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).

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-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.

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.

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.

[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.

[Robot Assisted Thoracic Surgery Procedure].

The advantages of robot-assisted surgery include true 3-dimensional imaging with binocular glasses and the use of multiarticular forceps that allow the performance of high-precision operations. This report described the surgical techniques of robot assisted major pulmonary resection and subxiphoid robot-assisted thymectomy. Future developments in the field of robotic engineering will lead to the creation of systems that allow for more advanced surgical techniques. We hope that robotic assisted surgery will be safely introduced into many medical facilities.

Vitamin B6 Prevents IL-1ß Protein Production by Inhibiting NLRP3 Inflammasome Activation.

Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5'-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood. Here, we showed that both PL and PLP suppressed the expression of cytokine genes in macrophages by inhibiting Toll-like receptor (TLR)-mediated TAK1 phosphorylation and the subsequent NF-κB and JNK activation. Furthermore, PL and PLP abolished NLRP3-dependent caspase-1 processing and the subsequent secretion of mature IL-1ß and IL-18 in LPS-primed macrophages. In contrast, PM and PN had little effect on IL-1ß production. PLP, but not PL, markedly reduced the production of mitochondrial reactive oxygen species (ROS) in peritoneal macrophages. Importantly, PL and PLP reduced IL-1ß production induced by LPS and ATP, or by LPS alone, in mice. Moreover, PL and PLP protected mice from lethal endotoxic shock. Collectively, these findings reveal novel anti-inflammatory activities for vitamin B6 and suggest its potential for preventing inflammatory diseases driven by the NLRP3 inflammasome.

Video-Assisted Thoracoscopic Pulmonary Metastasectomy in Patients with Colorectal Cancer: A Recent 10-Year Single-Institution Experience.

INTRODUCTION: The purpose of this study was to identify independent unfavorable prognostic factors for patients who underwent video-assisted thoracoscopic surgery for resection of pulmonary metastases from colorectal cancer (CRC). METHODS: Between January 2004 and December 2013, 131 patients with pulmonary metastases from CRC underwent the aforementioned procedure for the first time at our institution. Kaplan-Meier survival curves and log-rank tests were used to analyze the survival rates. Multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: The 5-year disease-free survival (DFS) rate of these 131 patients was 34 %. Multivariate analyses showed two variables to be independent significant unfavorable prognostic factors for DFS: preoperative high serum carcinoembryonic antigen (CEA) level and a greater number of pulmonary metastases. According to subgroup analyses that combined these two risk factors, the 5-year DFS rates were 58, 25, and 12 % for patients with 0, 1, or 2 risk factors, respectively. CONCLUSION: In patients who underwent video-assisted thoracoscopic surgery for pulmonary metastases from CRC, we identified two independent unfavorable prognostic factors for DFS: a high CEA level before metastasectomy and a greater number of pulmonary metastases. These factors can be used to identify higher- and lower-risk subgroups, which may help with selecting patients who would benefit the most from video-assisted thoracoscopic pulmonary metastasectomy.

Pyroptotic cells externalize eat-me and release find-me signals and are efficiently engulfed by macrophages.

Pathogenic intracellular bacteria often hijack macrophages for their propagation. The infected macrophages release IL-1ß and IL-18 and simultaneously commit suicide, which is called pyroptosis; both responses require caspase-1. Here, we found that pyroptotic cells induced by microbial infection were efficiently engulfed by human monocytic THP-1-cell-derived macrophages or mouse peritoneal macrophages. This engulfment was inhibited by the D89E mutant of milk fat globule (MFG) epidermal growth factor (EGF) factor 8 (MFG-E8; a phosphatidylserine-binding protein) that has been shown previously to inhibit phosphatidylserine-dependent engulfment of apoptotic cells by macrophages, suggesting that the engulfment of pyroptotic cells by macrophages was also phosphatidylserine dependent. Using a pair of cell lines that respectively exhibited pyroptosis or apoptosis after muramyl dipeptide treatment, we showed that both pyroptotic and apoptotic cells bound to a T-cell immunoglobulin and mucin domain-containing 4 (Tim4; another phosphatidylserine-binding protein)-coated plate, whereas heat-killed necrotic cells did not, indicating that phosphatidylserine was externalized in pyroptosis and apoptosis but not in accidental necrosis. Macrophages engulfed apoptotic cells most efficiently, followed by pyroptotic and then heat-killed necrotic cells. Pyroptotic cells also released a macrophage attractant(s), 'find-me' signal, whose activity was diminished by apyrase that degrades nucleoside triphosphate to nucleoside monophosphate. Heat-killed necrotic cells and pyroptotic cells released ATP much more efficiently than apoptotic cells. These results suggest that pyroptotic cells, like apoptotic cells, actively induce phagocytosis by macrophages using 'eat-me' and find-me signals. Based on these results, a possible role of coordinated induction of pyroptosis and inflammatory cytokine production is discussed.

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.

Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity.

The adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death. We have found that ASC activation induced caspase-8-dependent apoptosis or CA-074Me (cathepsin B inhibitor)-inhibitable necrosis depending on the cell type. Unlike necroptosis, another necrotic cell death, ASC-mediated necrosis, was neither RIP3-dependent nor necrostatin-1-inhibitable. Although acetyl-YVAD-chloromethylketone (Ac-YVAD-CMK) (caspase-1 inhibitor) did not inhibit ASC-mediated necrosis, comprehensive gene expression analyses indicated that caspase-1 expression coincided with the necrosis type. Furthermore, caspase-1 knockdown converted necrosis-type cells to apoptosis-type cells, whereas exogenous expression of either wild-type or catalytically inactive caspase-1 did the opposite. Knockdown of caspase-1, but not Ac-YVAD-CMK, suppressed the monocyte necrosis induced by Staphylococcus and Pseudomonas infection. Thus, the catalytic activity of caspase-1 is dispensable for necrosis induction. Intriguingly, a short period of caspase-1 knockdown inhibited IL-1ß production but not necrosis, although longer knockdown suppressed both responses. Possible explanations of this phenomenon are discussed.

Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells.

Toll-like receptors (TLRs) are widely expressed in immune cells and play a crucial role in many aspects of the immune response. Although some types of TLRs are also expressed in cancer cells, the effects and mechanisms of TLR signaling in cancer cells have not yet been fully elucidated. In the present study, we analyzed the effects of polyinosinic-polycytidylic acid [poly(I:C)], a TLR3 ligand, on three TLR3-expressing human prostate cancer cell lines (LNCaP, PC3, and DU145). We then further characterized the underlying mechanisms, focusing on the poly(I:C)-sensitive LNCaP cell line. Poly(I:C) significantly reduced the viability of LNCaP cells TLR3 and endosome dependently. One mechanism for the antitumor effect was caspase-dependent apoptosis, and another mechanism was poly(I:C)-induced growth arrest. Cell survival and proliferation of LNCaP cells depended on the PI3K/Akt pathway, and PI3K/Akt inhibitors induced apoptosis and growth arrest similar to poly(I:C) treatment. Additionally, poly(I:C) treatment caused dephosphorylation of Akt in LNCaP cells, but transduction of the constitutively active form of Akt rendered LNCaP cells resistant to poly(I:C). Immunoblot analysis of proliferation- and apoptosis-related molecules in poly(I:C)-treated LNCaP cells revealed participation of cyclinD1, c-Myc, p53, and NOXA. Interestingly, poly(I:C) treatment of LNCaP cells was accompanied by autophagy, which was cytoprotective toward poly(I:C)-induced apoptosis. Together, these findings indicate that TLR3 signaling triggers apoptosis and growth arrest of LNCaP cells partially through inactivation of the PI3K/Akt pathway and that treatment-associated autophagy plays a cytoprotective role.

Anti-inflammatory activity of PYNOD and its mechanism in humans and mice.

Many members of the nucleotide-binding and oligomerization domain (NOD)- and leucine-rich-repeat-containing protein (NLR) family play important roles in pathogen recognition and inflammation. However, we previously reported that human PYNOD/NLRP10, an NLR-like protein consisting of a pyrin domain and a NOD, inhibits inflammatory signal mediated by caspase-1 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in reconstitution experiments using HEK293 cells. In this study, we investigated the molecular mechanism of PYNOD's anti-inflammatory activity in vitro and its expression and function in mice. Human PYNOD inhibited the autoprocessing of caspase-1 and caspase-1-mediated IL-1beta processing and suppressed the aggregation of ASC, a hallmark of ASC activation. Interestingly, the NOD of human PYNOD was sufficient to inhibit caspase-1-mediated IL-1beta secretion, whereas its pyrin domain was sufficient to inhibit ASC-mediated NF-kappaB activation and apoptosis and to reduce ASC's ability to promote caspase-1-mediated IL-1beta production. Mouse PYNOD protein was detected in the skin, tongue, heart, colon, peritoneal macrophages, and several cell lines of hematopoietic and myocytic lineages. Mouse PYNOD colocalized with ASC aggregates in LPS + R837-stimulated macrophages; however, unlike human PYNOD, mouse PYNOD failed to inhibit ASC aggregation. Macrophages and neutrophils from PYNOD-transgenic mice exhibited reduced IL-1beta processing and secretion upon microbial infection, although mouse PYNOD failed to inhibit caspase-1 processing, which was inhibited by caspase-4 inhibitor z-LEED-fluoromethylketone. These results suggest that mouse PYNOD colocalizes with ASC and inhibits caspase-1-mediated IL-1beta processing without inhibiting caspase-4 (mouse caspase-11)-mediated caspase-1 processing. Furthermore, PYNOD-transgenic mice were resistant to lethal endotoxic shock. Thus, PYNOD is the first example of an NLR that possesses an anti-inflammatory function in vivo.

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.

Mechanism and repertoire of ASC-mediated gene expression.

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an adaptor molecule that mediates inflammatory and apoptotic signals. Although the role of ASC in caspase-1-mediated IL-1beta and IL-18 maturation is well known, ASC also induces NF-kappaB activation and cytokine gene expression in human cells. In this study, we investigated the molecular mechanism and repertoire of ASC-induced gene expression in human cells. We found that the specific activation of ASC induced AP-1 activity, which was required for optimal IL8 promoter activity. ASC activation also induced STAT3-, but not STAT1-, IFN-stimulated gene factor 3- or NF-AT-dependent reporter gene expression. The ASC-mediated AP-1 activation was NF-kappaB-independent and primarily cell-autonomous response, whereas the STAT3 activation required NF-kappaB activation and was mediated by a factor that can act in a paracrine manner. ASC-mediated AP-1 activation was inhibited by chemical or protein inhibitors for caspase-8, caspase-8-targeting small-interfering RNA, and p38 and JNK inhibitors, but not by a caspase-1 inhibitor, caspase-9 or Fas-associated death domain protein (FADD) dominant-negative mutants, FADD- or RICK-targeting small-interfering RNAs, or a MEK inhibitor, indicating that the ASC-induced AP-1 activation is mediated by caspase-8, p38, and JNK, but does not require caspase-1, caspase-9, FADD, RICK, or ERK. DNA microarray analyses identified 75 genes that were induced by ASC activation. A large proportion of them was related to transcription (23%), inflammation (21%), or cell death (16%), indicating that ASC is a potent inducer of inflammatory and cell death-related genes. This is the first report of ASC-mediated AP-1 activation and the repertoire of genes induced downstream of ASC activation.

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.