Does spinopelvic motion change after total hip arthroplasty?

PURPOSE: Spinopelvic motion plays an important role in functional acetabular cup position after total hip arthroplasty (THA). Sacral slope (SS) has been a useful surrogate for spinopelvic motion. The present study aimed to investigate statistical characteristics of spinopelvic motion before and after THA using changes in SS in supine, standing, and sitting positions. METHODS: A total of 76 patients (88 hips) were assessed. To classify spinopelvic mobility, defined as a change in SS from standing to sitting position (ΔSSstand/sit), 10° ≤ ΔSSstand/sit ≤ 30°, ΔSSstand/sit < 10°, and ΔSSstand/sit > 30° were considered normal, stiff, and hypermobile, respectively. RESULTS: Over ± 7° changes in SS between before and one year after THA were observed in 39 (44.3%) hips in the sitting position, 19 (21.6%) hips in the supine position, seven (7.9%) in the standing position. Percentages of hips with stiff spinopelvic mobility (11.4% vs. 22.7%) and hypermobile spinopelvic mobility (23.9% vs. 12.5%) between before THA and one year after THA were significantly different (p = 0.034 and p = 0.016, McNemar's test). At one year after THA, 40.0% (4/10) of hips with stiff spinopelvic mobility and 57.1% (12/21) of hips with hypermobile spinopelvic mobility shifted to normal spinopelvic mobility. CONCLUSIONS: Change in SS between before THA and one year after THA had a high inter-subject variability especially in the sitting position. In addition, there was a distinct shift to normal spinopelvic mobility postoperatively in hips with stiff and hypermobile spinopelvic mobility pre-operatively.

Factors affecting the diagnostic yield of endoscopic transpapillary forceps biopsy in patients with malignant biliary strictures.

BACKGROUND AND AIM: Transpapillary biliary forceps biopsy (TBFB) is a common method to obtain histological evidence for the differential diagnosis of biliary stricture. This study aimed to evaluate the factors associated with a positive cancer diagnosis from TBFB and the number of tissue samples required to increase the diagnostic yield in patients with malignant biliary strictures. METHODS: A total of 376 patients who underwent TBFB for investigation of biliary stricture were included. Factors affecting the diagnostic yield of TBFB were determined using univariate analysis and multivariate logistic regression analyses. RESULTS: Bile duct cancer (odds ratio [OR] = 3.50, P = 0.002), intraductal growing type (OR = 9.01, P = 0.001), and number of tissue samples (n < 5 vs 5 ≤ n < 10, OR = 4.13, P = 0.01; n < 5 vs n ≥ 10, OR = 12.25, P < 0.001; 5 ≤ n < 10 vs n ≥ 10, OR = 2.97, P = 0.046) were significant factors associated with positive results for malignancy. In patients with periductal infiltrating-type bile duct cancer, the number of tissue samples was a significant factor for diagnostic sensitivity (54.3% in the n < 5 group, 83.3% in the 5 ≤ n < 10 group and 98.2% in the n ≥ 10 group) (P < 0.001). CONCLUSIONS: Bile duct cancer, intraductal growing type, and five or more tissue samples were significant predictors of positive TBFB results in patients with malignant biliary stricture. Increasing the number of tissue samples by five or more led to higher sensitivity in bile duct cancer patients with the periductal infiltrating type.

Functional loss of ARID1A is tightly associated with high PD-L1 expression in gastric cancer.

Notwithstanding remarkable treatment success with anti-PD-1 monoclonal antibody, oncogenic mechanism of PD-L1 regulation in gastric cancer (GC) remains poorly understood. We hypothesized that ARID1A might be related to tumor PD-L1 expression in GC. We found that tumor PD-L1 positivity was associated with loss of ARID1A and showed trend toward better survival of patients with various molecular subtypes of GC (experimental set, n = 273). Considering heterogeneous ARID1A expression, we validated this using whole tissue sections (n = 159) and found that loss of ARID1A was correlated with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and PD-L1 positivity. Furthermore, for patients with MSI-H tumors, the degree of PD-L1 expression was significantly higher in ARID1A-deficient tumors. After ARID1A knockdown in GC cell lines, total and membranous PD-L1 protein, and PD-L1 mRNA levels were increased based on Western blot, flow cytometry, and qRT-PCR, respectively. With IFN-γ treatment, PD-L1 expression was significantly increased both in ARID1A-deficient cancer cells and controls, but the increase was not more pronounced in the former. Loss of ARID1A increased PD-L1 via activating AKT signaling, while LY294002 (PI3K inhibitor) decreased PD-L1 levels. Furthermore, we found that 3 MSI-H tumors showing highest expression of PD-L1 had simultaneous KRAS mutation and loss of ARID1A, suggesting a possible synergistic role boosting PD-L1. Our results strongly indicate that loss of ARID1A is tightly associated with high PD-L1 expression in GC. These results would increase our understanding of the oncogenic mechanism of PD-L1 regulation in GC, and also help to find the optimal candidates for immunotherapy.

Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma.

BACKGROUND: Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients. METHODS: This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed. RESULTS: The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. CONCLUSIONS: This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

A prospective randomized trial of EUS-guided tissue acquisition using a 25-gauge core biopsy needle with and without a stylet.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition has become the most effective method of obtaining specimens from a solid lesion adjacent to the gastrointestinal tract. No data exist regarding the use of a stylet in the core biopsy needle during EUS-guided tissue acquisition. The aims of this study were to evaluate the feasibility, safety, and diagnostic yield of a 25-gauge core biopsy needle without (S-) a stylet and to compare its performance with that of a 25-gauge core biopsy needle with (S+) a stylet in patients with solid lesions adjacent to the gastrointestinal tract. METHODS: From November 2013 to January 2016, we performed 114 EUS-guided tissue acquisitions for the diagnosis of solid lesions adjacent to the gastrointestinal tract in a randomized controlled trial. Patients were randomly assigned to the S+ group (n = 57) or the S- group (n = 57). EUS-guided tissue acquisition was performed using a 25-gauge core biopsy needle without an on-site cytopathologist. RESULTS: There were no significant differences in technical success (100 vs. 100%, p = 1.000), the mean number of needle passes (7.0 ± 1.6 vs. 6.8 ± 1.5, p = 0.556), needle malfunction (0 vs. 1.8%, p = 1.000), or complications (1.8 vs. 0%, p = 1.000) between the S+ and S- groups. Both groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (93.0 vs. 91.2%, p = 1.000) and histological diagnostic accuracy (86.0 vs. 87.7%, p = 1.000) for malignancy. The procedure time was significantly shorter in the S- group than in the S+ group (32.4 ± 11.7 vs. 39.7 ± 8.6 min, p < 0.001). CONCLUSIONS: EUS-guided tissue acquisition using a 25-gauge core biopsy needle without a stylet did not decrease the diagnostic yield for malignancy and was associated with a shorter procedure time than that associated with a stylet.

Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma.

BACKGROUND: Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target. METHODS: We conducted DDR1 immunohistochemistry using a tissue microarray of 202 gastric carcinoma specimens. We examined the effect of collagen-induced activation of DDR1 on cell signaling, tumorigenesis, and cell migration in gastric cancer cell lines, and tumor growth in a xenograft animal model of gastric cancer. RESULTS: Our results showed that 50.5% of gastric cancer tissues are positive for DDR1 expression, and positive DDR1 expression was significantly correlated with a poor prognosis (P = 0.015). In a subgroup analysis, DDR1 expression was prognostically meaningful only in patients receiving adjuvant treatment (P = 0.013). We also demonstrated that collagen was able to activate DDR1 and increase the clonogenicity and migration of gastric cancer cells. We observed that a DDR1 inhibitor, 7rh benzamide, suppressed tumor growth in gastric cancer xenografts. CONCLUSIONS: Our findings suggest a key role for DDR1 signaling in mediating the aggressive phenotype of gastric carcinoma. Importantly, inhibition of DDR1 is an attractive strategy for gastric carcinoma therapy.

Prognostic significance of systemic inflammatory response in stage II colorectal cancer.

BACKGROUND: It is considered that stage II colorectal cancers have heterogeneous oncological outcomes. It remains to be determined whether inflammatory markers can predict survival after curative surgery in these patients. The aim of this study was to investigate the prognostic impact of preoperative inflammatory markers after curative surgery in stage II colorectal cancers. METHODS: Two hundred sixty-one patients with stage II colorectal cancers who underwent curative surgery between January 2006 and December 2011 were reviewed. Oncologic outcomes were analyzed with neutrophil count, lymphocyte count, monocyte count, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio. RESULTS: Univariate analysis showed that high NLR (hazard ratio (HR), 3.506; 95% confidence interval [CI], 1.415-8.688; P = 0.007) and low LMR (HR, 2.436; 95% CI, 1.010-5.880; P = 0.048) were associated with worse disease-free survival (DFS), and high NLR (HR, 2.834; 95% CI, 1.419-5.662; P = 0.003) and low LMR (HR, 2.374; 95% CI, 1.188-4.742; P = 0.014) were associated with worse overall survival (OS) in stage II colorectal cancer. Cox multivariate analysis demonstrated that high NLR was independently associated with worse DFS (HR, 3.163; 95% CI, 1.058-9.455; P = 0.004) and OS (HR, 3.018; 95% CI, 1.467-6.207; P = 0.003) in stage II colorectal cancer. CONCLUSION: Among the systemic inflammatory markers, NLR is a strong predictor of worse DFS and OS in stage II colorectal cancer.

Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. BACKGROUND: Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. METHODS: One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. RESULTS: Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P < 0.001), and the presence of perineural invasion (P = 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (P < 0.001) and overall survival (P < 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288; P = 0.001) and overall survival (hazard ratio 2.503; P = 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial-mesenchymal transition, and RNA sequencing results confirmed these findings. CONCLUSIONS: The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.

Prognostic Significance of Lymphocyte Counts in Colon Cancer Patients Treated with FOLFOX Chemotherapy.

PURPOSE: There is increasing interest in immune function in combination with chemotherapy for cancer treatment. However, the effects of chemotherapy on the human immune system remain to be determined. The aim of this study was to investigate the prognostic impact of lymphocyte and neutrophil counts in colon cancer patients who were treated with curative surgery and adjuvant chemotherapy. METHODS: Two hundred thirty-one patients with colon cancers who underwent curative surgery and FOLFOX adjuvant chemotherapy between November 2005 and December 2011 were included. Oncologic outcomes were analyzed with neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR) before and after chemotherapy. RESULTS: The 5-year DFS rate was lower in colon cancer patients with low lymphocyte count during chemotherapy (61.9 vs. 76.7%, P = 0.026). Cox multivariate analysis demonstrated that low lymphocyte count during chemotherapy was independently associated with poor disease-free survival (HR 1.829; 95% CI 1.096-3.050; P = 0.021) in colon cancer patients who underwent FOLFOX adjuvant chemotherapy. CONCLUSION: Lymphocyte count during chemotherapy is a strong predictor of worse disease-free survival in colon cancer patients who have undergone FOLFOX adjuvant chemotherapy.

Plugged percutaneous biopsy of the liver in living-donor liver transplantation recipients suspected to have graft rejection.

Background Percutaneous biopsy is a widely-accepted technique for acquiring histologic samples of the liver. When there is concern for bleeding, plugged percutaneous biopsy (PPB) may be performed, which involves embolization of the biopsy tract. Purpose To evaluate the efficacy and safety of PPB of the liver in patients suspected to have graft rejection after living-donor liver transplantation (LDLT). Material and Methods During January 2007 and December 2013, 51 patients who underwent PPB of the liver under the suspicion of post-LDLT graft rejection were retrospectively analyzed. A total of 73 biopsies were performed. Biopsy was performed with a 17-gauge core needle and 18-gauge cutting needle. The needle tract was embolized using gelatin sponge (n = 44) or N-butyl cyanoacrylate (NBCA) (n = 29). The specimens were reviewed to determine their adequacy for histologic diagnosis. We reviewed all medical records after PPB. Results Specimens were successfully acquired in all procedures (100%). They were adequate for diagnosis in 70 cases (95.9%) and inadequate in three (1.3%). Average of 9.8 complete portal tracts was counted per specimen. One minor complication (1.4%) occurred where the patient had transient fever after the procedure. Conclusion PPB is easy and safe to perform in LDLT recipients and provides high diagnostic yield.

Quantitative Assessment of the Portal Pressure for the Liver Surgery Using Serological Tests.

OBJECTIVE: To establish a reliable equation to predict hepatic venous pressure gradient (HVPG) using serological tests for surgical patients with hepatocellular carcinoma (HCC). BACKGROUND: Accurate assessment of portal pressure for surgical patients with HCC is important for safe hepatic resection (HR). The HVPG is regarded as the most reliable method to detect portal hypertension. However, HVPG is not utilized in many medical centers due to invasiveness of procedure. METHODS: Between 2006 and 2008, 171 patients (Correlation cohort), who underwent liver surgery in a tertiary hospital, were enrolled. Preoperative measurements of the HVPG and serological tests were performed simultaneously. Correlation between the HVPG and serological tests were analyzed to establish an equation for calculated HVPG (cHVPG). Between 2008 and 2013, 510 surgical patients (Application cohort) were evaluated, and HR recommended when cHVPG < 10 mm Hg. The outcomes of HR were analyzed to evaluate reliability of the cHVPG for HR. RESULTS: In the correlation cohort, the equation for cHVPG was established using multivariate linear regression analysis; cHVPG (mm Hg) = 0.209 × [ICG-R15 (%)] - 1.646 × [albumin (g/dL)] - 0.01×[platelet count (10)] + 1.669 × [PT-INR] + 8.911. In the application cohort, 425 patients with cHVPG < 10 mm Hg underwent HR. Among them, 357 had favorable value of ICG-R15 < 20% (group A), and 68 had unfavorable value of ICG-R15 ≥ 20% (group B). There was no significant difference in patient demographics, tumor characteristics, operative outcome, and survival rates between group A and B. CONCLUSIONS: The equation for cHVPG of this study was established on statistical reliability. The cHVPG could be useful to predict portal pressure quantitatively for surgical patients with HCC using serological tests.

Feasibility of mesorectal vascular invasion in predicting early distant metastasis in patients with stage T3 rectal cancer based on rectal MRI.

OBJECTIVES: To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) METHODS: Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis. RESULTS: In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59%, and 89.47%, respectively) were significantly higher than those of LVI (64.86%, and 61.76%), but sensitivity and negative predictive value were not significantly different between MVI (60.71%, and 76.09%) and LVI (75.00%, and 77.42%). CONCLUSIONS: While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI. KEY POINTS: • Mesorectal vascular invasion (MVI) may be a radiologic prognostic factor for rectal cancer. • Specificity of MVI was higher than lymphovascular invasion in predicting early metastasis. • Mesorectal vascular invasion may be a better predictor for early distant metastasis.

Clinical Significance of the Endoscopic Finding in Predicting Complete Tumor Response to Preoperative Chemoradiation Therapy in Rectal Cancer.

BACKGROUND: There are reports that suggest conservative treatment when a tumor shows clinically complete response (CR) after preoperative chemoradiotherapy in rectal cancer. The aim of this study is to investigate the association between endoscopic complete response (E-CR) and pathologic CR (pCR) and to determine the sensitivity and specificity of E-CR and its clinical utility after preoperative chemoradiotherapy in rectal cancer. METHODS: We analyzed prospectively collected data of patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy, between January 2010 and January 2015. RESULTS: Nineteen patients (17.9 %) showed E-CR, and 87 patients showed E-non CR. Twenty-three patients (21.7 %) were confirmed to have pCR. E-CR was closely associated with pCR (p < 0.001). E-CR reflected pCR with an accuracy of 88.7 %, sensitivity of 65.2 %, specificity of 95.2 %, PPV of 78.9 %, NPV of 90.8 %, and a p value of <0.001. CONCLUSIONS: E-CR after preoperative chemoradiotherapy in rectal cancer is significantly associated with pCR. However, a wait and see policy should be performed carefully with current endoscopic prediction for pCR to avoid inadequate treatment in patients who show E-CR after preoperative chemoradiotherapy.

Non-neoplastic pathology results after endoscopic submucosal dissection for gastric epithelial dysplasia or early gastric cancer.

BACKGROUND AND STUDY AIMS: Endoscopists sometimes face paradoxical cases in which the endoscopic submucosal dissection (ESD) specimen reveals a non-neoplastic pathology result. The aims of the study were to determine the reasons for such results, and to compare the endoscopic characteristics of non-neoplastic and conventional neoplastic pathology groups after ESD. PATIENTS AND METHODS: A total of 1186 gastric ESDs performed between February 2005 and December 2011 were retrospectively reviewed. The ESD specimens included 52 (4.4 %) that were confirmed as negative or indefinite for neoplasia. Patient characteristics and endoscopic and pathological data were reviewed and compared. RESULTS: Non-neoplastic pathology after ESD was due to complete removal of the lesion at biopsy in 45 cases (86.5 %), pathology overestimation in 5 (9.6 %), and incorrect localization of the original tumor with subsequent ESD performed at the wrong site in 2 (3.8 %). The mean length and surface area of the non-neoplastic lesions were 9.2 ±â€Š2.6 mm and 49.6 ±â€Š23.6 mm (2), respectively. Mean sampling ratios were 3.0 ±â€Š1.5 mm/fragment and 16.3 ±â€Š10.0 mm(2)/fragment. Compared with 1134 cases confirmed as neoplastic on the final ESD specimen, non-neoplastic cases showed a significantly smaller tumor size and surface area, and lower sampling ratios in a logistic regression analysis adjusted for potential confounders (P < 0.001 for all). CONCLUSIONS: Complete lesion removal by biopsy, pathology overestimation, and incorrect localization of the original tumor with subsequent ESD at the wrong site were the main reasons for non-neoplastic results after ESD. Small tumor size and surface area, and low sampling ratios were associated with non-neoplastic pathology results after ESD.

Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer.

BACKGROUND: Recent studies have demonstrated that acetyl-CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined. METHODS: We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. RESULTS: Among 350 GCs, 219 cases (62.6%) were classified as ACSS2-low, whereas 131 cases (37.4%) were ACSS2-high. Loss of ACSS2 expression (ACSS2-low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1-loss (P = 0.003), and in cases with SIRT3-low (P < 0.001). The ACSS2-low cases showed significantly lower mean disease-free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036). CONCLUSIONS: We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC.

ALDH1 is a prognostic factor for patients treated with neoadjuvant chemoradiotherapy and radical resection for stage III rectal cancer.

BACKGROUND AND OBJECTIVES: The factors relating to changes within a tumor after preoperative chemoradiotherapy associated with rectal cancer prognosis remain to be determined. The aim of this study was to investigate the expression of CD133 and ALDH1 and to analyze the predictive and prognostic roles in patients with rectal cancer after chemoradiotherapy. METHODS: We analyzed the expression levels of ALDH1 and CD133 in patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy between March 2005 and December 2011. RESULTS: The expression of CD133 was not associated with survival. The 5-year overall survival rates were lower in patients with high ALDH1 expression compared to low ALDH1 expression in stage III rectal cancer (61.0% vs. 89.7%, P=0.031). Cox multivariate analysis demonstrated that high ALDH1 expression (HR, 5.425; 95% CI, 1.116-26.373; P=0.036), cT (HR, 12.861; 95% CI, 2.188-75.591; P=0.005), and pN2 (HR, 28.481; 95% CI, 4.757-170.518; P<0.001) were independently associated with overall survival in 51 patients with stage III rectal cancer. CONCLUSIONS: Expression of ALDH1 indicates a more aggressive feature of stage III rectal cancer and can stratify stage III rectal cancer into different survival groups.

Endoscopic ultrasound-guided sampling of solid pancreatic masses: 22-gauge aspiration versus 25-gauge biopsy needles.

BACKGROUND: Biopsy needles have recently been developed to obtain both cytological and histological specimens during endoscopic ultrasound (EUS). We conducted this study to compare 22-gauge (G) fine needle aspiration (FNA) needles, which have been the most frequently used, and new 25G fine needle biopsy (FNB) needles for EUS-guided sampling of solid pancreatic masses. METHODS: We conducted a retrospective cohort study of all EUS-guided sampling performed between June 2010 and October 2013. During the study period, 76 patients with pancreatic masses underwent EUS-guided sampling with a 22G FNA needle (n = 38) or a 25G FNB needle (n = 38) for diagnosis. An on-site cytopathologist was not present during the procedure. Technical success, the number of needle passes, cytological diagnostic accuracy, cytological sample quality (conventional smear and liquid-based preparation), histological diagnostic accuracy, and complications were reviewed and compared. RESULTS: There were no significant differences in technical success (100% for both), the mean number of needle passes (5.05 vs. 5.55, P = 0.132), or complications (0% for both) between the 22G FNA group and the 25G FNB group. The 22G FNA and 25G FNB groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (97.4% vs. 89.5%, P = 0.358) and histological diagnostic accuracy (34.2% vs. 52.6%, P = 0.105). In the cytological sample quality analysis, the 25G FNB group exhibited higher scores for the amount of diagnostic cellular material present (22G FNA: 0.92 vs. 25G FNB: 1.32, P = 0.030) and the retention of appropriate architecture (22G FNA: 0.97 vs. 25G FNB: 1.42, P = 0.010) in the liquid-based preparation. The 25G FNB group showed a better histological diagnostic yield for specific tumor discrimination compared with the 22G FNA group (60 % vs. 32.4%, P = 0.018). CONCLUSIONS: Use of the 25G FNB needle was technically feasible, safe, efficient, and comparable to use of the standard 22G FNA needle in patients with solid pancreatic masses in the absence of an on-site cytopathologist. The cytological sample quality in the liquid-based preparation and the histological diagnostic yield for specific tumor discrimination of EUS-guided sampling using a 25G FNB needle were significantly higher than those using a 22G FNA needle.

Dichloroacetate attenuates hypoxia-induced resistance to 5-fluorouracil in gastric cancer through the regulation of glucose metabolism.

In this study, we investigated whether gastric cancer with hypoxia-induced resistance to 5-fluorouracil (5-FU) could be re-sensitized following treatment with low-dose dichloroacetate (DCA), an inhibitor of the glycolytic pathway. The expression profiles of hypoxia-inducible factor-1α (HIF-1α) and pyruvate dehydrogenase kinase-1 (PDK-1) were analyzed in tissues from 10 patients with gastric cancer who had different responses to adjuvant 5-FU treatment. For the in vitro assays, cell viability and apoptosis were evaluated with and without treatment with 20mM DCA in the AGS and MKN45 cell lines, as well as in PDK1 knockdown cell lines. The expression levels of HIF-1α and PDK-1 were both elevated in the tumor tissues relative to the normal gastric tissues of most patients who showed recurrence after adjuvant 5-FU treatment. Cellular viability tests showed that these cell lines had a lower sensitivity to 5-FU under hypoxic conditions compared to normoxic conditions. Moreover, the addition of 20mM DCA only increased the sensitivity of these cells to 5-FU under hypoxic conditions, and the resistance to 5-FU under hypoxia was also attenuated in PDK1 knockdown cell lines. In conclusion, DCA treatment was able to re-sensitize gastric cancer cells with hypoxia-induced resistance to 5-FU through the alteration of glucose metabolism.

Comparison of Ultrasound-Guided Core Needle Biopsy and Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Solid Pancreatic Lesions.

OBJECTIVES: The objective of our study was to compare the diagnostic yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) using a 25-gauge needle and ultrasound (US)-guided core needle biopsy (CNB) using an 18-gauge core needle for diagnosis of solid pancreatic lesions. METHODS: This retrospective study was approved by our Institutional Review Board, and the requirement for informed consent was waived. Patients who underwent either EUS-guided FNA or US-guided CNB for a solid pancreatic lesion from January 2008 to December 2012 were included and reviewed. Fine-needle aspirations and CNBs were performed by experienced endoscopists and radiologists. The diagnostic yield, accuracy, technical failure rate, sensitivity, and specificity for malignancy were calculated and compared. RESULTS: A total of 106 biopsy attempts were undertaken in 89 patients (EUS-guided FNA, n = 70; US-guided CNB, n = 36). Biopsy specimens were successfully obtained in 98 biopsy attempts (EUS-guided FNA, n = 63; US-guided CNB, n = 35). The accuracy, technical failure rate, sensitivity, and specificity of EUS-guided FNA for malignancy (73.02%, 10.00%, 77.78%, and 44.44%, respectively) was not significantly different from those of US-guided CNB (88.57%, 2.78%, 87.10%, and 100%, respectively; P ≥ .089). Diagnostic performance did not differ between the modalities according to the size and the location of the lesion in the pancreas. However, the diagnostic yield of US-guided CNB (86.11%) was higher than that of EUS-guided FNA (65.71%, P = .035). CONCLUSIONS: The diagnostic yield of US-guided CNB for solid pancreatic lesions is superior to that of EUS-guided FNA.

Pretreatment selection of regimen according to genetic analysis improves the efficacy of chemotherapy in the first line treatment of metastatic colorectal cancer.

BACKGROUND AND OBJECTIVES: Metastatic colon cancer patients are treated with the chemotherapy regimens, FOLFOX and FOLFIRI, in either order. So far, we cannot predict the response of chemotherapeutic agent, so it is necessary to find which regimen is adequate before starting chemotherapy. METHODS: Enrolled patients are randomized into either conventional treatment or planned treatment preceded by pretreatment genetic analysis. Blood samples of patients in planned treatment group (N = 53) were analyzed for the genetic polymorphism before selection of chemotherapeutic agents. Target genes were XPD-751, GSTP-1-105, XRCC1-399 for oxaliplatin, UGT1A1 for irinotecan. The response was measured by computed tomographic scan after completion of three cycles of chemotherapy. RESULTS: Overall response rate was significantly higher in planned group (67.9% vs. 46.3%, P = 0.020). In FOLFOX group, response rate was significantly improved in the planned patients(77.1% vs. 50%, P = 0.018). In FOLFIRI group, the difference didn't reach statistical significance (50% vs. 42.5%, P = 0.776). CONCLUSIONS: We found significantly improved response rates in the chemotherapy of metastatic colon cancer by pretreatment genetic analysis, especially in FOLFOX group.