Combining PD-L1 Expression and Standardized Uptake Values in FDG-PET/CT Can Predict Prognosis in Patients With Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. RESULTS: PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) (P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) (P = 0.0012 and P < 0.0001). Kaplan-Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3. CONCLUSION: Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

Stimulus-triggered fate conversion of somatic cells into pluripotency.

Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection. STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.

[A case of pancreatic cancer with clusters of invasive micropapillary carcinoma markedly reduced by chemotherapy].

A man in his 60s was hospitalized with multiple cerebral infarctions and referred for Trousseau's syndrome. Computerized tomography confirmed a 60-mm mass in the pancreatic head and swollen lymph nodes around the abdominal aorta. Fine needle aspiration cytology of the pancreatic lesion and laparoscopic para-aortic lymph node biopsy revealed adenocarcinoma, including clusters of invasive micropapillary carcinoma (IMPC). Chemotherapy (gemcitabine and nab-paclitaxel) markedly decreased the primary and metastatic lesions, and no recurrence was clinically detected 24 months later. To the best of our knowledge, reports of pancreatic IMPCs are rare. Our case was the seventeenth case of pancreatic cancer with IMPC. In this case, chemotherapy was markedly effective.

Highest power magnification with narrow-band imaging is useful for improving diagnostic performance for endoscopic delineation of early gastric cancers.

BACKGROUND AND STUDY AIMS: Magnifying endoscopy with narrow-band imaging (ME-NBI) is more reliable than chromoendoscopy (CE) for delineating the horizontal extent of early gastric cancers prior to endoscopic submucosal dissection (ESD). However, the added benefits of ME-NBI over CE in terms of the difference in magnification level have yet to be elucidated. The aim of this study was to investigate the improvement in diagnostic accuracy for tumor delineation obtained with different magnification levels of ME-NBI following CE. PATIENTS AND METHODS: This was a retrospective study, performed at a single tertiary referral center. A series of 158 consecutive patients with 161 early gastric cancers resected en bloc using ESD was included in the study. The margins of each lesion were examined in their entirety using CE, followed by low power optical magnifying endoscopy with narrow-band imaging (LM-NBI), and finally the highest power optical magnifying endoscopy with narrow-band imaging (HM-NBI). The primary endpoint was the added benefit, as measured using the successful delineation rate, for the delineation of gastric cancer margins using CE + LM-NBI vs CE, and for CE + LM-NBI + HM-NBI vs CE + LM-NBI. RESULTS: The successful delineation rates (95 % CI) using CE, CE + LM-NBI and CE + LM-NBI + HM-NBI were 72.7 % (68.5-79.9 %), 88.9 % (84.2-93.8 %), and 98.1 % (95.8-100 %). The diagnostic accuracy improved significantly for CE + LM-NBI compared with CE (P < 0.001), and for HM-NBI compared with LM-NBI (P < 0.001). CONCLUSIONS: HM-NBI is useful for improving diagnostic performance for endoscopic delineation of early gastric cancers, following CE and LM-NBI.

A two-colored chewing gum test for assessing masticatory performance: a preliminary study.

This study was conducted to compare subjective and objective assessment methods of a two-colored chewing gum test and to find out whether these methods are capable of discriminating masticatory performances between sexes. 31 adults, 16 males and 15 females participated in this study. Each subject chewed five samples of two-colored chewing gum sticks for 5, 10, 20, 30 and 50 chewing strokes, respectively. The subjective color-mixing and shape indices for the gum bolus (SCMI-B, SSI-B) and the subjective color-mixing index and objective color-mixing ratio for the gum wafer (SCMI-W, OCMR-W) were evaluated by two independent examiners and, on a different day, re-evaluated by one of the examiners. The SCMI-B and SCMI-W assessments had inter- and intra-examiner reliable agreement at 20 or more chewing strokes. The OCMR-W measurement demonstrated high accuracy and low reproducibility between and within the examiners. There were significant gender differences in the distribution of SCMI-W scores (P = 0.044) and in the mean OCMI-W (P = 0.007). The SCMI-B and SCMI-W assessments and the OCMR-W measurement were reliable and valid at the 20 and 30 chewing strokes in this two-colored chewing gum test. The subjective color-mixing index (SCMI-W) and objective color-mixing ratio (OCMR-W) for the chewing gum wafer are capable of discriminating masticatory performance between sexes in this two-colored chewing gum test and that the OCMR-W measurement is discriminating better than the SCMI-W assessment.

Early chest tube removal within 6 hours after thoracic surgery results in improved postoperative prognosis and no adverse effects.

Background: Advances in minimally invasive surgery and drainage systems have caused earlier chest-tube-removal. This retrospective study aimed to assess the safety of early chest tube removal using the institution's new criteria 6 hours after thoracic surgery. Methods: Elective thoracic surgery patients from 2017 to 2023 were reviewed for meeting or not meeting the newer institutional requirement for early chest tube removal; (I) no air leak detected under the digital drainage device observation; (II) no fluid drainage of ≥100 mL/h; (III) no ≥3 combined risks [male, chronic obstructive pulmonary disease (COPD), body mass index (BMI) of <18.5 kg/m2, severe pleural adhesion, upper lobe lobectomy, or left upper division segmentectomy]. The incidence of adverse events, including chest tube replacement, subcutaneous tube placement, and postoperative thoracentesis, were investigated for 1 month postoperatively. Perioperative outcomes and factors involved in conventional chest tube removal were also assessed. Results: Of the 942 patient charts reviewed, 244 (25.9%) met the criteria for chest tube removal within 6 hours postoperatively. This patient group did not experience adverse events. They also demonstrated shorter postoperative hospital stay (4 vs. 6 days, P<0.001), and lesser postoperative complications (7.4% vs. 25.6%, P<0.001) compared to those for whom early chest tube removal was not done. A correlation with thoracotomy, COPD, and steroid and/or immunosuppressant use was observed for patients in the conventional chest tube removal group. Conclusions: Early chest tube removal after 6 postoperative hours was deemed safe for a selected group of patients who met the criteria for early chest tube removal. This study would support the potential expansion of our early removal criteria.

Interventional radiology using endoscopy: Blood supply route-targeted endoscopic injection sclerotherapy with multiple ligations for giant esophagogastric varices.

A case of high-risk giant esophagogastric varices was treated by blood supply route-targeted endoscopic injection sclerotherapy with multiple ligations (EISML). An endoscope was inserted in the left lower semi-lateral position under general anesthesia in the digital subtraction angiography room. The C-arm was rotated to obtain a frontal view for fluoroscopy. Before puncturing the esophageal varices, the balloon attached to the tip of the endoscope was inflated to block the variceal blood flow. At puncture, an intravascular injection was confirmed fluoroscopically, and a total of 18 m of 5% ethanolamine oleate with iopamidol was injected retrogradely at 5-minute intervals from the esophagogastric varices to the root of the left gastric vein, maintaining stagnation for 25 minutes. The variceal site of the injection was ligated immediately after the removal of the needle to prevent variceal bleeding. Multiple variceal ligations were added to stop the variceal blood flow. Contrast-enhanced CT 3 days after EISML showed the thrombus formation in esophagogastric varices and the left gastric vein. The blood supply route-targeted EISML can be a feasible procedure for giant esophagogastric varices.

Outcomes of Endoscopic Intervention Using Over-the-Scope Clips for Anastomotic Leakage Involving Secondary Fistula after Gastrointestinal Surgery: A Japanese Multicenter Case Series.

BACKGROUND: The over-the-scope clip (OTSC) is a highly effective clipping device for refractory gastrointestinal disease. However, Japanese data from multicenter studies for anastomotic leakage (AL) involving a secondary fistula after gastrointestinal surgery are lacking. Therefore, this study evaluated the efficacy and safety of OTSC placement in Japanese patients with such conditions. METHODS: We retrospectively collected data from 28 consecutive patients from five institutions who underwent OTSC-mediated closure for AL between July 2017 and July 2020. RESULTS: The AL and fistula were located in the esophagus (3.6%, n = 1), stomach (10.7%, n = 3), small intestine (7.1%, n = 2), colon (25.0%, n = 7), and rectum (53.6%, n = 15). The technical success, clinical success, and complication rates were 92.9% (26/28), 71.4% (20/28), and 0% (0/28), respectively. An age of <65 years (85.7%), small intestinal AL (100%) and colonic AL (100%), defect size of <10 mm (82.4%), time to OTSC placement > 7 days (84.2%), and the use of simple suction (78.9%) and anchor forceps (80.0%) were associated with higher clinical success rates. CONCLUSION: OTSC placement is a useful therapeutic option for AL after gastrointestinal surgery.

Minichromosome maintenance 2 is an independent predictor of survival in patients with lung adenocarcinoma.

Minichromosome maintenance (MCM) protein deregulation is associated with tumor formation, progression and malignant transformation. MCM2 is frequently expressed during premalignant lung cell proliferation and is a sensitive marker for the early detection of pulmonary malignant lesions. The present study was undertaken to investigate whether MCM2 expression is of clinical and prognostic value in patients who have undergone lung adenocarcinoma resection. Between January 2009 and December 2010, 102 consecutive patients underwent complete pulmonary resection (involving lobectomy or more extensive resection) for lung adenocarcinoma at St. Marianna Medical University Hospital (Kanagawa, Japan). Among those, 73 patients, who had a final pathological diagnosis of lung adenocarcinoma measuring ≥10 mm, were enrolled in the present study. High MCM2 expression was found in 35 patients (48.0%). Univariate analysis of the overall survival (OS) revealed that pathological stage and MCM2 expression were significant prognostic factors in lung adenocarcinoma (P<0.001 and P<0.002, respectively). Univariate analysis of the recurrence-free survival (RFS), the significant prognostic factors included pathological stage, EGFR mutation status and MCM2 expression (P<0.001, P<0.034 and P<0.003, respectively). On multivariate survival analysis, high MCM2 expression and pathological stage II-III were identified as independent strong prognostic factors (OS: HR=5.084, 95% CI: 1.715-15.080, P=0.003; RFS: HR=2.761, 95% CI: 1.090-6.998, P=0.032). Therefore, the findings of the present study demonstrated that MCM2 may serve as a potential biomarker and therapeutic target for lung adenocarcinoma.

Solid histological component of adenocarcinoma might play an important role in PD-L1 expression of lung adenocarcinoma.

BACKGROUND: In this study we aimed to clarify the PD-L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. METHODS: A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD-L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. RESULTS: When PD-L1 expression-positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD-L1 expression, SPA was the only subtype which was statistically significant when both PD-L1 expression-positive was defined by TPS ≥ 1% (p < 0.0001) and TPS â‰§ 50% (p < 0.0001). We then considered the solid component. We investigated 279 cases of the other subtype group excluding SPA. The group containing a solid component (≥5%) tended to be PD-L1 expression-positive both when defined by TPS ≥1% (p < 0.0001) and TPS â‰§50% (p = 0.0049). CONCLUSIONS: The PD-L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.

Diagnosis of histological type of early gastric cancer by magnifying narrow-band imaging: A multicenter prospective study.

Objectives: Distinguishing undifferentiated-type from differentiated-type early gastric cancers (EGC) is crucial for determining the indication of endoscopic resection. We aimed to investigate the diagnostic performance of white-light endoscopy (WLE) and magnifying narrow-band imaging (M-NBI) for the histological type of EGC. Methods: In this multicenter prospective study, patients with histologically proven cT1 EGC, macroscopically depressed or flat type, size ≥5 mm, and without erosion/ulcer, were recruited. The diagnostic criterion of WLE for undifferentiated-type EGC was pale color. The M-NBI algorithm was created based on microsurface and microvascular patterns, and lesions with absent microsurface pattern and opened-loop microvascular patterns were diagnosed as undifferentiated-type. The center of the lesion was defined as the evaluation point and was initially evaluated by WLE, then by M-NBI, and a biopsy specimen was taken as a reference standard. The primary and key secondary endpoints were overall diagnostic accuracy and specificity, respectively. Results: In total, 167 lesions (122 differentiated-type and 45 undifferentiated-type EGCs) in 167 patients were analyzed. The overall accuracy, sensitivity, specificity, and positive likelihood ratio of WLE for undifferentiated-type cancer were 80%, 69%, 84%, and 4.4, respectively, and those of M-NBI were 82%, 53%, 93%, and 7.2, respectively. There was no significant difference in overall accuracy (p = 0.755), but specificity was significantly higher in M-NBI (p = 0.041). Conclusions: The use of M-NBI did not improve the accuracy of WLE for the diagnosis of depressed/flat undifferentiated-type EGCs but improved the specificity. It may reduce surgical overtreatment by preventing misdiagnosis of differentiated-type EGC as undifferentiated-type.

Isoflurane decreases self-renewal capacity of rat cultured neural stem cells.

BACKGROUND: In models, isoflurane produces neural and behavioral deficits in vitro and in vivo. This study tested the hypothesis that neural stem cells are adversely affected by isoflurane such that it inhibits proliferation and kills these cells. METHODS: Sprague-Dawley rat embryonic neural stem cells were plated onto 96-well plates and treated with isoflurane, 0.7, 1.4, or 2.8%, in 21% oxygen for 6 h and fixed either at the end of treatment or 6 or 24 h later. Control plates received 21% oxygen under identical conditions. Cell proliferation was assessed immunocytochemically using 5-ethynyl-2'-deoxyuridine incorporation and death by propidium iodide staining, lactate dehydrogenase release, and nuclear expression of cleaved caspase 3. Data were analyzed at each concentration using an ANOVA; P < 0.05 was considered significant. RESULTS: Isoflurane did not kill neural stem cells by any measure at any time. Isoflurane, 1.4 and 2.8%, reduced cell proliferation based upon 5-ethynyl-2'-deoxyuridine incorporation, whereas isoflurane, 0.7%, had no effect. At 24 h after treatment, the net effect was a 20-30% decrease in the number of cells in culture. CONCLUSIONS: Isoflurane does not kill neural stem cells in vitro. At concentrations at and above the minimum alveolar concentrations required for general anesthesia (1.4 and 2.8%), isoflurane inhibits proliferation of these cells but has no such effect at a subminimum alveolar concentration (0.7%). These data imply that dosages of isoflurane at and above minimum alveolar concentrations may reduce the pool of neural stem cells in vivo but that lower dosages may be devoid of such effects.

Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair.

The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unclear from vascular repair studies whether endothelial implants recapitulate the vascular epithelial lining or expose injured tissues to endothelial cells (ECs) with unique healing potential because ECs line the vascular epithelium and the vasa vasorum. We examined this issue in a nonvascular tubular system, asking whether airway repair is controlled by bronchial epithelial cells (EPs) or by ECs of the perfusing bronchial vasculature. Localized bronchial denuding injury damaged epithelium, narrowed bronchial lumen, and led to mesenchymal cell hyperplasia, hypervascularity, and inflammatory cell infiltration. Peribronchial TE constructs embedded with EPs or ECs limited airway injury, although optimum repair was obtained when both cells were present in TE matrices. EC and EP expression of PGE(2), TGFbeta1, TGFbeta2, GM-CSF, IL-8, MCP-1, and soluble VCAM-1 and ICAM-1 was altered by matrix embedding, but expression was altered most significantly when both cells were present simultaneously. EPs may provide for functional control of organ injury and fibrous response, and ECs may provide for preservation of tissue perfusion and the epithelium in particular. Together the two cells optimize functional restoration and healing, suggesting that multiple cells of a tissue contribute to the differentiated biochemical function and repair of a tissue, but need not assume a fixed, ordered architectural relationship, as in intact tissues, to achieve these effects.

Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas.

BACKGROUND: The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS: From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS: PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION: The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.

Cephalometric evaluation of maxillary sinus sizes in different malocclusion classes.

We found few studies on the association between maxillary sinus size and malocclusion in an electronic search using PubMed. The purpose of this study was to investigate maxillary sinus size in different malocclusion groups and the association between maxillary sinus size and dentofacial morphology by the use of lateral cephalometric radiographs. A total of 120 lateral cephalograms were used. These radiographs were derived from subjects with skeletal Class I, Class II, and Class III malocclusions, classified on the basis of the A-N-B angle. Each malocclusion group consisted of 20 boys and 20 girls ranging in age from 12 to 16 years. Two linear measurements and three area measurements were made to evaluate maxillary sinus size, and four angular and eight linear measurements were made to evaluate dentofacial morphology. Analysis of variance and Pearson's correlation analysis were performed for statistical comparison. The maxillary sinuses showed no significant differences in size between the different classes of skeletal malocclusion or between sexes. However, the maxillary sinus measurements were significantly correlated with several dentofacial morphological measurements. When formulating an orthodontic treatment plan, orthodontists should take into consideration the fact that the patients 12 to 16 years old with large cranial bases and nasomaxillary complexes tend to have larger maxillary sinuses, but there is no significant association between maxillary sinus size and the A-N-B angle denoting the sagittal skeletal jaw relationship.

Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer: An Unusual Case Involving a Pulmonary Tumor.

Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.

Successful treatment with nivolumab in a patient with lung adenocarcinoma complicated by pulmonary aspergilloma.

Immune checkpoint inhibitors (ICIs) are the key drugs used in patients with non-small cell lung cancer (NSCLC). However, anti-PD-1 therapy might worsen chronic infection by reactivating the immune response to infectious diseases. Here, we describe a case of successful treatment with nivolumab in a patient with NSCLC complicated by pulmonary aspergilloma, which was safely treated by surgical resection before administration of nivolumab. In conclusion, to safely treat patients with locally limited chronic pulmonary aspergillosis (CPA), surgical resection should be considered before ICI therapy.