Multidisciplinary treatment for patients with stage IV gastric cancer: the role of conversion surgery following chemotherapy.

BACKGROUND: With advances in gastric cancer chemotherapy, conversion surgery has drawn attention as a new strategy to improve the outcome of stage IV disease. We investigated the efficacy of conversion surgery following chemotherapy for patients with stage IV gastric cancer. METHODS: We retrospectively reviewed clinico-pathologic variables and oncologic outcomes for 101 patients with stage IV gastric cancer who were treated with systemic chemotherapy followed by gastrectomy with intension of curative resection from January 2005 to December 2012. RESULTS: In terms of the best response from palliative chemotherapy, complete or partial response were observed in 65 patients (64.4%) in overall. Complete response of metastatic site were observed in 72 (71.3%) and 66 (65.3%) patients as best and pre-operative response, respectively. The overall complete macroscopic resection, rate was 56.4%. Eleven patients (10.9%) received combined metastasectomy. There was no postoperative surgery-related mortality for 1 month. The median overall survival time was 26.0 months. Multivariable analysis identified complete macroscopic resection, chemotherapy response (complete response/partial response) of metastatic sites, and change in CEA level as independent prognostic factors contributing to overall survival. CONCLUSIONS: Patients with stage IV gastric cancer who exhibit a good clinical response to chemotherapy might obtain greater survival benefit from gastrectomy following chemotherapy compared with patients who exhibit a poor response to chemotherapy. Prospective, randomized trials are required to determine the best strategy for combining initial chemotherapy with subsequent gastrectomy.

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. METHODS: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.

[Effect of MicroRNA-199 on Proliferation and Migration of Gastric Carcinoma Cells].

Objective To detect the expression of microRNA(miR)-199 in gastric carcinoma tissues and cell lines, and further explore the effect and molecular mechanism of miR-199 on the proliferation and migration of gastric carcinoma cell lines. Methods Reverse transcriptase-polymerse chain reaction was used to detect the expression of miR-199 in gastric carcinoma and adjacent normal tissue obtained from 51 patients and in gastric carcinoma cell lines and human gastric epithelial cell line GES-1. The gastric carcinoma cell lines over-expressing and low-expressing miR-199 were established to detect their proliferation and migration abilities. Dual-luciferase reporter assay was performed to detect the regulatory effect of miR-199 on the 3'untranslated region of TBL1XR1. Western blot was used to explore the miR-199-related mechanism. Results The relative expression of miR-199 in gastric carcinoma tissues was significantly lower than that in the adjacent normal tissue (0.2635±0.0303 vs. 1.6700±0.9613, t=13.95, P<0.001). The relative expressions of miR-199 in gastric carcinoma cell lines AGS (0.81, t=9.13, P<0.001), SGC-7901 (0.83, t=8.88, P<0.001), MKN28 (0.58, t=10.80, P<0.001), KATO-3 (0.60, t=10.31, P<0.001), MKN-45 (0.27, t=13.10, P<0.001) were significantly lower than that in the normal gastric cell line GES-1 (2.1). In miR-199 over-expressed cell lines, the cell proliferation and migration significantly decreased as compared with the control group of gastric carcinoma cells (731±13 vs. 345±18, t=24.90, P<0.001), and in miR-199 low-expressed group, the cell proliferation and migration increased compared with the control group of gastric carcinoma cells (257±16 vs. 657±8, t=32.59, P<0.001). Dual-luciferase reporter assay proved that miR-199 directly targeted on the 3' untranslated region of TBL1XR1. Western blot analysis showed that miR-199 inhibited the expression of TBL1XR1. Conclusion The over-expression of miR-199 in gastric carcinoma is associated with the decreased ability of proliferation and migration of gastric carcinoma cells by targeting TBL1XR1.

Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

BACKGROUND: The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue. METHODS: We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes. RESULTS: Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs <22; group B: HLNs≥22). The intraoperative and postoperative characteristics, including operative blood loss (P=0.096), operation time (P=0.430), postoperative hospital stay (P=0.142), complications (P=0.552), rate of reoperation (P=0.966) and postoperative mortality (P=1.000), were comparable between the two groups. T-stage-stratified Kaplan-Meier analyses revealed that the 5-year survival rate of patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis. CONCLUSIONS: Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.

The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival.

BACKGROUND: The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer. METHODS: We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study. RESULTS: We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival. CONCLUSIONS: For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.

Correlation analyses between pre- and post-operative adverse events in gastric cancer patients receiving preoperative treatment and gastrectomy.

BACKGROUNDS: Preoperative chemotherapy (PCT) and chemoradiotherapy (PCRT) showed promising results for gastric cancers. However, the influence of preoperative adverse events (AEs) on postoperative complications remains unknown. The aim of this study was to identify correlations between them. METHODS: Clinical data and laboratory findings were retrieved retrospectively for 115 patients who underwent gastrectomy after PCT or PCRT between 2010 and 2013. Preoperative AEs and postoperative complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo (CD) grading systems, respectively. Correlations between CTCAE grades and CD grades were analyzed, and clinical data and laboratory findings were compared among three groups classified according to CD grades: CD0, CD1/2, and CD3/4. RESULTS: There were 61 (53.0%) patients in the CD0 group, 44 (38.3%) patients in the CD1/2 group, and 10 (8.7%) patients in the CD3/4 group. The CTCAE grades did not correlate with the CD grades. Only estimated blood loss (P = 0.019) and transfusion rate (P < 0.001) differed among the three CD groups. CONCLUSION: There are no correlations between pre- and post-operative adverse events in the terms of severity grades in patients with advanced or metastatic gastric cancer who underwent gastrectomy after PCT or PCRT. Meticulous intraoperative manipulations should be emphasized.

Prognostic significance of cytoskeleton-associated membrane protein 4 and its palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma.

BACKGROUND: The functions of cytoskeleton-associated membrane protein 4 (CKAP4), one kind of type II transmembrane protein, are associated with the palmitoyl acyltransferase DHHC2. The objective of the current study was to investigate CKAP4/DHHC2 expression and its prognostic significance in patients with hepatocellular carcinoma (HCC). METHODS: Two independent cohorts of 416 patients with HCC were enrolled. All the patients included had defined clinicopathologic and follow-up data. Using real-time polymerase chain reaction and immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The association between CKAP4/DHHC2 expression and HCC-specific disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. RESULTS: The data documented that CKAP4 expression was much higher in HCC tumor tissues compared with adjacent normal tissues and its expression was significantly correlated with tumor size, intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients with high CKAP4 expression appeared to have a favorable overall survival and a longer disease-free survival compared with those with low expression. DHHC2 expression was also examined in tissue microarray analysis by immunohistochemistry and the results demonstrated that 87.6% of the cases had low expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2 expression predicted favorable overall survival and disease-free survival rates in both the training cohort and validation set. Furthermore, the combination of CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis prediction than either one alone. CONCLUSIONS: To the best of our knowledge, the current study is the first to demonstrate that the expression of CKAP4 and its palmitoyl acyltransferase DHHC2 correlates with disease progression and metastasis in patients with HCC and may provide prognostic and therapeutic value.

Signal regulatory protein α negatively regulates mast-cell activation following FcεRI aggregation.

Mast cells elicit allergic reaction through degranulation and release of proinflammatory mediators after aggregation of the IgE receptor FcεRI. Here we provide evidence to show that signal regulatory protein α (SIRPα), an ITIM-containing receptor, is an endogenous regulator of IgE-Ag induced mast-cell activation. SIRPα expression is promptly reduced in mast cells in response to FcεRI aggregation. Impaired expression of SIRPα in mast cells facilitates FcεRI-evoked degranulation and de novo synthesis of cytokines (IL-4, IL-13, IL-6, and TNF-α). We further demonstrate that SIRPα knockdown in mast cells accelerates calcium mobilization and affects cytoskeletal rearrangement (F-actin disassembly and polymeric tubulin formation) after FcεRI aggregation. Mechanistic studies highlight the prolonged activation of NF-κB and MAPKs as well as PLC-γ after FcεRI stimulation as a consequence of the inhibition of SIRPα expression in mast cells. Immunoprecipitation analysis shows that SIRPα knockdown markedly increases IgE-induced SHP2 interaction with PI3K regulatory subunit PI3Kp85 or IKK-ß in mast cells, indicating that SIRPα may accomplish this through its association and sequestration of SHP2. Collectively, our results strongly indicate that SIRPα is a biological important regulator of FcεRI signaling.

CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling.

CKAP4, one kind of type II trans-membrane protein, plays an important role to maintain endoplasmic reticulum structure and inhibits the proliferation of bladder cancer cells by combining its ligand anti-proliferative factor (APF). However, the biological function of CKAP4 in the progression of liver cancer has not been clearly demonstrated. In the present study, we knocked down or overexpressed CKAP4 in hepatocellular carcinoma (HCC) cells and cell proliferation, invasion, and migration capacities were investigated by CCK-8 and transwell assays. In vivo tumor model in mice was used to evaluate the role of CKAP4 on growth and metastasis of HCC. The data documented that HCC cells with high CKAP4 levels were featured by low proliferation capability as well as low invasion potential. Interestingly, we found that CKAP4 suppressed the activation of epithelial growth factor receptor (EGFR) signaling, which may partly explain the role of CKAP4 in cell biological behavior of HCC. Further study revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm. Thus, we demonstrate the novel mechanism, for the first time, expression of CKAP4 regulates progression and metastasis of HCC and it may provide therapeutic values in this tumor.

A novel cleaning process for industrial production of xylose in pilot scale from corncob by using screw-steam-explosive extruder.

Steam explosion is the most promising technology to replace conventional acid hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw-steam-explosive extruder was designed and explored for xylose production and lignocellulose biorefinery at the pilot scale. We investigated the effect of different chemicals on xylose yield in the screw-steam-explosive extrusion process, and the xylose production process was optimized as followings: After pre-impregnation with sulfuric acid at 80 °C for 3 h, corncob was treated at 1.55 MPa with 9 mg sulfuric acid/g dry corncob (DC) for 5.5 min, followed by countercurrent extraction (3 recycles), decoloration (activated carbon dosage 0.07 g/g sugar, 75 °C for 40 min), and ion exchange (2 batches). Using this process, 3.575 kg of crystal xylose was produced from 22 kg corncob, almost 90 % of hemicellulose was released as monomeric sugar, and only a small amount of by-products was released (formic acid, acetic acid, fural, 5-hydroxymethylfurfural, and phenolic compounds were 0.17, 1.14, 0.53, 0.19, and 1.75 g/100 g DC, respectively). All results indicated that the screw-steam-explosive extrusion provides a more effective way to convert hemicellulose into xylose and could be an alternative method to traditional sulfuric acid hydrolysis process for lignocellulose biorefinery.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination.

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19-71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS + HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1-18.9 months) but was only 10.4 months (95 % CI 8.5-12.2 months) in the CRS group (P = 0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS + HIPEC was significantly higher than that for the patients treated with CRS alone (P = 0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P = 0.141). A multivariate analysis revealed that CRS + HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.

Imatinib mesylate in clinically suspected gastric stromal tumors.

Gastrointestinal stromal tumors (GISTs) occur most frequently in the stomach. Diagnosis of gastric GIST is not always clear before surgery. Flexible endoscopy may suggest the nature of the lesion (a bulky tumor with preserved mucosa); however, biopsy is rarely diagnostic. Therefore, diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained. Based on the excellent efficacy of imatinib mesylate (IM) in the treatment of GIST, we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors. In conclusion, the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

[Effects of straw-returning combined with application of microbial inoculants on soil aggregates and related nutrients]. / ç§¸ç§†è¿˜ç”°é æ–½ä¿ƒè èŒå‰‚å¯¹åœŸå£¤å›¢èšä½“åŠå ¶å »åˆ†çš„å½±å“.

We analyzed the particle size distribution of soil aggregates in 0-20 and 20-40 cm soil layers of rice-wheat rotation field based on a field plot test with two treatments, conventional straw returning (CK) and straw returning with the addition of straw decomposition promoting microbial inoculants (IT). We evaluated the water stability indices of soil aggregates (the number of soil water stable large aggregates R0.25, the average weight diameter MWD, and the geometric average diameter GMD), and measured the contents of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) in the soil aggregates of ＜0.053, 0.053-0.25, 0.25-1, ＞1 mm. The results showed that: 1) The number of aggregates ＜0.053, 0.053-0.25, ＞0.25 mm in the 0-20 and 20-40 cm soil layers under IT decreased by 10.0% and 6.8%, increased by 3.0% and 5.7%, and 17.9% and 26.1% compared with CK, respectively. IT effectively increased R0.25, MWD, and GMD by 26.4%, 20.0%, 18.2% and 18.2%, 10.5%, 10.0% in 0-20 and 20-40 cm soil, respectively. 2) Compared to CK, the TP content of 0.25-1 mm aggregates in 0-20 and 20-40 cm soil under IT was significantly increased by 40.3% and 37.5%, respectively, without difference in TN and SOC contents. There was no significant difference in nutrient contents of the other aggregates between the treatments. The contents of SOC and TN in large aggregates (>0.25 mm) were higher than those in silty aggregates (<0.053 mm). Compared to CK, the cumulative contribution rates of SOC, TN and TP of <0.053 mm aggregates under IT were decreased in two soil layers. There was no significant difference in the nutrient cumulative contribution rates of 0.053-0.25 mm aggregates between treatments. The cumulative contribution rates of SOC, TN, and TP of large aggregates (>0.25 mm) under IT were 32.1%, 19.6%, 52.8% and 22.8%, 11.8%, 42.9% higher than those under CK in 0-20 and 20-40 cm soils, respectively. 3) The number of <0.053 mm aggregates was significantly negatively correlated with SOC and TP contents, while that of 0.053-0.25 mm aggregates was negatively correlated with nutrient content. The number of large aggregates (>0.25 mm) were significantly positively correlated with SOC, TN, and TP contents. In conclusion, straw returning with microbial-inoculant addition could promote the formation of soil macroaggregates (>0.25 mm), and improve the water stability of soil aggregates, increasing nutrient contents in soil macroaggregates, with the nutrients transferring from silty aggregates to macroaggregates.

Endovascular treatment for massive haemoptysis due to pulmonary pseudoaneurysm: report of 23 cases.

PURPOSE: To evaluate the safety and effectiveness of endovascular treatment for massive haemoptysis caused by pulmonary pseudoaneurysm (PAP). METHODS: The clinical data, imaging data, and endovascular treatment protocol of 23 patients with massive haemoptysis caused by continuous PAP were retrospectively analysed. The success, complications, postoperative recurrence rate, and influence of the treatment on pulmonary artery pressure were also evaluated. RESULTS: Nineteen patients with a bronchial artery-pulmonary artery (BA-PA) and/or nonbronchial systemic artery-pulmonary artery (NBSA-PA) fistula underwent bronchial artery embolization (BAE) and/or nonbronchial systemic artery embolization (NBSAE) + pulmonary artery embolization (PAE). The pulmonary artery (PA) pressures before and after embolization were 52.11 ± 2.12 (35-69 cmH2O) and 33.58 ± 1.63 (22-44 cmH2O), respectively (P = 0.001). Four patients did not have a BA-PA and/or NBSA-PA fistula. Embolization was performed in two patients with a distal PAP of the pulmonalis lobar arteria. Bare stent-assisted microcoils embolization was performed in the other two patients with a PAP of the main pulmonary lobar arteries. The PA pressures of the four patients before and after treatment were 24.50 ± 1.32 (22-28 cmH2O) and 24.75 ± 1.70 (22-29 cmH2O), respectively (P = 0.850). The technique had a 100% success rate with no serious complications and a postoperative recurrence rate of 30%. CONCLUSION: Endovascular treatment is safe and effective for massive haemoptysis caused by PAP. BAE and/or NBSAE can effectively reduce pulmonary hypertension in patients with a BA-PA and/or NBSA-PA fistula.

The significance of time interval between perioperative SOX/XELOX chemotherapy and clinical decision model in gastric cancer.

Introduction: To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses. Methods: Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC). Results: Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9-13 weeks, 63 (18.00%) over 13 weeks. Patients' 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit. Discussion: In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened.

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy.

BACKGROUND: Current tumor regression grade (TRG) evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results. The recent six-tier system (JGCA2017-TRG) recommended by the Japanese Gastric Cancer Association (JGCA) is worth investigating, as four-tier TRG systems are favored in various parts of the world. AIM: To compare the predictive accuracies of five published TRG systems. METHODS: Data were retrospectively collected from patients with locally advanced gastric cancer (LAGC) who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution. Outcomes were overall survival (OS) and disease-free survival (DFS), which were evaluated separately using the following TRG systems: JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard. RESULTS: All five published TRG systems were independent predictors for OS and DFS. Concordance indices of the JGCA2017, JGCA, Becker, AJCC/CAP-TRG, and Mandard systems were 0.651/0.648 0.652/0.649, 0.693/0.695, 0.688/0.685, and 0.674/0.675 for OS and DFS, respectively. The four-tier Becker system showed the highest c-index, which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems (P < 0.05 in OS and DFS). When residual tumor percentages were reset as: "no residual tumor", < 10%, < 100%, and "no response", the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS, which was superior to the other five systems. CONCLUSION: The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification. The four-tier Becker system is more suitable for LAGC patients. A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms.

BACKGROUND: Fumarase catalyzes the reversible hydration of fumarate to L-malate and is a key enzyme in the tricarboxylic acid (TCA) cycle and in amino acid metabolism. Fumarase is also used for the industrial production of L-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications. RESULTS: A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF) was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from Bacteroides sp. 2_1_33B and Parabacteroides distasonis ATCC 8503 (26% identical and 43% similar). The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in E. coli BL21(DE3)pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form L-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg(2+). The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: K(m) = 0.48 mM, V(max) = 827 µM/min/mg, and k(cat)/K(m) = 1900 mM/s. CONCLUSIONS: We isolated a novel fumarase gene, fumF, from a sequence-based screen of a plasmid metagenomic library from uncultivated marine microorganisms. The properties of FumF protein may be ideal for the industrial production of L-malate under higher temperature conditions. The identification of FumF underscores the potential of marine metagenome screening for novel biomolecules.

[Surgical treatment results and prognostic analysis of 514 cases with gastroesophageal junction carcinoma].

OBJECTIVE: To clarify the important clinicopathological and therapeutical factors affecting the prognosis of patients with gastroesophageal junction carcinoma. METHODS: Data of 514 cases with gastroesophageal junction carcinoma who underwent surgical treatment from September 1995 to January 2007 was retrospectively analyzed. Relevant prognostic factors were studied with univariate and multivariate analysis. RESULTS: For all 514 cases (424 men and 90 women), the median age was 63 years. The 1-, 3- and 5-year survival rates of this group were 74.8%, 42.1% and 29.1%, respectively. Gross type, TNM classification, histological type, vascular invasion and extent of surgical resection affected patients' survival remarkably. There was no significant difference in survival between operative approaches (via laparotomy or left thoracotomy) (P > 0.05). Long-term survival was similar between proximal subtotal gastrectomy and total gastrectomy in advanced cases (P > 0.05). For stage II and III tumors, patients with neoadjuvant chemotherapy had better prognosis than those without (P < 0.05). Cox multivariate regression analysis revealed TNM classification and vascular invasion were independent prognostic factors. CONCLUSIONS: TNM classification and vascular invasion are independent prognostic factors for gastroesophageal junction carcinoma. Neoadjuvant chemotherapy may improve prognosis of the patients with stage II and III tumors. Radical resection should be achieved with rational surgical procedures tailored by tumor position, size, staging and so on.

Cytoskeleton-Associated Protein 4, a Promising Biomarker for Tumor Diagnosis and Therapy.

Cytoskeleton-associated protein 4 (CKAP4) is located in the rough endoplasmic reticulum (ER) and plays an important role in stabilizing the structure of ER. Meanwhile, CKAP4 is also found to act as an activated receptor at the cell surface. The multifunction of CKAP4 was gradually discovered with growing research evidence. In addition to the involvement in various physiological events including cell proliferation, cell migration, and stabilizing the structure of ER, CKAP4 has been implicated in tumorigenesis. However, the role of CKAP4 is still controversial in tumor biology, which may be related to different signal transduction pathways mediated by binding to different ligands in various microenvironments. Interestingly, CKAP4 has been recently recognized as a serological marker of several tumors and CKAP4 is expected to be a tumor therapeutic target. Therefore, deciphering the gene status, expression regulation, functions of CKAP4 in different diseases may shed new light on CKAP4-based cancer diagnosis and therapeutic strategy. This review discusses the publications that describe CKAP4 in various diseases, especially on tumor promotion and suppression, and provides a detailed discussion on the discrepancy.

Management recommendations for patients with chronic kidney disease during the novel coronavirus disease 2019 (COVID-19) epidemic.

COVID-19 has become a pandemic and it has already spread to at least 171 countries/regions. Chronic kidney disease (CKD) is a global public health problem with a total of approximately 850 million patients with CKD worldwide and 119.5 million in China. Severe COVID-19 infection may damage the kidney and cause acute tubular necrosis, leading to proteinuria, hematuria and elevated serum creatinine. Since the SARS-CoV-2 enters the cells by binding to the angiotensin-converting enzyme 2 receptor, some doctors question its ability to increase the risk and severity of developing COVID-19. Neither clinical data nor basic scientific evidence supports this assumption. Therefore, patients who take angiotensin-converting enzyme inhibitor or angiotensin receptor blocker are not advised to change their therapy. Patients with CKD are generally the elderly population suffering from multiple comorbidities. Moreover, some patients with CKD might need to take glucocorticoids and immunosuppressants. Dialysis patients are recurrently exposed to a possible contaminated environment because their routine treatment usually requires three dialysis sessions per week. Considering all the above reasons, patients with CKD are more vulnerable to COVID-19 than the general population. The development of COVID-19 may worsen the impaired kidney function and further lead to rapid deterioration of kidney function and even death. Strict comprehensive protocols should be followed to prevent the spread of COVID-19 among patients with CKD. In this review, we provide some practical management recommendations for health care providers, patients with CKD, dialysis patients and dialysis facilities.