samples tested concurrently in routine clinical practice with the PD-L1 22C3 and SP263 assays were reviewed, and both assays were performed on 314 archives of surgically resected NSCLCs to assess PD-L1 expression in relation to variables such as FFPE block age and FFPE section storage condition. In routine clinical samples, 22C3 showed the highest concordance rate with 94.5% of SP263 tumor proportion score (TPS) ≥50% and 92.3% of SP263 TPS ≥1%, while SP263 showed a concordance rate with 79.6% of 22C3 TPS ≥50% and 89.9% of 22C3 TPS ≥1%. In the archival analysis, the high TPS of 22C3 and SP263 (versus TPS 1%) were significantly associated with a more recent block (<3 years versus ≥3 years) (p = 0.007 and p = 0.009, respectively). Only the TPS of 22C3 was reduced when FFPE sections were stored at room temperature compared to SP263. However, when stored at 4 °C, the storage duration had no effect on expression in either assay. For 22C3 TPS 1−49 percent and ≥50 percent (OR = 1.73, p = 0.006 and OR = 1.98, p = 0.002, respectively). There was a considerably larger chance of preserved 22C3 expression in recent room-temperature paraffin section storage, although SP263 demonstrated preserved expression in prolonged room-temperature section storage. Despite the good association between PD-L1 22C3 and SP263 in routine clinical samples, FFPE blocks older than 3 years and sections held at room temperature for more than 1 week may result in an underestimation of PD-L1 status, particularly for the 22C3 test. However, the SP263 assay was more sensitive under these conditions.