Comparison of therapeutic outcomes in esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A prospective observational cohort study.

BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.

Risk factors of stent migration in esophageal cancer patients who underwent fully-covered self-expanding metal stents for malignant dysphagia or tracheoesophageal fistula.

BACKGROUND: More than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration. METHODS: We conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients' nutritional outcomes were compared in the migration and non-migration groups. RESULTS: A total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope. CONCLUSION: Fully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

Lobectomy Versus Sublobar Resection in Simultaneous Bilateral Thoracoscopic Lung Resection.

BACKGROUND: Simultaneous bilateral thoracoscopic lung resection (SBTLR) has been shown to be a feasible and efficacious approach for a wide range of pulmonary conditions. Our aim was to evaluate the impact of different procedures on surgical outcomes in patients receiving SBTLR. METHODS: Between 2012 and 2021, 207 patients with bilateral lung neoplasms who underwent SBTLR were retrospectively reviewed. Fifty-one patients received ipsilateral plus contralateral lobectomy or sublobectomy (lobar group), whilst 156 patients received bilateral sublobectomy (sublobar group). Propensity scores were calculated and matched. Perioperative and clinicopathologic outcomes were compared. RESULTS: The lobar group had a greater mean age (64.5 vs. 60.0 years, p = 0.008), longer operative time (254 vs. 205 min, p < 0.001), and more blood loss (74 vs. 46 ml, p < 0.001). The sublobar group had fewer complications (6.4 vs. 19.6%, p = 0.006), shorter hospital stay (4.8 vs. 7.4 days, p < 0.001), and lower hospital costs (p = 0.03). Among 50 pairs of matched groups, significant differences were found only in operative time, hospital stay, and costs. Maximum tumor size and pathological features differed significantly before and after matching (all p < 0.05), with the lobar group consistently demonstrating a larger main tumor (median, 2.5 cm) and a higher percentage of primary lung cancer (84%). Multivariate logistic regression analysis showed that a longer operative time was the factor associated with more complications (OR: 1.01; 95% CI 1.00-1.02, p = 0.002). CONCLUSIONS: With regard to SBTLR, our data suggests that sublobectomy may reduce the prolonged recovery, hospital costs, and complications incurred by lobectomy, without compromising oncological outcomes.

Experience of Simultaneous Bilateral Open Surgery and VATS for Pulmonary Metastasectomy.

BACKGROUND: Resection is the current treatment of choice for resectable bilateral pulmonary metastases. This study aimed to compare the differences in outcomes between simultaneous bilateral open and video-assisted thoracic surgery (VATS) for pulmonary metastasectomy. METHODS: Forty-three patients underwent pulmonary metastasectomy through one-stage bilateral open thoracotomy (n = 16) and VATS (n = 27) between 2011 and 2020. Perioperative and oncological data were analyzed. RESULTS: The predominant primary tumor histology in both groups was colorectal cancer. The operative time, blood loss, and pain score on postoperative day 1 (POD1) were higher in the open group (p < 0.001, 0.009, and 0.03, respectively). No significant differences in pain score on POD2 and POD3, postoperative length of stay, or complications were found. Notably, numbers of the resected metastatic lung nodules were significantly greater in the open group (median number: 9.5 vs. 3, p < 0.001). Recurrence-free survival (RFS) and overall survival (OS) were comparable. The median RFS was 15 months (interquartile range [IQR], 6-22) in the open group and 18 months (IQR, 8-47) in the VATS group. The median OS was 28 months (IQR, 14-44) and 29 months (IQR, 15-54) in the open group and VATS group, respectively. CONCLUSION: One-stage bilateral pulmonary metastasectomy is safe and reduces medical expenditures in selected patients regardless of surgical approach. Although the open group harbored a greater number of metastatic foci, perioperative and oncological outcomes were similar to that of the VATS group.

Is a Chest Tube Necessary after Video-Assisted Thoracoscopic Mediastinal Tumor Resection?

BACKGROUND: The omission of chest tubes after thoracoscopic procedures such as sympathectomy, lung biopsy, and lung resection has proven efficacious in decreasing pain and length of hospital stay in some cases. However, its safety for mediastinal diseases remains unclear. This study evaluated the feasibility and outcome of eliminating chest drains after video-assisted thoracoscopic surgery (VATS) for mediastinal tumor resection. METHODS: We retrospectively investigated 70 patients receiving VATS mediastinal tumor resection in a single institution between January 2016 and November 2018. A total of 39 patients (drain group) received postoperative chest drains and 31 patients (no-drain group) did not. Group clinical outcomes and operation data were compared. A propensity score matching analysis was further performed to yield a fairer comparison. RESULTS: Before propensity score matching, the no-drain group had a higher prevalence of cystic lesions, a shorter operative time, and less blood loss compared with the drain group (p = 0.015, p = 0.018, and p < 0.001, respectively). After matching, the group differences in these perioperative variables lost significance (p = 0.095, 0.4, and 0.2, respectively). The no-drain group had lower postoperative day 2 pain scores and shorter postoperative hospital stays than the drain group, regardless of whether they were matched (pain: p = 0.028; hospital stay < 0.001) or not (pain: p = 0.003; hospital stay < 0.001). No major adverse events occurred in either group during hospitalization or follow-up period. CONCLUSION: Eliminating chest drain placement after VATS mediastinal tumor resection may benefit some patients and decrease postoperative pain and hospital stay without increasing complications or compromising patient safety.

Male adolescents with contralateral blebs undergoing surgery for primary spontaneous pneumothorax may benefit from simultaneous contralateral blebectomies.

BACKGROUND: In adults with primary spontaneous pneumothorax (PSP), contralateral recurrence occurs in about 25-28% when there are asymptomatic blebs. How to treat contralateral recurrence of PSP in pediatric populations remains controversial. This study evaluated the outcomes of excising contralateral blebs to prevent recurrence in adolescents being operated on for PSP under the same anesthesia. METHODS: One hundred thirty-two male PSP patients under age 19 were surgically treated in a single institution between January 2008 and December 2016. Thoracoscopic blebectomies with pleurodesis were performed in all patients. The patients were categorized into those with contralateral blebs receiving one-stage bilateral surgeries (32 patients), those with contralateral blebs only receiving unilateral surgeries (40 patients), and those without contralateral blebs only receiving unilateral surgeries (60 patients). Perioperative details and outcomes were retrospectively analyzed. RESULTS: Significant differences in contralateral recurrence rate were found among the three groups (0%, 30%, and 1%, respectively; P < 0.001). Multivariate analysis showed that being under 16.5 years old was a risk factor for overall recurrence (Hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.08-7.30, P = 0.034). Moreover, patients who had contralateral blebs and only received unilateral surgery were at greater risk of overall recurrence (HR 6.06, 95% CI 1.77-20.75, P = 0.004). Kaplan-Meier analysis showed that contralateral and overall recurrence-free survival differed among the three groups (P < 0.0001, P = 0.0002). CONCLUSIONS: Although younger male PSP adolescents treated with surgery were more likely to have postoperative recurrences, the performance of simultaneous contralateral blebectomies in those receiving one-stage bilateral surgeries significantly reduced future contralateral recurrence without compromising patient safety.

Enteral nutrition and quality of life in patients undergoing chemoradiotherapy for esophageal carcinoma: a comparison of nasogastric tube, esophageal stent, and ostomy tube feeding.

BACKGROUND AND AIMS: This study prospectively recruited esophageal squamous cell carcinoma patients who received esophageal stent, nasogastric tube (NGT), or jejunostomy/gastrostomy feeding to compare the changes in nutritional status and quality of life during chemoradiation therapy (CRT). METHODS: In total, 81 patients were analyzed (stent, 7; surgical ostomy, 26; NGT, 19; oral intake, 29). An NGT was inserted when, despite medication, dysphagia or pain worsened with oral feeding during CRT. Serial body weight and daily narcotic demand were recorded. Changes in serum albumin level and quality of life were also assessed. In subgroup analysis comparing NGT and prophylactic surgical ostomy feeding, 5 patients with total occlusion in the ostomy group were excluded. RESULTS: Patients in all groups had similar decreases in mean body weight with an overall change of -6.41% ± 5.21% at the end of CRT. The stent group had significantly worse pain, decreased albumin (-1.03 ± .9 mg/dL), and decreased quality of life across CRT compared with the other groups. In subgroup analysis the stent group had significantly higher weight loss, whereas the NGT group had higher narcotic demand and slightly worse quality of life. Two patients (7.7%) had ileus days after jejunostomy creation. Five patients (23.8%) among those received prophylactic ostomy creation and scarcely used it. CONCLUSIONS: These preliminary results raise concerns that use of esophageal stents may be less suitable in patients undergoing CRT. Tube feeding by means of transnasal or percutaneous routes appear to be comparably effective during CRT, but both have advantages and disadvantages. We suggest a careful endoscopic evaluation to select the population more appropriate for NGT feeding on an as-needed basis during CRT.

Pleural Tags on CT Scans to Predict Visceral Pleural Invasion of Non-Small Cell Lung Cancer That Does Not Abut the Pleura.

PURPOSE: To evaluate the association of pleural tags with visceral pleural invasion of non-small cell lung cancer (NSCLC) that does not abut the pleural surface. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. Informed consent was waived. The study of NSCLC that does not abut the pleura in 141 patients (44 patients [31.2%] with visceral pleural invasion proved by pathologic analysis and 97 patients [68.8%] without pleural invasion) was conducted at a single tertiary center. The pleural tags were classified into three types (type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; and type 3, one or more soft tissue cord-like pleural tag) and prioritized into types 3, 2, and 1 when more than one type was present. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR) were calculated. RESULTS: In the absence of pleural tags, no pleural invasion was found. The presence of type 2 pleural tags was moderately associated with visceral pleural invasion with the following results: positive LR, 5.06; accuracy, 71%; sensitivity, 36.4%; specificity, 92.8%; PPV, 76.2%; and NPV, 69.6%. Type 1 pleural tags provided weak evidence to rule out visceral pleural invasion (positive LR, 0.38). Type 3 pleural tags indicated minimal increase in the likelihood of visceral pleural invasion (positive LR, 1.68). CONCLUSION: Type 2 pleural tags on conventional CT images can increase the accuracy of early diagnosis of visceral pleural invasion by NSCLC that does not abut the pleura.

Obstructive laryngeal schwannoma in a young female.

Laryngeal schwannomas are rare, benign neurogenic tumors. They normally present as a slow-growing, encapsulated, submucosal mass in the supraglottic region. We describe a 20-year-old female presenting with a 2-year history of hoarseness and progressive worsening dyspnea. Fiberoptic laryngoscopy and computed tomography revealed a round, low-density submucosal mass at right false cord and arytenoepiglottic regions with glottic extension. Microlaryngoscopic biopsy and debulking for this solid tumor were performed without tracheostomy. Schwannoma was confirmed by histopathological study. However, rapidly worsening stridor occurred 2 weeks after the surgery. Fiberoptic laryngoscopy showed an exophytic tumor occupying the right hemilarynx with airway compromise. Definite complete excision of the tumor was performed by right vertical hemilaryngectomy. At 5-month follow-up, the laryngeal wound was clear without signs of recurrence. Rapid occurrence of airway obstruction after debulking and biopsy was demonstrated in this case. Vertical hemilaryngectomy was inevitable to cure this potentially life-threatening laryngeal schwannoma in this young female with postoperative serviceable voice.

Synergistic effect of lung tumor-associated dendritic cell-derived HB-EGF and CXCL5 on cancer progression.

The interaction between cancer cells and their microenvironment is a paradoxical cycle that exacerbates cancer progression and results in metastasis. Our study investigated the mechanism underlying the synergistic enhancement of release of soluble factors from tumor-associated dendritic cells and its effect on cancer development. The combination of HB-EGF (heparin-binding EGF-like growth factor) and CXCL5 (CXCL5/epithelial neutrophil-activating peptide-78) produced a strong synergistic effect on cancer proliferation, epithelial-mesenchymal transition, migration and invasion. CXCL5 not only potentiated the classical EGFR pathway and the AKT and ERK/RSK1/2 signaling pathways but also increased the phosphorylation of heat shock protein 27 (HSP27), which was slightly increased in A549 cells treated with either HB-EGF or CXCL5 only. Phosphorylated HSP27 stabilized sustained AKT activity by direct interaction, leading to enhanced tumor spheroid formation. Knockdown of HSP27 by shRNA decreased HB-EGF plus CXCL5-mediated tumor spheroid formation in a three-dimensional culture system, suggesting that AKT/HSP27 was required for HB-EGF/CXCL5-mediated cancer progression. Inhibiting RSK also reduces the modulation of c-Fos phosphorylation, Snail upregulation and cell migration by HB-EGF plus CXCL5, suggesting a synergistic effect of ERK/RSK and HB-EGF plus CXCL5 on cell migration. In mice, CXCL5 antibody synergistically enhances the efficiency of the tyrosine kinase inhibitor, gefitinib, without increasing its toxicity. These results provide evidence that elucidates potential cross-points between extracellular signals affecting lung cancer progression. Targeting CXCL5 may provide therapeutic benefits for lung cancer chemotherapy or immunotherapy.

Methylation status of retinoic acid receptor beta2 promoter and global DNA in esophageal squamous cell carcinoma.

BACKGROUND: Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARß2) and long interspersed nuclear elements (LINE-1) in different stages of esophageal squamous cell carcinoma (ESCC). METHOD: The tumor and adjacent normal esophageal tissues from 125 male ESCC patients who underwent primary surgery were analyzed for the methylation status of RARß2 promoter and LINE-1 through methylation-specific polymerase chain reaction and pyrosequencing. RESULTS: RARß2 hypermethylation was detected in 20% of the tumor samples, but not in the normal counterparts. The methylation frequency of LINE-1 was significantly lower in the tumor than in the normal parts (median: 67.7% vs. 80%, P < 0.0005). Ninety-eight patients (78.4%) had both RARß2 hypermethylation and LINE-1 hypomethylation or either one. There was a trend toward higher risk of advanced T stage (P for trend = 0.05) or lymph node metastasis (P for trend = 0.02) when more adverse gene methylation profiles were present. CONCLUSION: Methylation status of RARß2 and LINE-1 was related to the development and possibly the severity of ESCC.

A modified technique to improve the outcome of intubation with a left-sided double-lumen endobronchial tube.

BACKGROUND: The use of a video-assisted laryngoscope (VL) has been shown to reduce the time to achieve intubation with a double-lumen endobronchial tube (DLT). As the blade of the VL is curved differently to a standard laryngoscope, the DLT must be angled into a hockey stick shape to fit properly. We conducted a study to establish which direction of angulation was best to facilitate correct positioning of the DLT when using a VL. METHODS: We enrolled patients scheduled for thoracic surgery who required intubation with a DLT. They were prospectively randomized into one of two groups: those intubated with a DLT angled to conceal the tracheal orifice (the tracheal orifice-covered, TOC) group or the tracheal orifice-exposed (TOE) group. The composite primary outcome measures were time taken to intubate and the frequency of first-time success. The time taken to intubate was divided into: T1, the time from mouth opening to visualization of the vocal cords with the VL; and T2, the time taken to advance the DLT through the cords until its tip lay within the trachea and three carbon dioxide waveforms had been detected by capnography. The hemodynamic responses to intubation and intubation-related adverse events were also recorded. RESULTS: Sixty-six patients completed the study, with 33 in each group. Total intubation time was significantly shorter in the TOC group (mean 30.6 ± standard deviation 2.7 seconds versus 38.7 ± 3.3 seconds, p <0.0001). T2 was also significantly shorter in the TOC group than the TOE group (27.2 ± 2.5 seconds versus 34.9 ± 3.0 seconds, p <0.0001). The severity of hoarseness on the first postoperative day and sore throat on the fourth postoperative day were significantly lower in the TOC group than the TOE group (p = 0.02 and <0.0001, respectively). The hemodynamic responses to intubation were broadly similar between the groups. CONCLUSION: When placing a left-sided DLT using a VL, angling the bronchial lumen to a hockey stick shape that conceals the tracheal lumen saves time and ameliorates the severity of post-intubation complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01605591.

Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.

The interaction between tumors and their microenvironments leads to a vicious cycle, which strengthens both immune suppression and cancer progression. The present study demonstrates for the first time that tumor-associated dendritic cells (TADCs) are a source of resistin, which is responsible for increasing lung cancer epithelial-to-mesenchymal transition. In addition, large amounts of resistin in the condition medium (CM) of TADCs increase cell migration and invasion, as well as the osteolytic bone metastatic properties of lung cancer cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy-inducing features of TADC-CM. Significantly elevated levels of resistin have been observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+) DCs in human lung cancer samples and lung cancer patients' sera. Induction of lung cancer progression by TADC-derived resistin is associated with increased expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone 3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the promoter of Twist, resulting in an enhancement of the expression of Twist. Knockdown of WHSC1 by small interfering RNA transfection significantly decreases resistin-mediated cancer progression by decreasing the upregulation of Twist, suggesting that WHSC1 plays a critical role in the regulation of Twist by epigenetic modification. Furthermore, mice that received antiresistin antibodies showed a decreased incidence of cancer development and metastasis. These findings suggest that TADC-derived resistin may be a novel candidate in promoting the development of lung cancer.

Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associated dendritic cells by expressing heparin-binding EGF-like growth factor.

The interaction between cancer cells and their microenvironment is a vicious cycle that enhances the survival and progression of cancer, resulting in metastasis. This study is the first to indicate that lung cancer-derived galectin-1 secretion is responsible for stimulating tumor-associated dendritic cells (TADCs) production of mature heparin-binding EGF-like growth factor (HB-EGF), which, in turn, increases cancer progression. Treatment of galectin-1, present in large amounts in lung cancer conditioned medium and lung cancer patient sera, mimicked the inductive effect of lung cancer conditioned medium on the expression and ectodomain shedding of HB-EGF by TNFα-converting enzyme/a disintegrin and metalloproteinase 9 (ADAM9) and ADAM17. Significant up-regulation of HB-EGF has been seen in tumor-infiltrating CD11c(+) dendritic cells in human lung cancer samples. Active cleavage of HB-EGF in TADCs by ADAM9 and ADAM17 is associated with increased protein kinase C δ and Lyn signaling. Enhancement of HB-EGF production in TADCs increased the proliferation, migration, and epithelial-to-mesenchymal transition abilities of lung cancer. In contrast, inhibiting HB-EGF by siRNA suppressed TADC-mediated cancer progression. Moreover, mice injected with galectin-1 knockdown Lewis lung carcinoma showed decreased expression and ectodomain shedding of HB-EGF and reduced incidence of cancer development, resulting in increased survival rates. We demonstrate here for the first time that human and mouse DCs are a source of HB-EGF, an EGFR ligand with tumorigenic properties. Antagonists of the effect of lung cancer-derived galectin-1 on DCs and anti-HB-EGF blocking antibodies could, therefore, have therapeutic potential as antitumor agents.

Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model. METHODS: Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation, each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53, caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry (W/D) weight ratio. RESULTS: Compared with the saline + sham group, the saline + I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared with the saline + I/R group, sildenafil + I/R group had significant decreases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α level, and W/D weight ratio but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil + sham group, there were significant increases in p53 and TNF-α expression in the sildenafil + I/R group (P < 0.05). CONCLUSIONS: Pretreatment with sildenafil alleviates lung apoptosis and tissue injury in a rat model.

Lung tumor-associated dendritic cell-derived amphiregulin increased cancer progression.

The interaction of cancer within a microenvironment is an important factor determining cancer development. This study analyzed the soluble factors secreted by tumor-associated dendritic cells (TADCs), which are responsible for increasing lung cancer growth, migration, invasion, and epithelial-to-mesenchymal transition. Addition of amphiregulin, present in large amounts in TADC-conditioned medium (CM), mimicked the inductive effect of TADC-CM on lung cancer progression, supported by the enhancement of cell proliferation, migration, and invasion as well as osteolytic bone metastases phenotypes. In contrast, neutralization of amphiregulin from TADC-CM decreased the advanced malignancy-inductive properties of TADC-CM. Significant upregulation of amphiregulin has been seen in tumor-infiltrating CD11c(+) DCs in human lung cancer samples and patients' sera. The enhancement of amphiregulin in TADCs has also been noted in mice transplanted with lung cancer cells. Induction of lung cancer progression by TADC-derived amphiregulin is associated with increased STAT3 and AKT activation, which subsequently increases the expression of cyclin D, Twist, and Snail. Blocking AKT significantly decreases TADC-CM and amphiregulin-mediated migration by decreasing the upregulation of Snail, whereas inhibition of STAT3 reduced the modulation of TADC-derived amphiregulin on Twist and cyclin D expression, suggesting that cooperation of STAT3 and AKT plays a critical role in TADC-mediated cancer progression. Moreover, mice treated with anti-amphiregulin Abs showed decreased incidence of cancer development and increased survival rates. Our study suggests that inhibition of amphiregulin or amphiregulin-related signaling is an attractive therapeutic target in lung cancer patients.

Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway.

Lung cancer, one of the leading causes of death worldwide, is often associated with a state of immune suppression, but the molecular and functional basis remains enigmatic. Evidence is provided in this paper supporting the role of lung cancer-derived soluble lectin, galectin-1, as a culprit in dendritic cell (DC) anergy. We have shown that galectin-1 is highly expressed in lung cancer cell lines, together with the serum and surgical samples from lung cancer patients. Functionally, lung cancer-derived galectin-1 has been shown to alter the phenotypes of monocyte-derived DCs (MdDCs) and impair alloreactive T cell response, concomitant with the increase of CD4(+)CD25(+)FOXP3(+) regulatory T cells. The regulatory effect of galectin-1 is mediated, in part, through its ability to induce, in an Id3 (inhibitor of DNA binding 3)-dependent manner, the expression of IL-10 in monocytes and MdDCs. This effect is inhibited by the addition of lactose, which normalizes the phenotypic and functional alterations seen in MdDCs. Of note, significant upregulation of IL-10 was seen in tumor-infiltrating CD11c(+) DCs in human lung cancer samples. This was also noted in mice transplanted with lung cancer cells, but not in those receiving tumor cells with galectin-1 knockdown. Furthermore, a significant reduction was noted in lung cancer incidence and in the levels of IL-10-expressing, tumor-infiltrating DCs, in mice receiving galectin-1-silenced tumor cells. These results thus suggest that the galectin-1/IL-10 functional axis may be crucial in lung cancer-mediated immune suppression, and that galectin-1 may serve as a target in the development of lung cancer immunotherapy.

Identification of biomarkers for esophageal squamous cell carcinoma using feature selection and decision tree methods.

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

Incentive spirometry is an effective strategy to improve the quality of postoperative care in patients.

Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs, postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS was significantly shorter (1.8 days) than that in patients not receiving IS (MD = -1.80, 95% CI = -2.95 to -0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia (17.9%) with statistical significance than patients not undergoing IS (PPC: OR = 0.68, 95% CI = 0.51-0.90) (Pneumonia: OR = 0.821, 95% CI = 0.677-0.995).In meta-regression, the benefits of undergoing IS in patients with preoperative predicted FEV1 of <80% in a linear fashion with decreasing PPCs. IS is an effective modality to improve the quality of postoperative care for patients after pulmonary resection, compared with the control group without using IS; and applying IS has favorable outcomes of shorter length of hospital stay (1.8 days) and lower occurrence of PPCs (32% of risk reduction), which are conclusive and robust based on our validation via TSA. Moreover, the IS device is more beneficial for patients with preoperative predicted FEV1 of <80% than that in others.

Diastole/Body Mass Index Ratio Can Predict Post-Thoracoscopic Surgery Metastasis in Stage I Lung Adenocarcinoma.

BACKGROUND: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. METHODS: Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients' clinical and pathological characteristics were analyzed. RESULTS: Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). CONCLUSIONS: MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.