Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

Long-term outcomes following surgical treatment for thymic epithelial tumor in Japan and an analysis of prognostic factors based on the Japanese Association for Research on the Thymus nationwide database.

PURPOSE: Patients with a thymic epithelial tumor (TET), comprising thymoma, thymic carcinoma (TC), and thymic neuroendocrine neoplasm (TNEN), are rarely encountered. The present study was conducted to determine the recent outcomes of surgical treatment for TET in Japan and clarify the significance of prognostic factors by analyzing a nationwide database created by the Japanese Association for Research on the Thymus (JART). METHODS: The JART database includes records of 2471 thymoma, 285 TC, and 56 TNEN cases surgically treated between 1991 and 2010. At the time of the final follow-up examination, 439 patients had died, with tumor the cause of death in 188. The disease-specific survival was examined using the Kaplan-Meier method, with Cox's proportional hazards model utilized to determine independent prognostic factors. RESULTS: The 10-year survival rate according to TNM-based Stage I, II, IIIA, IIIB, IVA, and IVB classification was 98.7%, 76.8%, 85.0%, 68.9%, 66.2%, and 59.8%, respectively. The T factor, M factor, and tumor size were independent prognostic factors in both thymoma and thymic carcinoma cases, while the N factor had tendency to be a prognostic factor in thymoma but not in thymic carcinoma cases. The WHO histological type was an independent factor in thymoma cases. CONCLUSION: The significance of pathology and TNM classification as prognostic factors was confirmed.

Complex video-assisted thoracoscopic surgery lobectomy for locally advanced lung cancer: a prospective feasibility study.

PURPOSE: The limitations regarding indications for video-assisted thoracoscopic surgery lobectomy requiring complex surgery remain unclear. A prospective cohort study was conducted to elucidate the safety and feasibility of complex thoracoscopic lobectomy for patients with locally advanced non-small-cell lung cancer. METHODS: We planned to enroll patients who were suspected of needing thoracoscopic lobectomy or more with complex surgery, including tracheo-bronchoplasty, pulmonary arterioplasty, and combined resection of adjacent organs. Between February 2016 and January 2019, 28 consecutive patients were prospectively enrolled. RESULTS: After excluding 1 patient due to disease progression, 27 patients were included in this study. Three patients underwent thoracoscopic lobectomy without complex surgery. Of the remaining 24 patients, complex thoracoscopic lobectomy was successfully completed in 21 (88%), and the 3 conversions were due to surgery for the great vessels. All 27 patients achieved complete resection. Six patients (22%) suffered grade 2 complications, and the in-hospital, 30-day, and 90-day mortality rates were all 0%. At a median follow-up time of 900 days, the 3-year overall and disease-free survival rates were 75% and 54%, respectively. CONCLUSIONS: Complex thoracoscopic lobectomy was shown to be safe and feasible in select patients with locally advanced non-small-cell lung cancer excluding invasion to the great vessels. CLINICAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trials Registry, 000,019,441 (JAPAN). Institutional Review Board number: 46-15-0003 (accepted at September 7, 2015).

Low RAI2 expression is a marker of poor prognosis in breast cancer.

PURPOSE: Retinoic acid-induced 2 (RAI2) has been shown to be a putative suppressor of the early hematogenous dissemination of tumor cells to the bone marrow in breast cancer. Here, we investigated the associations of RAI2 mRNA and protein expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: Invasive breast cancer tissues (n = 604) were analyzed for RAI2 mRNA expression. We examined the associations of clinicopathological factors with the expression levels of RAI2 mRNA in these samples. We also analyzed RAI2 protein expression by immunohistochemistry in invasive breast cancer tissues (n = 422). RESULTS: We identified significant positive associations between low expression of RAI2 mRNA and shorter disease-free survival (DFS), breast-cancer-specific survival (BCSS), and overall survival (OS) in breast cancer patients. We also identified significant positive associations between negative for RAI2 protein expression and shorter DFS, BCSS, and OS in breast cancer patients. Low RAI2 mRNA and negative for RAI2 protein expression were positively associated with larger tumor size, higher tumor grade, and ERα-negativity. Multivariate analyses indicated that not only RAI2 mRNA but also RAI2 protein expression were independent risk factors for both DFS and BCSS in breast cancer patients. The median follow-up periods were 10.3 and 9.3 years for the RAI2 mRNA and protein expression analyses, respectively. CONCLUSIONS: Our findings suggest that RAI2 has a role in the metastasis of breast cancer, and that RAI2 expression could be a promising candidate biomarker of prognosis in breast cancer patients.

Expression of cancer testis antigens in thymic epithelial tumors.

Cancer testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. However, to our knowledge, expression of the antigens in thymic epithelial tumors has not been examined yet. We examined the immunohistochemical expression of five CTAs (MAGE-A, NY-ESO-1, MAGE-C1, SAGE and GAGE7) in 192 cases of thymic epithelial tumor. The CTAs were variably expressed in the thymic epithelial tumors. Type B component of type AB thymomas, type B1/B2/B3 thymomas, and thymic carcinomas showed a generally positive correlation between the malignancy grades and positive expression rates in four CTAs other than MAGE-C1. In thymic squamous cell carcinomas (SqCCs), four antigens except for MAGE-C1 showed high expression rates ranging from 23.1% to 43.6%. In the prognostic analysis, a positive expression of SAGE (P = 0.0485) and GAGE7 (P = 0.0289) were associated with a shorter overall survival in type B2/B3 thymomas, respectively. In thymic SqCC, a positive MAGE-A expression was significantly associated with an increased level of programmed death ligand in tumor-infiltrating lymphocytes (P = 0.0181). We showed (i) a frequent CTA expression, (ii) a general correlation of CTA expression with tumor malignancy grades and (iii) a prognostic impact in some of the CTAs.

"Interchangeability" of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy.

Different clones, protocol conditions, instruments, and scoring/readout methods may pose challenges in introducing different PD-L1 assays for immunotherapy. The diagnostic accuracy of using different PD-L1 assays interchangeably for various purposes is unknown. The primary objective of this meta-analysis was to address PD-L1 assay interchangeability based on assay diagnostic accuracy for established clinical uses/purposes. A systematic search of the MEDLINE database using PubMed platform was conducted using "PD-L1" as a search term for 01/01/2015 to 31/08/2018, with limitations "English" and "human". 2,515 abstracts were reviewed to select for original contributions only. 57 studies on comparison of two or more PD-L1 assays were fully reviewed. 22 publications were selected for meta-analysis. Additional data were requested from authors of 20/22 studies in order to enable the meta-analysis. Modified GRADE and QUADAS-2 criteria were used for grading published evidence and designing data abstraction templates for extraction by reviewers. PRISMA was used to guide reporting of systematic review and meta-analysis and STARD 2015 for reporting diagnostic accuracy study. CLSI EP12-A2 was used to guide test comparisons. Data were pooled using random-effects model. The main outcome measure was diagnostic accuracy of various PD-L1 assays. The 22 included studies provided 376 2×2 contingency tables for analyses. Results of our study suggest that, when the testing laboratory is not able to use an Food and Drug Administration-approved companion diagnostic(s) for PD-L1 assessment for its specific clinical purpose(s), it is better to develop a properly validated laboratory developed test for the same purpose(s) as the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic, than to replace the original PD-L1 Food and Drug Administration-approved immunohistochemistry companion diagnostic with a another PD-L1 Food and Drug Administration-approved companion diagnostic that was developed for a different purpose.

Sentinel lymph node biopsy may be unnecessary for ductal carcinoma in situ of the breast that is small and diagnosed by preoperative biopsy.

BACKGROUND: Current guidelines do not recommend that sentinel lymph node biopsy is routinely performed for ductal carcinoma in situ; thus, indications for sentinel lymph node biopsy in patients with ductal carcinoma in situ remain controversial. In this study, we investigated whether sentinel lymph node biopsy can be safely omitted when ductal carcinoma in situ has been diagnosed by preoperative biopsy. METHODS: We retrospectively analysed sentinel lymph node metastasis rates and upstaging to invasive cancer in surgical specimens, performed receiver operating characteristic analysis for ductal carcinoma in situ lesion size and assessed correlations with preoperative clinicopathological factors of 277 patients with ductal carcinoma in situ diagnosed by preoperative biopsy at our institution. RESULTS: Among 277 patients with sentinel lymph node biopsy, six (2.2%) had sentinel lymph node metastasis. All six were upstaged to invasive cancer by pathological examination of surgical specimens. In total, 69 patients (24.9%) were upstaged to invasive cancer. The mean size of ductal carcinoma in situ lesions on preoperative imaging was significantly larger for the 69 upstaged patients (50.0 mm) than for the non-upstaged patients (34.4 mm; P < 0.0001). Of the 277 patients with sentinel lymph node biopsy, 117 (42.2%) had preoperative ductal carcinoma in situ lesions <31.8 mm, which was identified as the optimal cut-off size by receiver operating characteristic analysis. Of these 117 patients, 96 (82.1%, 95% confidence interval: 73.9-88.5%) could be safely omitted from sentinel lymph node biopsy because all of them remained as ductal carcinoma in situ and had negative sentinel lymph nodes at surgery. CONCLUSIONS: Size of ductal carcinoma in situ lesions on preoperative diagnostic imaging is a predictor of diagnosis of invasive cancer on pathological examination of surgical specimens. Sentinel lymph node biopsy may be unnecessary in ductal carcinoma in situ diagnosed by preoperative biopsy in patients with small lesions.

Acute Colchicine Poisoning Causes Endotoxemia via the Destruction of Intestinal Barrier Function: The Curative Effect of Endotoxin Prevention in a Murine Model.

BACKGROUND: Colchicine binds to intracellular tubulin and prevents mitosis. Colchicine is also used as an anti-inflammatory drug. Meanwhile, excess administration of medication or accidental ingestion of colchicine-containing plants can cause acute colchicine poisoning, which initially results in gastrointestinal effects that may be followed by multiorgan dysfunction. However, the mechanism of colchicine poisoning remains unclear, and there are no standard therapeutic strategies. AIMS: We focused on intestinal barrier function and attempted to reveal the underlying mechanism of colchicine poisoning using an animal model. METHODS: Colchicine was orally administered to C57Bl/6 mice. Then, we performed histopathological analysis, serum endotoxin assays, and intestinal permeability testing. Additionally, the LPS-TLR4 signaling inhibitor TAK-242 was intraperitoneally injected after colchicine administration to analyze the therapeutic effect. RESULTS: We observed villus height reduction and increased numbers of apoptotic cells in the gastrointestinal epithelium of colchicine-treated mice. Both intestinal permeability and serum endotoxin levels were higher in colchicine-treated mice than in control mice. Although colchicine-poisoned mice died within 25 h, those that also received TAK-242 treatment survived for more than 48 h. CONCLUSION: Colchicine disrupted intestinal barrier function and caused endotoxin shock. Therapeutic inhibition of LPS-TLR4 signaling might be beneficial for treating acute colchicine poisoning.

The costochondral length in patients with pectus excavatum is longer than that of the normal thorax.

PURPOSE: Recently, several investigators reported that costal cartilage does not overgrow in pectus excavatum (PE). We wished to clarify whether costochondral length is longer in PE than the normal thorax and we tried to clarify the change of the shape of precordial concavity according to the growth in PE. METHODS: We evaluated 243 CT axial images of patients with PE and 246 CT axial images of patients without thoracic deformity. We divided the fifth costal cartilage into several lengths. We considered each part to be a straight line and calculated the length of the lines. We compared the approximate costochondral length between PE and normal thorax. We analyzed the distance between both anterior tips of fifth rib, and the ratio of the width and the depth of concavity to thoracic diameter in PE. CONCLUSIONS: The costochondral length in patients with PE is highly likely to be longer than that of the normal thorax. The length of costal cartilage may be longer in asymmetric PE than symmetric PE. It may start in infantile period in PE that the thoracic shape turns into asymmetry from symmetry. The precordial concavity of PE may be shaped by overgrowth of both costal cartilages and ribs.

Repeated Exposure to 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an Active Metabolite of Bisphenol A, Aggressively Stimulates Breast Cancer Cell Growth in an Estrogen Receptor ß (ERß)-Dependent Manner.

Bisphenol A (BPA), recognized as an endocrine disruptor, is thought to exert its activity through a mechanism involving the activation of estrogen receptors (ERs) α/ß However, a major problem is that very high concentrations of BPA are required (i.e., those in excess of environmental levels) for effective activation of ERα/ß-mediated transcriptional activities in vitro, despite the BPA-induced estrogenic effects observed in vivo. To elucidate the causal reasons, we successfully identified a BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which exhibits highly potent estrogenic activity both in vivo and in vitro. We have focused on the biologic relationship between breast tumor promotion and MBP/BPA, because BPA is considered to be a human carcinogen owing to its breast tumor-promoting properties. In general, humans are exposed to many endocrine disruptors, including BPA. In the present study, we used the ERα/ß-positive human breast cancer cell line MCF-7 as an experimental model to investigate the effects of repeated exposure to BPA/MBP at concentrations found in the environment on the expression of ERα/ß and to determine the particular ER subtype involved. We demonstrated that repeated exposure to MBP, but not to BPA, significantly downregulated ERα protein expression and stimulated the proliferation of MCF-7 cells through the activation of ERß-mediated signaling.

Overproduction of thrombopoietin by BRAFV600E-mutated mouse hepatocytes and contribution of thrombopoietin to hepatocarcinogenesis.

In hepatocarcinogenesis induced by diethylnitrosamine (DEN) in B6C3F1 mice, the BrafV637E mutation, corresponding to the human BRAFV600E mutation, plays a pivotal role. The livers of transgenic mice with a hepatocyte-specific human BRAFV600E mutation weighed 4.5 times more than that of normal mice and consisted entirely of hepatocytes, resembling DEN-induced preneoplastic hepatocytes. However, these transgenic mice spontaneously died 7 wk after birth, therefore this study aimed to clarify the causes of death. In the transgenic mice, the liver showed thrombopoietin (TPO) overexpression, which is associated with eventual megakaryocytosis and thrombocytosis, and activated platelets were deposited in hepatic sinusoids. TPO was also overexpressed in the DEN-induced hepatic tumors, and sinusoidal platelet deposition was observed in the hepatic tumors of humans and mice. Podoplanin was expressed in some of the Kupffer cells in the liver of the transgenic mice, indicating that platelet activation occurred via the interaction of podoplanin with C-type lectin receptor 2 (CLEC-2) on the platelet membrane. Additionally, erythrocyte dyscrasia and glomerulonephropathy/interstitial pneumonia associated with platelet deposition were observed. In the transgenic mice, aspirin (Asp) administration prevented platelet activation, reduced the liver/body weight ratio, decreased the platelet deposition in the liver, kidney, and lung, and prevented erythrocyte dyscrasia and ameliorated the renal/pulmonary changes. Thrombopoietin overproduction by BRAFV600E-mutated hepatocytes may contribute to hepatocyte proliferation via thrombocytosis, platelet activation, and the interaction of platelets with hepatic sinusoidal cells, while hematologic, renal, and pulmonary disorders due to aberrant platelet activation may lead to spontaneous death in the transgenic mice.

A mutation analysis of the EGFR pathway genes, RAS, EGFR, PIK3CA, AKT1 and BRAF, and TP53 gene in thymic carcinoma and thymoma type A/B3.

AIMS: Thymic carcinoma is rare and usually has a fatal outcome. Gene mutations in the epidermal growth factor receptor (EGFR) signalling pathway and TP53 have not been well analysed in thymic carcinoma. METHODS AND RESULTS: We examined a large cohort of thymic carcinoma and thymoma type A/B3 and looked for gene mutations in the RAS family, EGFR, PIK3CA, AKT1, BRAF and TP53. Among 54 thymic carcinoma cases, RAS family mutations were detected in 10 cases, EGFR in two, PIK3CA in one, AKT1 in one, BRAF in none and TP53 in five. Among 33 thymoma type A/B3 cases, HRAS gene mutation were found in one, PIK3CA in two and AKT1 in one. All these mutations were those of missense type activating mutations. RAS family mutations were significantly more frequent in thymic carcinoma than in thymoma type A/B3 (P = 0.0461). A prognostic analysis focusing on thymic squamous cell carcinoma cases (n = 44) showed that the overall survival was significantly shorter in patients with EGFR pathway mutations (n = 9) than in those without in a univariate analysis (P = 0.0173). Subsequently, EGFR pathway mutations were selected as an independent factor for a poor overall survival in a multivariate analysis (P = 0.0389). CONCLUSIONS: Mutations in the EGFR pathway and TP53 in thymic carcinoma may be frequent, and the EGFR pathway mutations may be associated with a poor prognosis in thymic squamous cell carcinoma patients. The therapeutic significance of gene mutations in thymic carcinoma should be further clarified.

Prognostic impact of TP53INP1 gene expression in estrogen receptor α-positive breast cancer patients.

BACKGROUND: Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a key stress protein with tumor suppressor function. Several studies have demonstrated TP53INP1 downregulation in many cancers. In this study, we investigated the correlations of TP53INP1 mRNA expression in breast cancer tissues with prognosis and the correlations of microRNAs that regulate TP53INP1 expression in breast cancer patients with long follow-up. METHODS: A total of 453 invasive breast cancer tissues were analyzed for TP53INP1 mRNA expression. We examined correlations of clinicopathological factors and expression levels of TP53INP1 mRNA in these samples. The expressions of miR-155, miR-569 and markers associated with tumor-initiating capacity were also analyzed. The median follow-up period was 9.0 years. RESULTS: We found positive correlations between low expression of TP53INP1 mRNA and shorter disease-free survival and overall survival in breast cancer patients (P = 0.0002 and P < 0.0001, respectively), as well as in estrogen receptor α (ERα)-positive patients receiving adjuvant endocrine therapy (P = 0.01 and P = 0.0008, respectively). No correlations were found in ERα-negative patients. Low TP53INP1 mRNA levels positively correlated with higher grade and ERα-negativity. Multivariate analysis indicated that TP53INP1 mRNA level was an independent risk factor for overall survival both in overall breast cancer patients (hazard ratio, 2.13; 95% confidence interval, 1.17-3.92) and ERα-positive patients (hazard ratio, 2.34; 95% confidence interval, 1.18-4.64). CONCLUSIONS: We show that low expression of TP53INP1 is an independent factor of poor prognosis in breast cancer patients, especially ERα-positive patients. TP53INP1 might be a promising candidate biomarker and therapeutic target in ERα-positive breast cancer patients.

Effects of serum estradiol and progesterone on estrogen-regulated gene expression in breast cancers of premenopausal patients.

BACKGROUND: Expression of estrogen receptor α in breast cancer is essential for estrogen-dependent growth and partially determines the breast cancer subtype. In premenopausal women, expression of estrogen-regulated genes in estrogen receptor-positive breast cancer tissues are reportedly influenced by the menstrual cycle. METHODS: We investigated correlations between serum estradiol (E2; tested on the day of surgery) and expression of estrogen-regulated genes and proliferation genes in strongly estrogen receptor α-positive breast cancer tissues from 91 premenopausal women by quantitative reverse transcription-polymerase chain reaction. We also investigated correlations between serum progesterone levels on the day of surgery and mRNA expression of progesterone-regulated genes and proliferation genes. RESULTS: The serum E2 level affected expression of estrogen-regulated genes, including progesterone receptor (P = 0.016, Rs = 0.07) but showed no correlation with expression of genes associated with proliferation. We also observed strong positive correlations between mRNA expression of ESR1 and that of estrogen-regulated genes (P < 0.0001, Rs = 0.329-0.756) and proliferation genes (P < 0.0001, Rs = 0.753-0.843). The serum progesterone level affected expression of RANKL mRNA. However, we observed no correlations between serum progesterone and expression of Wnt-4 or proliferation genes. CONCLUSIONS: The serum E2 level on the day of surgery influences estrogen-regulated gene expression moderately in patients found to be strongly positive for estrogen receptor α by immunohistochemistry. Changes in serum E2 levels might influence the results of molecular profiling tests in premenopausal women with breast cancer.

Long-term outcomes of video-assisted thoracoscopic surgery lobectomy vs. thoracotomy lobectomy for stage IA non-small cell lung cancer.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is performed widely for patients with clinical stage I non-small cell lung cancer (NSCLC) because of its superior short-term outcomes to those of thoracotomy lobectomy. However, the long-term outcomes of VATS lobectomy vs. thoracotomy lobectomy remain controversial. METHODS: We reviewed the clinical data of 202 consecutive patients who underwent lobectomy for clinical stage IA NSCLC at our institution between January, 2008 and December, 2013. Stage IA NSCLC was confirmed pathologically in 162 of these patients, 60 of whom underwent VATS lobectomy and 102 of whom underwent thoracotomy lobectomy. We compared the perioperative clinical factors and outcomes of these two groups, using a propensity score-matched analysis. RESULTS: In an analysis of 58 matched cases, the VATS group showed less blood loss, a shorter duration of chest tube placement, a shorter postoperative hospital stay, and a lower peak C-reactive protein value, despite a longer operative time. The VATS group also had significantly longer survival than the thoracotomy group [5-year overall survival, 100% vs. 87%, respectively (p = 0.01); 5-year disease-free survival, 100% vs. 86% (p = 0.03)]. CONCLUSIONS: These findings suggest that VATS may have better long-term as well as short-term outcomes than thoracotomy for patients with early-stage NSCLC.

Paraquat toxicity is attenuated by 4-phenylbutyrate-induced phosphorylation of ERK2 via PI3K in A549 cells.

Paraquat (PQ) is a widely used herbicide in the world despite being highly toxic to humans. PQ causes fatal damage to multiple organs, especially the lungs. While oxidative stress is the main toxic mechanism of PQ, there is no established standard therapy for PQ poisoning. In this study, we investigated the cytoprotective effect of 4-phenylbutyrate (4PBA) on PQ toxicity in human lung adenocarcinoma A549 cells. Phosphorylation levels of major survival signaling kinases Akt and ERK, as well as expression levels of antioxidant enzymes catalase and superoxide dismutase 2 (SOD2) were examined. The cytoprotective mechanism of 4PBA against PQ was compared with the antioxidant reagent trolox. We demonstrated that both 4PBA and trolox attenuated PQ toxicity, but their mechanisms were different. 4PBA increased ERK2 phosphorylation levels, which could be inhibited by the PI3K inhibitor LY294002. The cytoprotective effect of 4PBA was also inhibited by LY294002. Catalase expression levels were increased by 4PBA, although this increase was not inhibited by LY294002. 4PBA did not increase SOD2 expression. Trolox did not affect phosphorylation of Akt or ERK, or the expression of antioxidant enzymes. These results suggest that 4PBA attenuated PQ cytotoxicity by ERK2 activation via PI3K. Our study may provide new findings for understanding the molecular mechanism underlying cytoprotection by 4PBA, as well as new therapeutic targets for PQ poisoning.

Thymothymectomy with pulmonary partial resection using the subxiphoid approach: how to do it?

An open approach by sternotomy is still selected for locally advanced anterior mediastinal tumors. Technical and instrumental improvements to video-assisted thoracic surgery (VATS) have enabled the treatment of anterior mediastinal tumor in the last decade, and the indications of VATS for an anterior mediastinal tumor are thus expanding. Recently, a single-port thymectomy procedure using the subxiphoid approach has gained popularity worldwide because of its low invasiveness. Improvements to the thoracoscopic instruments and the development of a single-port device are expanding the adoption of single-port VATS in the thoracic surgical field, including resection of anterior mediastinal tumors. We, herein, report a case of thymothymectomy with pulmonary partial resection using the subxiphoid approach. This approach is useful for extended operation for anterior mediastinal tumors and provides favorable results regarding postoperative pain and cosmetic outcomes.

The Subxiphoid Approach Leads to Less Invasive Thoracoscopic Thymectomy Than the Lateral Approach.

OBJECTIVE: Video-assisted thoracic surgery (VATS) is widely used in thoracic surgery. This study investigated the usefulness of the subxiphoid approach in thymectomy using VATS techniques. METHODS: Sixty operations were performed using the lateral approach (n = 46) and subxiphoid approach (n = 14). Using the lateral approach, 39 partial thymectomies (PT), 5 total or subtotal thymectomies (TT), and 2 total or subtotal thymectomies with combined resection of the surrounding organs (or tissues) (CR) were performed. Using the subxiphoid approach, 11 TT and 3 CR were performed. RESULTS: There were 33 females and 27 males, with a mean age of 55 years. The mean maximum tumor diameter was 4.0 cm. The operation time was prolonged according to the volume of thymectomy (PT: 119, TT: 234, CR: 347 min). Additionally, the intraoperative blood loss increased according to the volume of thymectomy (PT: 29, TT: 47, CR: 345 g). To compare the invasiveness of both approaches, we compared 16 TT operations. In the group using the subxiphoid approach, the operation time became shorter (158 vs. 392 min), and the blood loss decreased (5 vs. 135 g) compared with the lateral approach. Regarding laboratory data, white blood cell counts on postoperative day 1 (1POD) (8200 vs. 10,300/µl) and CRP on 1POD and 3POD (2.8 and 2.8 vs. 7.9 and 10.2 mg/dl, respectively) decreased in the subxiphoid approach compared with the lateral approach. CONCLUSIONS: The subxiphoid approach leads to a less invasive operation for anterior mediastinal tumors and extends the indications for VATS for invasive anterior mediastinal tumors.

Multicolor-based discrimination of 21 short tandem repeats and amelogenin using four fluorescent universal primers.

The aim of this study was to develop a cost-effective genotyping method using high-quality DNA for human identification. A total of 21 short tandem repeats (STRs) and amelogenin were selected, and fluorescent fragments at 22 loci were simultaneously amplified in a single-tube reaction using locus-specific primers with 24-base universal tails and four fluorescent universal primers. Several nucleotide substitutions in universal tails and fluorescent universal primers enabled the detection of specific fluorescent fragments from the 22 loci. Multiplex polymerase chain reaction (PCR) produced intense FAM-, VIC-, NED-, and PET-labeled fragments ranging from 90 to 400 bp, and these fragments were discriminated using standard capillary electrophoretic analysis. The selected 22 loci were also analyzed using two commercial kits (the AmpFLSTR Identifiler Kit and the PowerPlex ESX 17 System), and results for two loci (D19S433 and D16S539) were discordant between these kits due to mutations at the primer binding sites. All genotypes from the 100 samples were determined using 2.5 ng of DNA by our method, and the expected alleles were completely recovered. Multiplex 22-locus genotyping using four fluorescent universal primers effectively reduces the costs to less than 20% of genotyping using commercial kits, and our method would be useful to detect silent alleles from commercial kit analysis.

The advantages of selecting cartridges with a 1.8 mm height for pulmonary stapling.

PURPOSES: The purpose of this study was to retrospectively analyze the complications arising from stapling of the pulmonary parenchyma and to determine the most appropriate cartridges to use for pulmonary stapling. METHODS: A retrospective multi-institutional review was conducted by the Central Japan Lung Cancer Surgery Study Group. We analyzed both Echelon™ (EC) and EndoGIA™ (EGIA) staplers in this study. The stapling cartridges were classified into 3 colors according to the height of the ß loops: green (2.0 mm), gold (1.8 mm), and blue (1.5 mm). RESULTS: Stapling of the pulmonary parenchyma was performed 9016 times. The total number of complications related to stapling was 61 (0.68 %). These complications were mainly caused by stapler-tissue thickness mismatch (n = 30, 49.2 %) and tissue fragility (n = 27, 44.3 %). The number and rate of complications of the different cartridges were 19 and 0.63 % for EGIA blue, 25 and 0.94 % for EGIA green, 1 and 0.067 % for EC gold, 12 and 0.98 % for EC blue, and 4 and 0.64 % for EC green, respectively. Complications associated with stapling using EC gold cartridges occurred less frequently than with the other cartridges (p = 0.0022). CONCLUSION: The gold cartridge appears to cause the least complications and may therefore be the most appropriate cartridge for stapling the pulmonary parenchyma among the tested staplers.