Effects of traction methods in inexperienced endoscopists during colorectal endoscopic submucosal dissection.

BACKGROUND: colorectal endoscopic submucosal dissection (ESD) remains a technical challenge, but traction devices show promise in making this procedure easier. However, the efficacy of traction techniques for colorectal ESD is still unknown for inexperienced endoscopists. METHODS: We selected 400 patients who underwent colorectal ESD performed by four inexperienced endoscopists. Each patient in the traction-assisted ESD (TA-ESD) group was matched to a patient in the conventional ESD (C-ESD) group according to propensity scores. RESULTS: One-to-one propensity score-matching analysis created 87 matched pairs. The self-completion rate in the TA-ESD group is significantly higher than that in the C-ESD group (100% [87/87] vs. 92% [80/87], p < 0.001). The median resection speed was significantly faster in the TA-ESD group than that in the C-ESD group (27 mm2/min [IQR, 19.5-47.3] vs.18 mm2/min [IQR, 13.5-33.8], p < 0.001) and the procedure time in the TA-ESD group was significantly shorter than that in the C-ESD group (33 min [IQR, 27-47] vs.53 min [IQR, 38-73], p < 0.001). However, the histologic complete resection rate was not significantly different between the TA-ESD and C-ESD groups (93.1% [6/87]) vs. 96.6% [3/87], p < 0.1888, respectively). The en bloc resection rate (96.6%) and perforation rate (4.6%) were equivalent between the TA-ESD group and the C-ESD group. CONCLUSION: Traction techniques seem to improve resection speed and self-completion rate of colorectal ESD for inexperienced endoscopists.

Conventional versus hybrid knife endoscopic submucosal dissection in large colorectal laterally spreading tumors: A propensity score analysis.

Background: Colorectal endoscopic submucosal dissection (CR-ESD) has become a promising treatment for laterally spreading tumors (LSTs), but is accompanied by great challenges. .: This study aimed to evaluate the efficacy and safety of CR-ESD with a hybrid knife, versus the conventional technique for LSTs ≥30 mm in diameter, and analyze the risk factors for piecemeal resection and perforation. Methods: Patients eligible for CR-ESD were divided into two groups according to the use of the hybrid knife (HK group) or the use of the conventional technique, with an interchange of injection and hook knife (C-group). We performed propensity score matching (PSM) to compare the HK group and the C-group. Risk predictors for perforation and piecemeal resection were identified. Results: PSM identified 61 (132 patients) and 61 (129 patients) patients in the C-group and the HK group, respectively. Resection speed was significantly faster in the HK group than in the C-group (18.86 vs. 13.33 mm2/min, P < 0.001). The rate of knife exchange was significantly lower in the HK group than in the C-group (1.6% vs. 49.2%, P < 0.001). Multivariate analysis revealed that unfavorable locations, including the splenic flexure, hepatic flexure, or cecum, were predictive of piecemeal resection. The presence of severe fibrosis and a semilunar fold were independent risk factors for perforation. Conclusions: : The use of a hybrid knife appears to increase CR-ESD resection speed. The indicators for piecemeal resection or perforation in CR-ESD identified herein might help to assess the technical difficulties of CR-ESD.

Two-step artificial intelligence system for endoscopic gastric biopsy improves the diagnostic accuracy of pathologists.

Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS). Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance. Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00). Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.

RREB1 promotes the development of parafollicular carcinogenesis through the Ras-Raf-1-ELK3 signaling pathway.

Thyroid cancer (TC) is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) is derived from parathyroid follicle cells (C cells) secrete calcitonin, accounting for approximately 5-10% of all thyroid cancers. The malignancy is between differentiated and undifferentiated thyroid cancer and undifferentiated thyroid cancer and has a relatively poor prognosis. In MTC tumor cells, RREB1 regulates the differentiation of parathyroid cells via RAS-Raf-1-ELK3 signaling and induce calcitonin secretion. Therefore, it is easy to induce parathyroid parafollicular cells canceration and medullary thyroid carcinoma. Here, we investigated the correlation between RREB1, RAS-Raf-1-ELK3 signaling pathway and medullary thyroid carcinoma with various phases. Our results suggest that RREB1 promotes parafollicular carcinoma through the Ras-Raf1-elk3 signaling pathway, providing a rationale to further investigate the role of RREB1 in parafollicular carcinoma. It provides theoretical guidance for the clinical treatment of medullary thyroid cancer.

Endoscopic resection of large subepithelial esophageal lesions via submucosal tunneling endoscopic resection and endoscopic submucosal dissection: a single-center, retrospective cohort study.

BACKGROUND: This study aimed to compare the clinical outcomes between submucosal tunneling endoscopic resection (STER) and endoscopic submucosal dissection (ESD) for large subepithelial esophageal lesions (SELs) and analyze risk factors for perforation and piecemeal resection. METHODS: The clinicopathological features and outcomes of endoscopic treatment of 56 patients with SELs with diameters ≥30 mm, diagnosed between June 2017 and December 2020, were reviewed in this retrospective cohort study. Patients were divided into two groups (ESD group and STER group). RESULTS: The complete resection rates of the STER and ESD groups were 88.1% and 78.6%, respectively (p = .398). The operation time of STER was longer than ESD (p = .03), while the hospital stay of STER was shorter than ESD (p = .02). The rate of major adverse events associated with ESD was considerably higher than STER group (p = .035). The extraluminal growth pattern was a risk factor for piecemeal resection, and ESD was an independent risk factor for perforation. Regarding tumors with extraluminal growth patterns, the ESD group's perforation rate was significantly higher than the STER group (p = .009). There were no recurrence or metastases found during a mean follow-up of 24.4 months. CONCLUSION: The STER technique has advantages of shorter hospital stays and fewer major adverse events than ESD. The extraluminal growth pattern seems to be a risk factor for piecemeal resection in both ESD and STER. STER appears to be a preferable choice for large SELs with extraluminal growth patterns.

The correlation between the expression of ATF4 and procalcitonin combined with the detection of RET mutation and the pathological stage and clinical prognosis of medullary thyroid carcinoma.

To explore the correlation between the activating transcription factor 4 (ATF4) and procalcitonin (PCT) expressions combined with RET mutation and the pathological staging and clinical prognosis of sporadic medullary thyroid carcinoma (SMTC). Fifty cases (tumor tissue) of SMTC diagnosed by clinicopathology were collected and the patients with nodular goiter were selected as normal control. The RET mutation site was analyzed by detection kit and expressions of PCT and ATF4 in SMTC were analyzed by Western blot and immunohistochemistry. Multiple linear regression was used to analyze the correlation of risk factors (PCT or ATF4 expression, RET mutation, tumor differentiation, SMTC stage, lymphatic metastasis) for 5-year recurrence and survival of SMTC. The ATF4 and PCT expressions were significantly decreased and increased, respectively, with the increase of the SMTC stage. The most frequent mutation of RET gene in cancer tissue was M 22458A in exon 16. The ATF4 and PCT expressions, as well as RET mutation, were significantly associated with a 5-year recurrence, while the ATF4 expression was significantly related to better 5-year survival. ATF4 and PCT expressions combined with RET mutation are related to the clinical prognosis of SMTC and can predict SMTC staging.

Minimally invasive management of large duodenal lipoma: endoscopic submucosal dissection.

OBJECTIVE: This study was performed to compare the clinical outcomes of large duodenal lipomas (DLs) of ≥2 cm between endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR). METHODS: This retrospective study included patients who underwent endoscopic resection of large DLs from June 2017 to March 2021 at our hospital. Clinicopathologic features, clinical outcomes, and follow-up endoscopy findings were retrospectively reviewed. RESULTS: Twenty-three patients (12 men) with a mean age of 57.4 years were included. The median tumor size was 28.4 ± 13.3 mm. ESD was performed in 19 patients, and EFTR was performed in 4. Complete resection was achieved in 21 patients. The operative time and postoperative hospital stay were significantly shorter in the ESD than EFTR group. Four patients in the EFTR group developed a fever; no other adverse events occurred. No patients required surgical intervention. During the average follow-up of 21.1 months, no residual tumor, recurrence, or metastasis was observed. CONCLUSION: Both ESD and EFTR provide minimally invasive, localized treatment of selected DLs. ESD might have some advantages in resecting large DLs in terms of procedure time and hospitalization.

LINC00355 triggers malignant progression of hepatocellular carcinoma via the sponge effect on miR-217-5p with the involvement of the Wnt/ß-catenin signaling.

PURPOSE: To uncover the biological role of LINC00355 in regulating the proliferative and apoptotic potentials in hepatocellular carcinoma (HCC), and the underlying mechanism. METHODS: LINC00355 levels in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of LINC00355 or miR-217-5p in Hub7 and Hep3B cells, proliferative and apoptotic potentials were assessed by cell counting kit-8 (CCK-8), colony formation assay and flow cytometry. The interaction between LINC00355 and miR-217-5p was determined by dual-luciferase reporter assay and Pearson correlation test. Western blot analysis was conducted to illustrate the regulatory effects of LINC00355 and miR-217-5p on the Wnt/ß-catenin signaling. RESULTS: LINC00355 was upregulated in HCC tissues and cell lines. Knockdown of LINC00355 reduced viability in Hub7 and Hep3B cells, which was much pronounced on days 3 and 4. Clonality was attenuated by transfection of shLINC00355 as well. In addition, apoptosis rate increased by knockdown of LINC00355 in HCC cells. Protein levels of ß-catenin, GSK3ß, c-myc and cyclin D1 were downregulated in Hub7 and Hep3B cells transfected with shLINC00355. MiR-217-5p was the target gene binding LINC00355. It displayed exactly opposite regulations on HCC cell phenotypes and protein levels of vital genes in the Wnt/ß-catenin signaling to those of LINC00355. CONCLUSIONS: LINC00355 is upregulated in HCC specimens, LINC00355 triggers proliferative rate and inhibits apoptosis in HCC cells by negatively regulating miR-217-5p and activating the Wnt/ß-catenin signaling.

TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer.

KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer cells. However, whether TFCP2 plays an important role in pancreatic cancer cell senescence is not clear. In this study, we found upregulation of TFCP2 expression in pancreatic cancer was associated with KRAS mutation. Overexpression of TFCP2 inhibited cell senescence. Knockdown of TFCP2 promoted cell senescence. Mechanistically, the interaction between TFCP2 and SREBP2 (sterol regulatory element binding transcription factor 2) synergistically activated the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis, and statins could reverse the inhibitory effect of TFCP2 on senescence. In conclusion, our study reveals a new mechanism underlying the TFCP2 regulation of pancreatic cancer cell senescence, providing a new target for the treatment of pancreatic cancer.

Comparative study on artificial intelligence systems for detecting early esophageal squamous cell carcinoma between narrow-band and white-light imaging.

BACKGROUND: Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience. AIM: To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI). METHODS: A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI (P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI (P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively. CONCLUSION: The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI.

Phosphorylation at Ser10 triggered p27 degradation and promoted gallbladder carcinoma cell migration and invasion by regulating stathmin1 under glucose deficiency.

Gallbladder carcinoma (GBC) is a considerable challenge because of its high metastatic potential. The tumor microenvironment is characterized by nutrient starvation, which promotes tumor metastasis. Stathmin1, an important microtubuleregulating protein, is overexpressed and promotes metastasis in GBC. It remains unclear how the harsh tumor microenvironment regulates stathmin1 expression to affect GBC metastasis. We employed glucose deficiency to mimic nutrient starvation and found that glucose deficiency upregulated stathmin1 transcription. However, glucose deficiency also promoted p27 degradation. There was a significant negative correlation between stathmin1 and p27 protein levels under glucose deficiency. Further study revealed that, under glucose deficiency, human kinase interacting with stathmin (hKIS) induced phosphorylation at Ser10 of p27 and its translocation to the cytoplasm for degradation, which upregulated the transcription factor E2F1 to promote stathmin1 transcription. hKIS knockdown significantly inhibited p27 cytoplasmic translocation and its consequent degradation. Stathmin1 knockdown significantly inhibited GBC cell migration and invasion in vitro. Our study revealed the role of the hKIS/p27/E2F1 axis in upregulating stathmin1 transcription to promote GBC cell migration and invasion under glucose deficiency conditions.

Prediction Efficacy for Clinical Outcome of Prognostic Nutritional Index in Patients with Resectable Biliary Tract Cancer Depends on Sex and Obstructive Jaundice Status.

BACKGROUND: The Prognostic Nutritional Index (PNI), a marker of nutritional status and systemic inflammation, is a proven prognostic biomarker in some cancers. The predictive value of PNI in biliary tract cancer (BTC) has not been established. OBJECTIVE: The aim of this study was to determine the relationship between the PNI and outcomes of resectable BTC. METHODS: In total, 430 patients with stage I-III resectable BTC [gallbladder cancer (GBC), n = 212; cholangiocarcinoma (CHO), n = 218] who had attended Fudan University Zhongshan Hospital were enrolled. The relationship between the PNI and clinical outcomes was evaluated both in the whole cohort and in selected subgroups. RESULTS: Eligible patients were classified into PNI-low (PNI < 45) and PNI-high (PNI ≥ 45) groups. The PNI-low group had significantly worse overall survival (OS) in both the whole cohort (p = 0.002) and in the GBC subgroup (p = 0.001), but had similar OS as the PNI-high group in the CHO subgroup (p = 0.328). Multivariate analysis revealed that low PNI is an independent risk factor for worse survival in GBC (hazard ratio 1.623, 95% confidence interval 1.063-2.480, p = 0.026). PNI was found to predict clinical outcome in women (p < 0.001) and patients without obstructive jaundice (p = 0.017) with GBC, but was not a prognostic factor in any subgroup with CHO. The estimated area under the time-dependent receiver operating characteristic curve was significantly greater when TNM stage was combined with PNI in women with GBC. CONCLUSIONS: PNI is an independent predictor of OS in GBC, but not in CHO. It has no prognostic value in men with GBC or patients with obstructive jaundice.

3D laparoscopic common bile duct exploration versus 2D in choledocholithiasis patients: a propensity score analysis.

BACKGROUND: This study was designed to investigate whether 3D laparoscopic common bile duct (LCBDE) could improve surgical outcomes in choledocholithiasis patients compared with 2D LCBDE. METHOD: Propensity score-matched analysis was performed to balance the bias in baseline characteristic between two groups. RESULTS: 213 patients underwent 3D LCBDE and 212 patients receiving 2D LCBDE were enrolled in this study. The operation time and blood loss in 3D group were significantly less than that in 2D group. After propensity score matching, a total of 114 paired cases were selected from the two groups. The operation time and blood loss in 3D group remain significantly lower than in 2D group. In the end, the subgroup analysis based on abdominal adhesion level was performed and it was observed that for patients with adhesion level 1 and level 2, 3D surgery could obviously decrease the operation time and intraoperative blood loss. CONCLUSIONS: 3D LCBDE would significantly reduce operation time, blood loss, and conversion rate to laparotomy in choledocholithiasis patients versus 2D LCBDE. For patients with abdominal adhesions level 1 and level 2, 3D LCBDE could provide better surgical outcomes than 2D LCBDE.

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer.

Recent studies have reported that tumor-infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine-based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine-based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM-activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell-related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine-based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.

Modified staging classification of gallbladder carcinoma on the basis of the 8th edition of the American Joint Commission on Cancer (AJCC) staging system.

PURPOSE: The 8th edition of the American Joint Commission on Cancer (AJCC) Staging System for gallbladder cancer (GBC) has been used in clinical practice, but we have found some deficiencies in this edition. METHODS: Survival analyses were performed to evaluate the application of various editions of the AJCC staging systems using the Surveillance, Epidemiology, and End Results (SEER) database (N = 9616 patients) and Fudan University Zhongshan Hospital (FUZH) database (N = 327 patients). A modified staging system was proposed based on the 8th edition of the AJCC Staging System. RESULTS: Although all N2 diseases were grouped into stage IVB as M1 in the 8th edition, some patients with N2 diseases could undergo R0 resection, and had longer survival than patients with M1 diseases had in both cohorts (p < 0.001 in SEER, p = 0.041 in FUZH). Furthermore, in the SEER database, stage IIIA patients aberrantly had poorer survival than stage IIIB patients had (p < 0.001). Therefore, we proposed a modified staging system by rearranging the substages. N2 disease was subdivided and reappraised according to T stage, and the aberrant survival reversal of stage IIIA and stage IIIB disease was also corrected. Through our modification, the C-index of the 8th AJCC Staging System was elevated from 0.596 [95% confidence interval (CI): 0.585-0.607] to 0.623 (95% CI: 0.612-0.634) for local disease in the SEER cohort. Similar findings were also observed in the FUZH cohort. CONCLUSION: Our modified 8th AJCC Staging System is more suitable for GBC and could be adopted for clinical practice.

Landscape of distant metastasis mode and current chemotherapy efficacy of the advanced biliary tract cancer in the United States, 2010-2016.

BACKGROUND: The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed. METHOD: A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias. RESULT: The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P < .05 in all the subtypes) where the multi-metastasis and distant lymph node (dLN) only always indicated the worst and best prognosis, respectively. Chemotherapy presented the most significant survival impact with the lowest hazard ratio by multivariate cox model and still provided a survival improvement after PSM (all P < .001) in all subtypes. However, the median months manifested different between patients with and without chemotherapy among the subtypes (ICC, from 5 to 9; PHCC, from 6 to 10; AVC, from 4 to 9; GBC, from 6 to 7; DCC from 6 to 8). CONCLUSION: We provided a landscape about the detailed DM mode of the advanced BTC in a large population, found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes.

Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer.

Use of immune index is a new potential approach for cancer classification and prediction. To investigate the status and clinical effect of immune index in gallbladder cancer (GBC), 238 GBC patients from Zhongshan Hospital affiliated to Fudan University were involved in the present study, including 113 patients in a training set and 125 patients in a validation set. Five immune cells (macrophages, neutrophils, regulatory T cells, cytotoxic T cells and mast cells) were selected based on a literature review and the immune index for each patient was calculated using the LASSO regression. A low immune index (<1) was defined as immunotype A and a high immune index (≥1) was defined as immunotype B. The 5-year overall survival rate for immunotype A was higher than that for immunotype B in the training set and the validation set (70.0% vs 37.0%, P < 0.001; 68.9% vs 47.5%, P = 0.002; respectively). Moreover, the immune index showed higher prediction efficiency compared with all the single immune cells which we selected. When combined with the immune index, the areas under the curve (AUC) of the TNM staging system in both sets were elevated from 0.677 to 0.787 and from 0.631 to 0.694, respectively. Interestingly, gemcitabine-based chemotherapy only benefits stage II patients of immunotype B and stage III patients of both immunotype A and immunotype B (P = 0.015, P = 0.030, P = 0.011, respectively) but does not work in stage II patients of immunotype A (P = .307). Taken together, the immune index could effectively predict prognosis and the benefits of gemcitabine-based chemotherapy and might improve on the TNM staging system.

PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to chemotherapies in gallbladder carcinoma.

Gallbladder carcinoma (GBC) is always diagnosed at an advanced stage, and patients often miss the opportunity for surgery. Gemcitabine (GEM) and platinum-based drugs, including oxaliplatin (OXA), are mainstays of chemotherapy. However, drug resistance causes treatment failure. Hence, salvage mechanisms are critical to improve outcomes. This study revealed the positive correlation between placenta-specific protein 8 (PLAC8) overexpression and PD-L1 overexpression in GBC. Given the roles of PLAC8 and PD-L1 in chemotherapy resistance, GEM-resistant and OXA-resistant cell lines (SGC966GR and SGC966OR, respectively) were established to test whether and how PLAC8 and PD-L1 function in chemotherapy resistance. Drug-insensitive SGC966GR and SGC966OR cells upregulated MRP and MDR1 and had high expression of PLAC8. PLAC8 blockade using siRNA reversed chemotherapy resistance and downregulated MRP and MDR1 in SGC966GR and SGC966OR cells, suggesting that PLAC8 mediates chemotherapy resistance in GBC. Consistent with the increased mRNA levels of PD-L1 after the acquisition of resistance, PLAC8 knockdown reduced PD-L1 mRNA expression in SGC966GR and SGC966OR cells. In conclusion, PLAC8 overexpression in GBC patients positively correlated with PD-L1 expression. PLAC8 conferred resistance to GEM and OXA by upregulating PD-L1 expression, and PLAC8 or PD-L1 blockade may have potential for overcoming chemotherapy resistance, providing therapeutic options for chemotherapy-refractory GBC patients.

Identification and analysis of genes associated with papillary thyroid carcinoma by bioinformatics methods.

The molecular mechanism of the occurrence and development of papillary thyroid carcinoma (PTC) has been widely explored, but has not been completely elucidated. The present study aimed to identify and analyze genes associated with PTC by bioinformatics methods. Two independent datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PTC tissues and matched non-cancerous tissues were identified using GEO2R tool. The common DEGs in the two datasets were screened out by VennDiagram package, and analyzed by the following tools: KOBAS, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Search tool for the retrieval of interacting genes/proteins (STRING), UALCAN and Gene expression profiling interactive analysis (GEPIA). A total of 513 common DEGs, including 259 common up-regulated and 254 common down-regulated genes in PTC, were screened out. These common up-regulated and down-regulated DEGs were most significantly enriched in cytokine-cytokine receptor interaction and metabolic pathways, respectively. Protein-protein interactions (PPI) network analysis showed that the up-regulated genes: FN1, SDC4, NMU, LPAR5 and the down-regulated genes: BCL2 and CXCL12 were key genes. Survival analysis indicated that the high expression of FN1 and NMU genes significantly decreased disease-free survival of patients with thyroid carcinoma. In conclusion, the genes and pathways identified in the current study will not only contribute to elucidating the pathogenesis of PTC, but also provide prognostic markers and therapeutic targets for PTC.

Potential therapeutic value of primary tumor resection in ampullary cancer patients with distant metastases at initial diagnosis: a population-based study.

OBJECTIVE: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. PATIENTS AND METHODS: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan-Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. RESULTS: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0-22.0 vs 8.0, 95% CI: 5.0-11.0 for median OS; 22.0, 95% CI: 13.0-33.0 vs 9.0, 95% CI: 5.0-11.0 for median CSS; both log-rank P<0.001). Patients receiving PTR plus chemotherapy showed better survival compared with those receiving only chemotherapy (median OS: 18, 95% CI: 13-27 vs 9.0, 95% CI: 8.0-11.0; median CSS: 23.0, 95% CI: 14.0-36.0 vs 9.0, 95% CI: 8.0-13.0; both log-rank P<0.001). CONCLUSION: PTR might bring a survival benefit to ampullary cancer patients with distant metastasis at the initial presentation and might provide a more favorable prognosis when combined with chemotherapy.