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Purpose: To assess the risk factors for thrombosis in the pulmonary vein stump (PVT) and the efficacy of proximal ligation in preventing PVT after lobectomy. Methods: In total, 649 surgical patients with lung cancer were retrospectively reviewed. To compare the clinical effectiveness of PV proximal ligation, the simple stapler group (290 patients) and the proximal ligation group (359 patients who underwent thread ligation at the pericardial reflection with/without a stapler) were analyzed. Results: In the simple stapler group, 12 of 290 patients (4.1%) developed PVT. Among these, 9 of 58 underwent left upper lobectomy (LUL). In contrast, 5 of the 359 patients (1.4%) in the proximal ligation group developed PVT. All five patients received LUL. The incidence of PVT in the proximal ligation group was significantly lower than that in the simple stapler group (p = 0.0295) as well as in the analysis by LUL alone (p = 0.0263). A logistic regression analysis indicated that higher BMI and LUL were associated with the development of PVT (p = 0.0031, p < 0.0001), and PV proximal ligation reduced PVT (p = 0.0055). Conclusion: Proximal ligation of the PV has the potential to prevent PVT, especially after LUL. [ABSTRACT FROM AUTHOR]

When a mass occurs at the staple line following lung resection, it can be difficult to distinguish between local cancer recurrence and granuloma. We present a case of a staple‐line granuloma with 18F‐fluorodeoxyglucose‐positron emission tomography uptake and elevated serum carbohydrate antigen 19–9 (CA19‐9) in a patient with ovarian cancer lung metastasis. After granuloma resection, serum CA19‐9 levels normalized, and CA19‐9 positive cells were identified in the resected tumor. Therefore, serum CA19‐9 elevation does not rule out a staple‐line granuloma. Whereas granulomas on computed tomography (CT) scans tend to show smooth shadows along the staple line unilaterally, detailed CT evaluation may help diagnostic differentiation. Differentiation based on imaging and tumor markers has limitations. However, core needle biopsy has the risk of misdiagnosis and tumor cell dissemination, therefore surgical resection should be considered when comprehensive findings indicate a potential recurrence. [ABSTRACT FROM AUTHOR]

Background: Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal cancer. Several studies have investigated short-term outcomes after esophagectomy and the impact of periodontal disease, but few have examined the impact of periodontal disease on long-term outcomes. The purpose of this study was to investigate the rate of periodontitis among esophagectomy patients and the prognostic value of periodontitis and its effect on prognosis after esophagectomy. Methods: A total of 508 patients who underwent esophagectomy received oral health care from a dentist before cancer treatment at Akita University Hospital between January 2009 and December 2021. We assessed the presence and severity of the patients' periodontitis and divided them into no-periodontitis, mild periodontitis, severe periodontitis and edentulous jaw groups. We then assessed 10-year overall survival (OS) and disease-specific survival (DSS) and determined whether periodontitis was an independent prognostic factor affecting OS and DSS. Results: We found that 101 (19.9%) patients had no periodontitis, 207 (40.8%) had mild periodontitis, 176 (34.6%) had severe periodontitis requiring tooth extraction, and 24 (4.7%) had edentulous jaw. Both OS and DSS were significantly poorer in the periodontitis than no-periodontitis group (p < 0.001). In detail, the edentulous jaw group had the poorest prognosis (p < 0.001). Multivariate analysis showed that periodontitis was an independent risk factor affecting OS and DSS. Conclusion: Esophageal cancer patients had a high prevalence of periodontitis. Moreover, the presence of periodontitis and severity of periodontitis are independent risk factors contributing to a poorer prognosis after esophagectomy. [ABSTRACT FROM AUTHOR]

Aim: Because the optimal treatment strategy for borderline resectable (cT3br) thoracic esophageal cancer patients remains unclear, it is of great interest whether preoperative neoadjuvant therapy for cT3br could achieve results comparable to those seen with resectable T3 cancer (cT3r). We speculated that preoperative neoadjuvant chemoradiotherapy (NACRT) would be particularly effective in cT3br thoracic esophageal cancer patients and compared to cT3br and cT3r. Methods: Of 186 cT3 thoracic esophageal cancer patients treated with intended NACRT, 162 received radical esophagectomy. More than 97% were squamous cell carcinomas. Patients were partitioned into two groups according to whether invasion of adjacent organs was suspected (cT3br and cT3r). Treatment outcomes and survival were analyzed. Results: Sixty‐eight patients (36.6%) were classified as cT3br and 118 (63.4%) as cT3r. The cT3br group had significantly more tumors in the upper and middle mediastinum (p < 0.0001) and more cases with cM1 (lymph node) (p = 0.0104) than the cT3r group. In addition, the cT3br patients receiving esophagectomy exhibited a significantly lower pathological complete response rate than the cT3r patients (p = 0.0374). However, the R0 resection rate did not differ between the cT3br and cT3r patients (p = 0.0978), and the two groups treated with intended NACRT had similar 5‐year overall (OS) and disease‐specific survival (DSS) (p = 0.3831 and p = 0.9020). In addition, the incidence and patterns of recurrence did not differ between the cT3br and cT3r patients receiving esophagectomy (p = 0.8109 and p = 0.3128). Conclusions: Preoperative neoadjuvant chemoradiotherapy appears to be a promising treatment for patients with borderline resectable thoracic esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Osimertinib is a standard treatment for patients with EGFR-mutated non-small cell lung carcinoma (NSCLC). We evaluated the relationship between plasma osimertinib concentrations and treatment outcome in patients with NSCLC for this cohort study. The plasma levels of osimertinib and its metabolite AZ5104 were measured a week after the start of treatment (P1). The primary endpoint was to evaluate the correlation between plasma concentration and adverse events (AEs). The correlation with treatment efficacy was one of the secondary endpoints. In patients with CNS metastases, the concentration in the cerebrospinal fluid was also measured. Forty-one patients were enrolled. The frequency of AEs was highest for rash, followed by anorexia and thrombocytopenia. Thirty-eight cases provided measurements for P1. The median plasma concentration of osimertinib was 227 ng/mL, and that of AZ5104 was 16.5 ng/mL. The mean CNS penetration rate of two cases was 3.8%. The P1 in the group with anorexia was significantly higher than that in the group without anorexia (385.0 ng/mL vs. 231.5 ng/mL, p = 0.009). Divided into quartiles by P1 trough level, Q2 + Q3 (164–338 ng/mL) had longer PFS, while Q1 and Q4 had shorter PFS. An appropriate plasma level of osimertinib may avoid some adverse events and induce long PFS. Further large-scale trials are warranted. [ABSTRACT FROM AUTHOR]

Tumor‐derived G‐CSF is a well‐known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G‐CSF in squamous cell carcinoma (SCC). High expression of G‐CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR‐S1M cells produce considerable amount of G‐CSF, which expression is correlated with its metastatic potentials. Deletion of G‐CSF in NR‐S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR‐S1M tumors in the mice. Mechanistically, G‐CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR‐S1M tumor‐bearing mice, accumulation of plasma G‐CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8+ T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G‐CSF produced by NR‐S1M cells facilitates tumor progression in mice through bi‐functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G‐CSF expression. [ABSTRACT FROM AUTHOR]

Aim: Akita Prefecture has the largest proportion of older inhabitants and the highest cancer mortality rate in Japan. Lung cancer is one of the biggest killers, and early detection is critical. Chest X‐ray examinations are the main screening method for lung cancer; however, the COVID‐19 pandemic has affected the screening system. Here, we evaluate how COVID‐19 has affected lung cancer screening in Akita Prefecture. Methods: Using the Akita General Health Corporation database, the average annual number of chest X‐ray screening tests, close examinations and lung cancer diagnoses (stratified by sex and age) was evaluated during 2016–2019, and compared with the 2020 values. Furthermore, data on lung cancer registrations from 2018 to 2020 were obtained from the Collaborative Akita Prefecture Hospital‐Based Cancer Registration System and analyzed. Results: The average annual number of screening tests, close examinations and lung cancer diagnoses declined (by >50%) between 2016 to 2019 and 2020, especially among older people (aged ≥65 years). Furthermore, by stage, the number of patients with early‐stage lung cancer (stage 0–I) decreased, and the number with advanced‐stage cancer (stage IV) increased. Conclusions: The COVID‐19 pandemic reduced lung cancer screening participation, especially among the older adult population in Akita Prefecture, resulting in a decrease in lung cancer diagnoses through screening. This might have reduced the number of early‐stage cancer registrations. It is necessary to improve health education among the public regarding the importance of chest X‐ray screening. Geriatr Gerontol Int 2023; 23: 622–627. [ABSTRACT FROM AUTHOR]

Background: Tracheobronchial injury (TBI) is a rare but potentially life-threatening trauma that requires prompt diagnosis and treatment. We present a case in which a patient with COVID-19 infection was successfully treated for a TBI through surgical repair and intensive care with extracorporeal membrane oxygenation (ECMO) support. Case presentation: This is the case of a 31-year-old man transported to a peripheral hospital following a car crash. Tracheal intubation was performed for severe hypoxia and subcutaneous emphysema. Chest computed tomography showed bilateral lung contusion, hemopneumothorax, and penetration of the endotracheal tube beyond the tracheal bifurcation. A TBI was suspected; moreover, his COVID-19 polymerase chain reaction screening test was positive. Requiring emergency surgery, the patient was transferred to a private negative pressure room in our intensive care unit. Due to persistent hypoxia and in preparation for repair, the patient was started on veno-venous ECMO. With ECMO support, tracheobronchial injury repair was performed without intraoperative ventilation. In accordance with the surgery manual for COVID-19 patients in our hospital, all medical staff who treated this patient used personal protective equipment. Partial transection of the tracheal bifurcation membranous wall was detected and repaired using 4-0 monofilament absorbable sutures. The patient was discharged on the 29th postoperative day without postoperative complications. Conclusions: ECMO support for traumatic TBI in this patient with COVID-19 reduced mortality risk while preventing aerosol exposure to the virus. [ABSTRACT FROM AUTHOR]

Most so-called "beneficial bacteria" in gut microbiota are Gram-positive, and TLR6 recognizes the peptidoglycan (PGN) present in their cell walls. We hypothesized that a high TLR6 expression status predicts a more favorable prognosis after esophagectomy. We used an ESCC tissue microarray (TMA) to examine TLR6 expression status in ESCC patients and to determine whether TLR6 expression status correlates with prognosis after curative esophagectomy. We also examined whether PGN influences the cell proliferation activity of ESCC lines. Clinical ESCC samples from 177 patients tested for the expression of TLR6 were categorized as 3+ (n = 17), 2+ (n = 48), 1+ (n = 68), or 0 (n = 44). High TLR6 expression (3+ and 2+) correlated with significantly more favorable 5-year overall survival (OS) and disease-specific survival (DSS) after esophagectomy than a lower TLR6 expression (1+ and 0). Univariate and multivariate analyses showed that TLR6 expression status is an independent prognostic factor that affects 5-year OS. PGN significantly inhibited the cell proliferation activity of ESCC lines. This is the first study to show that high TLR6 expression status predicts a more favorable prognosis in locally advanced thoracic ESCC patients after curative esophagectomy. PGN released from "beneficial bacteria" seems to have potential to inhibit the cell proliferation activity of ESCC. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenia and chronic obstructive pulmonary disease (COPD) are risk factors for postoperative pulmonary complications (PPCs). Preoperative inspiratory muscle weakness is also a risk factor for PPCs. Sarcopenia and COPD are often associated with inspiratory muscle weakness. Respiratory sarcopenia has been defined as the coexistence of whole‐body sarcopenia and respiratory muscle weakness. We report our experience with preoperative pulmonary rehabilitation, including inspiratory muscle training (IMT), in a patient with lung cancer and comorbid respiratory sarcopenia and COPD. Case presentation: A 73‐year‐old man with squamous cell lung cancer (cStage IA2) was hospitalized for pulmonary rehabilitation before lung resection. He had comorbid severe sarcopenia and COPD (GOLD stage III). He also had inspiratory muscle weakness and a thin diaphragm. We conducted IMT on the patient in addition to aerobic exercise and instruction regarding sputum expectoration for 2 weeks before the surgery. Consequently, his pulmonary function, respiratory muscle strength, and exercise capacity improved. Segmentectomy was performed using video‐assisted thoracic surgery. No postoperative complications occurred. Conclusion: IMT in a patient with lung cancer and comorbid respiratory sarcopenia and COPD resulted in improved respiratory muscle strength and pulmonary function. IMT may have reduced the risk of PPCs by strengthening the respiratory muscles and improving pulmonary function. [ABSTRACT FROM AUTHOR]

Background: Sleeve lobectomy is recommended to avoid pneumonectomy and preserve pulmonary function in patients with central lung cancer. However, the relationship between postoperative pulmonary functional loss and resected lung parenchyma volume has not been fully characterized. The aim of this study was to evaluate the relationship between pulmonary function and lung volume in patients undergoing sleeve lobectomy or pneumonectomy. Methods: A total of 61 lung cancer patients who had undergone pneumonectomy or sleeve lobectomy were analyzed retrospectively. Among them, 20 patients performed pulmonary function tests, including vital capacity (VC) and forced expiratory volume in 1 s (FEV1) tests, preoperatively and then about 6 months after surgery. VC and FEV1 ratios were calculated (measured postoperative respiratory function/predicted postoperative respiratory function) as the standardized pulmonary functional loss ratio. Results: Thirty‐day operation‐related mortality was significantly lower after sleeve lobectomy (3.2%) than pneumonectomy (9.6%). The 5‐year relapse‐free survival rate was 46.67% versus 29.03%, and the 5‐year overall survival rate was 63.33% versus 38.71% in patients receiving sleeve lobectomy versus pneumonectomy. The VC ratio in the pneumonectomy group was better than in the sleeve lobectomy group (1.003 ± 0.117 vs. 0.779 ± 0.12; p = 0.0008), as was the FEV1 ratio (1.132 ± 0.226 vs. 0.851 ± 0.063; p = 0.0038). Conclusions: Both short‐term and long‐term outcomes were better with sleeve lobectomy than pneumonectomy. However, actual postoperative pulmonary function after pneumonectomy may be better than clinicians expect, and pneumonectomy should still be considered a treatment option for patients with sufficient pulmonary reserve and in whom sleeve lobectomy is less likely to be curative. [ABSTRACT FROM AUTHOR]

Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (H&E)‐stained frozen sections is the gold standard, but reliable pathology requires time‐consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid‐IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high‐voltage, low‐frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3–6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple H&E staining. With H&E staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors. [ABSTRACT FROM AUTHOR]

Intimal sarcoma is an extremely rare mesenchymal tumor arising in the great vessels. To date, intimal sarcoma has not been reported in patients with Lynch syndrome (LS), even though this syndrome lacks DNA mismatch repair ability genetically and is prone to various malignancies. This patient was diagnosed with LS by the Revised Amsterdam Criteria II, and she suffered from intimal sarcoma in the left pulmonary artery. She had a germline missense variant of PMS2 (c.1399G>A, pV467I) which is classified as a variant of unknown significance. In her intimal sarcoma, PMS2 expression was decreased. Additionally, it exhibited microsatellite instability and a high tumor mutational burden (69 mutations/Mb) which are features of mismatch repair deficiency, although PMS2 (c.1399G>A, pV467I) missense is a variant of unknown significance. The metastatic lesions of intimal sarcoma in this patient responded heterogeneously to pembrolizumab, an immune checkpoint inhibitor. Cytotoxic agents and radiation were also effective for some metastatic lesions, but some lesions, including her liver metastases, were resistant. The hypermutable nature of the LS genotype might acquire resistance to an immune checkpoint inhibitor and other cytotoxic agents such as occurred with her liver metastases. [ABSTRACT FROM AUTHOR]

Objective: Sublobar resection is considered the gold standard for selected patients with pulmonary metastasis or who are compromised in some way. However, an unfavorable outcome after sublobar resection is local/margin recurrence. The aim of this study was to evaluate the clinical reliability of a new rapid-stapler lavage immunocytochemistry (ICC) technique for assessing margin malignancy. The method uses non-contact alternating current (AC) mixing to achieve more stable staining. Methods: Twenty-one patients who underwent sublobar resection, including 16 wedge resections, for pulmonary metastasis or lung cancer in a compromised host between September 2016 and December 2017 were retrospectively reviewed. All margin specimens were intraoperatively evaluated with HE staining of frozen sections and stapler lavage cytology using Papanicolaou staining and rapid-ICC. Results: Rapid-stapler lavage ICC can be used to diagnose surgically safe margins within 20 min during sublobar resections. Although in all cases margins were diagnosed as cancer free based on HE staining of frozen sections, two of four patients diagnosed with malignant-positive margins based on rapid ICC experienced local/margin recurrence. Conclusions: Rapid-stapler lavage ICC with AC mixing could potentially serve as a clinical tool for prompt determination of margin malignant status after pulmonary sublobar resection. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer. Methods: Preoperative PET/CT findings (pStage IB–III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C‐SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data. Results: Based on ROC analyses, the cutoff I/C‐SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC‐SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively. Conclusions: When diagnosing nodal stage, a lymph node I/C‐SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer. [ABSTRACT FROM AUTHOR]

Objectives: For thymic epithelial tumors, simple contact with adjacent structures does not necessarily mean invasion. The purpose of our study was to develop a simple noninvasive technique for evaluating organ invasion using routine pretreatment computed tomography (CT). Methods: This retrospective study analyzed the pathological reports on 95 mediastinal resections performed between January 2003 and June 2020. Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) and maximum tumor diameter (Dmax) was measured, after which Adist/Dmax (A/D) ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the Adist and A/D ratios. Results: An Adist cut-off of 37.5 mm best distinguished between invaded and non-invaded mediastinal great veins based on ROC curves. When Adist > 37.5 mm was used for diagnosis of invasion of the brachiocephalic vein (BCV) or superior vena cava (SVC), the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the ROC curve for diagnosis of invasion were 61.9%, 92.5%, 81.25%, 82.2%, 81.97%, and 0.76429, respectively. Moreover, there were significant differences between BCV/SVC Adist > 37.5 mm and ≤ 37.5 mm for 10-year relapse-free survival and 10-year overall survival (p < 0.01). Conclusions: When diagnosing invasion of the mediastinal great veins based on Adist > 37.5 mm, we achieved a higher performance level than the conventional criteria such as irregular interface with an absence of the fat layer. Measurement of Adist is a simple noninvasive technique for evaluating invasion using CT. Key Points • Simple contact between the primary tumor and adjacent structures on CT does not indicate direct invasion. • Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) is a simple noninvasive technique for evaluating invasion. • Adist > 37.5 mm can be a supportive tool to identify invaded mediastinal great veins and surgical indications for T3 and T4 invasion by thymic epithelial tumors. [ABSTRACT FROM AUTHOR]

Background: Patients with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)-positive lymph nodes before treatment have a poor prognosis after esophagectomy. This study investigated whether FDG uptake into lymph nodes on FDG-PET (PET-N) during the pre- or posttreatment stage is more predictive of survival for thoracic esophageal squamous cell carcinoma (TESCC) patients who received neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy. Methods: Of 129 TESCC patients with clinical lymphatic metastasis who underwent curative-intent esophagectomy after NACRT between 2010 and 2018, 97 who received PET before and after NACRT were enrolled in the study. The study defined lymph nodes with a maximum standardized uptake value (SUVmax) greater than 2.5 on FDG-PET before NACRT as cPET-N(+) and after NACRT as CRT-cPET-N(+). Both the cPET-N(+) and CRT-cPET-N(–) patients were defined as PET-N responders. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. Results: No significant difference in survival was detected between the cPET-N(+) and cPET-N(–) patients. However, the CRT-cPET-N(–) patients had significantly better 5-year overall survival (OS) and disease-specific survival (DSS) than the CRT-cPET-N (+) patients. The PET-N responders had significantly better 5-year OS and DSS than the PET-N non-responders, and PET-N response was an independent prognostic factor for 5-year DSS. Conclusion: The PET-N response is a highly predictive prognostic marker for TESCC patients who undergo NACRT followed by esophagectomy. The PET-N response may help clinicians to establish a strategy for perioperative treatments that improves survival for patients with lymph node metastasis in TESCC. [ABSTRACT FROM AUTHOR]

Background: Platinum agents are taken up into cells by copper transporter (CTR) 1 (gene code: SLC31A1) and are excreted from cells by copper-transporting P-type adenosine triphosphatase (ATP7B) and multidrug resistance-associated protein (MRP) 2 (gene code: ABCC2). In addition, glutathione S transferase (GST) P1 is involved in the metabolism of platinum agents. The present study aimed to determine whether the rate of grade 3–4 hematological toxicity associated with platinum plus 5-fluorouracil (5-FU) therapy in 239 patients with esophageal cancer was affected by the SLC31A1 rs10981694A>C and rs12686377G>T, ATP7B rs9535828A>G, GSTP1 rs1695A>G, and ABCC2 −24C>T polymorphisms. Methods: Chemotherapy consisted of protracted infusion of 5-FU (800 mg/m2/day) on days 1–5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. Results: A total of 82 of 239 patients developed grade 3–4 hematological toxicity after chemotherapy. Univariate analysis showed that ABCC2 −24C/T + T/T genotypes (P = 0.038), radiation therapy (P = 0.013), baseline white blood cell count < 6000/μL (P = 0.003), and baseline neutrophil count < 3900/μL (P = 0.021) were statistically significant predictors of grade 3–4 hematological toxicity. Multivariate analysis revealed that ABCC2 −24C/T + T/T genotypes (P = 0.036), radiation therapy (P = 0.005), and baseline white blood cell count < 6000/μL (P < 0.001) were significant risk factors. Conclusions: We determined that ABCC2 −24C>T is significantly associated with grade 3–4 hematological toxicity after platinum plus 5-FU therapy. These findings might contribute to improved treatment strategies for patients with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT.Methods: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT.Results: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant.Conclusions: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words). [ABSTRACT FROM AUTHOR]

To address the major issue of regional disparity in the treatment for elderly cancer patients in an aging society, we compared the treatment strategies used for elderly patients with thoracic esophageal cancer and their survival outcomes in metropolitan areas and other regions. Using the national database of hospital‐based cancer registries in 2008‐2011, patients aged 75 years or older who had been diagnosed with thoracic esophageal cancer were enrolled. We divided the patients into two groups: those treated in metropolitan areas (Tokyo, Kanagawa, Osaka, Aichi, Saitama, and Chiba prefectures) with populations of 6 million or more and those treated in other areas (the other 41 prefectures). Compared were patient backgrounds, treatment strategies, and survival curves at each cancer stage. In total, 1236 (24%) patients from metropolitan areas and 3830 (76%) patients from nonmetropolitan areas were enrolled. Patients in metropolitan areas were treated at more advanced stages. There was also a difference in treatment strategy. The 3‐year survival rate among cStage I patients was better in metropolitan areas (71.6% vs. 63.7%), and this finding mainly reflected the survival difference between patients treated with radiotherapy alone. For cStage II‐IV patients, there were no differences. Multivariable Cox proportional hazard analysis including interaction terms between treatment areas, cStage, and the first‐line treatments revealed that treatments in the metropolitan areas were significantly associated with better survival among patients treated with radiotherapy alone for cStage I cancer. Treatment strategies for elderly patients with thoracic esophageal cancer and its survival outcomes differed between metropolitan areas and other regions. [ABSTRACT FROM AUTHOR]

Esophageal cancer recurrence in solitary mediastinal lymph node that may possibly been left behind in the first surgery differs from other recurrence patterns because it is still local disease and offers the possibility of complete cure through resection, but it is technically difficult. We resected recurrent mediastinal lymph nodes in six cases. A left transthoracic approach was used in three patients. Other approaches were left thoracoabdominal, right open transthoracic and transcervical. R0 resections were achieved in five patients without severe surgical stress or postoperative complications. Overall survival after resection of recurrent lymph nodes was 43 (16–82) months. Approaches to resection of recurrent solitary mediastinal lymph nodes after esophagectomy should be consider to perform curative treatment safely and less invasively. [ABSTRACT FROM AUTHOR]

Background: Video-assisted thoracoscopic surgery (VATS) is being used to treat esophageal submucosal tumors (SMTs) all over the world. However, this technique is difficult when the tumor is large and located on the left side wall of the esophagus, within the upper mediastinum. This is because, with VATS, the surgical forceps have a limited range of motion. Robot-assisted thoracoscopic surgery (RATS) using the da Vinci surgical system may be extremely useful for enucleation of esophageal SMTs within the narrow upper mediastinum. Case presentation: A female in her thirties experiencing epigastric pain visited our hospital and was diagnosed with a large esophageal leiomyoma within the upper mediastinum. From its size (10 cm), it was judged to have malignant potential. We performed SMT enucleation using RATS with a da Vinci surgical system Xi. This was our second case using this system. The patient was placed in the left lateral position. Four da Vinci trocars (8 mm) were inserted into the 10th, 7th, 5th and 3rd intercostal spaces (ICS), and an assist port was added in the 5th ICS. We opened the superior mediastinal pleura cranially and caudally from the arch of the azygos vein and expanded the superior mediastinum after dividing the azygos vein. We made an incision in the muscular layer of the esophagus and, using a monopolar hook and monopolar scissors, enucleated the esophageal tumor in a protective manner so as not to damage its capsule or mucosa while applying appropriate robot-specific counter traction. We then sewed up the muscularis using 4–0 Vicryl, inserting the endoscope into the thoracic esophagus to substitute for a bougie. In addition, the pleura was sutured using barbed suture. The surgical procedure was straightforward and smooth. The patient was discharged on postoperative day 4 with no surgical complications. The tumor was definitively diagnosed pathologically from paraffin sections as a benign esophageal leiomyoma. Conclusions: RATS enables more delicate and precise esophageal SMT enucleation without surgical complications, though various challenges remain to be overcome. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are a promising advance in the treatment of patients with lung cancer. However, each ICI has been tested with an independently designed companion diagnostic assay that is based on a unique antibody. Consequently, the different trial‐validated programmed death ligand 1 (PD‐L1) immunohistochemistry (IHC) assays should not be considered interchangeable. Our aim was to compare the performance of each available PD‐L1 antibody for its ability to accurately measure PD‐L1 expression and to investigate the possibility of harmonization across antibodies through the use of a new rapid IHC system, which uses noncontact alternating current (AC) mixing to achieve more stable staining. Methods: First, 58 resected non‐small cell lung cancer (NSCLC) specimens were stained using three PD‐L1 IHC assays (28–8, SP142, and SP263) to assess the harmonization achieved with AC mixing IHC. Second, specimens from 27 patients receiving ICIs for postoperative recurrent NSCLC were stained using the same IHC method to compare the clinical performance of ICIs to PD‐L1 scores. All patients received a tumor proportion score (TPS) with the 22C3 companion diagnostic test. Results: Better staining was achieved with the new AC mixing IHC method than the conventional IHC in PD‐L1‐positive cases, and the interchangeability of some combinations of assays was increased in PD‐L1‐positive. In addition, AC mixing IHC provided more appropriate overall response rates for ICIs in all assays. Conclusions: Stable PD‐L1 IHC driven by AC mixing helped to improve TPS scoring and patient selection for ICIs through interchangeable assays. [ABSTRACT FROM AUTHOR]

Background: A pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) ensures long-term survival in esophageal squamous cell carcinoma (ESCC) patients following esophagectomy, but pCR patients are a minority. The aim here was to identify prognostic factors in patients with non-pCR ESCC after NACRT. Methods: This is a retrospective study. Investigated were 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) among non-pCR ESCC patients divided into pT0N0, primary site pCR (pT0N+), lymph node pCR (pT+N0), and non-pCR in both the tumor and lymph node (pT+N+) subgroups after NACRT and esophagectomy. Focusing on the SUVmax reduction rate in the primary tumor in 88 patients who underwent FDG-PET before and after NACRT, we used univariate and multivariate Cox proportional hazard models to identify prognostic factors. Results: Although there were no significant survival differences among non-pCR ESCC patients with pT0N+, pT+N0, or pT+N+, survival rate among pT+N+patients was the poorest. After setting a 60% cutoff for the SUVmax reduction rate in the tumor, RFS curves for non-pCR patients significantly differed between patients above the cutoff and those below it. For pT+N+ patients, the SUVmax reduction rate (<60% vs ≥ 60%) was an independent prognostic factor of OS, DSS, and RFS. Conclusion: Because ESCC patients with SUVmax reduction rates of <60% in the tumor after NACRT and categorized as pT+N+ after NACRT had significantly poorer prognoses, even after esophagectomy, a change in treatment strategy may be an option to improve survival. [ABSTRACT FROM AUTHOR]

Background: The interval between preoperative chemoradiotherapy and surgery reportedly affects perioperative outcomes and survival; however, the optimal interval in esophageal cancer patients remains uncertain. Objective: Our aim was to determine whether a prolonged interval between preoperative neoadjuvant chemoradiotherapy (NACRT) and esophagectomy affects the outcomes of esophageal cancer patients. Methods: A total of 131 patients with esophageal cancer received curative surgery following NACRT at Akita University Hospital between 2009 and 2017. We divided these patients into two groups based on the median interval from NACRT to esophagectomy, and compared the rates of pathological complete response (pCR), surgical outcomes, and survival. Results: The median interval from NACRT to esophagectomy was 39 days (range 21–95). Of the 131 patients, 70 (53%) received esophagectomy after 39 days or more from completion of NACRT. There were no significant differences in the clinicopathological features, including pCR rates, between the two groups. Prolongation of the interval from NACRT to esophagectomy was significantly associated with an increased rate of anastomotic leakage and recurrent laryngeal nerve palsy (p = 0.0225 and p = 0.0022, respectively); however, no association with overall survival was detected. Conclusions: A prolonged interval between NACRT and esophagectomy had no impact on pCR rates or survival. However, delaying esophagectomy may increase the likelihood of surgical complications such as anastomotic leakage and recurrent laryngeal nerve palsy. [ABSTRACT FROM AUTHOR]

The oncological advantages of robot-assisted thoracoscopic esophagectomy (RATE) over conventional thoracoscopic esophagectomy (TE) for thoracic esophageal cancer have yet to be verified. In this study, we retrospectively analyzed clinical data to compare the incidences of recurrence within the surgical field after RATE and TE as an indicator of local oncological control. Among 121 consecutive patients with thoracic esophageal or esophagogastric junction cancers for which thoracoscopic surgery was indicated, 51 were treated with RATE while 70 received TE. The number of lymph nodes dissected from the mediastinum, duration of the thoracic portion of the surgery, and morbidity due to postoperative complications did not differ between the two groups. However, the rate of overall local recurrence within the surgical field was significantly (P = 0.039) higher in the TE (9%) than the RATE (0%) group. Lymph node recurrence within the surgical field occurred in left recurrent nerve, left tracheobronchial, left main bronchus and thoracic paraaortic lymph nodes, which were all difficult to approach to dissect. The other two local failures occurred around the anastomotic site. This study indicates that using RATE enabled the incidence of recurrence within the surgical field to be reduced, though there were some limitations. [ABSTRACT FROM AUTHOR]

The relationship between the SLC31A1 (protein: copper transporter 1) rs10981694 A > C and ATP7B (protein: P-type adenosine triphosphatase 7B) rs9535828 A > G polymorphisms on the overall survival and disease-free survival of 104 Japanese patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemoradiotherapy (CRT) was investigated. Chemotherapy consisted of protracted infusion of 5-fluoracil (800 mg/m2/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. The median (range) follow-up was 47 (6-127) months. The 5-year overall and disease-free survival rates were 71.2% and 60.6%, respectively. The 5-year overall survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (91.7% vs. 65.0%, P = 0.018). The 5-year disease-free survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (79.2% vs. 55.0%, P = 0.043). In addition, univariate and multivariate analyses showed the SLC31A1 rs10981694 A > C polymorphism to be a significant prognostic factor affecting 5-year overall survival after neoadjuvant CRT. However, the overall and disease-free survival rates after surgery did not differ significantly among the ATP7B rs9535828 genotypes. In conclusion, only the SLC31A1 rs10981694 A/A genotype was an independent predictor of a poorer 5-year overall survival. Therefore, in neoadjuvant CRT for ESCC patients, the effect of platinum was affected by the SLC31A1 rs10981694 A > C polymorphism. The presence of this polymorphism should be considered when devising neoadjuvant CRT regimens or treatment strategies for ESCC. [ABSTRACT FROM AUTHOR]

Background: Although lobectomy is considered the standard surgery for any non‐small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid‐IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. Methods: This retrospective study analyzed the pathological reports from NSCLC resections over a six‐year period between 2014 and 2020. Using a new device for rapid‐IHC, we applied a high‐voltage, low‐frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid‐IHC can provide a nodal diagnosis within 20 minutes. Results: Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid‐IHC. In addition, rapid‐IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid‐IHC received complete lobectomies. Five‐year relapse‐free survival and overall survival among patients receiving segmentectomy with rapid‐IHC were 88.77% and 88.79%, respectively. Conclusions: Rapid‐IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating‐current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer. Key points: Significant findings of the study: Rapid immunohistochemistry driven by alternating‐current field mixing (completed within 20 minutes intraoperatively) is simple, highly accurate, and preserves lymph node tissue for subsequent pathological examination, including molecular assessments. What this study adds: Segmentectomy for lung cancer is oncologically safe, but only when there is adequate intraoperative node staging. Rapid immunohistochemistry will assist clinicians when making intraoperative nodal diagnoses. [ABSTRACT FROM AUTHOR]

Background: Poor oral health is an independent risk factor for upper aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). The pattern recognition receptor Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide in the cell walls of Gram-negative periodontal pathogens associated with the development and progression of ESCC. It is, therefore, plausible that TLR4 plays a crucial role in the pathogenesis of ESCC. Methods: We used an ESCC tissue microarray to confirm expression of TLR4 in patients with ESCC and to determine whether TLR4 expression status correlates with the clinicopathological features of these patients or their prognosis after esophagectomy. We also tested whether the combined expression statuses of TLR4 and TLR3 better correlate with prognosis in these patients than either parameter alone. Results: Clinical ESCC samples from all 177 patients tested showed expression of TLR4. Moreover, high TLR4 expression (3 + and 2 +) correlated with poorer 5-year overall survival after esophagectomy than lower TLR4 expression (1 +) (p = 0.0491). Patients showing high TLR4 expression tended to have a poorer prognosis whether treated with surgery alone or with surgery and adjuvant chemotherapy. Univariate and multivariate analyses showed TLR4 expression status to be an independent prognostic factor affecting 5-year overall survival. Patients exhibiting high TLR4 expression with low TLR3 expression had a much poorer prognosis than other patients (p = < 0.0001). Conclusion: High TLR4 expression predicts a poor prognosis in advanced thoracic ESCC patients after esophagectomy. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal types of malignant tumors worldwide. Epitranscriptome, such as N6‐methyladenosine (m6A) of mRNA, is an abundant post‐transcriptional mRNA modification and has been recently implicated to play roles in several cancers, whereas the significance of m6A modifications is virtually unknown in ESCC. Analysis of tissue microarray of the tumors in 177 ESCC patients showed that higher expression of m6A demethylase ALKBH5 correlated with poor prognosis and that ALKBH5 was an independent prognostic factor of the survival of patients. There was no correlation between the other demethylase FTO and prognosis. siRNA knockdown of ALKBH5 but not FTO significantly suppressed proliferation and migration of human ESCC cells. ALKBH5 knockdown delayed progression of cell cycle and accumulated the cells to G0/G1 phase. Mechanistically, expression of CDKN1A (p21) was significantly up‐regulated in ALKBH5‐depleted cells, and m6A modification and stability of CDKN1A mRNA were increased by ALKBH5 knockdown. Furthermore, depletion of ALKBH5 substantially suppressed tumor growth of ESCC cells subcutaneously transplanted in BALB/c nude mice. Collectively, we identify ALKBH5 as the first m6A demethylase that accelerates cell cycle progression and promotes cell proliferation of ESCC cells, which is associated with poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Preoperative clinical diagnosis of lymph node (LN) metastasis and subsequent pathological diagnosis are often not in agreement. Detection of false-negative LNs is essential in selecting an optimal treatment strategy, and most importantly, the presence of false-negative LN is itself a significant prognostic indicator. Therefore, at present, there is an urgent need to establish more accurate and individualized evaluation methods for LN metastasis. Methods: Of 213 cN0 patients who underwent curative esophagectomy without preoperative neoadjuvant treatment, 60 (28%) had LN metastasis diagnosed pathologically. There were 129 false-negative LNs, of which 85 were detectable by preoperative computed tomography (CT). We retrospectively investigated the distribution, frequency, and characteristics of pathologically positive nodes in patients with clinically N0 esophageal cancer. Results: The paracardial region was the most frequent region of false-negative LNs, accounting for 26% (22 LNs) of the total incidence. False-negative LNs distributed widely from the neck to the abdomen in patients with a primary tumor in the middle thoracic esophagus. In patients with a primary tumor in the lower thoracic esophagus, four false-negative LNs were detected in the superior mediastinum. When the short-axis diameter, shape, and attenuation patterns of the LNs were used as criteria for metastasis diagnosis, they were insufficient for an accurate diagnosis. However, false-negative LNs in the most frequently occurring sites are characterized by smaller short-axis, suggesting that accurate diagnosis cannot be made unless the diagnostic criteria for the short-axis are reduced in addition to shape and attenuation. Conclusions: Although restrictive to the most frequent regions of false-negative LNs occur, reducing size criterion and consideration of their shape and attenuation may contribute to improved diagnosis. [ABSTRACT FROM AUTHOR]

Background: Despite wide acknowledgement of the importance of sarcopenia and prognostic markers such as the neutrophil-to-lymphocyte ratio, the impact on cancer patient survival of the timing of sarcopenia's emergence and its severity is not well understood, nor is the association between sarcopenia and prognostic markers. The aim of this study, therefore, was to investigate the effect of the severity and timing of changes in the psoas muscle index (PMI) on survival of advanced esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (NACRT) plus esophagectomy and the association between PMI and known prognostic markers. Methods: Included in this study were 113 ESCC patients who underwent NACRT followed by esophagectomy. PMI and prognostic markers were measured at their initial visit, just before surgery (after NACRT), and 3 months postoperatively. Results: All patients were classified into four groups according to the percent decrease in PMI after NACRT and after NACRT plus esophagectomy. Patients exhibiting a larger PMI decrease (≥20%) after NACRT plus esophagectomy had significantly poorer overall survival than those showing a smaller PMI decrease. Furthermore, multivariable analysis showed that a larger decrease in PMI after NACRT plus esophagectomy was a significant risk factor for overall (P < 0.0001) and recurrence-free (P = 0.0097) survival. Neither pretherapeutic PMI nor a decrease in PMI after NACRT significantly affected survival. PMI also showed weak, but significant, correlations with several prognostic markers postoperatively. Conclusions: Decreased PMI after NACRT plus esophagectomy is a strong prognostic indicator in ESCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Surgery remains the best curative treatment option for non-small cell lung cancer (NSCLC), but is of benefit only to patients with localized disease. A meta-analysis showed a significant beneficial effect of induction chemotherapy on survival, but there is still no clear evidence. This phase II study was conducted to establish whether induction chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) plus bevacizumab prior to surgery reduces the risk of progression. Methods: The subjects of this study were 29 patients with treatment-naive nonsquamous NSCLC (clinical stages IIIA to IV). Patients received PTX (200 mg/m2), CBDCA (area under the curve, 5), and bevacizumab (15 mg/kg) followed by surgery. Chemotherapy was repeated every 3 weeks for up to six cycles. Results: The overall response rate was 72.4%. Of the 29 patients, ten underwent surgery after the induction chemotherapy and complete resection was achieved in 7 (70%). The median progression-free-survival (PFS) time and the 3-year PFS rate were 0.92 years and 16.2%, respectively. The median overall survival (OS) time and the 3-year OS rate were 1.96 years and 44.9%, respectively. Conclusion: Combined modality therapy with surgery after induction chemotherapy with CBDCA and PTX plus bevacizumab is clinically feasible and tolerable for patients with unknown or negative molecular profiles. [ABSTRACT FROM AUTHOR]

A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared. It was demonstrated that 1/20 patients (5.0%) exhibited positive PD-L1 expression in the metastatic lesions, as well as in the primary lung tumor. DLL3 was highly expressed in 14/20 patients (70%) and EZH2 was positive in 17/20 patients (85%). None of these cases exhibited any correlation with age, sex, smoking, stage or treatment, whereas IHC staining was able to identify candidate responders to anti-PD-L1/PD-1 immunotherapy, Rova-T therapy, or EZH2 inhibitor therapy. [ABSTRACT FROM AUTHOR]

Purpose: To establish whether Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SphK1) contribute to lymph node metastasis in esophageal squamous cell carcinoma. Methods: Immunohistochemical analysis of SphK1 expression was performed using a tissue microarray containing 177 thoracic squamous cell esophageal cancer specimens resected at surgery, to investigate the association between intratumoral SphK1 expression and lymph node metastasis. Serum S1P levels and intratumoral SphK1 mRNA and protein expression were also evaluated in mice with vs. mice without lymph node metastasis in a murine lymph node metastasis model. Results: Among 177 esophageal cancer patients, 127 (72%) were defined as being SphK1-positive. In univariate and multivariate analyses, SphK1 expression status was a significant factor contributing to lymph node metastasis and poorer 5-year overall survival. In the murine lymph node metastasis model, there was no difference in tumor volume or weight between the lymph node metastasis-negative and lymph node metastasis-positive groups. However, levels of SphK1 mRNA and protein and serum S1P levels were all much higher in the metastasis-positive group. Conclusions: S1P/SphK1 may be novel targets for inhibiting lymph node metastasis in esophageal squamous cell carcinoma, and may provide the basis for a therapeutic strategy to suppress lymph node metastasis. [ABSTRACT FROM AUTHOR]

Purpose: miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. Methods: We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. Results: The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. Conclusion: This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique for improving nodal staging using preoperative PET/CT in patients with resectable non-small cell lung cancer (NSCLC). Methods: Preoperative PET/CT findings (163 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images, lymph node section area (SA), the maximum standardized uptake value (SUV), SA of SUV ≥2.5 and ≥3.0 were drawn freehand and measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze those data. Results: Based on ROC analyses, the cut-off values for SA of SUV ≥2.5, SA of SUV ≥3.0, SUV ≥2.5 SA/node SA and SUV ≥3.0 SA/node SA for diagnosis of lymph node metastasis were 200 mm, 30 mm, 1.0 and 0.4. SUV ≥2.5 SA/node SA ≥1.0 had the highest negative predictive value, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of nodal staging were 61.1, 73.4, 36.7, 88.2 and 70.9%. Conclusions: When diagnosing nodal staging based a lymph node SUV ≥2.5 SA/node SA ratio of ≥1.0, it can be an effective criterion for use to determine surgical indications. [ABSTRACT FROM AUTHOR]

In thoracic surgery, we occasionally encounter vessel anomalies. We herein report an extremely rare surgical case with the absence of the azygos vein. Mediastinal vascular abnormalities are said to be rare. The etiology of vascular abnormalities of the whole body, including the chest is known gene mutations, hormone abnormalities, infection, and trauma. But, many causes have been unknown. In thoracic surgery field, there is some reports and literature about pulmonary arteriovenous malformation, pulmonary sequestration, and partial anomalous pulmonary venous return. But reports about absence of azygos vein are not much. It is considered that it is less likely to become a problem in clinical. As we discussed in the paper, it will be more interesting if the association with PLSVC reveals from more cases. A 58-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected absence of the azygos vein by preoperative computed tomography (CT). Furthermore, three-dimensional angiography (3D-angiography) showed that the right superior intercostal vein and hemiazygos vein in the left thoracic cavity were more developed than usual. Then, we discuss the key points during surgery and suggest the potential association between the absence of the azygos vein and a persistent left superior vena cava (PLSVC). [ABSTRACT FROM AUTHOR]

Mediastinal aneurysms are rare but potentially life-threatening. Among these, bronchial artery aneurysms are most frequently reported, whereas up to now aneurysms of the proper esophageal artery had never been reported. A 69-year-old woman was referred to our hospital for treatment of a massive mediastinal hematoma. Enhanced computed tomography and selective proper esophageal arteriography revealed a 5-mm aneurysm in the proper esophageal artery that arises from the thoracic aorta at the Th8 level and has an anastomotic branch with the bronchial artery peripherally. Transcatheter arterial embolization was successfully performed using a mixture of N-butyl cyanoacrylate and lipiodol (1:3 ratio, 0.3 ml). Post-embolization angiography showed no filling into the aneurysm. The patient recovered with no complications and was discharged on the 25th post-procedure day. [ABSTRACT FROM AUTHOR]

Background: A reliable marker of the sensitivity of esophageal cancer to chemoradiotherapy (CRT) as well as a personal biomarker predictive of adverse events during treatment has long been sought. The purpose of the present study was to test whether there is an association between interleukin-6 (IL-6) and/or monocyte chemoattractant protein-1 (MCP-1) polymorphisms and CRT-induced bone-marrow suppression--i.e., reductions in white blood cell and/or platelet counts. Methods: The study participants were 103 Japanese patients treated with definitive or pre-operative CRT for squamous cell esophageal cancer at Akita University Hospital. The patients were divided into two groups, with or without adverse events during or up to 1 month after CRT. Results: Patient backgrounds--i.e., white blood cell and platelet counts before CRT and doses of chemotherapy and irradiation--did not differ between groups. However, there was a significantly higher incidence of grade 2-4 platelet count reductions (<75,000/mm) among patients carrying the IL-6 −634C/G+G/G genotype than among those carrying the C/C genotype. Similarly, there was a significantly higher incidence of grade 2-4 platelet count reductions among patients carrying the MCP-1 −2518G/G genotype than among those carrying the A/A+A/G genotype. Univariate and multivariate logistic regression models revealed that the IL-6 −634C>G and MCP-1 −2518A>G polymorphisms were significantly associated with grade 2-4 platelet count reductions following CRT. Conclusion: These polymorphisms may thus be clinically relevant and should be taken into consideration when devising CRT regimens or treatment strategies for esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Poor oral health is a risk factor for causing upper aerodigestive tract tumors, including esophageal cancer. Our aim was to determine the periodontitis rate in our cohort of esophageal cancer patients. We also analyzed whether preoperative dental examination and care reduces the likelihood of severe pneumonia after esophagectomy. Study Design: Between 2003 and 2014, 529 esophageal cancer patients received esophagectomy at Akita University Hospital. We studied 232 patients who had preoperative dental examinations and care (dental care group) retrospectively and assessed the severity of their periodontitis. Thedental care group was compared to 297 patients who did not have preoperative dental care (control group) with respect to the incidence of severe pneumonia after esophagectomy. Results: Ninety-one patients (39.2%) in the dental care group were diagnosed with slight periodontitis and 69 (29.7%) were diagnosed with severe periodontitis. Among all the patients, 69 patients (13.0%) were diagnosed with grade 3B postoperative severe pneumonia. The dental care group had a significantly lower incidence of severe pneumonia than the control group. Moreover, multivariable logistic regression analysis revealed that anastomotic leakage, preoperative dental care, gender and %VC were correlated significantly with the occurrence of postoperative severe pneumonia. Conclusion: Preoperative dental examination and care by a dentist are essential to reduce the likelihood of postoperative severe pneumonia in esophageal cancer patients. [ABSTRACT FROM AUTHOR]

There is no doubt that, along with surgery, chemoradiotherapy is an important treatment for esophageal squamous cell carcinoma (ESCC). Patients who respond well to chemoradiotherapy obtain great benefits toward overcoming their cancer, and so a more favorable prognosis. On the other hand, patients who do not respond well have wasted valuable time and experienced severe toxicity and seriously diminished quality of life, only to have their cancer recur with an unfavorable prognosis. For this reason, a reliable biomarker of chemoradiosensitivity in ESCC has long been sought. In this review, we will enumerate recently reported candidate biomarkers of chemoradiosensitivity in ESCC that have the potential for future clinical application. [ABSTRACT FROM AUTHOR]

Background: CXCL10, a member of the CXC chemokine family, is known to mediate chemotaxis, apoptosis, angiogenesis, and cell growth. It is also reportedly involved in tumor development and can affect prognosis in several cancers. However, the precise relationship between CXCL10 and the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is not fully understood. Methods: We used ESCC tissue microarrays containing samples from 177 patients to test whether the CXCL10 expression status, determined using immunohistochemical analysis, is predictive of prognosis. We also tested whether CXCL10 expression status could serve as a clinically useful marker for evaluating the need for adjuvant chemotherapy after surgery. Results: We found that high CXCL10 expression in clinical samples was an independent prognostic factor and was predictive of a favorable 5-year overall survival and disease-specific survival ( p = 0.0102 and 0.0332, respectively). Additionally, no significant difference was detected between patients in the CXCL10-high group treated with surgery alone and those treated with surgery followed by adjuvant chemotherapy. In the CXCL10-low group, on the other hand, patients treated with surgery followed by adjuvant chemotherapy had better 5-year overall survival than those treated with surgery alone. Conclusions: High CXCL10 expression is an independent prognostic factor and has the potential to serve as a clinically useful marker of the need for adjuvant chemotherapy after surgery in patients with advanced thoracic ESCC. [ABSTRACT FROM AUTHOR]