A component of high-grade fetal lung adenocarcinoma diagnosed as the cause of lymph node metastasis.

High-grade fetal lung adenocarcinoma (H-FLAC) is a rare type of tumor. There have been no reports demonstrating the degree of metastatic susceptibility of this tumor type. In this report, we describe a case in which 15% of the adenocarcinoma components were H-FLAC diagnosed as the cause of lymph node metastasis. A 75-year-old man presented with suspected primary lung cancer (clinical stage IIA, T2bN0M0) and underwent left upper lobectomy and superior mediastinal lymph node dissection. Postoperative histopathology revealed lung cancer with only lobar bronchial lymph node (#11) metastasis. Approximately 60% of the invasive adenocarcinoma showed a papillary morphology, 25% showed a lepidic morphology, and 15% showed a fetal morphology. The histomorphological and immunohistological features of #11 metastasis were similar to those of H-FLAC. Herein, we report a rare and important case of H-FLAC with proven lymph node metastasis, showing that even a small amount of H-FLAC tissue can cause metastasis.

The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

[Inflammatory Polyp due to Peanut Aspiration, Needed to Differentiate from Malignant Tumor: Report of a Case].

The patient was in his 70s. He was addmitted to our hospital because of obstructive pneumonia for 3 months. Chest computed tomography( CT) showed a nodule at the base of the right B8, obstructing the basal branch, with consolidation of the peripheral lung. Bronchoscopy revealed the right basal trunk obstruction by a tumorous lesion. FDG-PET showed heterogeneous FDG uptake at the right hilum and the lower lobe suggesting malignancy, and a thoracoscopic right lower lobectomy was performed. Pathology showed a granulation-like nodule and a brown oval foreign body incarcerated in the peripheral bronchus, which was later revealed to be a peanut, and no obvious malignant findings were observed.

[Invasive Mucinous Adenocarcinoma that Invades the Wall of a Cystic Lesion:Report of a Case].

Invasive mucinous adenocarcinoma (IMA) is a rare and special type of lung adenocarcinoma. We report a case of IMA presenting as a cystic lesion in the S10 of the right lung, diagnosed by surgical biopsy and treated with right lower lobectomy. The patient was a 60-year-old man who was found to have a 10-mm-sized frosted ground-glass opacity with a 10-mm-sized air space in the S10 of the right lung while undergoing follow-up after renal cancer surgery in 2018. The air space gradually enlarged and, in 2022, began to show a 40-mm-sized cyst, with partial wall thickening and nodularity on the caudal side. A thoracoscopic partial pneumonectomy was performed to confirm the diagnosis of IMA, and a thoracoscopic radical resection of the right remaining lower lobe was performed. It is important to recognize that adenocarcinoma may occur in patients with thin-wall cavity, as in this case. Additionally, it is necessary to determine the treatment strategy based on the assumption that the tumor may extend to the entire cavity wall, even if it is thin-walled.

Perceptual Translucency in 3D Printing Using Surface Texture.

We propose a method of reproducing perceptual translucency in three-dimensional printing. In contrast to most conventional methods, which reproduce the physical properties of translucency, we focus on the perceptual aspects of translucency. Humans are known to rely on simple cues to perceive translucency, and we develop a method of reproducing these cues using the gradation of surface textures. Textures are designed to reproduce the intensity distribution of the shading and thus provide a cue for the perception of translucency. In creating textures, we adopt computer graphics to develop an image-based optimization method. We validate the effectiveness of the method through subjective evaluation experiments using three-dimensionally printed objects. The results of the validation suggest that the proposed method using texture may increase perceptual translucency under specific conditions. As a method for translucent 3D printing, our method has the limitation that it depends on the observation conditions; however, it provides knowledge to the field of perception that the human visual system can be cheated by only surface textures.

Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma A549 cells.

Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-ß type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-ß1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-ß1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-ß1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-ß-dependent cell metabolism in human lung adenocarcinoma.

Vaginal Microbiota and Pregnancy Outcomes of Patients with Conization Histories.

Background: One of the major risks of preterm birth is a history of conization. However, the risk of infection due to this procedure is still not well known. Using next-generation sequencing, we aimed to reveal the influence of conization on vaginal microbiota in the following pregnancy, and their relationship between spontaneous preterm birth (sPTB). Methods: We conducted a prospective cohort study including 133 pregnant patients, of whom 25 had conization histories and 108 did not. Vaginal microbiome samples were collected using swabs by an obstetrician upon inclusion in the first trimester and during delivery. V1-V2 of the 16S rRNA gene were amplified and analyzed to identify the bacteria. Results: The conization group had a significantly lower delivery week (34 weeks vs. 36 weeks, p = 0.003) and higher sPTB rate (64% vs. 8.3%, p ≤ 0.001) than the control group. In the conization group, alpha (Chao 1, p = 0.02; phylogenetic diversity whole tree, p = 0.04) and beta diversity (permutational multivariate analysis of variance test, p = 0.04) of the vaginal microbiota was significantly higher during delivery in patients who delivered preterm than in those who delivered term. Community-state type IV in the first trimester was significantly associated with sPTB (overall odds ratio 3.80, 95% confidence interval 1.33-10.8, p = 0.01). Conclusions: Conization is a risk factor for sPTB. Increased risk of sPTB in patients after conization may belong to the vulnerable defense mechanism, due to the shortened cervix and decreased cervical mucus.

Endometrial and vaginal microbiomes influence assisted reproductive technology outcomes.

OBJECTIVE: The role of Lactobacillus-dominant microbiota in the endometrium in reproductive function is unclear. We therefore aimed to explore the impact of the balance of Lactobacillus and pathological bacteria in the endometrial and vaginal microbiomes on the pregnancy outcomes of women treated with assisted reproductive technology (ART). METHODS: This study included 35 women with infertility submitted to good-quality embryo transfers. The cutoff values for abundance of Lactobacillus species (spp.) and pathological bacteria in the endometrium and vagina were calculated. Women with Lactobacillus spp. and pathological bacteria abundance above the cutoff values were categorized in the high-abundance group, whereas those with abundance below cutoff values were categorized in the low abundance group. We divided the patients into four groups based on the combination of high/low abundance of Lactobacillus spp. and pathological bacteria. RESULTS: The 35 cases of good-quality embryo transfer resulted in 21 pregnancies. Pregnant women were present in significantly higher proportions in the high Lactobacillus spp. abundance and low pathological bacteria abundance group, whereas the opposite combination (i.e., low Lactobacillus spp. abundance and high pathological bacteria abundance) saw a significantly higher proportion of nonpregnant women (p=0.022). CONCLUSIONS: The balance between Lactobacillus and pathological bacterial abundance in the endometrial and vaginal microbiomes is associated with pregnancy from ART.

Number of lymph nodes dissected and upstaging rate of the N factor in robot-assisted thoracic surgery versus video-assisted thoracic surgery for patients with cN0 primary lung cancer.

PURPOSE: The accuracy of lymph node (LN) dissection in robotic surgery for lung cancer remains controversial. We compared the accuracy of LN dissection in robot-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS). METHODS: The subjects of this retrospective analysis were 226 patients with cN0 primary lung cancer who underwent robot-assisted or video-assisted thoracic lobectomy with LN dissection, in our department, between April, 2016 and February, 2021. We compared the numbers of all LNs and mediastinal LNs dissected, the time required for LN dissection, complications, and upstaging rates of the N factor between the groups. Furthermore, we performed an inverse probability of treatment weighting-adjusted analysis to reduce potential bias between the groups. RESULTS: The number of dissected LNs was higher in the RATS group in both the unweighted and weighted analyses. The time required for lymph node dissection was also longer in RATS. There was no significant difference in complications or in the upstaging rate of the N factor between the groups. CONCLUSION: More LNs were dissected with RATS. Thus, the usefulness of robot-assisted surgery for LN dissection needs to be investigated further.

Clinical effect of soft coagulation for air leak treatment during pulmonary lobectomy.

BACKGROUND: Soft coagulation using the VIO soft coagulation system is used to treat minor lung air leaks during pulmonary resection in Japan. We previously reported that it has a similar effect as the air leak treatment with fibrin glue. We evaluated the efficacy of soft coagulation using the VIO soft coagulation system for lung air leakage during pulmonary resection. METHODS: Intraoperative air leaks from the interlobar lung parenchyma were observed in 42 of the 283 patients who underwent video-assisted thoracoscopic surgery lobectomy between 2016 and 2018. We retrospectively reviewed these 42 patients who were treated using the VIO soft coagulation system for air leaks. We classified the air leaks in to grades using the Macchiarini scale score and evaluated the surgical outcomes of air leak treatment. RESULTS: Air leaks from the interlobar lung parenchyma having Macchiarini scale scores 1, 2, and 3 occurred in 8, 17, and 17 patients, respectively. In all the 8 patients with score 1 air leaks (100%), the air leaks could be controlled using the VIO soft coagulation system alone, and none had delayed pneumothorax requiring intervention. Of the score 2 and 3 air leaks, 52.9% and 35.3% were controlled using the VIO soft coagulation system alone, respectively. CONCLUSIONS: Macchiarini scale score 1 air leaks from the interlobar lung parenchyma could be well controlled using the VIO soft coagulation system. Therefore, soft coagulation with this system may be an alternative method for treating minor air leaks during pulmonary resection surgery.

Robot-assisted vs. video-assisted thoracoscopic surgery in lung cancer.

Background: The major advantages of robot-assisted surgery are the fine field of view provided by the high-precision three-dimensional (3D) images and the good operability provided by the robotic arms that enables precise movements. A growing number of retrospective studies have compared robotic-assisted thoracoscopic surgery (RATS) with video-assisted thoracoscopic surgery (VATS), but the number of cases is limited and the results are contradictory. Methods: We studied the medical records of primary lung cancer patients who underwent lobectomy with lymph node dissection between 2017 and 2020. Four hundred and eleven patients fulfilled the inclusion criteria in this study (RATS: 103; VATS: 308). We compared the perioperative factors and postoperative results of the VATS and RATS groups. Further, we adjusted background factors using propensity score matching (PSM) then compared the results of 200 patients (100 patients in each group). In this study, we matched interlobar fissure completeness, which affects operative difficulty and operative time; however, this has been superficially compared in previous studies. Results: After PSM, a significant difference was observed in the intraoperative blood loss (RATS: 53.3 mL, VATS: 120.3 mL, P=0.04). The rates of surgical complications were comparable between the groups (10.0% vs. 13.0%, P=0.66) with similar mean operation times (RATS: 215.0 min, VATS: 210.1 min, P=0.57). The mean postoperative stay in the RATS group was shorter than that in the VATS group (10.0 vs. 11.5 days, P=0.04). Conclusions: Initial experience of RATS had no obvious drawbacks when compared with that of VATS on propensity-matched analysis.

Microbiome analysis in women with endometriosis: Does a microbiome exist in peritoneal fluid and ovarian cystic fluid?

Purpose: To investigate the relationship between the microbiome of the female genital tract and endometriosis. Methods: This prospective cohort study included 36 women who underwent laparoscopic surgery for ovarian tumor from July 2019 to April 2020. Of them, 18 had endometriosis, and 18 did not have endometriosis. Vaginal secretions, endometrial fluid, peritoneal fluid, and ovarian cystic fluid were collected during surgery. Next-generation sequencing of bacterial 16S rRNA was performed to characterize the microbiome. Results: Specific microbiomes were not detected in either peritoneal fluid or ovarian cystic fluid regardless of the presence or absence of endometriosis and the type of cyst. When the cutoff value of infectious bacterial abundance in the vagina was set as 64.3%, there were many cases more than a cutoff value in the endometriosis group significantly (p = 0.01). When the cutoff value of infectious bacterial abundance in the endometrium was set as 18.6%, there were many cases more than a cutoff level in the endometriosis cases significantly (p = 0.02). Conclusion: Peritoneal fluid and ovarian cystic fluid are almost sterile, although dysbiosis may occur in the vaginal and endometrial microbiome in women with endometriosis.

Fabrication of a Human Skin Mockup with a Multilayered Concentration Map of Pigment Components Using a UV Printer.

In this paper, we propose a pipeline that reproduces human skin mockups using a UV printer by obtaining the spatial concentration map of pigments from an RGB image of human skin. The pigment concentration distributions were obtained by a separating method of skin pigment components with independent component analysis from the skin image. This method can extract the concentration of melanin and hemoglobin components, which are the main pigments that make up skin tone. Based on this concentration, we developed a procedure to reproduce a skin mockup with a multi-layered structure that is determined by mapping the absorbance of melanin and hemoglobin to CMYK (Cyan, Magenta, Yellow, Black) subtractive color mixing. In our proposed method, the multi-layered structure with different pigments in each layer contributes greatly to the accurate reproduction of skin tones. We use a UV printer because the printer is capable of layered fabrication by using UV-curable inks. As the result, subjective evaluation showed that the artificial skin reproduced by our method has a more skin-like appearance than that produced using conventional printing.

Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells.

Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells.

[Congenital Pericardial Defect Incidentally Found at Thoracoscopic Left Upper Lobe Resection:Report of a Case].

We report a rare case of a congenital pericardial defect that was incidentally found at thoracoscopic left upper lobe resection in a patient with lung cancer. A 75-year-old man with a left upper lobe lung cancer was referred to our hospital. We performed thoracoscopic left upper lobectomy and incidentally found a pericardial defect intraoperatively. Careful lymph node dissection was necessary to avoid injury of phrenic nerve and pulmonary artery. Surgery for lung cancer was completed without pericardial repair. After surgery, no complications associated with the pericardial defect has not been encountered.

[Spinal Cord Infarction after Right Upper Lobectomy Combined with Chest Wall Resection].

A 42-year-old man presented with a one-month history of back pain. Chest computed tomography revealed a mass (7.6×5.7 cm) in the right upper lobe, suspicious of chest wall invasion. We performed right upper lobectomy combined with chest wall resection. Partial dissections of the second to sixth ribs and the third and fourth vertebral bodies were conducted. Postoperatively, motor paralysis of the right lower extremity was observed and a diagnosis of spinal infarction was made. After cerebrospinal fluid drainage and administration of edaravone with early rehabilitation, he was able to walk with a brace and was discharged from the hospital.

Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection.

Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.

Vessel sealing system for video-assisted lung resection for cancer reduces chylothorax and bleeding.

BACKGROUND: The objective of this study was to analyze the efficacy of the LigaSureTM vessel sealing system for lung cancer resection with node dissection, as this has not been sufficiently evaluated. METHODS: From 2004 to 2018, 948 patients underwent anatomical pulmonary resection with node dissection for non-small cell lung carcinoma (NSCLC) via the video-assisted thoracoscopic surgery (VATS) approach. Medical records of these patients were reviewed retrospectively. Univariate and multivariate analyses were conducted to determine the risk factors for chylothorax and blood loss. RESULTS: Of the 948 patients, 318 (33.5%) who underwent anatomical lung resection with node dissection by conventional methods without vessel sealing system and 630 (66.5%) who underwent lung resection with node dissection with the vessel sealing system were included. The median intraoperative blood loss was 100 mL. Postoperative chylothorax occurred in 9 (2.8%) patients in the conventional method group with 2 (0.3%) patients in the vessel sealing system group (P=0.001). Patients in the vessel sealing group who developed chylothorax were cured by conservative treatment. Univariate and multivariate analyses identified male sex [odds ratio (OR) 2.053; 95% confidence interval (CI): 1.494-2.820; P<0.001] and the use of vessel sealing system (OR 0.342; 95% CI: 0.256-0.457; P<0.001) as independent predictors of intraoperative blood loss. The univariate and multivariate analyses identified the use of the vessel sealing system (OR 0.108; 95% CI: 0.023-0.504; P=0.005) as an independent predictor of chylothorax incidence. CONCLUSIONS: Vessel sealing system for lung cancer resection could decrease chest tube duration, amount of intraoperative bleeding, and incidence of chylothorax in patients who undergo lung resection with node dissection.

Two cases of left recurrent laryngeal nerve paralysis after right superior mediastinal node dissection.

BACKGROUND: Ipsilateral recurrent laryngeal nerve paralysis is one of the rare complications during the superior mediastinal node dissection for lung cancer. However, very few reports of contralateral recurrent laryngeal nerve paralysis during the procedure are available. CASE PRESENTATION: Two women aged 74 and 80 years developed hoarseness after undergoing right upper lobectomy and right superior mediastinal node dissection for primary lung cancer. Postoperative laryngoscopy in the two patients confirmed left vocal cord paralysis. CONCLUSION: Node dissection is performed in the standard procedure for right upper lobe lung cancer. At this time, care must be taken not to cause damage not only to the recurrent laryngeal nerve on the ipsilateral side but also to the recurrent laryngeal nerve on the contralateral side.

Effects of histone deacetylase inhibitors Tricostatin A and Quisinostat on tight junction proteins of human lung adenocarcinoma A549 cells and normal lung epithelial cells.

Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for non-small cell lung cancer (NSCLC). However, more preclinical studies of HDAC inhibitors in NSCLC and normal lung epithelial cells are required to evaluate their antitumor activities and mechanisms. The bicellular tight junction molecule claudin-2 (CLDN-2) is highly expressed in lung adenocarcinoma tissues and increase the proliferation of adenocarcinoma cells. Downregulation of the tricellular tight junction molecule angulin-1/LSR induces malignancy via EGF-dependent CLDN-2 and TGF-ß-dependent cellular metabolism in human lung adenocarcinoma cells. In the present study, to investigate the detailed mechanisms of the antitumor activities of HDAC inhibitors in lung adenocarcinoma, human lung adenocarcinoma A549 cells and normal lung epithelial cells were treated with the HDAC inibitors Trichostatin A (TSA) and Quisinostat (JNJ-2648158) with or without TGF-ß. Both HDAC inhibitors increased anguin-1/LSR, decrease CLDN-2, promoted G1 arrest and prevented the migration of A549 cells. Furthermore, TSA but not Quisinostat with or without TGF-ß induced cellular metabolism indicated as the mitochondrial respiration measured using the oxygen consumption rate. In normal human lung epithelial cells, treatment with TSA and Quisinostat increased expression of LSR and CLDN-2 and decreased that of CLDN-1 with or without TGF-ß in 2D culture. Quisinostat but not TSA with TGF-ß increased CLDN-7 expression in 2D culture. Both HDAC inhibitors prevented disruption of the epithelial barrier measured as the permeability of FD-4 induced by TGF-ß in 2.5D culture. TSA and Quisinostat have potential for use in therapy for lung adenocarcinoma via changes in the expression of angulin-1/LSR and CLDN-2.