Accuracy of preoperative T2 gallbladder tumor localization and the adequate surgical resection.

INTRODUCTION: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations. METHODS: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes. RESULTS: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS. CONCLUSION: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location.

Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.

Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.

We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

MRI features and texture analysis for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy and tumor recurrence of locally advanced rectal cancer.

OBJECTIVES: This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). METHODS: Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. RESULTS: In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). CONCLUSIONS: Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. KEY POINTS: • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.

Expression patterns of programmed death-1 and programmed death-1 ligand-1 on T cells in gastric cancer.

The aim of the present study was to evaluate programmed death-1 (PD-1) and programmed death-1 ligand-1 (PD-L1) expression in gastric carcinoma and to assess their effect on survival rate. A total of 170 surgically resected specimens were obtained from patients diagnosed with gastric carcinoma at St. Vincents Hospital, The Catholic University of Korea. Paraffin tissue sections from tissue microarray blocks were subjected to immunohistochemical analysis of PD-1 and PD-L1. In addition, PD-1 expression on CD4+ and CD8+ T cells isolated from peripheral blood mononuclear cells and gastric cancer tissues was evaluated by multicolor flow cytometry. PD-1 and PD-L1 were expressed in 30.0 and 60.5% of the gastric cancer tissues, respectively. The expression of PD-L1 was higher in patients with advanced T (P=0.035) and Tumor, Node and Metastasis stage (P=0.05). The patients with positive PD-L1 expression had shorter disease-free survival time than those without PD-L1 expression (P=0.005). Additionally, PD-L1 expression was significantly associated with poor prognosis (P=0.015). PD-1 and PD-L1 expression levels were significantly higher on CD8+ T cells than on CD4+ T cells (P<0.001). The data of the present study suggested that PD-L1 expression may be an independent indicator of poor prognosis in patients with gastric cancer. Furthermore, PD-L1 expression may play a role in immune evasion of gastric cancer.

Significance of perineural and lymphovascular invasion in locally advanced rectal cancer treated by preoperative chemoradiotherapy and radical surgery: Can perineural invasion be an indication of adjuvant chemotherapy?

PURPOSE: To investigate the prognostic significance of lymphovascular space invasion (LVI) and perineural invasion (PNI) in rectal cancer. METHODS AND MATERIALS: Clinical data of 1,232 stage II-III rectal cancer patients from six tertiary institutions were analyzed. All patients were treated by long-course preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME). Adjuvant systemic chemotherapy was performed for 962 (78.1%) patients according to the multidisciplinary team's decision. Treatment outcomes and prognostic factors were evaluated according to the lymphovascular invasion (LVI) and perineural invasion (PNI) status. RESULTS: Five-year overall survival (OS) and recurrence-free survival (RFS) rates of the entire cohort were 84.1% and 71.1%, respectively. There is a significant difference in 5-year OS among both-absent, LVI+ only, PNI+ only, and both-present groups (89.1% vs. 77.9% vs. 67.6% vs. 56.2%; p < 0.001). RFS at five years was significantly different among both-absent, LVI+ only, PNI+ only, and both-present groups (78.7% vs. 58.7% vs. 44.6% vs. 38.6%; p < 0.001). The 5-year distant failure-free survival (DFFS) rate was also significantly different among four groups (84.6% vs. 61.4% vs. 54.2% vs 48.6%; p < 0.001). Although adjuvant chemotherapy did not affect 5-year DFFS in the entire cohort, adjuvant chemotherapy significantly reduced the distant failure rate in patients with PNI+ patients (44.9% vs. 54.6%, p = 0.048), not LVI+ patients (65.0% vs. 56.1%, p = 0.487). CONCLUSION: Compared to LVI, PNI is a more significant prognostic factor in stage II-III rectal patients treated by preoperative CRT and TME surgery. The status of PNI rather than LVI could be an indicator for identifying patients who could benefit from adjuvant systemic chemotherapy.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer.

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer.

Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768-5.885 for DSS and HR 1.824, 95% CI 1.824-6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102-4.777) and with luminal subtype (HR 4.039, 95% CI 1.905-8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer.

Application of adipocyte-related antibodies in undifferentiated sarcomas to identify dedifferentiated liposarcomas based on histological and clinical analysis.

BACKGROUND: Due to morphologic similarities between undifferentiated sarcoma (US) and dedifferentiated liposarcoma (DDLPS), some portions of US could be identified as DDLPS. In this study, we applied adipocyte-related antibodies in order to discriminate possible cases of DDLPS from US. MATERIALS AND METHODS: A total of 46 cases, previously diagnosed as US, were examined. Immunohistochemistry for MDM2, CDK4, calreticulin, FABP4, and stathmin were performed. Histological findings were reviewed and clinical data was analyzed retrospectively. RESULTS: MDM2, CDK4, calreticulin, FABP4, and stathmin were positive in 17 (37.0%), 14 (30.4%), 3 (6.5%), 1 (2.2%), and 12 (26.1%) of the total 46 cases, respectively. MDM2/CDK4 positive cases showed more frequent positivity for calreticulin/FABP4/stathmin. Survival analysis, based on staining pattern, revealed a significantly better survival in the group where either MDM2 and CDK4 were positive and at least one of calreticulin, FABP4, or stathmin staining were positive. CONCLUSIONS: We conclude that when either MDM2-positive or CDK4-positive cases show any other positive results for calreticulin, FABP4, or stathmin, they have a significantly better survival and the possibility of DDLPS should be considered. Additional use of calreticulin, FABP4, or stathmin immunohistochemistry helps us to narrow the pool for further studies such as molecular analysis for a definite diagnosis.

Florid cystic endosalpingiosis associated with a retroperitoneal leiomyoma mimicking malignancy: a case report.

Florid cystic endosalpingiosis (FCE) is a rare type of endosalpingiosis that presents as a mass-like lesion. Here we report an unusual case of FCE associated with a retroperitoneal leiomyoma. A 46-year old female presented with a palpable abdominal mass. A pelvic CT revealed a 23.5×16.3×9.4 cm sized multilocular cystic and solid mass in the retroperitoneum. Surgical excision of the mass was performed. Microscopically, the cystic spaces were lined by a single layer of ciliated tubal epithelium. The solid areas consisted of thick bundles of spindle cells. There were no cytologic atypia, mitosis or necrosis. The spindle cells were positive for actin and desmin, and were negative for c-kit, CD34, S100 and HMB-45, confirming the diagnosis of FCE associated with retroperitoneal leiomyoma.

Laparoscopic Gastrectomy Followed by Chemotherapy for Advanced Gastric Cancer Diagnosed During Pregnancy: A Case Report.

BACKGROUND: Gastric cancer in pregnant women is rare. When physicians encounter a patient with pregnancy-associated gastric cancer, it is important to take a multidisciplinary approach and respect the will of the patient. We herein describe a case of gastric cancer during pregnancy. CASE REPORT: A 36-year-old woman at 18 weeks of gestation was diagnosed with advanced gastric cancer. She underwent totally laparoscopic distal gastrectomy at 23 weeks of gestation and four cycles of FOLFOX6 without any severe toxicity. At 36 weeks of gestation, a healthy baby was born. After delivery, the patient was treated with additional chemotherapy. She has finished chemotherapy and has been followed-up without recurrence for 1 year after operation. CONCLUSION: Laparoscopic gastrectomy followed by chemotherapy for gastric cancer during pregnancy might be a safe option.

Long interspersed nuclear element (LINE)-1 methylation level as a molecular marker of early gastric cancer.

BACKGROUND/AIMS: This study was performed to examine the state of long interspersed nuclear element (LINE)-1 methylation level in gastric epithelial dysplasias (GEDs) and evaluate as a molecular marker for gastric carcinogenesis when it was compared with RUNX3 expression. METHODS: We examined 89 patients with GEDs subcategorized by the Vienna classification - 41 category 3 (low grade) and 48 category 4 (high grade/intramucosal carcinoma) lesion. All tissue samples were evaluated for RUNX3 immunohistochemical staining and the level of LINE-1 methylation. RESULTS: The rate of negative expression of RUNX3 in category 4 lesion was significant higher than category 3 (P<0.01). LINE-1 methylation level was statistically different between category 3 and category 4 lesion (P<0.01). Between positive and negative expression of RUNX3 in GEDs, there was a significant difference of LINE-1 methylation level (P<0.01). The area under the ROC curve (AUC) of LINE-1 methylation level for diagnosis of category 4 lesion was 0.88 (95% CI, 0.76-1.00). CONCLUSIONS: LINE-1 methylation level was well correlated with the Vienna classification of GED and it had a close relationship with the negative expression of RUNX3 in category 4 lesion. LINE-1 methylation level could be a good candidate for a molecular marker of early gastric cancer.

Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer.

Accurate prediction of regional lymph node metastasis (LNM) in endoscopically resected T1-stage colorectal cancers (CRCs) can reduce unnecessary surgeries. To identify miRNA markers that can predict LNM in T1-stage CRCs, the study was conducted in two phases; (I) miRNA classifier construction by miRNA-array and quantitative reverse transcription PCR (qRT-PCR) using 36 T1-stage CRC samples; (II) miRNA classifier validation in an independent set of 20 T1-stage CRC samples. The expression of potential downstream target genes of miRNAs was assessed by immunohistochemistry. In the discovery analysis by miRNA microarray, expression of 66 miRNAs were significantly different between LNM-positive and negative CRCs. After qRT-PCR validation, 11 miRNAs were consistently significant in the combined classifier construction set. Among them, miR-342-3p was the most significant one (P=4.3×10-4). Through logistic regression analysis, we developed a three-miRNA classifier (miR-342-3p, miR-361-3p, and miR-3621) for predicting LNM in T1-stage CRCs, yielding the area under the curve of 0.947 (94% sensitivity, 85% specificity and 89% accuracy). The discriminative ability of this system was consistently reliable in the independent validation set (83% sensitivity, 64% specificity and 70% of accuracy). Of the potential downstream targets of the three-miRNAs, expressions of E2F1, RAP2B, and AKT1 were significantly associated with LNM. In conclusion, this classifier can predict LNM more accurately than conventional pathologic criteria and our study results may be helpful to avoid unnecessary bowel surgery after endoscopic resection in early CRC.

Role of autophagy-related protein expression in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Autophagy, a cellular degradation process, has complex roles in tumourigenesis and resistance to cancer treatment in humans. The aim of this study was to explore the expression levels of autophagy-related proteins in patients with rectal cancer and evaluate their clinical role in the neoadjuvant chemoradiotherapy setting. METHODS: All specimens evaluated were obtained from 101 patients with colorectal cancer who had undergone neoadjuvant chemoradiotherapy and curative surgery. The primary outcomes measured were the expression levels of two autophagy-related proteins (microtubule-associated protein 1 light chain 3 beta (LC3ß) and beclin-1) by immunohistochemistry and their association with clinicopathological parameters and patient survival. RESULTS: Among the 101 patients, the frequency of high expression of beclin-1 was 31.7% (32/101) and that of LC3ß was 46.5% (47/101). A pathologic complete response was inversely associated with LC3ß expression (P = 0.003) and alterations in the expression of autophagy-related proteins (P = 0.046). In the multivariate analysis, however, autophagy-related protein expression did not show prognostic significance for relapse-free survival or overall survival. CONCLUSIONS: High expression of autophagy-related proteins shows a strong negative association with the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer. Autophagy has clear implications as a therapeutic target with which to improve the efficacy of neoadjuvant chemoradiotherapy.

Correlation between Histological Activity and Endoscopic, Clinical, and Serologic Activities in Patients with Ulcerative Colitis.

Objectives. Recent studies suggest that histological healing is a treatment goal in ulcerative colitis (UC). We aimed to evaluate the correlation between histological activity and clinical, endoscopic, and serologic activities in patients with UC. Methods. We retrospectively reviewed medical records from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsies. The Mayo endoscopic subscore was used to assess endoscopic activity. Biopsy specimens were reviewed by two blinded pathologists and scored using the Geboes scoring system. Results. We analyzed 154 biopsy specimens from 82 patients with UC. Histological scores exhibited strong correlation with endoscopic subscores (Spearman's rank correlation coefficient r = 0.774, p < 0.001) and moderate correlation with C-reactive protein levels (r = 0.422, p < 0.001) and partial Mayo scores (r = 0.403, p < 0.001). Active histological inflammation (Geboes score ≥ 3.1) was observed in 6% (2 of 33) of the endoscopically normal mucosa samples, 66% (19 of 29) of mild disease samples, and 98% (90 of 92) of moderate-to-severe disease samples. Conclusions. Histological activity was closely correlated with the endoscopic, clinical, and serologic UC activities. However, several patients with mild or normal endoscopic findings exhibited histological evidence of inflammation. Therefore, histological assessment may be helpful in evaluating treatment outcomes and determining follow-up strategies.

Evaluation of treatment response and tissue necrosis as prognostic indicators following neoadjuvant chemoradiotherapy in rectal cancer patients.

BACKGROUND/AIMS: The objective of this study was to assess the prognostic roles of treatment response and tissue necrosis after chemoradiotherapy (CRT) in locally advanced rectal cancer. METHODS: A total of 243 patients with locally advanced rectal cancer who underwent neoadjuvant CRT were included. Three treatment response groups were classified by their pathological stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified based on tissue pathological results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). RESULTS: Overall survival (OS) and recurrence-free survival (RFS) rate at three years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR groups were 83.7%, 75.9%, and 69.7%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p < 0.001). The 3-year OS rates of the CNR, INR, and PNR groups were 83.7%, 80.6%, and 61.8%, respectively (p < 0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p < 0.001). When compared to CTR/CNR, PTR/PNR was strongly related to an increased risk of recurrence (hazard ratio [HR], 5.53; 95% confidence interval [CI], 2.01 to 15.23 vs. HR, 6.37; 95% CI, 2.29 to 17.74, respectively) in univariate Cox regression. Both PTR and PNR were strongly associated with shorter RFS and OS when compared with CTR and CNR in the multivariate Cox regression. CONCLUSIONS: Tissue necrosis is an equally important prognostic marker as treatment response for oncologic outcomes in locally advanced rectal cancer.

HMGA1/HMGA2 protein expression and prognostic implications in gastric cancer.

BACKGROUND: The high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of multiple malignant tumors, including gastric cancer. The aim of this study was to explore the roles of HMGA1 and HMGA2 in gastric carcinogenesis. METHODS: The expression of HMGA1 and HMGA2 was examined in 110 gastric adenocarcinomas, 29 gastric adenomas, and 30 normal controls. The results were correlated with the clinicopathological parameters of the tumors and patient outcome. RESULTS: The levels of HMGA1 and HMGA2 proteins were significantly increased in gastric cancer samples compared with adenoma and normal gastric tissues. High HMGA1 nuclear immunoreactivity was not correlated with clinicopathological features; however, high levels of HMGA2 protein were significantly associated with T stage, N stage, lymphatic invasion, perineural invasion, and TNM stage. Moreover, HMGA2 expression was significantly associated with shorter recurrence free survival. Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for tumor recurrence. CONCLUSIONS: Our results suggest that HMGA1 and HMGA2 are implicated in gastric carcinogenesis and may play a role in tumor progression towards a more malignant phenotype. The HMGA2 protein may be a useful prognostic marker for predicting tumor recurrence.

Clinicopathological significance of N-cadherin and VEGF in advanced gastric cancer brain metastasis and the effects of metformin in preclinical models.

Gastric cancer is the second most common cause of cancer-related death worldwide. Although brain metastasis is a rare complication of gastric cancer, no standard therapy for gastric cancer brain metastasis has been established. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate such markers. A case-control study of patients newly diagnosed with gastric cancer who had developed brain metastasis during follow-up, was conducted. These patients were compared with patients who had advanced gastric cancer but no evidence of brain metastasis. Immunohistochemistry was used to analyze the expression of E-cadherin, N-cadherin, MSS1, claudin-3, claudin-4, Glut1, clusterin, ITGB4, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and p53. The expression of VEGF tended to be higher in the case group (33.3 vs. 0%, p=0.055). Median survival was significantly correlated with vascular invasion (12 vs. 33 months, p=0.008) and N-cadherin expression (36 vs. 12 months, p=0.027). We also investigated the effects of metformin in tumor-bearing mouse models. VEGF expression was decreased and E-cadherin increased in the metformin­treated group when compared with the control group. The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group. Brain metastasis of advanced gastric cancer was associated with the expression of VEGF. Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition.

Intramural florid cystic endosalpingiosis of the uterus: a case report and review of the literature.

OBJECTIVE: We report a case of intramural florid cystic endosalpingiosis in the lower uterine segment of the uterus. CASE REPORT: A 43-year-old female presented with vaginal bleeding. Abdominal computed tomography suggested a leiomyoma with cystic degeneration. A total hysterectomy revealed a 4.0 cm × 3.8 cm cystic mass in the lower uterine segment. The cystic space microscopically was lined with a single layer or stratified layer of ciliated columnar cells that resembled tubal epithelium without cytologic atypia. The glandular spaces were surrounded by normal myometrium with no evidence of periglandular endometrial stroma, which was consistent with the diagnosis of florid cystic endosalpingiosis. CONCLUSION: Florid cystic endosalpingiosis involving the uterus is a rare and clinically unexpected finding; however, it should be considered in the differential diagnosis of a uterine mass.