Evaluation of first-line and salvage therapies for unresectable malignant mesothelioma: A systematic review and network meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis. METHODS: Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences were searched until February 29, 2024. The main outcomes of interest were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). RESULTS: We analyzed 16 RCTs with a total of 5018 patients. Among first-line therapies, nivolumab and ipilimumab significantly increased OS and resulted in fewer grade ≥3 TRAEs. Bevacizumab plus chemotherapy significantly increased PFS. Among salvage therapies, ramucirumab and chemotherapy was associated with the best OS and PFS, but resulted in more grade ≥3 TRAEs. Subgroup analysis by histologic types suggested that in first-line settings, bevacizumab and chemotherapy increase OS the most for epithelioid type, while the nivolumab plus ipilimumab treatment increases OS the most for non-epithelioid type. In salvage therapies, ramucirumab and chemotherapy increase OS for both epithelioid and non-epithelioid types. CONCLUSION: Nivolumab plus ipilimumab was associated with the best OS among first-line treatments. Ramucirumab and chemotherapy was associated with the best clinical outcomes in salvage settings. Treatment for malignant mesothelioma should be tailored based on different clinicopathological characteristics.

Immature Sacrococcygeal Teratoma: A Case Report and Extensive Review of the Literature.

Immature sacrococcygeal teratoma represents a histological form with rapid tumor growth, a risk of premature birth, an enhanced rate of complications, an increased risk of recurrence, and a higher mortality rate than the mature type. Thus, prenatal diagnosis of immature forms would significantly improve the prognosis of these cases. To this end, we performed an extensive literature review on the diagnosis, therapeutic management, and follow-up of immature teratomas. Regarding this medical conduct, we also presented our case. In conclusion, the early identification of immature sacrococcygeal teratomas with or without other associated structural abnormalities and their correct therapeutic approach are basic principles for a favorable evolution of these cases.

Impact of surgical approach on progress of disease by type of histology in stage IA endometrial cancer: a matched-pair analysis.

BACKGROUND: To compare the impact of surgical approach on progression free survival (PFS) stratified by histologic type in women diagnosed with stage IA endometrial cancer. METHODS: Myometrial invasion is classified into no myometrial invasion, <50% and ≥50%, with only no myometrial invasion and <50% are included in stage IA patients. A retrospective study is designed by collecting data from women diagnosed as stage IA endometrial cancer from January 2010 to December 2019 in a tertiary hospital. A propensity score is conducted for 1:1 matching in the low-risk histologic patients. Progression free survival and disease-specific survival data are evaluated by the Kaplan-Meier method and compared by the log-rank test in both the whole population and the matched-pair groups. A sub-group analysis is performed to figure out risk factors associated with the effect of surgical approach on PFS and disease-specific survival (DSS). RESULTS: 534 (84.49%) low-risk histologic endometrial cancer women, with 389 (72.85%) operated by minimally invasive surgery and 145 (27.15%) by open approach, and 98 (15.51%) high-risk histology, with 71 (72.45%) by laparoscopy and 27 (27.55%) by open surgery, are included. Compared to open surgery, laparoscopy results in lower progression free survival in low-risk patients before and after matching (p = 0.039 and p = 0.033, respectively), but shows no difference in high-risk patients (p = 0.519). Myometrial invasion is associated with lower progression free survival in laparoscopy in low-risk histology (p = 0.027). CONCLUSION: Surgical approaches influence progression free survival in stage IA low-risk histologic diseases, especially in those with myometrial invasion, but not in high-risk histologic endometrial cancer.

Risk factors of additional surgery after non-curative endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: The criteria for surgical intervention after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer are unclear. We aimed to clarify the risk factors for residual cancer and lymph node metastasis after non-curative ESD and to identify recommendations for additional surgery. METHODS: We collected data on 133 consecutive patients who underwent additional surgery after non-curative ESD of early gastric cancer at Nanjing Drum Tower Hospital from January 2013 to July 2022. Univariate and multivariate analyses were performed to seek risk factors of residual cancer and lymph node metastasis. RESULTS: The incidence rates of residual cancer and lymph node metastasis were 13.5% (18/133) and 10.5% (14/133), respectively. There was neither residual tumor nor lymph node metastasis in 104 (78.2%) cases. Multivariate analyses elucidated that horizontal margin was an independent risk factor for local residual cancer, whereas lymphatic infiltration was an independent risk factor for lymph node metastasis. Patients with mixed histological types were more likely to suffer lymph node metastasis and further undergo additional surgery after non-curative ESD than pure histological type. CONCLUSIONS: Additional gastrectomy with lymph node dissection was strongly recommended in patients with lymphatic infiltration after non-curative ESD of early gastric cancer. Patients with mixed histological type have a high propensity for lymph node metastasis and should be treated as a separate subtype.

Prognosis determination of endocervical adenocarcinomas morphologically reclassified as HPV associated or HPV independent.

OBJECTIVE: To evaluate the prognosis of endocervical adenocarcinomas after reclassification according to the morphologic type based on the 2020 World Health Organization Classification. METHODS: A retrospective longitudinal study with cases admitted at the University of Campinas, Brazil, from 2013 to 2020. The sample included 140 cases morphologically reclassified: 100 cases as adenocarcinoma HPV-associated (HPVA), 17 as HPV-independent (HPVI), and 23 non-HPVA/HPVI. Clinic and pathologic variables were evaluated. Analyses were performed by χ2 , Fisher exact, and Mann-Whitney U tests, Kaplan-Meier curves, Log-rank test, and Cox regression. RESULTS: Compared with the HPVA group, advanced stage (FIGO Stage II+) was more frequent in the HPVI group (P = 0.009), which also showed older patients (P = 0.032), and a higher proportion of deaths (P = 0.006). The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005). At the multivariate analysis, the risk of death was 6.7 (95% confidence interval 1.9-23.0) times higher in patients diagnosed in advanced stages. CONCLUSION: HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS. The morphology-based approach of the new WHO classification appears to be prognostically valuable and applicable in lower- and middle-income settings.

Mixed Histologic Type is a Risk Factor for Lymph Node Metastasis in Submucosal Invasive Early Gastric Cancer.

INTRODUCTION: The treatment regimen for early gastric cancer (EGC) with mixed histologic type remains controversial. We aimed to clarify the relationship between mixed histologic type and lymph node metastasis (LNM) in EGC, with emphasis on submucosal invasive EGC. METHODS: We collected data on 730 consecutive EGC patients at Nanjing Drum Tower hospital between June 2010 and May 2019. Risk factors of LNM and overall survival were analyzed to compare the prognostic differences between different histologic types. RESULTS: Mixed-type EGC patients had higher LNM rates than differentiated-type patients (29.2 % versus 10.6 %, P < 0.001), while no significant difference was found between mixed-type and undifferentiated-type EGC patients (29.2% versus 24.0%, P = 0.225). Multivariate analyses identified tumor location (cardiac and bottom versus antrum), larger tumor size, submucosal invasion, histologic differentiation (undifferentiated-type, mixed-type versus differentiated-type), and lymphovascular invasion as independent risk factors for LNM in EGC patients. Subgroup analysis further elucidated that mixed histologic type was associated with LNM in submucosa invasive EGC, but not in mucosa-confined EGC. There was no statistical significance in overall survival and disease-specific survival of submucosal invasive EGC patients who underwent radical gastrectomy with lymphadenectomy between different histologic types (P = 0.151). CONCLUSIONS: Mixed histologic type may be an independent risk factor for LNM in submucosal invasive EGC. Curative resection with lymphadenectomy should be considered the appropriate treatment for submucosal invasive EGC with mixed histologic type.

Evaluation of the role of intraoperative frozen section and magnetic resonance imaging in endometrial cancer.

OBJECTIVE: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. METHODS: This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. RESULTS: Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. CONCLUSION: Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.

Sex-specificity in Surgical Stages of Lung Cancer in Young Adults.

Background: Young Patients with lung cancer represent a distinct subset of patients with this neoplasm. Young International studies show increased lung cancer rates in females, while the incidence in males continues to decline. There is evidence to suggest that this trend recurs in younger patients. We studied the effects of gender differences on the incidence of surgical stages of lung cancer in young adults and its mortality rate. Methods: This study is a retrospective review (2010-2020) of young adults (aged under 45 years) with surgical-stage of lung cancer. We calculated female-to-male differences in incidence rate ratios, tumor characteristics, surgical management, and survival. Cumulative survival curves were generated by the Kaplan-Meier method. Results: We examined 46 men and 24 women, under 45 years. Female patients were diagnosed at earlier stages. The proportion of stage IA disease was significantly higher in women than in men (46% versus 13%, respectively) (p=0.03). Women were more likely never smokers (42% versus 83%, p=0.02). A histologic subtype, females were more likely to have typical carcinoid tumors (13.54% versus 10.21% for males) (p>0.05). The largest histological type in men was adenocarcinoma (25.53% versus 4.16%, p>0.05). All the patients were operated. Three men had neoadjuvant chemotherapy and one was operated on for cerebral oligometastatic before his chest surgery. Adjuvant chemotherapy was given to 7 women and 21 men. Despite the small number of postoperative complications in our study (n= 8, 11.2%), the male sex was significant in predicting this complication (p<0.05). The mortality rate was 1.4%. The 5-year overall survival rates were 84% in men and 87% in women. Conclusion: Our study identified sex differences in the incidence and mortality rates for surgical lung cancers in young adults, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined.

Expression of Programmed Cell Death 1 Ligand 2 in Patients With Thymoma and Thymomatous Myasthenia Gravis.

OBJECTIVES: This study aimed to examine the expression of programmed cell death 1 ligand 2 (PD-L2) in thymoma and thymomatous myasthenia gravis (MG). METHODS: The records of 70 patients with thymoma receiving surgical resection between January 2017 and December 2018 were retrospectively reviewed. Thymoma PD-L2 expression was evaluated by immunohistochemistry staining. Associations between PD-L2 expression and clinicopathologic features were examined. RESULTS: PD-L2 expression was positive in 41 patients (58.6%) and negative in 29 patients (41.4%). Of them, 33 had thymomatous MG. Patients with MG were more likely to be 50 years of age or younger (69.70% vs 35.14%); have more World Health Organization (WHO) type B thymomas (84.85% vs 64.86%); have tumors of smaller size (4.09 ± 2.33 cm vs 6.47 ± 2.42 cm); have positive PD-L2 expression (78.79% vs 40.54%); and have a higher percentage of PD-L2-positive cells, higher PD-L2 expression intensity, and score (all P < .05). Positive PD-L2 expression was associated with more type B thymomas, higher Masaoka-Koga stage, smaller tumor size, ectopic thymus, and MG (all P < .05). Factors significantly associated with MG were age under 50 years, tumor size less than 5 cm, and positive PD-L2 expression (all P < .05). CONCLUSIONS: Thymoma PD-L2 expression is significantly associated with thymomatous MG and WHO histologic types B2 and B3.

The association between serum lipid levels and histological type of breast cancer.

BACKGROUND: Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC. MATERIALS AND METHODS: 220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients' demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance. RESULTS: There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p < 0.05). Patients with PR-negative BC were more likely to have high LDL-c and high LP(a) levels than patients with PR-positive one (p < 0.05). Multivariate logistic regression analysis showed that serum HDL-c (odds ratio (OR): 0.27, 95% confidence interval (CI) 0.10-0.76), LDL-c (OR: 0.19, 95%CI 0.04-0.93) and LP(a) (OR: 0.23,95%CI 0.07-0.80) levels were negatively associated with ER-positive BC, and serum HDL-c and LDL-c levels were significantly negatively associated with PR-positive BC (OR: 0.32, 95%CI 0.12-0.82; OR: 0.14, 95%CI 0.03-0.77). In addition, ER and PR positive BC was negatively associated with serum HDL-c and LDL-c levels (OR = 0.39, 95% CI 0.17-0.91; OR = 0.22, 95% CI 0.06-0.85) after adjusting with confounders. Serum HDL-c level (OR = 0.13, 95% CI 0.02-0.87) was still independently associated with ER and PR positive BC in postmenopausal women. The area under the curves (AUCs) of HDL-c to identify ER-positive BC, PR-positive BC, and ER and PR positive BC were 0.65 (95%CI 0.58-0.73, P < 0.01), 0.62 (95%CI 0.54-0.69, P < 0.01) and 0.64 (95%CI 0.56-0.72, P < 0.01), respectively. CONCLUSIONS: Serum HDL-c and LDL-c levels were related to ER or PR positive BC. Lipid levels may also have acceptable performance in identifying BC histological type.

Association between exposures to radon and γ-ray radiation and histologic type of lung cancer in Eldorado uranium mining and milling workers from Canada.

BACKGROUND: The authors assessed the association between radon decay products (RDP) exposure and histologic types of incident lung cancer in a cohort of 16,752 (91.6% male) Eldorado uranium workers who were first employed from 1932 to 1980 and were followed through 1969-1999. METHODS: Substantially revised identifying information and RDP exposures were obtained on workers from the Port Radium and Beaverlodge uranium mines and from the Port Hope radium and uranium refinery and processing facility in Canada. Poisson regression was conducted using the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VI-type models to estimate the risks of lung cancer by histologic type from RDP exposures and γ-ray doses. RESULTS: Lung cancer incidence was significantly higher in workers compared with the general Canadian male population. Radiation risks of lung cancer for all histologic types (n = 594; 34% squamous cell, 16% small cell, 17% adenocarcinoma) increased with increasing RDP exposure, with no indication of curvature in the dose response (excess relative risk per 100 working level months = 0.61; 95% confidence interval, 0.39-0.91). Radiation risks did not differ by histologic type (p = .144). The best-fitting BEIR VI-type model included adjustments for the significant modifying effects of time since exposure, exposure rate, and attained age. The addition of γ-ray doses to the model with RDP exposures improved the model fit, but the risk estimates remained unchanged. CONCLUSIONS: The first analysis of radiation risks of lung cancer histologic types in the Eldorado cohort supported the use of BEIR VI-type models to predict the future risk of histologic types of lung cancer from past and current RDP exposures. LAY SUMMARY: Lung cancer survival depends strongly on the cell type of lung cancer. The best survival rates are for patients who have the adenocarcinoma type. This study included 16,752 Eldorado uranium workers who were exposed to radon and γ-ray radiation during 1932-1980, were alive in 1969, and were followed for the development of new lung cancer during 1969-1999. One third of all lung cancers were of the squamous cell type, whereas the adenocarcinoma and small cell types accounted for less than 20% each. Radiation risks of lung cancer among men increased significantly with increasing radon exposure for all cell types, with the highest risks estimated for small cell and squamous cell lung cancers.

The Impact of Histological Subtype on Survival Outcome of Patients with Stage IIB-IVA Cervical Cancer Who Received Definitive Radiotherapy.

The impact of histologic subtype on definitive radiotherapy for patients with locally advanced cervical cancer remains unclear. The aim of this retrospective analysis was to assess clinicopathological findings and clinical outcome by histological type in patients with stage IIB-IVA cervical cancer. Ninety-two patients with stage IIB-IVA [International Federation of Gynecology and Obstetrics (FIGO) 2008] cervical cancer, who underwent definitive radiotherapy between 2013 to 2018, were identified as eligible for this study. The clinical information of the eligible patients was obtained from medical records of our hospital. Seventy-eight patients underwent concurrent chemoradiotherapy, and the remaining 14 patients received radiotherapy alone. Of 92 patients, 83 had squamous cell carcinoma (SCC) and 9 had non-SCC histology. Progression-free survival (PFS) rate of patients with non-SCC was significantly worse than of those with SCC (2-year PFS: 62.0% vs. 12.5%, p = 0.0020), but overall survival (OS) rate did not statistically differ between the two subtypes (2-year OS: 82.4% vs. 62.5%, p = 0.2157). Pelvic failure-free (PFF) rate of patients with non-SCC histology was significantly worse than of those with non-SCC (2-year PFF; 88.2% vs. 25.0%, p < 0.0001). In univariate analysis, non-SCC histology was associated with PFS rate, although there was no association with OS rate. In multivariate analysis, non-SCC histology and lymph node metastasis were independent prognostic factors for shorter PFS. In patients with stage IIB-IVA cervical cancer who underwent definitive radiotherapy, patients with non-SCC showed significantly worse PFS rate than those with SCC.

Level of Combined Estrogen and Progesterone Receptor Expression Determines the Eligibility for Adjuvant Endocrine Therapy in Breast Cancer Patients.

Hormone receptor (HR)-positive breast cancer has a heterogeneous pattern according to the level of receptor expression. Patients whose breast cancers express low levels of estrogen receptor (ER) or progesterone receptor (PgR) may be eligible for adjuvant endocrine therapy, but limited data are available to support this notion. We aimed to determine whether HR expression level is related to prognosis. Tumors from 6042 patients with breast cancer were retrospectively analyzed for combined HR levels of ER and PgR. Low expression was defined as ER 1-10% and PgR 1-20%. Four HR groups were identified by combining ER and PgR expression levels. Patients whose tumors expressed high levels of a single receptor showed the worst survival outcomes, and their risk continuously increased even after the 10-year follow-up. Endocrine therapy had a significant benefit for patients whose tumors expressed high HR levels and a favorable tendency for patients with tumors expressing low HR levels. We established the possible benefit of endocrine therapy for patients whose breast tumors expressed low HR levels. Thus, HR level was a prognostic factor and might be a determinant of extended therapy, especially for patients with high expression of a single receptor.

Residential radon and lung cancer characteristics at diagnosis.

PURPOSE: This study sought to ascertain whether there might be an association between radon concentrations and age, gender, histologic type, and tumor stage at diagnosis. MATERIALS AND METHODS: Lung cancer cases from different multicenter case-control studies were analyzed, and clinical data were retrieved from electronic health records and personal interviews. A radon device was placed in all dwellings of participants, and we then tested the existence of an association between residential radon and lung cancer characteristics at diagnosis. RESULTS: Of the total of 829 lung cancer cases included, 56.7% were smokers or ex-smokers. There was no association between indoor radon concentrations and age, gender, histologic type or tumor stage at diagnosis. Median indoor radon concentrations increased with age at diagnosis for men, but not for women. When analyzing participants exposed to more than 1000 Bq/m3, a predominance of small cell lung cancer and a higher presence of advanced stages (IIIB and IV) were observed. CONCLUSIONS: There seems to be no association between radon and age, gender, histologic type or tumor stage at diagnosis. Higher radon exposure is more frequent in the case of small-cell lung cancer.

Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival.

Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.

Histological Aspects and Quantitative Assessment of Ki67 as Prognostic Factors in Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study.

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan-Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients' cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis.

Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein-Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088-0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096-0.194), 0.103 (95% CI: 0.077-0.137), 0.080 (95% CI: 0.061-0.106), and 0.042 (95% CI: 0.016-0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428-0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.

Association between the MUC1 rs4072037 Polymorphism and Risk of Gastric Cancer and Clinical Outcomes.

PURPOSE: Mucin 1 (MUC1) was identified as a gastric cancer (GC) susceptibility gene by genome-wide association studies in Asians and candidate gene studies in Europeans. This study aimed to investigate the association between the MUC1 rs4072037 polymorphism and GC in terms of the Lauren classification and long-term clinical outcomes. MATERIALS AND METHODS: A total of 803 patients with GC and 816 unrelated healthy controls were enrolled in the study. The association between the MUC1 rs4072037 variant and GC histological types and clinical outcomes, including tumor recurrence and prognosis was investigated. RESULTS: The major A allele of rs4072037 was associated with increased GC risk (P<0.05). In subtype analysis, the association was most significant for diffuse-type GC (P<0.05) and in a dominant model (P<0.05), whereas there was no association with intestinal-type GC (P>0.05). Cox proportional hazards analysis revealed the heterozygote AG rs4072037 allele as an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC (P<0.05). but not in intestinal-type GC (P>0.05). CONCLUSIONS: The exonic single nucleotide polymorphism rs4072037 in MUC1 was associated with diffuse-type GC and was an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC.

Risk of lymph node metastasis and prognostic outcome in early gastric cancer patients with mixed histologic type.

BACKGROUND: Whether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type. METHODS: We retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated. RESULTS: Histopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P < 0.01). However, there was no significant difference between mixed type and pure undifferentiated type for LNM (32.4% vs 21.1%, P = 0.139). Multivariate analysis revealed that tumor size >2 cm (odds ratio [OR]: 2.153, 95% confidence interval [CI]: 1.113-4.164, P < 0.05), submucosal invasion (OR: 3.881, 95%CI: 1.832-8.222, P < 0.001), lymphovascular invasion (OR: 8.797, 95% CI: 2.643-29.277, P < 0.001), undifferentiated type (OR: 3.146, 95% CI: 1.352-7.320, P < 0.01), and mixed histologic type (OR: 3.635, 95% CI: 1.272-10.390, P < 0.05) were independent risk factors for LNM in early gastric cancer patients. However, mixed histologic type did not affect the survival outcome of these patients (hazard ratio: 0.629, 95% CI: 0.074-5.311, P > 0.05). CONCLUSION: Mixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients. The decisions regarding endoscopic submucosal dissection for mixed histologic type should be carefully considered.

Factors associated with nodal metastasis in 2-centimeter or less non-small cell lung cancer.

OBJECTIVE: Lymph node involvement is an important determinant of treatment and prognosis in non-small cell lung cancer (NSCLC) and must be determined via surgical lymph node (LN) evaluation. However, lymphadenectomy is associated with multiple significant morbidities. Recent studies have suggested LN evaluation can be foregone in some or all patients with NSCLC ≤2.0 cm. Our objective was to identify whether these patients may be safely spared the morbidity of lymphadenectomy. METHODS: We undertook a retrospective study of patients treated for NSCLC ≤2.0 cm at a single institution from 2005 to 2017. We examined patient, demographic, and tumor variables for associations with LN metastases via univariable and multivariable analyses. RESULTS: In total, 555 patients met our inclusion criteria. Our primary independent variables included tumor size, histology, and histologic subtype. Although tumors ≤1 cm were less likely to have LN metastases than 1.1- to 2-cm tumors (6.8% vs 13.3%), there was no statistically significant difference. Histologic type was not associated with LN status. In an adenocarcinoma subgroup analysis, micropapillary predominant tumors were more likely to have LN metastases. All invasive mucinous adenocarcinomas and minimally invasive adenocarcinomas were N0. CONCLUSIONS: LN evaluation may be unnecessary in patients with minimally invasive adenocarcinoma or invasive mucinous adenocarcinomas ≤2.0 cm. However, this information is rarely available pre- or intraoperatively. Thus, we recommend LN evaluation always be performed when possible, even for subcentimeter NSCLC, unless the histology is absolutely certain. To our knowledge, this is the largest dataset published to study patients with NSCLC ≤2.0 cm.