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Background: Loss of body weight is regarded as a marker of malnutrition after esophagectomy. This study investigated changes in body weight and risk factors for weight loss after esophagectomy for esophageal cancer.Methods: We retrospectively reviewed records of 181 patients who underwent esophagectomy and gastric pull-up from 2012 to June 2016. Patients with operative mortality and recurrences were excluded. Percent change in body weight was defined as change in body weight (%) = (1-year body weight - preoperative body weight) × 100/preoperative body weight.Results: Mean age of patients was 62.98 ± 8.23 years with 164 men (90.6%). Mean preoperative body weight was 63.12 ± 9.42 kg, and body weight at 1 year was 56.04 ± 8.59 kg. Mean change in body weight was - 10.95 ± 7.50%, and 98 (54.1%) patients showed weight loss more than 10% compared to initial body weight. Univariable analysis showed that initial body weight, narrow gastric tube, thoracotomy, laparotomy, and postoperative vocal cord palsy (VCP) were related to more than 10% weight loss. Multivariable analysis showed that initial body weight (odds ratio [OR] = 1.041, p = 0.031) and postoperative VCP (OR = 2.772, p = 0.025) were adverse risk factors for weight loss 1 year after esophagectomy, whereas conduit type, route of reconstruction, postoperative complications, anastomotic complications, minimally invasive esophagectomy, and adjuvant therapy were not.Conclusions: Initial body weight and postoperative VCP were related to weight loss. Patients with VCP need additional nutritional monitoring and support. [ABSTRACT FROM AUTHOR]

The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]

Abstract: Polyvinyl pyrrolidone (PVP) was used as a binder in spray-drying a slurry containing zirconia/alumina composite powder and its influence on granulation and granule deformability was compared with those of polyvinyl alcohol (PVA) and polyethylene glycol–hydroxyethyl cellulose cobinder (PEG–HEC). Although the most spherical solid granules were obtained from the slurry containing PEG–HEC, the granules containing PVP were the most deformable during compaction. It was apparent that a high-viscosity organic additive mixture added to the slurry resulted in highly spherical solid granules, and a low T g of the mixture led to a high deformability. The flexural strengths of composites prepared from granules containing PVP, PEG–HEC, and PVA were 634, 578, and 468MPa, respectively, which corresponds to the ascending order of T g of the binders mixed with plasticizers. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study was to investigate the properties of tape cast alumina composite produced using a water-based solvent and its possible clinical use as an all ceramic crown system in a fixed partial denture. Durability of the system will be measured by fatigue test to simulate the masticating conditions of the oral cavity. Methods: The optimal weight ratio of water-based alumina tape was determined by tensile strength, shrinkage ratio and durability. The coefficient of thermal expansion, fracture toughness, biaxial flexural strength and flexural strength after fatigue test of a composite produced from alumina tape at optimal weight ratios were determined and compared to In-Ceram alumina core (control). Results: The weight ratio of alumina/(alumina+binder+plasticizer) of 0.84 and binder/(binder+plasticizer) of 0.5 was observed to be the optimal composition for achieving excellent composite properties. Coefficient of thermal expansion of the sintered alumina tape was observed to be 7.3×10−6/°C, and this value was increased to 7.5×10−6/°C after infiltrating the sintered tape with glass. The fracture toughness and biaxial flexural strength of glass infiltrated alumina tape was observed to be 4.6MPam1/2 and 498MPa, respectively. After cyclic loading for 102–106 cycles, no significant change in the biaxial flexural strength was observed between the glass infiltrated alumina core and the In-Ceram alumina core (p >0.05). Significance: The observed properties provide evidence that the water-based tape cast alumina–glass composite is suitable for clinical use as an all ceramic crown system in a fixed partial denture. [Copyright &y& Elsevier]

Abstract: Objective: Neurotrophins are known to exert a variety of pleiotropic responses in different target tissues, but little is known about their effect on thymic epithelial tumors. Therefore, we analyzed the expression of neurotrophin receptors in surgically resected thymic epithelial tumors and evaluated their clinical relevance. Methods: The expression of neurotrophin receptors (Trk-A, Trk-B, Trk-C and p75NTR) in thymic epithelial tumors was evaluated in 99 consecutive patients based on immunohistochemical staining. The pattern of expression was analyzed according to the WHO classification, and survival outcomes were estimated. Results: Thymic tumors were classified as type A (n=6), AB (n=21), B1 (n=15), B2 (n=24), B3 (n=22) or C (n=11). All tumors, except one type C thymoma, demonstrated cytoplasmic Trk-A immunostaining, and no thymic tumors showed Trk-B or Trk-C immunoreactivity. p75NTR immunostaining demonstrated characteristic patterns according to the WHO subtypes of thymomas. All type A and type AB thymomas showed p75NTR immunoreactivity, except one type A tumor. The expression of p75NTR was negative in 6 patients (40%) with type B1 thymomas, 19 patients (79.2%) with type B2 thymomas, 17 patients (77.3%) with type B3 thymomas and 10 patients (90.9%) with type C thymomas. Tumor-related survival at 5 and 10 years was 95.5 and 89.5%, respectively, in p75NTR-positive thymomas and 82.8 and 77.2%, respectively, in p75NTR-negative thymomas; however, the differences were not statistically significant (P=0.14). Conclusions: Among the neurotrophin receptors examined, the pattern of p75NTR expression closely correlated with the WHO subtypes of thymomas. Further study of p75NTR expression may aid in understanding the biology of thymic epithelial tumors. [Copyright &y& Elsevier]

Abstract: A cobinder, consisting of polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) and gelatin, was used to prepare aqueous-based alumina tapes for three-dimensional forming. The tensile strength, humidity dependent strength degradation, and drying rate of the tapes were investigated by varying the amounts of PVA and gelatin. Gelatin was beneficial for increasing the tape strength and the drying rate, and the addition of PVA alleviated the humidity sensitive strength degradation. The overall performance of the alumina tape was optimized with the use of a cobinder containing 89.5wt.% PVP, 10wt.% PVA, and 0.5wt.% gelatin. [Copyright &y& Elsevier]

Four commercial alumina powders having different particle sizes (0.44, 2.85, 7.08 and 39.81 μm) were presintered for 2 h at 1120 °C and then lanthanum–aluminosilicate glass was infiltrated for up to 4 h at 1100 °C to prepare the densified alumina–glass composites. Alumina having a bimodal and broader particle size distribution was the most effective to the packing. The penetration rate constant increased with raising the alumina particle size having a parabolic dependence of infiltration distance on time described by the Washburn equation. However, the optimum mechanical properties were observed for the composite containing the 2.85 μm alumina. Although the higher fracture toughness of the composites may be achieved by increasing the alumina particle size probably due to the dispersion toughening, the larger alumina particles reduce the strength. [Copyright &y& Elsevier]

ZrO2/Al2O3 composites were prepared by mixing a tetragonal ZrO2, stabilized with 5.31 mol% Y2O3 and 4.45 mol% Nb2O5, and Al2O3 having different particle size (0.2 μm and 2.8 μm) to investigate the influence of the Al2O3 particle size on flaw tolerance of the composites. The composites exhibited rising R-curve behavior and plateau fracture toughness of 7.9 and 8.8 MPa√m for the additions of 20 vol.% of 0.2 and 2.8 μm Al2O3 particles, respectively. The difference in the fracture resistance was attributed mainly to the grain size of tetragonal phase in the composites, which scaled with the Al2O3 particle diameter, and partially to the dispersion toughening. [ABSTRACT FROM AUTHOR]

Computer-aided design and manufacturing technology has been closely associated with implant-supported restoration. The digital system employed for prosthodontic restorations comprises data acquisition, processing, and manufacturing using subtractive or additive methods. As digital implantology has developed, optical scanning, computer-based digital algorithms, fabricating techniques, and numerical control skills have all rapidly improved in terms of their accuracy, which has resulted in the development of new ceramic materials with advanced esthetics and durability for clinical application. This study reviews the application of digital technology in implant-supported dental restoration and explores two globally utilized ceramic restorative materials: Yttria-stabilized tetragonal zirconia polycrystalline and lithium disilicate glass ceramics. [ABSTRACT FROM AUTHOR]

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4’s transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis. [ABSTRACT FROM AUTHOR]

Background Esophageal complications consensus group (ECCG) recommended that readmissions to primary or secondary hospital within 30 days of discharge after esophagectomy can be an important quality outcome indicator for esophagectomy. This retrospective study was performed to investigate the frequencies and risk factors for readmission after esophagectomy. Methods We retrospectively reviewed 291 patients who received the esophagectomy and mediastinal lymphadenectomy for curative aim from January 2006 to June 2017. Results The mean age was 63.02 ± 8.02 years and male patients were 264 (90.7%). Thirty-nine (13.4%) patients readmit within 30 days after discharge. The mean readmission day after discharge was 14.76 ± 8.84. The common causes of readmission were anastomotic stricture requiring the ballooning (12, 30.7%), wound problem (7, 17.9%), pneumonia (6, 15.4%), and poor oral intake (4, 10.2%). Other causes of readmission were delayed gastric emptying (3), jejunostomy tube problem (2), ileus (2), pain (1), pneumothorax (1) and pleural effusion (1). On multivariate analysis, anastomotic leakage (odd ratio = 2.872, P  = 0.022) were related to readmission, whereas age, pathologic stage, vocal cord palsy and neoadjuvant therapy were not related to readmission. In 30 patients with postoperative anastomotic leakage, the frequency of readmission due to wound problem (13.3% vs. 1.1%, P  = 0.003) and anastomotic stricture (13.3% vs. 3.4%, P  = 0.034) were significantly higher. Conclusion The incidence of readmission within 30 days after discharge was 13.4% and postoperative anastomotic leakage was related to the readmission, and it might be related to the wound problem and anastomotic stricture. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

• Addition of Al 2 O 3 result in decrease in sintering shrinkage and relative density. • Different forms of Al 2 O 3 in Al 2 O 3 –ZrO 2 composite result in different mechanical properties. • Addition of microfibre form Al 2 O 3 result in enhanced mechanical properties of Al 2 O 3 –ZrO 2. • Addition of microfibre form Al 2 O 3 result in lowest Weibull modulus. • Addition of greater than 20 vol% of microfibre form Al 2 O 3 result in agglomeration. This study evaluates the difference in physical and mechanical properties of ZrO 2 ceramics, commonly used in dental applications, altered by three different forms of Al 2 O 3 content; microparticles (m), nanoparticles (n), and microfiber (f). Three different types of ZrO 2 –Al 2 O 3 composites were formed using microparticle (m), nanoparticle (n), or microfibre (f) forms of Al 2 O 3. The physical and mechanical properties such as sintering shrinkage, relative density, Vickers hardness, fracture toughness, and biaxial strength were evaluated. A Weibull analysis was performed to assess the strength reliability of the specimens. All data were calculated using the t-test and ANOVA. The sintering shrinkage and relative density of all ceramic composite groups were decreased with the addition of Al 2 O 3. The mechanical properties of ZrO 2 –Al 2 O 3 (f) composite were higher than that of ZrO 2 –Al 2 O 3 (m) composite and ZrO 2 –Al 2 O 3 (n) composite. The maximum hardness, fracture toughness, and biaxial flexural strength were observed for 10 vol% of Al 2 O 3 fibre. When the content of Al 2 O 3 fibre in the matrix was increased above 20 vol%, agglomeration occurred and resulted in a decrease of hardness and toughness. The Weibull modulus value of the ZrO 2 –Al 2 O 3 (f) composite was the lowest compared to that of other groups. However, characteristic strength (σ 0) of ZrO 2 –Al 2 O 3 (f) the highest value. The current study demonstrated that the addition of right amount of Al 2 O 3 microfibre into the ZrO 2 matrix enhanced the mechanical properties of ZrO 2 -Al 2 O 3 (f) composite, which would be favourable for dental applications. [ABSTRACT FROM AUTHOR]

Sunlight exposure is a significant risk factor for UV‐induced deteriorating transformations of epidermal homeostasis leading to skin carcinogenesis. The ability of UVB radiation to cause melanoma, as well as basal and squamous cell carcinomas, makes UVB the most harmful among the three known UV ranges. UVB‐induced DNA mutations and dysregulation of signaling pathways contribute to skin cancer formation. Among various signaling pathways modulated by UVB, tyrosine phosphorylation signaling which is mediated by the action of protein tyrosine kinases (PTKs) on specific tyrosine residues is highly implicated in photocarcinogenesis. Following UVB irradiation, PTKs get activated and their downstream signaling pathways contribute to photocarcinogenesis by promoting the survival of damaged keratinocytes and increasing cell proliferation. While UVB activates oncogenic signaling pathways, it can also activate tumor suppressive signaling pathways as initial protective mechanisms to maintain epidermal homeostasis. Tyrosine dephosphorylation is one of the protective mechanisms and is mediated by the action of protein tyrosine phosphatases (PTPs). PTP can counteract UVB‐mediated PTK activation and downregulate oncogenic signaling pathways. However, PTPs have not been studied extensively in photocarcinogenesis with previous studies regarding their inactivation induced by UVB. This current review will summarize the recent progress in the protective function of PTPs in epidermal photocarcinogenesis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC).Methods: One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology.Results: Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %.Conclusions: LN density is useful for the characterization of LNs with mild 18F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both 18F-FDG uptake and LN density.Key Points: • SUVmax showed the highest diagnostic ability for detecting malignant LNs. • LN density was useful in characterization of LNs with mild FDG uptake. • SUVmax and LN density together could stratify the risk of LN metastasis. [ABSTRACT FROM AUTHOR]

• IASLC grading system has acceptable performance in diverse populations. • We proposed IASLC modification for increasing predictability in Korean patients. • Lepidic proportion further differentiated IASLC grade 2 patients. We aimed to measure the validity of the International Association for the Study of Lung Cancer (IASLC) grading system in Korean patients and propose a modification for an increase of its predictability, especially in grade 2 patients. From 2012 to 2017, histopathologic characteristics of 1358 patients with invasive pulmonary adenocarcinoma (stage I–III) from two institutions were retrospectively reviewed and re-classified according to the IASLC grading system. Considering the amount of the lepidic proportion, the validity of the revised model (Lepidic-10), derived from the training cohort (hospital A), was measured using the validation cohort (hospital B). Its predictability was compared to that of the IASLC system. Of the 1358 patients, 259 had a recurrence, and 189 died during follow-up. The Harrell's concordance index and area under the curve of the IASLC system were 0.685 and 0.699 for recurrence-free survival (RFS) and 0.669 and 0.679 for death, respectively. From the training cohort, the IASLC grade 2 patients were divided into grades 2a and 2b (Lepidic-10 model) with a 10 % lepidic pattern. This new model further distinguished patients in both institutions that had better performance than the IASLC grading (Hospital A, p < 0.001 for RFS and death; Hospital B, p = 0.0215 for RFS, p = 0.0429 for death). The IASLC grading system was easily applicable; its clinical use in predicting the prognosis of Korean patients with pulmonary adenocarcinoma was validated. Furthermore, the introduction of the lepidic proportion as an additional criterion to differentiate grade 2 patients improved its predictability. [ABSTRACT FROM AUTHOR]

Background: The prognosis of invasive mucinous adenocarcinoma (IMA) remains controversial and should be clarified by comparison with the International Association for the Study of Lung Cancer (IASLC) histologic grading system for invasive nonmucinous adenocarcinoma (INMA). Methods: This study included patients with IMA who underwent curative resection. Their clinicopathological outcomes were compared with those of patients with INMA. Propensity score matching was performed to compare the prognosis of IMA with IASLC grade 2 or 3. Kaplan–Meier survival curves and log‐rank tests were used to analyze recurrence‐free survival (RFS) and overall survival (OS). Results: The prognoses of IMA and IASLC grade 2 were similar in terms of RFS and OS. Although patients with IMA had better RFS than patients with IASLC grade 3, the OS was not significantly different. After propensity score matching, IMA demonstrated similar RFS to IASLC grade 2 but superior to IASLC grade 3; there was no difference in the OS compared with grades 2/3. Multivariate analysis revealed that tumor size (hazard ratio [HR] = 1.20, p = 0.028), lymphovascular invasion (HR = 127.5, p = 0.003), and maximum standardized uptake value (HR = 1.24, p = 0.005) were poor prognostic predictors for RFS. Patients with IMA demonstrated RFS similar to and significantly better than that of patients with IASLC grades 2 and 3, respectively. For OS, IMA prognosis was between that of IASLC grades 2 and 3. Conclusions: Since the prognosis of IMA among lung adenocarcinomas appears to be relatively worse, further clinical studies investigating IMA‐specific treatment and follow‐up plans are necessary to draw more inferences. [ABSTRACT FROM AUTHOR]

Purpose: Left upper mediastinal lymph node dissection (UMLND)—a technically demanding step of McKeown esophagectomy—is frequently complicated by recurrent laryngeal nerve (RLN) palsy. Under the hypothesis that robotic esophagectomy (RE) could increase the safety and feasibility of UMLND, we retrospectively investigated the degree to which a pre-existing experience in video-assisted thoracoscopic esophagectomy (VATE) may affect the learning curves of this critical part of RE. Methods: Surgeon A had previously performed > 150 VATE procedures before transitioning to RE. While surgeon B had previously assisted to 50 RE, his pre-existing VATE experience consisted of less than five procedures. A total of 103 and 76 McKeown RE procedures were performed by surgeons A and B, respectively. The learning curve of left UMLND for each surgeon was examined using the cumulative sum method. Results: The inflection point of RLN palsy for surgeon A occurred at patient 31. While the nerve palsy rate decreased from 32.3 to 4.2% (p < 0.001), the number of nodes harvested during left UMLND did not appreciably change. Surgeon B showed a bimodal learning curve for RLN palsy with primary and secondary inflection points at patients 15 and 49, respectively. The RLN palsy rate initially decreased from 66.7% (patients 1–15) to 14.7% (patients 16–49), followed by an additional decline to 3.7% (patients 50–76). However, the number of nodes harvested during left UMLND showed a downtrend which was paralleled by decreasing rates of RLN palsy. These results indicate that surgeon B has not yet reached an ideal balance between an extensive UMLND and nerve protection. Conclusion: The pre-existing VATE experience seems to affect the learning curves of left UMLND during RE. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the results of postoperative bronchopleural fistula repair and to identify adverse factors for its success. Methods: We retrospectively reviewed the surgical results of 39 patients who underwent surgical repair for postoperative bronchopleural fistula between January 2010 and June 2020. Success of bronchopleural fistula repair was defined as the visual closure of the bronchopleural fistula with the absence of an air leak, a recurrence of bronchopleural fistula and infection in the thoracic cavity. Results: Twenty‐five (64.1%) bronchopleural fistulas occurred after pulmonary resection and 14 (35.9%) after lung transplantation. Bronchopleural fistula was diagnosed 19 days (median) and repaired 28 days (median) after the initial operation by primary closure in 27 (69.2%) patients, and by additional resection in 12 (30.8%) patients. The overall success rate was 59% (23/39) and the overall mortality was 56.4% (22/39). Multivariable analysis revealed that the patients who were supported by mechanical ventilation at the time of repair had significantly lower success rates than those without (15.4%, 2/13 vs. 80.8%, 21/26, respectively, p < 0.001). The omental flap group tended to have a better success rate than the muscle flap group (p = 0.07). Conclusions: There was a high overall mortality rate after bronchopleural fistula repair and a low success rate. Mechanical ventilation at the time of bronchopleural fistula repair was significantly related to the failure of bronchopleural fistula repair. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the characteristics and pretreatment risk factors for postoperative pulmonary complications (PPCs) after neoadjuvant concurrent chemoradiotherapy (CRTx) in patients with non‐small cell lung cancer (NSCLC). Methods: We retrospectively reviewed data of 122 patients who underwent curative resection after neoadjuvant CRTx for NSCLC between 2007 and December 2019. Clinical data, including pulmonary function and body mass index (BMI) at the time of concurrent CRTx initiation, were analyzed. We performed logistic regression analyses to identify the risk factors for PPCs and built a nomogram with significant factors. Results: Of the 122 patients included (mean age, 60.1 ± 9.7 years; 69.7% male), 27 experienced PPCs (severity grade ≥ 2). The most common PPCs were pneumonia (n = 17). Patients with PPCs had a significantly longer hospital stay (median 6.0 vs. 17 days, p < 0.001) and a higher in‐hospital mortality rate (1.1% vs. 29.6%, p < 0.001). In multivariable analysis, lower BMI (odds ratio [OR] 0.796, 95% confidence interval [CI] 0.628–0.987, p = 0.038), no comorbidity (OR 0.220, 95% CI: 0.059–0.819, p = 0.048), smoking history (OR 4.362, 95% CI: 1.210–15.720, p = 0.024), and %predicted DLCO <60% (OR 3.727, 95% CI: 1.319–10.530, p = 0.013) were independent risk factors for PPCs. The predictive accuracy of the nomogram built with factors was excellent (concordance index: 0.756). Conclusions: The nomogram constructed with factors identified in multivariable analysis could serve as a reliable tool for evaluating the risk of PPCs in the patients who underwent neoadjuvant CRTx for NSCLC. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to estimate the effects of zirconia implants and recombinant human bone morphogenetic protein-2 (rh BMP-2) gel on the acceleration of local bone formation and osseointegration in the canine mandible. Materials and Methods Four groups of 48 implants with identical geometry were installed in the mandibles of beagle dogs: alumina-blasted zirconia implants applied with rh BMP-2, alumina-blasted zirconia implants applied with demineralized bone matrix ( DBM), alumina-blasted zirconia implants, and resorbable blast media-treated titanium ( Ti) implants. For the first two groups, zirconia implants were inserted after the surgical sites were filled with rh BMP-2 or DBM gel. For the other two groups, zirconia or Ti implants were installed with no adjunctive treatment. Fluorescent bone markers were administered to monitor bone remodeling at weeks 2, 4, and 5 postimplantation. After healing periods of 3 weeks and 6 weeks, the animals were sacrificed, and fluorescent microscopy, histology, and histomorphometric analyses were performed. Results Fluorescent microscopy showed that bone formation around the zirconia implants installed with rh BMP-2 gel was the most prominent at 2 weeks postimplantation, while the Ti implants acquired bone apposition mainly at week 5. No significant differences were found in bone area among the groups ( P > 0.05). The zirconia implants showed similar bone-to-implant contact to the Ti implants. There were no significant differences in bone-to-implant contact between the zirconia implants with rh BMP-2 gel and those with DBM ( P > 0.05). Conclusions The zirconia implants with alumina-blasted surfaces may achieve osseointegration in much the same manner as the well-established Ti implants. The area influenced by rh BMP-2 gel, including the alveolar crest, may cause active remodeling and early bone formation. [ABSTRACT FROM AUTHOR]

Background: The benefits of mediastinal lymph node dissection (MLND) in colorectal cancer‐related pulmonary metastasectomy (PM) have been poorly reported. This study aimed to determine whether MLND affects survival in patients undergoing PM and to identify the prognostic factors for survival. Methods: We retrospectively reviewed 275 patients who had undergone colorectal cancer‐related PM from January 2010 to December 2016. MLND was defined as the resection of at least six mediastinal lymph node stations according to the International Association for the Study of Lung Cancer criteria (N1, ≥3 stations; N2, ≥3 stations). The propensity score matching method was used to reduce bias. Results: Thirty‐three (12%) patients underwent MLND, and 13 (4.7%) patients had mediastinal lymph node involvement. This study showed no difference in 5‐year overall survival (no MLND, 52.7% vs. MLND, 53.5%; p = 0.81). On multivariable analysis, negative prognostic factors for overall survival were preoperative carcinoembryonic antigen (CEA) level (p < 0.001), a higher number of metastatic nodules (p < 0.001), metastatic nodule size ≥2 cm (p < 0.001), and lymph node involvement (p = 0.006). Conclusions: Mediastinal lymph node involvement, preoperative CEA level, higher metastatic nodule number, and nodule size negatively affected survival whereas MLND in PM was not associated with survival. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although designated as T4 or M1 in the current TNM classification system revised in 1997, non-small cell lung cancer with ipsilateral pulmonary metastases is treated as a locally advanced disease and reported survival rates are relatively good. We intended to analyze the prognosis of ipsilateral pulmonary metastases and validate current TNM classification system. Methods: Data of 1213 surgically treated patients with non-small cell lung cancer from January 1990 to December 2004 were retrospectively reviewed. Overall and disease-free survival rates of patients with ipsilateral pulmonary metastases and other T stages were obtained by the Kaplan–Meier method and compared by the log rank test. Prognostic impact of ipsilateral pulmonary metastases on disease-free survival was sought by multivariate analysis. Results: Among 49 patients with ipsilateral pulmonary metastases (IPM), 23 patients had metastasis in primary lobe (IPM1) and 26 had metastasis in non-primary lobe (IPM2). Five-year overall and disease-free survival rates of IPM1 and IPM2 were not significantly different (30.3% vs 30.7%, p =0.95, 21.9% vs 23.1%, p =0.78). Prognoses of IPM1 and IPM2 were not significantly different than those of T3 disease (30.1%, 26.6%). Resected T4 disease excluding IPM1 had a tendency to show the worse prognosis (16.2%, 7.5%) without significant difference with IPM1 and IPM2. In the univariate analysis of prognostic factors for disease-free survival, IPM1 and IPM2 were prognostic factors. In the multivariate analysis, IPM2 (1.554, 1.02–2.34, p =0.039) was one of independent negative prognostic factors. However, IPM1 was not an independent prognostic factor (1.31, 0.84–2.04, p =0.23). Conclusions: Regarding prognosis, prognostic strength, extent of disease and surgical treatment the current TNM classification system may be inappropriate in designation of ipsilateral pulmonary metastases and needs revision. The authors suggest that the IPM1 should be staged as T3 or designated as upstaging co-parameter of T stage as like in 1992 TNM classification and IPM2 can be staged as T4 as like in 1992 TNM classification. [Copyright &y& Elsevier]

Background: Although perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial. Here, we investigated the prognostic role of perineural invasion in surgically treated esophageal squamous cell carcinoma. Methods: We retrospectively reviewed the medical records of 316 patients who underwent esophagectomy and lymph node dissection for esophageal squamous cell carcinoma between 2007 and 2016. Results: Overall, 287 men (mean age: 62.73 ± 7.97 years) were included in the study. The median follow‐up period was 35.97 ± 30.99 months, perineural invasion was confirmed in 25 patients, and three‐year overall and disease‐free survival were significantly lower in the perineural invasion group than in the no‐perineural invasion group (75.9% vs. 40.0%, p < 0.001; 70.3% vs. 21.6%, p < 0.001). Cumulative incidences of locoregional recurrence and distant metastasis over three years were higher in the perineural invasion group (13.8% vs. 9.6%, p = 0.009 and 52.8% vs. 14.6%, p < 0.001). On performing multivariable analysis, perineural invasion, pathological stage, incomplete resection, and neoadjuvant therapy were adverse risk factors for disease‐free survival. The concordance index increased when perineural invasion was included in the model (0.712 vs. 0.723). On subgroup analysis, perineural invasion demonstrated a prognostic value in node‐negative patients (79.4% vs. 35.7%, p = 0.012). Conclusions: Perineural invasion was found to be an adverse risk factor for disease‐free survival in surgically treated patients with esophageal squamous cell carcinoma. Close observation and individualized adjuvant therapy may be helpful for patients with perineural invasion. [ABSTRACT FROM AUTHOR]

Background: After esophagectomy, various reconstruction routes can be considered for technical and oncologic objectives. The substernal route is believed to cause more dysphagia or delayed gastric emptying symptoms than the posterior mediastinal route. We evaluated and compared the quality of life (QoL) after reconstruction by either the substernal or posterior mediastinal routes in the McKeown procedure. Methods: Between 2011 and 2018, 378 patients who received an esophagectomy and cervical esophagogastrostomy for esophageal cancer were followed up. Among these patients, 278 received reconstruction via the substernal route and 100 via the posterior mediastinal route. Patients completed the validated questionnaires, EORTC QLQ-C30 and QLQ-OES18, before surgery and at 1, 2, 3, 6, 12, and 24 months after surgery. Linear mixed-effects models were used to examine changes in questionnaire scores over time. Results: One month after surgery, patients QoL deteriorated and more symptoms were observed than at baseline. Global health status, nausea and vomiting, and esophageal pain gradually recovered from 2 months and recovered to initial levels at 2 years. However, the other functional and symptom scales of the QLQ-C30 and OES18 were not normalized at 2 years after the operation. When comparing the substernal and posterior mediastinal routes, QLQ-OES18 symptom scales, such as eating, dysphagia, trouble with swallowing saliva trouble with taste and reflux, were no different between the two groups, even after adjusting confounding factors at 2 years after the operation. Conclusion: The cervical esophagogastrostomy with a substernal route showed comparable QoL to reconstruction with a posterior mediastinal route. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES We previously reported a transthoracic approach using the da Vinci Single-Site™ platform. This study describes the outcomes of robotic single-site thymectomy via a subxiphoid approach based on our previous experiences. METHODS This study included patients, who underwent single-site robotic thymectomy via the subxiphoid approach between September 2018 and October 2019. A 3- to 4-cm vertical incision was made over the subxiphoid area, and the Lapsingle port with CO2 gas was introduced. After docking at the single site, a 5-mm curved cannula, 5-mm cardiere grasper and Maryland bipolar forceps or permanent cautery hook was inserted. The single-site robotic platform was used to conduct all surgical procedures except the dissection around the inferior portion of the thymic tissue performed via a thoracoscopic approach through the same incision. RESULTS Overall, 13 patients, including 2 with myasthenia gravis, were enrolled. The mean duration of the surgery and chest drainage were 167.3 ± 52.8 (range 73–253) min and 2.2 ± 0.9 (range 1–5) days, respectively. All surgeries were successfully completed without conversion to an open surgery, and there were no major post-surgical complications. The diagnoses based on histopathology included thymoma in 10 patients, thymolipoma in 2 patients and atypical carcinoid tumour in 1 patient with free resection margin. CONCLUSIONS This study demonstrated that robotic single-site-assisted thymectomy via the subxiphoid approach is a safe and technically feasible procedure. Although this initial series comprised relatively simple cases, more advanced and complex procedures can soon be performed with the advent of single-port robotic platform. [ABSTRACT FROM AUTHOR]

Postoperative pulmonary complications (PPCs) significantly impact surgical outcome. We investigated the predictive ability of controlling nutritional status (CONUT) for PPC after lung resection in patients with non-small cell lung cancer (NSCLC). We retrospectively reviewed data of 922 patients with NSCLC who underwent complete resection from January 2016–December 2017. We analyzed the frequency and characteristics of PPCs and compared receiver operating characteristic (ROC) curves of various prognostic models to predict PPCs. A CONUT score higher than 1 was considered as a high CONUT score. Total incidence of PPCs was 8.6% (n = 79). The proportion of pneumonia was significantly larger in the high CONUT group (P < 0.05). The CONUT consistently had a higher area under curve (AUC) value (0.64) than other prognostic models (prognostic nutritional index (PNI): AUC = 0.61, Glasgow prognostic score (GPS): AUC = 0.57, and assessment of respiratory risk in surgical patients in Catalonia (ARISCAT): AUC = 0.54). Multivariate analysis identified underweight [Odds ratio (OR) = 4.57, P = 0.002] and high CONUT score (OR = 1.91, P = 0.009) as independent PPCs prognostic factors. One-year mortality rate for high CONUT score was significantly higher (hazard ratio = 7.97; 95% confidence interval, 1.78–35.59). Preoperative CONUT score is an independent predictor of PPCs and 1-year mortality in patients with resectable NSCLC. [ABSTRACT FROM AUTHOR]

• Frozen sections have low sensitivity for identifying STAS. • GGO percentage of ≥75% on CT predicts STAS negativity. • SUV T/L ratio ≤0.65 predicts STAS negativity. • A lepidic predominant pattern predicts STAS negativity. • Our flowchart is more suitable as it gives a stratified process. The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection. Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression. The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively. The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection. [ABSTRACT FROM AUTHOR]

Scratch tests were performed on porous 3 mol% Y2O3‐stabilized zirconia dental blocks to relate compaction processing and partial sintering temperature to shrinkage and machinability of the blocks and microstructures and transmittance after full sintering. Scratch hardness of the blocks varied with increasing loads, and the variation was related to the sequential events of densification, densification and cleaving, disruption of the densified region, and chipping and longitudinal cracking. The shrinkage during final sintering was inversely proportional to the compact pressure and temperature with compact pressure having a greater impact. In contrast, the transmittance of fully sintered blocks depended largely on the partial sintering temperature because it governed the number and size of pores after completion of the sintering. Based on the influence of the variable on scratch hardness, a scratch response measure that possibly reflects the machinability of porous CAD/CAM blocks was proposed. [ABSTRACT FROM AUTHOR]

With the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3+ TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3+ TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade. [ABSTRACT FROM AUTHOR]

• The positive highest mediastinal LN is one of the criteria of uncertain resection. • The positive highest or most distant mediastinal LN was not related to poor survival. • The subcategories of N2 and T stage were highly associated with overall survival. The positive highest nodal station after operation is one of the definitions of "uncertain resection" proposed by the International Association for the Study of Lung Cancer. This study was performed to determine the prognostic value of positive highest or the most distant nodal station in patients with N2 non-small-cell lung cancer (NSCLC). Three hundred thirty-nine patients who underwent complete anatomical resection and mediastinal lymph node (LN) dissection for N2 NSCLC between 2000 and 2015 were reviewed. Cases of operative mortality, extracapsular invasion of LN and incomplete resection were excluded from analysis. The mean age was 61.58 ± 9.43 years, and 235(69.3%) patients were male. The numbers of total dissected LNs and positive LNs were 29.90 ± 11.92 and 5.49 ± 5.90, respectively. The subcategory of N stage was divided as follows: N2a1, 91(26.8%); N2a2, 132(38.9%); and N2b, 116(34.2%). One hundred forty-two (41.9%) patients showed highest LN metastasis, and 162(47.8%) patients showed most distant LN metastasis. Kaplan–Meier analysis revealed no differences between distant LN negative and positive patients regarding 5-year overall survival (43.1% vs. 39.2%; p = 0.428) and between highest LN negative and positive patients regarding 5-year overall survival (42.1% vs. 40.0%; p = 0.539). On multivariable analysis, metastasis to the most distant mediastinal LN (hazard ratio (HR): 1.050; p = 0.755) and metastasis to the highest mediastinal LN (HR: 1.015; p = 0.924) were not related to overall survival. The current definition of uncertain resection based on metastasis of the highest or most distant LNs did not show survival differences in completely resected N2 NSCLC. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES Anastomotic leakage after oesophageal cancer surgery is a serious complication. The purpose of this study was to evaluate the possibility of anastomotic leakage by repeatedly measuring amylase levels in the fluid obtained from the drainage tube inserted at the cervical anastomotic site. METHODS Ninety-nine patients who underwent oesophagectomy and cervical oesophagogastrostomy between April 2014 and March 2017 were retrospectively reviewed. A drainage tube was placed at the anastomotic site, and amylase levels were measured daily from postoperative day (POD) 1 until oral feeding or confirmation of anastomotic leakage. The amylase levels were analysed with a linear mixed model. RESULTS The mean age of the patients was 64.9 ± 9.0 years, and there were 89 (89%) male patients. Almost all pathologies (92%) were squamous cell carcinomas. The anastomotic methods were as follows: 63 (63%) circular stapled, 33 (33%) hand-sewn and 3 (3%) semistapled. Anastomotic leakage was confirmed in 10 (10%) patients. The amylase levels increased until POD 2 in both the leakage and non-leakage groups, but the levels subsequently decreased in the non-leakage group, whereas the levels peaked on POD 3 in the leakage group. On performing the linear mixed model analysis, anastomotic leakage was significantly associated with the trends in postoperative amylase levels in the drainage tube (P  < 0.001). Trends in the serum C-reactive protein levels and white blood cell count were not significantly associated with anastomotic leakage. CONCLUSIONS Amylase level trends measured in the cervical drain fluid can be a useful indicator of anastomotic leakage after cervical oesophagogastrostomy. [ABSTRACT FROM AUTHOR]

Video‐assisted thoracoscopic surgery (VATS) is regarded as the standard treatment for lung cancer. However, the feasibility and safety of VATS for lung cancer after neoadjuvant chemoradiotherapy (CRT) is unclear. This study evaluated the feasibility and safety of VATS in patients who had received neoadjuvant CRT. Methods: Between January 2008 and December 2017, 85 patients who were administered neoadjuvant CRT and underwent anatomic lung resection were enrolled. Fifty‐nine patients underwent open thoracotomy and 26 patients underwent VATS. The clinical characteristics and perioperative outcomes were reviewed. Results: In six of the initial 32 patients who underwent VATS, the procedure was converted to thoracotomy. Adjacent structural invasion (33.9% vs. 11.5%; P = 0.037) and combined resection (16.9% vs. 0%; P = 0.025) were higher in the open group than in the VATS group. Surgical duration was higher in the open group than in the VATS group (203.86 ± 65.97 vs. 173.27 ± 59.87 minutes; P = 0.046). With regard to postoperative outcomes, the length of the hospital stay was longer in the open group compared to the VATS group (14.46 ± 16.94 vs. 8.62 ± 4.72 days; P = 0.017). There was no significant difference in the three‐year disease‐free survival (69.3% vs. 67.9%; P = 0.879) or overall survival rates (76.6% vs. 61.9%; P = 0.516). Conclusion: In selected patients, VATS pulmonary resection after neoadjuvant CRT showed results comparable to that of thoracotomy in terms of postoperative outcomes, operative morbidities, and survival rate. [ABSTRACT FROM AUTHOR]

Objectives: Complete resection of thymic neoplasms is important for achieving a favorable prognosis; however, the efficacy of neoadjuvant therapy remains controversial. We investigated the effect of induction therapy on complete resection and survival using 3-dimensionally reconstructed images to measure tumor volume. Methods: Eighty-nine patients who underwent surgical resection for Masaoka-Koga stage III–IV thymic neoplasms between January 2000 and December 2013 were enrolled, including 71 and 18 in the primary surgery and neoadjuvant therapy groups, respectively. Baseline characteristics, postoperative outcomes, and survival rates were analyzed. Moreover, baseline and post-neoadjuvant therapy tumor volumes were compared among patients in the neoadjuvant group. Results: Adjacent mediastinal structure invasion was significantly rarer in the primary surgery group than in the neoadjuvant group (1.27±1.09 vs. 2.61±1.42, p<0.001). On subgroup analysis of patients who underwent neoadjuvant therapy, tumor volumes decreased significantly from 206.08±132.32 cm3 to 81.25±71.24 cm3 post-therapy (p = 0.001). Interestingly, only the pre-neoadjuvant tumor volume was significantly associated with complete resection, while the post-neoadjuvant volume was not (p = 0.012 and p = 0.458, respectively). Moreover, despite significantly reduced tumor volumes, patients in the neoadjuvant therapy group did not exhibit significantly different R0 resection rates (odds ratio 1.490, p = 0.581) or overall survival (p = 0.285) compared to those in the primary surgery group. Conclusions: Neoadjuvant therapy does not significantly influence the R0 resection rate or overall survival relative to primary surgery. Nevertheless, it may by useful for patients planning surgical resection because it significantly reduces the presurgical tumor volume and extent of invasion. [ABSTRACT FROM AUTHOR]

Highlights • We established 41 NSCLC PDXs by directly implanting tumor specimens of patients. • These established PDXs were genetically and clinically annotated. • The clinical response was recapitulated by PDXs. • PDXs is a robust tool for biomarker, therapeutic target, and drug discovery. Abstract Background Preclinical models that can better predict therapeutic activity in clinical trials are needed in this era of personalized cancer treatment. Herein, we established genomically and clinically annotated patient-derived xenografts (PDXs) from non-small-cell lung cancer (NSCLC) patients and investigated whether these PDXs would faithfully recapitulate patient responses to targeted therapy. Methods Patient-derived tumors were implanted in immunodeficient mice and subsequently expanded via re-implantation. Established PDXs were examined by light microscopy, genomic profiling, and in vivo drug testing, and the successful engraft rate was analyzed with the mutation profile, histology, or acquisition method. Finally, the drug responses of PDXs were compared with the clinical responses of the respective patients. Results Using samples from 122 patients, we established 41 NSCLC PDXs [30 adenocarcinoma (AD), 11 squamous cell carcinoma (SQ)], among which the following driver mutation were observed: 13 EGFR-mutant, 4 ALK-rearrangement, 1 ROS1-rearrangement, 1 PIK3CA-mutant, 1 FGFR1-amplification, and 2 KRAS-mutant. We rigorously characterized the relationship of clinical features to engraftment rate and latency rates. The engraft rates were comparable across histologic type. The AD engraft rate tended to be higher for surgically resected tissues relative to biopsies, whereas similar engraft rates was observed for SQ, irrespective of the acquisition method. Notably, EGFR-mutants demonstrated significantly longer latency time than EGFR-WT (86 vs. 37days, P = 0.007). The clinical responses were recapitulated by PDXs harboring driver gene alteration (EGFR, ALK, ROS1, or FGFR1) which regressed to their target inhibitors, suggesting that established PDXs comprise a clinically relevant platform. Conclusion The establishment of genetically and clinically annotated NSCLC PDXs can yield a robust preclinical tool for biomarker, therapeutic target, and drug discovery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate the utility of total mediastinal lymphadenectomy (ML) in superficial esophageal squamous cell carcinoma (ESCC).Methods: The medical records of 129 patients who underwent esophagectomy and lymph node dissection for pathologically confirmed pT1 ESCC between July 2006 and December 2014 were retrospectively reviewed. Limited ML, such as traditional 2-field or transhiatal esophagectomy, was performed in 42 patients (group 1), and total ML, including the bilateral recurrent laryngeal nerve nodes, was performed in 87 patients (group 2).Results: R0 resection was achieved in all patients, and the number of dissected nodes was 28.0 ± 11.4 and 44.8 ± 16.1 in groups 1 and 2 (p < 0.001), respectively. The complication profile was similar in the two groups, but there were two operative mortalities in group 2. During a median follow-up of 32.4 months, loco-regional failure was found in 14.3% of group 1 and 3.5% of group 2 (p = 0.001). There was a significant difference in the 3-year overall survival (95.1% in group 2 vs. 83.3% in group 1, p = 0.043), and the 3-year disease-free survival rates (92.3% in group 2 vs. 73.7% in group 1, p = 0.001). On multivariate analysis, the extent of ML (HR, 5.200; 95% CI, 1.532 ~ 17.645; p = 0.008) and pT1b lesion classification (HR, 4.747; 95% CI, 1.024 ~ 21.997; p = 0.047) was a factor predictive of disease-free survival.Conclusions: Total ML might be beneficial, especially in cases of pT1b ESCC, because it could lead to a lower incidence of recurrence and longer survival times. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas.Materials: Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6 years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis.Results: Of the 37 thymic tumours, 23 (62.2 %) were low-risk thymomas, five (13.5 %) were high-risk thymomas and nine (24.3 %) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high-risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92 mg/ml vs. 0.99 mg/ml vs. 1.18 mg/ml, p < 0.001, respectively).Conclusion: DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning.Key Points: • IHU and IC were lower in high-risk thymomas/carcinomas than in low-risk thymomas • IHU and IC were lower in advanced-stage thymomas than in early-stage thymomas • Dual-energy CT helps differentiate among thymic epithelial tumours. [ABSTRACT FROM AUTHOR]

Objectives For early-stage thymoma, complete thymectomy has classically been regarded as the standard treatment protocol. However, several studies have shown that limited thymectomy may be an alternative treatment option for thymoma. This study compared perioperative outcomes, survival, and recurrence rates between patients undergoing limited thymectomy and complete thymectomy. Materials and methods Between January 2000 and December 2013, a total of 762 patients underwent thymectomy for stage I or II thymomas at four institutions participating in the Korean Association for Research on the Thymus. Patients were divided into two groups: limited thymectomy group (n = 295) and complete thymectomy group (n = 467). Comparative clinicopathological, surgical, and oncological features were reviewed retrospectively. Results The median follow-up time was 49 months (range: 0.2–189 months). A propensity score-matching analysis, based on seven variables (age, sex, surgical approach, tumor size, WHO histological type, Masaoka-Koga stage, and adjuvant radiotherapy), was performed using 141 patients selected from each group. The 5- and 10-year freedom-from-recurrence rates in the limited thymectomy group were 96.3% and 89.7%, respectively, and those in the complete thymectomy group were 97.0% and 85.0%, respectively. No significant differences in these rates were observed between groups (p = 0.86). A multivariate Cox regression analysis showed that overall survival and freedom-from-recurrence rates did not significantly differ by surgery extent (p = 0.27, 0.66, respectively). Perioperative outcomes were better in the limited thymectomy group. Conclusion Limited thymectomy was not inferior to complete thymectomy with respect to recurrence, and had better perioperative outcomes. Limited thymectomy may be a viable treatment option for early-stage thymoma. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the current study was to examine whether the nanoindentation parameters can assess the alteration of bone quality resulting from different degrees of bone remodeling between bone tissue ages around the dental implant interface with different treatments and healing periods. Materials and methods: Dental implants were placed in mandibles of six male dogs. Treatment groups included: resorbable blast media-treated titanium (Ti) implants, alumina-blasted zirconia implants (ATZ), alumina-blasted zirconia implants applied with demineralized bone matrix (ATZ-D), and alumina-blasted zirconia implants applied with rhBMP-2 (ATZ-B). Nanoindentation modulus ( E), hardness ( H), viscosity ( η), and viscoelastic creep (Creep/ P ) were measured for new and old bone tissues adjacent to the implants at 3 and 6 weeks of post-implantation. A total of 945 indentations were conducted for 32 implant systems. Results: Significantly lower E, H, and η but higher Creep/ P were measured for new bone tissues than old bone tissues, independent of treatments at both healing periods ( p < 0.001). All nanoindentation parameters were not significantly different between healing periods ( p > 0.568). ATZ-D and ATZ-B implants had the stiffer slope of correlation between E and Creep/ P of the new bone tissue than Ti implant ( p < 0.039). Conclusions: Current results indicated that, in addition to elastic modulus and plastic hardness, measurement of viscoelastic properties of bone tissue surrounding the implant can provide more detailed information to understand mechanical behavior of an implant system. Clinical relevance: Ability of energy absorption in the interfacial bone tissue can play a significant role in the long-term success of a dental implant system. [ABSTRACT FROM AUTHOR]

Objectives Recurrence of resected thymoma frequently occurs during follow-up, with pleural recurrence as the most common type. The aim of our study was to identify risk factors for pleural recurrence after complete resection of thymoma by investigating clinical, radiological, surgical, and pathological findings. Materials and methods Retrospective study was performed with 309 patients who had undergone complete resection of thymoma between January 2000 and December 2013. Among these cases, the patients were divided into the no pleural recurrence group (n = 285) and the pleural recurrence group (n = 24). Radiologic parameters such as maximum tumor diameter, tumor perimeter that contacted the lung (TPCL) and lobulated tumor contour were measured based on computed tomography. A multivariate analysis was performed to estimate risk factors for pleural recurrence including maximum tumor diameter, TPCL, lobulated tumor contour, World Health Organization (WHO) histologic classification, and Masaoka-Koga (M-K) stage. Results The median follow-up period was 62 months. The pleural recurrence rate was 7.8% (24/309). After univariate analysis, longer maximum tumor diameter ( p < 0.001), longer TPCL ( p < 0.001), lobulated tumor contour ( p = 0.001), WHO histologic type B2, B3 ( p = 0.002), and M-K stage III/IV ( p < 0.001) demonstrated significant differences with risk factors of pleural recurrence. Multivariate analysis revealed that TPCL (per 1 cm increase: hazard ratio [HR]: 1.040, 95% confidence interval [CI]: 1.019–1.061, p < 0.001), lobulated tumor contour (HR: 5.883, CI: 1.201–28.824, p = 0.029), WHO histologic classification B2/B3 (HR: 5.331, CI: 1.453–19.558, p = 0.012) and advanced M-K stage (HR: 3.900, CI: 1.579–9.632, p = 0.003) were significantly associated with pleural recurrence. Conclusion TPCL and lobulated tumor contour as well as WHO histologic classification and M-K stage were independent predictors of pleural recurrence after thymoma resection. Our study demonstrated that radiologic parameters could be useful predictor of pleural recurrence in patients with resected thymoma. [ABSTRACT FROM AUTHOR]

Background: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance. Methods: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue Results: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naïve cancer tissue in Western blot. Conclusion: Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop chitosan composite scaffolds with high strength and controlled pore structures by homogenously dispersed nano-sized hydroxyapatite (nano-HAp) powders. In the fabrication of composite scaffolds, nano-HAp powders distributed in an alginate (AG) solution with a pH higher than 10 were mixed with a chitosan (CS) solution and then freeze dried. While the HAp content increased up to 70 wt.%, the compressive strength and the elastic modulus of the composite scaffolds significantly increased from 0.27 MPa and 4.42 MPa to 0.68 MPa and 13.35 MPa, respectively. Higher content of the HAp also helped develop more differentiation and mineralization of the MC3T3-E1 cells on the composite scaffolds. The uniform pore structure and the excellent mechanical properties of the HAp/CS composite scaffolds likely resulted from the use of the AG solution at pH 10 as a dispersant for the nano-HAp powders. [ABSTRACT FROM AUTHOR]

Objectives Fibroblast growth factor receptor 1 (FGFR1) plays a critical role in many human cancers. We tried to identify the frequency of FGFR1 amplifications among Korean patients with small cell lung cancer (SCLC). Additionally, we examined the clinical significance of FGFR1 amplifications for overall survival (OS) and progression-free survival (PFS) among SCLC patients who received standard chemotherapies. Materials and methods Tumor tissues from 158 Korean patients diagnosed with SCLC from September 2009 to February 2013 were collected and analyzed using an FGFR1 FISH assay with a probe that hybridized to chromosome region 8p12–8p11.23 (Abbott Molecular, Abbott Park, IL). Results and conclusion FGFR1 amplification was detected in three patients (1.9%) harboring extensive disease (ED). A multivariate analysis showed that among the patients with ED, FGFR1 amplification was associated with shorter disease-free survival to first-line chemotherapy with etoposide plus cisplatin or carboplatin (hazard ratio [HR] = 7.1; 95% confidence interval [CI] = 2.0–25.4; P = 0.003). The median overall survival time of the patients with ED was 8.2 and 10.2 months among patients with and without FGFR1 amplification, respectively ( P = 0.37). Although FGFR1 amplification is rare in SCLC compared to non-small cell lung cancer or other malignancies with squamous histology, it is associated with poor survival following standard chemotherapy in SCLC. Further studies in large cohorts of patients with SCLC are needed to verify these results. Our results imply that FGFR1 may be a potential therapeutic target in SCLC and it could be confirmed in a clinical trial. [ABSTRACT FROM AUTHOR]

MgAl2O4 (spinel) was utilized as a packing powder in the sintering of hydroxyapatite (HAp) and the composite of HAp/3 mol% Y2O3-stabilized tetragonal zirconia (3Y- TZP). The influence of spinel on phase stability of HAp was investigated using X-ray diffraction ( XRD), scanning electron microscopy ( SEM), Raman spectroscopy, and electron probe microanalysis ( EPMA) to reveal the reaction in the vicinity of the interface between HAp and spinel. When covered with spinel powder, decomposition temperatures for both HAp monolith and HAp in the composite were raised from 1360°C to 1470°C and from 930°C to 1280°C, respectively. SEM images supported the role of spinel on retardation of the decomposition, showing a dense cross section of the monolith after sintering for 2 h at 1400°C with the spinel as opposed to a porous feature without the covering. XRD results indicated that the increase in the decomposition temperatures was accompanied by a decrease in the a-axis dimension of the hexagonal structure of HAp, probably as a result of the substitution of F− for OH−. EPMA revealed that negligible reaction occurred between HAp and spinel even at 1500°C, but the Ca2+ in HAp diffused about 20 μm into 3Y- TZP to form a cubic zirconia solid solution at 1275°C, resulting in the decomposition. The involvement of F− ion in the contraction of a-axis parameter and the consequent phase stability were manifested by an increase in the Raman band of the symmetric stretching of the P-O bonds at 962.3 cm−1 and the appearance of a band for fluoroapatite at 3538 cm−1. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to determine prognostic factors associated with postrecurrence survival in cases with postoperative brain metastasis but with no extracranial metastasis in non-small cell lung cancer (NSCLC). Material and methods Between 1992 and 2012, a total of 2832 patients underwent surgical resection for NSCLC. Among those, 86 patients had postoperative brain metastasis as the initial recurrence. Those patients were retrospectively reviewed. Results The median follow-up time after the initial lung resection was 24.0 months (range, 2.0–126.0 months). The median overall survival after initial lung cancer resection was 25.0 months and the median overall postrecurrence survival was 11 months. An initial lesion of adenocarcinoma (hazard ratio, 0.548; 95% confidence interval, 0.318 to 0.946; p = 0.031), non-pneumonectomy, and a disease-free interval longer than 10.0 months (hazard ratio, 0.565; 95% confidence interval, 0.321–0.995; p = 0.048) from the initial lung resection to the diagnosis of brain metastasis positively related to a good postrecurrence survival. Solitary brain metastasis and a size of less than 3 cm for the largest brain lesion were also positive factors for postrecurrence survival. Systemic chemotherapy for brain metastasis (hazard ratio, 0.356; 95% confidence interval, 0.189–0.670; p = 0.001) and local treatment of surgery and/or stereotactic radiosurgery (SRS) for brain lesions (hazard ratio, 0.321; 95% confidence interval, 0.138–0.747; p = 0.008) were positive factors for better postrecurrence survival. Conclusion In patients with brain metastasis after resection for NSCLC with no extracranial metastasis, adenocarcinoma histologic type, longer disease-free interval, systemic chemotherapy for brain metastasis and local treatment of surgery and/or SRS for brain metastasis are independent positive prognostic factors for postrecurrence survival. [ABSTRACT FROM AUTHOR]

To maintain tissue homeostasis, apoptosis is functionally linked to the cell cycle through the retinoblastoma (Rb)/E2F pathway. When the Rb tumor suppressor protein is functionally inactivated, E2F1 elicits an apoptotic response through both intrinsic (caspase-9 mediated) and extrinsic (caspase-8 mediated) apoptotic pathways in order to eliminate hyperproliferative cells. Rb/E2F-associated apoptosis has been demonstrated to be associated with the loss of constitutive transcriptional repression by Rb/E2F complexes and mediated by caspase-8. Protein tyrosine phosphatases (PTPs) PTP-1B and SHP-2 have been previously shown to be directly activated by loss of Rb/E2F repression during Rb/E2F-associated apoptosis. In this current study, we demonstrate that the PTEN tumor suppressor is also directly activated by loss of Rb/E2F repression. We also demonstrate that PTP-1B, SHP-2, and PTEN play a functional role in Rb/E2F-associated apoptosis. Knockdown of PTP1B, SHP2, or PTEN expression with small interfering RNA (siRNA) in apoptotic cells increases cell viability and rescues cells from the Rb/E2F-associated apoptotic response. Furthermore, rescue from apoptosis coincides with inhibition of caspase-8 and caspase-3 cleavage (activation). Our results indicate PTP-1B, SHP-2, and PTEN all play a functional role in Rb/E2F-associated apoptotic signal transduction and provide further evidence that PTP-1B, SHP-2, and PTEN can contribute to tumor suppression through an Rb/E2F-associated mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Among non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations, ∼20–30% exhibit de novo resistance to EGFR-tyrosine kinase inhibitor (TKI). The aim of this study was to examine whether mutations in the EGFR-downstream genes may be associated with de novo resistance to EGFR-TKIs in EGFR mutation-positive patients. Materials and methods: Sixty-eight never-smoker adenocarcinoma patients with an activating EGFR mutation were included in the mutational analysis and 55 patients treated with EGFR-TKIs were analyzed for the treatment outcomes to EGFR-TKIs. We concurrently analyzed mutations in PIK3CA, PTEN, AKT and STK11, which are all EGFR-downstream genes. Mutations in PIK3CA, PTEN, AKT, and STK11 were analyzed by polymerase chain reaction-based sequencing. Results: PIK3CA mutations were detected in 4.4% (3/68) of patients, PTEN mutations in 16.1% (11/68), AKT mutations in 5.9% (4/68), and STK11 mutations in 13.2% (9/68). One patient with an activating exon 21 L858R mutation concomitantly had an exon 20 T790M mutation in EGFR. The proportion of patients who had mutations in EGFR-downstream genes was 32.4% (22/68). When we analyzed the treatment outcome of 55 patients treated with EGFR-TKI, the presence of mutations in EGFR-downstream genes correlated with a poor overall response rate to EGFR-TKIs (63.6 vs.14.5% in patients with mutation in EGFR-downstream gene, P <0.0001), shorter median progression-free survival (12.0 vs. 3.0 months, P =0.060), and shorter median overall survival (18.9 vs. 25.0 months, P =0.048). Conclusion: Mutations in the EGFR-downstream genes may confer resistance to EGFR-TKIs and result in poor treatment outcomes in never-smoker adenocarcinoma patients with activating EGFR mutations. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma. Methods: We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors. Results: Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p =0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p =0.022; hazard ratio, 2.11; 95% confidence interval, 1.19–4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. Conclusion: This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery. [Copyright &y& Elsevier]

Abstract: Background: Smoking is a well-known carcinogen for lung cancer. However, whether smoking affects the biological behavior of lung cancer remains uncertain. This study aimed to investigate the influences of smoking intensity on the clinicopathologic characteristics of and survival in non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed 2238 consecutive patients who underwent surgical resection for NSCLC between 1990 and 2010. Smoking intensity was defined as pack-years (PY). The patients were divided into three groups according to the median value of smoking intensity (40 PY): group A (never smokers), group B (smoking intensity less than 40 PY) and group C (smoking intensity more than 40 PY). Results: There were 1629 (72.8%) male patients, and the mean age was 61.71±13.17 years. Adenocarcinoma was reported in 1058 (47.3%) patients. The median follow-up period was 30.7 months (range: 0.0–261.7 months). The 5-year overall survivals for groups A, B and C were 60.1%, 51.6% and 43.2%, respectively (p <0.001). In subset analysis by histology, the 5-year overall survival was significantly different according to smoking intensity in adenocarcinoma (p <0.001), but there was no difference in the non-adenocarcinoma. In adenocarcinoma, the incidences of vascular invasion (p =0.028), pleural invasion (p =0.013) and poor differentiation (p <0.001) were higher and tumor sizes (p <0.001) were greater in group C than others. On multivariate analysis, smoking intensity was an adverse risk factor for overall survival in surgically treated adenocarcinoma patients (hazard ratio=1.008, p =0.028). Conclusion: Smoking intensity was an adverse prognostic factor after surgical resection of adenocarcinoma. Heavy smoking was correlated with poor pathologic characteristics in adenocarcinoma. [Copyright &y& Elsevier]

Objectives The aim of this prospective cohort study was to compute the long-term clinical survival and complication rates of alumina-toughened zirconia abutments used for implant-supported restorations and to evaluate the effects of several clinical variables on these rates. Material and methods From May 1998 to September 2010, 213 patients aged 18 years or older were recruited. The patients received 611 external hex implants and 328 implant-supported fixed restorations using alumina-toughened zirconia abutments. During the follow-up, each restoration was coded as a dental event, which included loosening or fracture of abutment screws, and abutment fracture. From the coded data, the effects of the investigated clinical variables-restored area (anterior/posterior), number of prosthodontic units (one/two units or over), prosthesis type (single-unit/multiunit without pontic/multiunit with pontic), implant system, and patient gender-on the survival of the abutments were evaluated. Survival analysis using Kaplan- Meier method and Cox proportional hazard model was applied. The 5-year survival and complication rates of the abutments were assessed. Results The number of prosthodontic units and the type of prosthesis had a significant association with complication rates ( P < 0.05). Kaplan- Meier survival analysis estimated that the cumulative 5-year complication rate of the abutments used in single restorations was 19.7%. Multiunit-fixed dental prostheses without and with pontics had complication rates of 3.9% and 3.8%, respectively. The 5-year survival rate of the abutments was more than 95%, regardless of the type of prosthesis. Conclusions Alumina-toughened zirconia abutments are likely to exhibit excellent long-term survival in clinical use for fixed restorations. Single tooth replacement with the abutment at the molar region may require special care and extra attention. [ABSTRACT FROM AUTHOR]