Uniportal video-assisted thoracoscopic surgery for pediatric cases.

The potential advantages of video-assisted thoracoscopic surgery (VATS) for children include better cosmetic outcomes and reduced risk of postoperative musculoskeletal deformities. The uniportal approach is expected to promote minimally invasive surgery and help reduce the incidence of postoperative musculoskeletal deformities. Uniportal VATS was performed safely in three children (mean age of 23.3 months) with congenital pulmonary airway malformation or extralobar pulmonary sequestration. Our findings suggest that minimally invasive lobectomy may be achieved through uniportal VATS in children.

Honeycomb lung is a major risk factor for preoperative radiological tumor size underestimation in patients with primary lung cancer.

Background: Lung cancer frequently occurs in lungs with background idiopathic interstitial pneumonias (IIPs). Limited resection is often selected to treat lung cancer in patients with IIPs in whom respiratory function is already compromised. However, accurate surgical margins are essential for curative resection; underestimating these margins is a risk for residual lung cancer after surgery. We aimed to investigate the findings of lung fields adjacent to cancer segments affect the estimation of tumor size on computed tomography compared with the pathological specimen. Methods: This analytical observational study retrospectively investigated 896 patients with lung cancer operated on at Fujita Health University from January 2015 to June 2020. The definition of underestimation was a ≥10 mm difference between the radiological and pathological maximum sizes of the tumor. Results: The lung tumors were in 15 honeycomb, 30 reticulated, 207 emphysematous, and 628 normal lungs. The ratio of underestimation in honeycomb lungs was 33.3% compared to 7.4% without honeycombing (P=0.004). Multivariate analysis showed that honeycombing was a significant risk factor for tumor size underestimation. A Bland-Altman plot represented wide 95% limits of agreement, -40.8 to 70.2 mm, between the pathological and radiological maximum tumor sizes in honeycomb lungs.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Lateral approach using grasping technic for uniportal major lung resection.

We report a lateral approach using the grasping technique for uniportal major lung resection. Grasping dissected tissue with grasping forceps enables the dissected surface to be three-dimensionally dissected from important organs, such as blood vessels, which, therefore, makes the procedure safe. Furthermore, there is an incision wound on the middle axillary line at the 6th intercostal space, and therefore, either the anterior or posterior side of the hilum can be easily observed, and a stapler can pass through all structures of the hilum easily.

Emerging cardioprotective mechanisms of vitamin B6: a narrative review.

Although overt vitamin B6 deficiency is rare, marginal vitamin B6 deficiency is frequent and occurs in a consistent proportion of the population. The marginal vitamin B6 deficiency appears to relate to an increased risk of inflammation-related diseases, such as cardiovascular diseases and cancers. Of all the cardiovascular diseases, heart failure is a complex clinical syndrome associated with a high mortality rate. So far, information regarding the cardioprotective mechanisms of vitamin B6 has been limited. Meanwhile, recent studies have revealed that vitamin B6 treatment increases cardiac levels of imidazole dipeptides (e.g., carnosine, anserine, and homocarnosine), histamine, and γ-aminobutyric acid (GABA) and suppresses P2X7 receptor-mediated NLRP3 inflammasome. These modulations may imply potential cardioprotective mechanisms of vitamin B6. These modulations may also be involved in the underlying mechanisms through which vitamin B6 suppresses oxidative stress and inflammation. This review provides an up-to-date evaluation of our current understanding of the cardioprotective mechanisms of vitamin B6.

[Resection of Multiple Metastases after Liver Resection from Colon Cancer-A Case Report].

A 49-year-old female was underwent laparoscopic right hemicolectomy for ascending colon cancer and liver metastasis. Then, she was underwent laparoscopic hepatectomy. She received BEV plus mFOLFOX6 therapy as postoperative adjuvant chemotherapy, but she had liver recurrence. She received FOLFOXIRI therapy. Although tumor tended to progressive, it was localized, so laparoscopic hepatectomy was performed again. She received AFL plus FOLFIRI therapy. Fourteen months after hepatic resection, disseminated nodules and lung metastases were found. However, both of peritoneal dissemination, and lung metastasis were localized, so it was judged that peritoneal dissemination and lung metastasis could be resectable. Then, peritoneal dissemination resection and sigmoid colectomy were performed, and then lung resection was performed to perform R0 resection. R0 resection and multimodal therapy for simultaneous and heterotopic metastases of colorectal cancer can contribute to provide a long-term prognosis.

Gasdermin D mediates the maturation and release of IL-1α downstream of inflammasomes.

IL-1α serves as a pro-inflammatory cytokine. Although pro-IL-1α has cytokine activity, proteolytic maturation increases its potency and release from cells. IL-1α maturation occurs in a caspase-1-dependent manner following inflammasome activation. However, pro-IL-1α is not a substrate of caspase-1, and it remains unclear what mediates the maturation of this cytokine downstream of inflammasomes. Here, we show that gasdermin D (GSDMD), an executor of pyroptosis, is required for the rapid induction of IL-1α maturation by non-particulate inflammasome activators. Ablation of GSDMD abrogates the maturation of IL-1α, but not of IL-1ß. Inflammasome-induced maturation of IL-1α relies on extracellular Ca2+ and calpains. Ca2+ influx and calpain activation are induced in a GSDMD-dependent manner. Glycine, which inhibits cell lysis, but not GSDMD pore formation, does not affect IL-1α maturation. These results suggest that during inflammasome activation, GSDMD processed by caspase-1 forms plasma membrane pores that mediate Ca2+ influx, resulting in the calpain-dependent maturation of IL-1α.

Evaluation of prognosis after thoracoscopic lobectomy for primary lung cancer.

INTRODUCTION: Thoracoscopic lobectomy for primary lung cancer is performed at many institutions. However, few reports are available on postoperative prognosis for progressive stages. In 2004, we adopted lobectomy by video-assisted thoracoscopic surgery (VATS), which would be applicable to the clinical stages up to stage IIIA. This study reports long-term outcomes of surgery for primary lung cancer at several stages, including IIIA. METHODS: We compared the long-term outcomes of 315 VATS cases with those of 159 open thoracotomy cases. RESULTS: The overall 5-year survival rate was 78.1% for the VATS group and 61.9% for the open thoracotomy group. A statistically significant difference between the survival curves of the two groups was observed (P = .001). When analyzing the survival curves for both groups by pathological (p) stage, significant differences were observed for p-stages IB and IIIA, with the VATS group producing better results than the open thoracotomy group. CONCLUSION: The long-term outcomes of patients with primary lung cancer at our institution were more favorable in the group undergoing VATS lobectomy than in the group undergoing open thoracotomy.

Subxiphoid uniportal bilateral lung wedge resection.

Subxiphoid uniportal bilateral lung wedge resection, in which all manipulations are performed via a 3-cm wound positioned below the xiphoid process, can be performed in the supine position without the patient having to change positions. It also enables one-stage bilateral lung resection. We report the surgical procedure and initial results of subxiphoid uniportal bilateral lung wedge resection. A 3-cm transverse incision was made 1 cm caudally below the xiphoid process. A port for uniportal surgery was inserted. After CO2 insufflation at 8 mmHg, the lung was grasped and lifted with bent grasping forceps, and by bending the tip of a stapler, the surgeon resected the affected portion of the bilateral lungs. In this approach, there is one incision, no intercostal nerve damage and bilateral surgery can be performed in the same procedure; therefore, the technique may have the benefit of lesser invasiveness for the patient. Furthermore, a detailed comparison of subxiphoid uniportal bilateral lung wedge resection with the one-stage lateral intercostal approach with a larger subject sample is needed.

Early outcomes in 147 consecutive cases of subxiphoid single-port thymectomy and evaluation of learning curves.

OBJECTIVES: The aim of the present study was to examine some initial results and learning curves concerning subxiphoid single-port thymectomy (SSPT), thereby clarifying the safety of this surgical approach and describing the precautions for adopting it. METHODS: From March 2011 to August 2019, a total of 203 patients underwent thymectomy for either anterior mediastinal tumours or myasthenia gravis at Fujita Health University Hospital. Of these 203 patients, 147 patients who had undergone SSPT were selected as participants for the present study. RESULTS: Of the 147 cases, transition to a different approach was required in three (2.0%) cases: two (1.3%) cases transitioned to median sternotomy, whereas one (0.7%) case transitioned to the side chest trans-intercostal approach. The two cases that transitioned to median sternotomy were the second cases for different operators after they began performing this technique. There were six (4.0%) cases with complications and no deaths. The operation time cumulative summation learning curve analysis revealed that the curves descended from the 38th case. In the 83 cases handled by one surgeon, the learning curves descended from the 31st case. CONCLUSIONS: SSPT is a safe modality with few complications and no associated cases of mortality reported. Operators are required to experience 31-38 cases until the operation time for SSPT was stabilized. Special care should be exercised to prevent vascular damage in the vicinity of the innominate veins during the early stages after SSPT introduction.

Gasdermin D-independent release of interleukin-1ß by living macrophages in response to mycoplasmal lipoproteins and lipopeptides.

Interleukin-1ß (IL-1ß) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1ß by caspase-1, which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell-death-mediated release of IL-1ß. Living cells can also release IL-1ß via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and Mycoplasma pneumoniae (MpLP) and an M. salivarium-derived lipopeptide (FSL-1), which are activators of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, induce IL-1ß release from mouse bone-marrow-derived macrophages (BMMs) without inducing cell death. The levels of IL-1ß release induced by MsLP, MpLP and FSL-1 were more than 100 times lower than those induced by the canonical NLRP3 activator nigericin. The IL-1ß release-inducing activities of MsLP, MpLP and FSL-1 were not attenuated in BMMs from GSDMD-deficient mice. Furthermore, both active caspase-1 and cleaved GSDMD were detected in response to transfection of FSL-1 into the cytosol of BMMs, but the release of IL-1ß was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane-stabilizing agent, drastically down-regulated the release of IL-1ß in response to FSL-1. These results suggest that mycoplasmal lipoprotein/lipopeptide-induced IL-1ß release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability.

[Uniportal Pulmonary and Mediastinal Video-assisted Thoracic Surgery Procedure].

In recent years, uniportal video-assisted thoracoscopic surgery, which performs all surgical procedures from 1 wound, has been spreading for the purpose of performing less invasive surgery. The uniportal surgery requires a device because it interferes with instruments, but is a surgical technique that is cosmetically excellent and can be expected to reduce postoperative pain. This new minimally invasive surgical technique is now widely spread, especially in Asia and Europe. In addition, uniportal surgery using the subxiphoid approach has attracted attention. This method has an advantage that intercostal neuropathy does not occur because it does not pass through the intercostal space, and is a useful method for patients. These uniportal surgery is expected to be further developed as a new minimally invasive surgery. In the future, it is necessary to develop more operable devices and instruments, including robot systems, and to prove the usefulness of uniportal surgery.

Uniportal video-assisted thoracic surgery lowers the incidence of post-thoracotomy pain syndrome.

OBJECTIVE: We compared post-thoracotomy pain syndrome (PTPS) incidence in patients who underwent uniportal or multiportal video-assisted thoracoscopic surgery (VATS). METHODS: We included 223 patients who underwent either uniportal or multiportal VATS between January 2017 and October 2018 (pulmonary lobectomies and pulmonary segmentectomies-uniportal: n=19, multiportal: n=133; wedge lung resections-uniportal: n=16, multiportal: n=55). We retrospectively studied incidences of PTPS in all subgroups. RESULTS: Incidences of PTPS were significantly less for uniportal procedures for both the pulmonary lobectomy/segmentectomy group (P=0.024) and the wedge lung resection group (P=0.0315) than for multiportal procedures. CONCLUSION: Patients who underwent uniportal VATS procedures had lower incidences of PTPS than the multiportal VATS group. The uniportal VATS approach is therefore beneficial for patients.

Prediction of pulmonary function after major lung resection using lung perfusion scintigraphy with single-photon emission computed tomography/computed tomography.

OBJECTIVE: Precise prediction of postoperative pulmonary function is extremely important for accurately evaluating the risk of perioperative morbidity and mortality after major surgery for lung cancer. This study aimed to compare the accuracy of a single-photon emission computed tomography/computed tomography (SPECT/CT) method that we recently developed for predicting postoperative pulmonary function versus the accuracy of both the conventional simplified calculating (SC) method and the method using planar images of lung perfusion scintigraphy. METHODS: The relationship between the postoperative observed % values of the forced expiratory volume in 1 second (FEV1) or diffusing capacity for carbon monoxide (DLCO or DLCO') and the % predicted postoperative (%ppo) values of FEV1, DLCO, or DLCO' calculated by the three methods were analyzed in 30 consecutive patients with lung cancer undergoing lobectomy. RESULTS: The relationship between the postoperative observed % values and %ppo values calculated by the three methods exhibited a strong correlation (Pearson r>0.8, two-tailed p<0.0001). The limits of agreement between the postoperative % values and %ppo values did not differ among the three methods. The absolute values of the differences between the postoperative % values and %ppo values for FEV1 and DLCO' were comparable among the three methods, whereas those for DLCO of SPECT/CT were significantly higher than those of the planar method. Conversely, in patients with preoperative %DLCO' of <80% predicted, the absolute values of the differences between the postoperative %DLCO' and %ppoDLCO' of SPECT/CT tended to be smaller than those of the SC and planar methods. CONCLUSION: The accuracy of SPECT/CT for predicting postoperative pulmonary function is comparable with that of conventional methods in most cases, other than in some patients with diffusion impairment.

Caspase-7 mediates caspase-1-induced apoptosis independently of Bid.

Inflammasomes are innate immune mechanisms that activate caspase-1 in response to a variety of stimuli, including Salmonella infection. Active caspase-1 has a potential to induce two different types of cell death, depending on the expression of the pyroptosis mediator gasdermin D (GSDMD); following caspase-1 activation, GSDMD-sufficient and GSDMD-null/low cells undergo pyroptosis and apoptosis, respectively. Although Bid, a caspase-1 substrate, plays a critical role in caspase-1 induction of apoptosis in GSDMD-null/low cells, an additional mechanism that mediates this cell death independently of Bid has also been suggested. This study investigated the Bid-independent pathway of caspase-1-induced apoptosis. Caspase-1 has been reported to process caspase-6 and caspase-7. Silencing of caspase-7, but not caspase-6, significantly reduced the activation of caspase-3 induced by caspase-1, which was activated by chemical dimerization, in GSDMD/Bid-deficient cells. CRISPR/Cas9-mediated depletion of caspase-7 had the same effect on the caspase-3 activation. Moreover, in the absence of GSDMD and Bid, caspase-7 depletion reduced apoptosis induced by caspase-1 activation. Caspase-7 was activated following caspase-1 activation independently of caspase-3, suggesting that caspase-7 acts downstream of caspase-1 and upstream of caspase-3. Salmonella induced the activation of caspase-3 in GSDMD-deficient macrophages, which relied partly on Bid and largely on caspase-1. The caspase-3 activation and apoptotic morphological changes seen in Salmonella-infected GSDMD/Bid-deficient macrophages were attenuated by caspase-7 knockdown. These results suggest that in addition to Bid, caspase-7 can also mediate caspase-1-induced apoptosis and provide mechanistic insights into inflammasome-associated cell death that is one major effector mechanism of inflammasomes.

Development of a Water-Soluble Indolylmaleimide Derivative IM-93 Showing Dual Inhibition of Ferroptosis and NETosis.

The indolylmaleimide (IM) derivative IM-17 shows inhibitory activity against oxidative-stress-induced necrotic cell death and cardioprotective activity in rat ischemia-reperfusion injury models. In order to develop a more potent derivative, we conducted a detailed structure-activity relationship study of IM derivatives and identified IM-93 as the most potent derivative with good water solubility. IM-93 inhibited ferroptosis and NETosis, but not necroptosis or pyroptosis. In contrast, ferrostatin-1 (Fer-1), a ferroptosis inhibitor, did not inhibit NETosis, although the accompanying lipid peroxidation was partially inhibited by Fer-1, as well as by IM-93. Thus, IM derivatives have a unique activity profile and appear to be promising candidates for in vivo application.

Video-assisted thoracoscopic surgery for ectopic mediastinal parathyroid tumor: subxiphoid and lateral thoracic approach.

BACKGROUND: This study aimed to investigate the initial results of an endoscopic surgical approach for the treatment of intramediastinal ectopic parathyroid adenoma and to evaluate the effectiveness of a single-incision resection using the subxiphoid approach. METHODS: Five cases of patients (1.89%) were diagnosed with ectopic mediastinal parathyroid tumor and underwent resection from 2008 to 2017 in Fujita Health University Hospital. They were retrospectively analyzed. RESULTS: Four patients underwent single-port mediastinal tumor resection using the subxiphoid approach and 1 patient underwent multi-port mediastinal tumor resection using the lateral thoracic approach. The operation time was 134±83.52 min, and the amount of blood loss was 81.8±173.41 mL. The rate of conversion to thoracotomy was 0%, and no intraoperative or postoperative complications were observed. The amount of postoperative oral analgesics was 112.83±209.12 tablets, and their administration period was 561.6±1,229.5 days. The length of hospital stay was 4±2.35 days, and the duration of chest tube drainage was 1.33±1.95 days. The patient who underwent multi-port mediastinal tumor resection using the lateral thoracic approach reported postoperative pain. Serum calcium levels decreased from 10.56±1.52 mg/dL preoperatively to 8.96±0.5 mg/dL postoperatively, and serum phosphorous levels increased from 2.84±0.42 mg/dL preoperatively to 3.6±0.51 mg/dL postoperatively. Intact-PTH hormone levels decreased from 221±169.84 pg/dL preoperatively to 70.2±44.28 pg/dL postoperatively. No recurrence of hyperparathyroidism has been observed in any patient. CONCLUSIONS: The single-incision mediastinal tumor resection via the subxiphoid approach, without going through the intercostal space, is considered as a useful endoscopic surgical approach for the treatment of mediastinal ectopic parathyroid adenomas due to the limited occurrence of post-thoracotomy pain syndrome and the superior esthetic outcomes associated with the procedure as compared to thoracotomy and median sternotomy.

Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation.

Chronic activation of the IL-1ß system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and activation in the tissue has remained unexplored. Here, we demonstrate that IL-1ß transcript was enriched in neutrophils of white adipose tissue (WAT) from lean mice. Mechanistically, the interaction of neutrophils with adipocytes induced IL-1ß expression via NF-κB pathway. Lipolysis of adipocytes accumulated neutrophils prior to macrophages in WAT and produced high levels of IL-1ß via an inflammasome pathway. Leukotriene B4 (LTB4) production in WAT also contributed to neutrophil accumulation. Furthermore, an LTB4-inflammasome axis contributed to the expression of chemotactic molecules involved in high-fat diet-induced macrophage infiltration into WAT. We have identified previously unappreciated roles for neutrophils in the development of adipose tissue inflammation: robust IL-1ß production and infiltration of macrophages to initiate chronic inflammation.-Watanabe, Y., Nagai, Y., Honda, H., Okamoto, N., Yanagibashi, T., Ogasawara, M., Yamamoto, S., Imamura, R., Takasaki, I., Hara, H., Sasahara, M., Arita, M., Hida, S., Taniguchi, S., Suda, T., Takatsu, K. Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation.