Expression and clinicopathologic significance of TUFM and p53 for the normal-adenoma-carcinoma sequence in colorectal epithelia.

BACKGROUND: Evidence indicates that most cases of colorectal carcinoma (CRC) develop from adenoma. A previous study demonstrated that mitochondrial Tu translation elongation factor (TUFM) might serve as an independent prognostic factor for colorectal cancer. However, the expression and function of TUFM in the normal-adenoma-cancer sequence have not been reported. In this study, we investigated the clinicopathologic significance of TUFM and p53 expression for the normal-adenoma-carcinoma sequence in colorectal epithelia and evaluated the roles of TUFM during the progression of colorectal tumors. METHODS: Paraffin-embedded specimens from 261 colorectal normal mucosa samples, 157 adenomas, and 104 early carcinomas were analyzed for TUFM and p53 expression by immunohistochemistry. RESULTS: Expression of TUFM and p53 was significantly increased during the colorectal normal-adenoma-carcinoma sequence (all P < 0.05). The expression of TUFM and p53 was associated with histologic type of adenomas (P = 0.028; P = 0.001) and grade of dysplasia (all P = 0.001). Expression of TUFM was positively correlated with that of p53 (r = 0.319, P = 0.001). CONCLUSIONS: Upregulated TUFM expression may play an important role in the transformation from colorectal normal mucosa to carcinoma through adenoma. Combined immunohistochemical detection of TUFM and p53 may be useful for evaluating the biological behavior of colorectal adenoma.

Imaging classification of prostate cancer with extracapsular extension and its impact on positive surgical margins after laparoscopic radical prostatectomy.

Abstract: To explore the impact of different imaging classifications of prostate cancer (PCa) with extracapsular extension (EPE) on positive surgical margins (PSM) after laparoscopic radical prostatectomy. Methods: Clinical data were collected for 114 patients with stage PT3a PCa admitted to Ningbo Yinzhou No. 2 Hospital from September 2019 to August 2023. Radiologists classified the EPE imaging of PCa into Type I, Type II, and Type III. A chi-square test or t-test was employed to analyze the factors related to PSM. Multivariate regression analysis was conducted to determine the factors associated with PSM. Receiver operating characteristic curve analysis was used to calculate the area under the curve and evaluate the diagnostic performance of our model. Clinical decision curve analysis was performed to assess the clinical net benefit of EPE imaging classification, biopsy grade group (GG), and combined model. Results: Among the 114 patients, 58 had PSM, and 56 had negative surgical margins. Multivariate analysis showed that EPE imaging classification and biopsy GG were risk factors for PSM after laparoscopic radical prostatectomy. The areas under the curve for EPE imaging classification and biopsy GG were 0.677 and 0.712, respectively. The difference in predicting PSM between EPE imaging classification and biopsy GG was not statistically significant (P>0.05). However, when used in combination, the diagnostic efficiency significantly improved, with an increase in the area under the curve to 0.795 (P<0.05). The clinical decision curve analysis revealed that the clinical net benefit of the combined model was significantly higher than that of EPE imaging classification and biopsy GG. Conclusions: EPE imaging classification and biopsy GG were associated with PSM after laparoscopic radical prostatectomy, and their combination can significantly improve the accuracy of predicting PSM.

Membrane Protein Bcest Is Involved in Hyphal Growth, Virulence and Stress Tolerance of Botrytis cinerea.

Botrytis cinerea is a necrotrophic model fungal plant pathogen that causes grey mould, a devastating disease responsible for large losses in the agriculture sector. As important targets of fungicides, membrane proteins are hot spots in the research and development of fungicide products. We previously found that membrane protein Bcest may be closely related to the pathogenicity of Botrytis cinerea. Herein, we further explored its function. We generated and characterised ΔBcest deletion mutants of B. cinerea and constructed complemented strains. The ΔBcest deletion mutants exhibited reduced conidia germination and germ tube elongation. The functional activity of ΔBcest deletion mutants was investigated by reduced necrotic colonisation of B. cinerea on grapevine fruits and leaves. Targeted deletion of Bcest also blocked several phenotypic defects in aspects of mycelial growth, conidiation and virulence. All phenotypic defects were restored by targeted-gene complementation. The role of Bcest in pathogenicity was also supported by reverse-transcriptase real-time quantitative PCR results indicating that melanin synthesis gene Bcpks13 and virulence factor Bccdc14 were significantly downregulated in the early infection stage of the ΔBcest strain. Taken together, these results suggest that Bcest plays important roles in the regulation of various cellular processes in B. cinerea.

Can a single-port robot be safely used for robotic total gastrectomy for advanced gastric cancer? First experience using the da Vinci SP platform.

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

Comparison of short-term efficacy between totally laparoscopic gastrectomy and laparoscopic assisted gastrectomy for elderly patients with gastric cancer.

BACKGROUND: Totally laparoscopic gastrectomy (TLG) entails both gastrectomy and gastrointestinal reconstruction under laparoscopy. Compared with laparoscopic assisted gastrectomy (LAG), TLG has been demonstrated in many studies to require a smaller surgical incision, result in a faster postoperative recovery and less pain and have comparable long-term efficacy, which has been a research hotspot in recent years. Whether TLG is equally safe and feasible for elderly patients remains unclear. AIM: To compare the short-term efficacy of and quality of life (QOL) associated with TLG and LAG in elderly gastric cancer (GC) patients. METHODS: The clinicopathological data of 462 elderly patients aged ≥ 70 years who underwent LAG or TLG (including distal gastrectomy and total gastrectomy) between January 2017 and January 2022 at the Department of General Surgery, First Medical Center, Chinese PLA General Hospital were retrospectively collected. A total of 232 patients were in the LAG group, and 230 patients were in the TLG group. Basic patient information, clinicopathological characteristics, operation information and QOL data were collected to compare efficacy. RESULTS: Compared with those in the LAG group, intraoperative blood loss in the TLG group was significantly lower (P < 0.001), and the time to first flatus and postoperative hospitalization time were significantly shorter (both P < 0.001). The overall incidence of postoperative complications in the TLG group was significantly lower than that in the LAG group (P = 0.01). Binary logistic regression results indicated that LAG and an operation time > 220 min were independent risk factors for postoperative complications in elderly patients with GC (P < 0.05). In terms of QOL, no statistically significant differences in various preoperative indicators were found between the LAG group and the LTG group (P > 0.05). Compared with the laparoscopic-assisted total gastrectomy group, patients who received totally laparoscopic total gastrectomy had lower nausea and vomiting scores and higher satisfaction with their body image (P < 0.05). Patients who underwent laparoscopic-assisted distal gastrectomy were more satisfied with their body image than patients in the totally laparoscopic distal gastrectomy group (P < 0.05). CONCLUSION: TLG is safe and feasible for elderly patients with GC and has outstanding advantages such as reducing intracorporeal blood loss, promoting postoperative recovery and improving QOL.

Short and long-term outcomes between laparoscopic and open total gastrectomy for advanced gastric cancer after neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) combined with surgery is regarded as an effective treatment for advanced gastric cancer (AGC). Laparoscopic surgery represents the mainstream of minimally invasive surgery. Currently, surgeons focus more on surgical safety and oncological outcomes of laparoscopic gastrectomy after NACT. Thus, we sought to evaluate short- and long-term outcomes between laparoscopic total gastrectomy (LTG) and open total gastrectomy (OTG) after NACT. AIM: To compare the short and long-term outcomes between LTG and OTG for AGC after NACT. METHODS: We retrospectively collected the clinicopathological data of 136 patients who accepted gastrectomy after NACT from June 2012 to June 2019, including 61 patients who underwent LTG and 75 who underwent OTG. Clinicopathological characteristics between the LTG and OTG groups showed no significant difference. SPSS 26.0, R software, and GraphPad PRISM 8.0 were used to perform statistical analyses. RESULTS: Of the 136 patients included, eight acquired pathological complete response, and the objective response rate was 47.8% (65/136). The LTG group had longer operation time (P = 0.015), less blood loss (P = 0.003), shorter days to first flatus (P < 0.001), and shorter postoperative hospitalization days (P < 0.001). LTG spent more surgical cost than OTG (P < 0.001), while total hospitalized cost of LTG was less than OTG (P < 0.001). 21 (28.0%) patients in the OTG group and 14 (23.0%) in the LTG group had 30-d postoperative complications, but there was no significant difference between the two groups (P = 0.503). The 3-year overall survival (OS) rate was 60.6% and 64.6% in the LTG and OTG groups, respectively [hazard ratio (HR) = 0.859, 95% confidence interval (CI): 0.522-1.412, P = 0.546], while the 3-year disease-free survival (DFS) rate was 54.5% and 51.8% in the LTG and OTG group, respectively (HR = 0.947, 95%CI: 0.582-1.539, P = 0.823). Multivariate cox analysis showed that body mass index and pTNM stage were independent risk factors for OS while vascular invasion and pTNM stage were independent risk factors for DFS (P < 0.05). CONCLUSION: After NACT, LTG shows comparable 30-d postoperative morbidity as well as 3-year OS and DFS rate to OTG. We recommend that experienced surgeons select LTG other than OTG for proper AGC patients after NACT.

Neutrophil extracellular traps in gastrointestinal cancer.

Gastrointestinal (GI) cancer is a high-risk malignancy and is characterized by high mortality and morbidity worldwide. Neutrophil extracellular traps (NETs), a weblike structure consisting of chromatin DNA with interspersed cytoplasmic and granule proteins, are extruded by activated neutrophils to entrap and kill bacteria and fungi. However, accumulating evidence shows that NETs are related to the progression and metastasis of cancer. In clinical studies, NETs infiltrate primary GI cancer tissues and are even more abundant in metastatic lesions. The quantity of NETs in peripheral blood is revealed to be associated with ascending clinical tumour stages, indicating the role of NETs as a prognostic markers in GI cancer. Moreover, several inhibitors of NETs or NET-related proteins have been discovered and used to exert anti-tumour effects in vitro or in vivo, suggesting that NETs can be regarded as targets in the treatment of GI cancer. In this review, we will focus on the role of NETs in gastric cancer and colorectal cancer, generalizing their effects on tumour-related thrombosis, invasion and metastasis. Recent reports are also listed to show the latest evidences of how NETs affect GI cancer. Additionally, notwithstanding the scarcity of systematic studies elucidating the underlying mechanisms of the interaction between NETs and cancer cells, we highlight the potential importance of NETs as biomarkers and anti-tumour therapeutic targets.

Status quo and future prospects of artificial neural network from the perspective of gastroenterologists.

Artificial neural networks (ANNs) are one of the primary types of artificial intelligence and have been rapidly developed and used in many fields. In recent years, there has been a sharp increase in research concerning ANNs in gastrointestinal (GI) diseases. This state-of-the-art technique exhibits excellent performance in diagnosis, prognostic prediction, and treatment. Competitions between ANNs and GI experts suggest that efficiency and accuracy might be compatible in virtue of technique advancements. However, the shortcomings of ANNs are not negligible and may induce alterations in many aspects of medical practice. In this review, we introduce basic knowledge about ANNs and summarize the current achievements of ANNs in GI diseases from the perspective of gastroenterologists. Existing limitations and future directions are also proposed to optimize ANN's clinical potential. In consideration of barriers to interdisciplinary knowledge, sophisticated concepts are discussed using plain words and metaphors to make this review more easily understood by medical practitioners and the general public.

Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR-Hippo-YAP pathway.

The long-term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

Chinese expert consensus and practice guideline of totally implantable access port for digestive tract carcinomas.

Totally implantable access port is a fully implantable drug delivery system that is implanted subcutaneously and can be retained for a long time. Advantages of ports include a simple nursing process, low risk of infection and embolism, and high patient comfort. In order to promote the standardized application of ports in the treatment of digestive tract tumors and reduce port-related complications, the Chinese Research Hospital Association Digestive Tumor Committee, the Chinese Association of Upper Gastrointestinal Surgeons, the Chinese Gastric Cancer Association, and the Gastrointestinal Surgical Group of Chinese Surgical Society Affiliated to Chinese Medical Association have organized multidisciplinary expert discussions at the General Hospital of the People's Liberation Army and nation-wide expert letter reviews and on-site seminars, and formulated an expert consensus of the operation guidelines.

Comparing prognostic values of the 7th and 8th editions of the American Joint Committee on Cancer TNM staging system for gastric cancer.

BACKGROUND AND AIM: Our aim was to compare the prognostic value of the American Joint Committee on Cancer (AJCC) 7th and 8th editions staging systems for patients with gastric cancer in China. METHODS: A total of 1326 gastric cancer patients diagnosed between 2008 and 2012 were included. The discriminative ability of the AJCC 8th and 7th editions was compared using the Harrell's concordance index (C-index). RESULTS: There are two main modifications in the 8th edition. (i) pN3 staging was divided into pN3a and pN3b. The gastric cancer patients with pN3a experienced significantly better overall survival compared with those with pN3b (5-year overall survival: 34.5% vs. 15.6%, P < 0.001) (stratified by pT: pT3: 5-year overall survival: 33.9% vs. 13.2%, P < 0.001; pT4a: 32.8% vs. 16.9%, P = 0.056; pT4b: 17.0% vs. 11.1%, P = 0.048). (ii) Subgroup staging adjustments. The subgroup staging adjustments (T3N3bM0 (IIIB→IIIC), T4aN3aM0 (IIIC→IIIB), T4bN0M0 (IIIB→IIIA), and T4bN2M0 (IIIC→IIIB)) resulted in more gastric cancer patients being accurately staged. Furthermore, the C-index value of the 8th edition tumor node metastasis (TNM) staging system was significantly higher than that of the AJCC 7th TNM staging system to predict the survival of gastric cancer patients (0.701 vs. 0.685, P < 0.001). CONCLUSIONS: The 8th edition of the TNM staging system is superior to the 7th edition staging system for prediction of survival of gastric cancer patients in China.

Establishment and validation of a nomogram to predict the risk of ovarian metastasis in gastric cancer: Based on a large cohort.

BACKGROUND: Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer. The pathogenesis of ovarian metastasis is incompletely understood, and the treatment options are controversial. Few studies have predicted the risk of ovarian metastasis. It is not clear which type of gastric cancer is more likely to metastasize to the ovary. A prediction model based on risk factors is needed to improve the rate of detection and diagnosis. AIM: To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features. METHODS: A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center, and patients with distant metastasis other than ovary and peritoneum metastasis were excluded. Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression. Independent risk factors were chosen to construct a nomogram which received internal validation. RESULTS: Ovarian metastasis occurred in 83 of 1696 female patients. Univariate analysis showed that age, Lauren type, whether the primary lesion contained signet-ring cells, vascular tumor emboli, T stage, N stage, the expression of estrogen receptor, the expression of progesterone receptor, serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer (all P < 0.05). Multivariate analysis showed that age ≤ 50 years, Lauren typing of non-intestinal, gastric cancer lesions containing signet-ring cell components, N stage > N2, positive expression of estrogen receptor, serum carbohydrate antigen 125 > 35 U/mL, and a neutrophil-to-lymphocyte ratio > 2.16 were independent risk factors (all P < 0.05). The independent risk factors were constructed into a nomogram model using R language software. The consistency index after continuous correction was 0.840 [95% confidence interval: (0.774-0.906)]. After the internal self-sampling (Bootstrap) test, the calibration curve of the model was obtained with an average absolute error of 0.007. The receiver operating characteristic curve of the obtained model was drawn. The area under the curve was 0.867, the maximal Youden index was 0.613, the corresponding sensitivity was 0.794, and the specificity was 0.819. CONCLUSION: The nomogram model performed well in the prediction of ovarian metastasis. Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination, to ensure early detection and treatment.

Preoperative albumin levels predict prolonged postoperative ileus in gastrointestinal surgery.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a prolonged state of "pathological" gastrointestinal (GI) tract dysmotility. There are relatively few studies examining the influence of preoperative nutritional status on the development of PPOI in patients who underwent GI surgery. The association between preoperative albumin and PPOI has not been fully studied. We hypothesized that preoperative albumin may be an independent indicator of PPOI. AIM: To analyze the role of preoperative albumin in predicting PPOI and to establish a nomogram for clinical risk evaluation. METHODS: Patients were drawn from a prospective hospital registry database of GI surgery. A total of 311 patients diagnosed with gastric or colorectal cancer between June 2016 and March 2017 were included. Potential predictors of PPOI were analyzed by univariate and multivariable logistic regression analyses, and a nomogram for quantifying the presence of PPOI was developed and internally validated. RESULTS: The overall PPOI rate was 21.54%. Advanced tumor stage and postoperative opioid analgesic administration were associated with PPOI. Preoperative albumin was an independent predictor of PPOI, and an optimal cutoff value of 39.15 was statistically calculated. After adjusting multiple variables, per unit or per SD increase in albumin resulted in a significant decrease in the incidence of PPOI of 8% (OR = 0.92, 95%CI: 0.85-1.00, P = 0.046) or 27% (OR = 0.73, 95%CI: 0.54-0.99, P = 0.046), respectively. Patients with a high level of preoperative albumin (≥ 39.15) tended to experience PPOI compared to those with low levels (< 39.15) (OR = 0.43, 95%CI: 0.24-0.78, P = 0.006). A nomogram for predicting PPOI was developed [area under the curve (AUC) = 0.741] and internally validated by bootstrap resampling (AUC = 0.725, 95%CI: 0.663-0.799). CONCLUSION: Preoperative albumin is an independent predictive factor of PPOI in patients who underwent GI surgery. The nomogram provided a model to screen for early indications in the clinical setting.

Nomogram to predict prolonged postoperative ileus after gastrectomy in gastric cancer.

BACKGROUND: Prolonged postoperative ileus (PPOI) is one of the common complications in gastric cancer patients who underwent gastrectomy. Evidence on the predictors of PPOI after gastrectomy is limited and few prediction models of nomogram are used to estimate the risk of PPOI. We hypothesized that a predictive nomogram can be used for clinical risk estimation of PPOI in gastric cancer patients. AIM: To investigate the risk factors for PPOI and establish a nomogram for clinical risk estimation. METHODS: Between June 2016 and March 2017, the data of 162 patients with gastrectomy were obtained from a prospective and observational registry database. Clinical data of patients who fulfilled the criteria were obtained. Univariate and multivariable logistic regression models were performed to detect the relationship between variables and PPOI. A nomogram for PPOI was developed and verified by bootstrap resampling. The calibration curve was employed to detect the concentricity between the model probability curve and ideal curve. The clinical usefulness of our model was evaluated using the net benefit curve. RESULTS: This study analyzed 14 potential variables of PPOI in 162 gastric cancer patients who underwent gastrectomy. The incidence of PPOI was 19.75% in patients with gastrectomy. Age older than 60 years, open surgery, advanced stage (III-IV), and postoperative use of opioid analgesic were independent risk factors for PPOI. We developed a simple and easy-to-use prediction nomogram of PPOI after gastrectomy. This nomogram had an excellent diagnostic performance [area under the curve (AUC) = 0.836, sensitivity = 84.4%, and specificity = 75.4%]. This nomogram was further validated by bootstrapping for 500 repetitions. The AUC of the bootstrap model was 0.832 (95%CI: 0.741-0.924). This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION: We have developed a prediction nomogram of PPOI for gastric cancer. This novel nomogram might serve as an essential early warning sign of PPOI in gastric cancer patients.

Comparing PET/MRI with PET/CT for Pretreatment Staging of Gastric Cancer.

18F-FDG PET/MRI has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MRI in gastric cancer are rare because of motion artifacts. We investigated the value of PET/MRI for preoperative staging compared with PET/CT in gastric cancer (GC). Thirty patients with confirmed GC underwent PET/CT and PET/MRI. TNM staging for each patient was determined from the PET/MRI and PET/CT images. The diagnostic performance of PET/MRI and PET/CT was calculated compared with the pathologic TNM stage. The two methods were compared using statistical analyses. The accuracy for T staging between PET/MRI and PET/CT was 76.9% vs. 57.7%, respectively. In T1 and T4a staging, the sensitivity and specificity for PET/MRI vs. PET/CT was 1.0 vs. 0.6 and 1.0 vs. 0.8, respectively. The area under the curve (AUC) for PET/MRI vs. PET/CT was 1.00 vs. 0.78 in the T1 stage, 0.73 vs. 0.66 in the T2 stage, 0.72 vs. 0.57 in the T3 stage, and 0.86 vs. 0.83 in the T4 stage. The accuracy for N staging of PET/MRI vs. PET/CT was 53.9% vs. 34.0%, and that for N0 vs. N+ was 85.0% vs. 77.0%. The sensitivity for PET/MRI in N3 staging was 0.67 and 0 for PET/CT. There was a statistically significant difference in the AUC for N1 staging (PET/MRI vs. PET/CT, 0.63 vs. 0.53, p = 0.03). SUVmax/ADC positively correlated with tumor volume and Ki-67. PET/MRI performs more accurately in TNM staging compared with PET/CT and is optimal for accurate N staging. SUVmax/ADC has positive correlations with tumor volume and Ki-67.

Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes.

AIM: To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval time significantly impacts the pathological complete response (pCR) rate and long-term survival. METHODS: One hundred and seventy-six patients with gastric cancer undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NACT-surgery interval time (< 4 wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS). RESULTS: The NACT-surgery interval time and clinician T stage were independent predictors of pCR. The interval time > 6 wk was associated with a 74% higher odds of pCR as compared with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of clinical T3vs clinical T4 stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041). In Cox regression analysis of long-term survival, post-neoadjuvant therapy pathological N (ypN) stage significantly impacted OS (N0vs N3: HR = 0.16, 95%CI: 0.37-0.70, P = 0.015; N1vs N3: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and disease-free survival (DFS) (N0vs N3: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005; N1vs N3: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36-0.44, P = 0.001) for DFS. CONCLUSION: The NACT-surgery interval time is associated with pCR but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pCR.

Comparison between laparoscopic and open surgery for large gastrointestinal stromal tumors: A meta-analysis.

AIM: To investigate whether laparoscopic surgery is as safe and feasible as open resection for patients with larger gastrointestinal stromal tumors (GISTs) (≥ 5 cm). METHODS: A systematic search of PubMed, EMBASE, Web of Science and the Cochrane Library database was performed. Relevant studies of laparoscopic and open surgery for GISTs of > 5 cm published before December 2016 were identified from these databases. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. The tumor size, operation time, blood loss, postoperative hospital stay, complication rate, and disease-free survival rate were assessed. The software Stata (version 12.0) was used for the meta-analysis. RESULTS: Five clinical trials comprising 209 patients with GISTs of similar larger sizes were evaluated. The pooled analysis of 100 patients in the laparoscopic resection group and 109 patients in the open resection group demonstrated that laparoscopic surgery was significantly associated with a shorter postoperative hospital stay (P < 0.001) and less blood loss (P = 0.002). Moreover, there were no statistically significant differences in the operation time (P = 0.38), postoperative complication rate (P = 0.88), or disease-free survival rate (P = 0.20) between two groups. CONCLUSION: Our findings revealed that for patients with large GISTs of comparable sizes, laparoscopic surgery did not significantly influence the operation factors or clinical outcomes compared with open surgery. This suggests that laparoscopic resection is as acceptable as open surgery for treatment of large gastric GISTs.

Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer.

AIM: To investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer. METHODS: A total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescence in situ hybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients. RESULTS: Serum HER2 ECD was significantly correlated with tissue HER2 status (P < 0.001), tumor size (P < 0.001), and intestinal type of gastric cancer (P = 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87, P < 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38, P = 0.006). CONCLUSION: Serum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.

RNAi-mediated inhibition of Lgr5 leads to decreased angiogenesis in gastric cancer.

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel gastric cancer marker. However, it is unclear whether it can play roles in tumor angiogenesis. In this study, we aim to investigate the role of Lgr5 on gastric cancer angiogenesis. Lgr5, VEGF expression levels and microvessel density (MVD) were detected in tumor tissue. Then, Lgr5 mRNA was downregulated by small interference RNA technique. Western blotting and real-time quantitative PCR (qRT-PCR) were performed to detect the expression of Lgr5 and VEGF protein and mRNA in Lgr5 siRNA-transfected gastric cancer cells. The effect of silencing Lgr5 on angiogenesis was examined by assessing human umbilical vein endothelia cell (HUVEC) capillary tube formation. The results indicated that Lgr5 expression was upregulated in gastric cancer and positively correlated with VEGF (r=0.305, P=0.001) and MVD (r=0.312, P=0.001). Silencing of Lgr5 expression resulted in suppression of VEGF mRNA and protein (all P=0.001). Moreover, when HUVECs were stimulated with conditioned medium from Lgr5 siRNA-transfected gastric cancer cells, tube formation was significantly decreased (2.51 ± 0.19 mm/mm2) compared with the treatment with regular cell culture medium (DMEM) (7.34 ± 0.30 mm/mm2) or medium from control siRNA-transfected cells (7.18 ± 0.33 mm/mm2) (all P=0.001). In conclusion, Lgr5 plays important roles in angiogenesis. Lgr5-specific siRNA could be designed into an effective therapeutic agent to inhibit gastric cancer angiogenesis.