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1.
Gastric Cancer ; 24(1): 245-257, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32712769

RESUMO

BACKGROUND: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. METHODS: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. RESULTS: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. CONCLUSIONS: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

2.
Oncologist ; 26(1): e99-e110, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32864840

RESUMO

BACKGROUND: The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging. PATIENTS AND METHODS: Clinicopathological data of 1,791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy. RESULTS: In the development cohort, the 5-year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < .001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < .001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p < .001), and model stability (time-dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p < .05). CONCLUSION: We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy. IMPLICATIONS FOR PRACTICE: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi-institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy.

3.
Asian J Surg ; 44(1): 116-122, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32467008

RESUMO

BACKGROUND: Compared with other histologic types, signet ring cell gastric carcinoma (SRC) has unique oncological characteristics, and its implication on the prognosis of gastric cancer patients remains unclear. The purpose of this study was to evaluate the prognostic impact of body mass index (BMI) on SRC patients. METHODS: A retrospective analysis was performed using the clinical records of 3342 patients with SRC or tubular adenocarcinoma who underwent radical gastrectomy between 2000 and 2014. Patients were divided into three groups according to histologic subtype: SRC, well-to-moderately differentiated adenocarcinoma (WMD), and poorly differentiated adenocarcinoma (PD). We compared the survival of SRC patients with that of tubular adenocarcinoma patients according to BMI. RESULTS: The 5-year survival of SRC was significantly worse than that of WMD (P < 0.001) but superior to that of PD (P < 0.001). BMI-stratified analysis showed that in the high-BMI group, the prognosis of SRC was similar to that of WMD (P > 0.05) and better than that of PD (P < 0.001). In normal-BMI patients, SRC had a worse prognosis than WMD (P < 0.001) but a more favorable prognosis than PD (P < 0.001). SRC among low-BMI patients displayed much poorer survival than did both WMD (P < 0.001) and PD (P = 0.005). Multivariate analysis indicated that the risk of death was the lowest in SRC patients with a high BMI and highest for SRC patients with a low BMI (low-BMI hazard ratio: SRC 1 vs. WMD 0.51 and PD 0.53). CONCLUSION: SRC has worse prognostic impact as BMI decreases. BMI leads to differing prognosis of SRC compared with tubular adenocarcinoma.

5.
Surg Endosc ; 35(1): 113-123, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31953725

RESUMO

BACKGROUND: Numerous studies have shown that the short-term efficacy of three-dimensional (3D) laparoscopic radical gastrectomy (LG) is comparable to that of two-dimensional (2D)-LG. Whether 3D-LG affects the recurrence patterns of gastric cancer (GC) patients has not been investigated. METHODS: From January 2015 to April 2016, a total of 419 patients were recruited for a phase III clinical trial (NCT02327481), which compared the short-term outcomes between the 2D and 3D groups. The long-term efficacy including recurrence patterns was compared between the 2D and 3D groups in this retrospective study. Multivariate analyses were performed to determine whether 3D-LG affects the recurrence patterns. RESULTS: Ultimately, 401 patients were analyzed (197 in the 2D-LG group and 204 in the 3D-LG group), and no differences were observed in the clinicopathological data between the two groups. There were no significant differences between the two groups in the recurrence types, first recurrence time or recurrence-free survival (RFS) (all p > 0.05). According to the 7th American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system, both groups were stratified into pathological stages I, II, and III. The stratified analysis showed no significant differences in RFS or overall survival (OS) among patients in each subgroup (all p > 0.05). The multivariate analysis of RFS showed that tumor diameter, pTNM stage, lymphovascular invasion, and adjuvant chemotherapy were independent factors (all p < 0.05). The multivariate analysis of post-recurrence survival (PRS) showed that adjuvant chemotherapy was an independent protective factor (p = 0.043). CONCLUSIONS: 3D-LG for GC did not differ significantly from 2D-LG in the effects on 3-year recurrence patterns, RFS and OS, which provides more tumor-related evidence for 3D technology. And due to the technological similarity, it may have certain reference value for robotic-assisted gastrectomy. Further multicenter, large-scale clinical trials are warranted.

6.
Cancer Med ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270989

RESUMO

BACKGROUND: Perioperative C-reactive protein (CRP) levels have effects on the prognosis of cancer patients. We intended to determine the prognostic value of combining the two for gastric cancer (GC). METHODS: Data were extracted from a clinical trial. By calculating the area under the curve (AUC) and the C-index, the predictive value of CRPs among different time points, including preoperative (pre-CRP), postoperative days 1, 3, and 5 (post-CRPs), and postoperative maximum CRP (post-CRPmax ), was derived. Multivariate analysis was performed to further explore the independent variates for recurrence-free survival (RFS). RESULTS: Finally, 401 patients were available in the present study. For RFS, higher AUC (0.692) and concordance index (0.678) of pre-CRP were observed when compared with those of post-CRPs. Further, among post-CRPs, post-CRPmax had the highest predictive values (AUC: 0.591; concordance index: 0.585) among the other post-CRPs. The threshold values in predicting RFS for pre-CRP and post-CRPmax were 3.1 mg/L and 77.1 mg/L. Multivariate analysis showed both pre-CRP≥3.1 mg/L (high-pre-CRP) and post-CRPmax ≥77.1 mg/L (high-post-CRPmax ) were risk factors for RFS. Postoperative chemotherapy benefit was further analyzed for patients with stage II/III GC and indicated that patients with pre-CRP<3.1 mg/L had better prognosis without benefit from postoperative adjuvant chemotherapy (ACT), p = 0.557. In high-pre-CRP patients, only patients with post-CRPmax ≥77.1 mg/L but not post-CRPmax <77.1 mg/L benefited from postoperative ACT (RFS: 33.2% vs 49.9% for non-chemotherapy group and chemotherapy group, respectively, p = 0.037). Analyses for overall survival obtained the similar outcomes. CONCLUSIONS: Both high-pre-CRP and high-post-CRPmax are associated with worse prognosis in GC. ACT seems to only improve the prognosis for stage II/III GC with pre-CRP≥3.1 mg/L and post-CRPmax ≥77.1 mg/L after radical gastrectomy. Further studies are needed to confirm these findings and explore the potential mechanism.

7.
Nat Commun ; 11(1): 6352, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311518

RESUMO

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.


Assuntos
Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Proteína HMGB1/metabolismo , Neoplasias Gástricas/imunologia , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Moléculas de Adesão Celular/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Lectinas/metabolismo , Masculino , Pessoa de Meia-Idade , Nectinas/metabolismo , Estadiamento de Neoplasias , Prognóstico , Receptores Virais/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo
8.
BMC Musculoskelet Disord ; 21(1): 736, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176762

RESUMO

BACKGROUND: We investigate the safety of the application of the Rigidfix cross-pin system via different tibial tunnels in the tibial fixation during anterior cruciate ligament (ACL) reconstruction. METHODS: Five adult fresh cadaver knees were fixed with the Rigidfix cross-pins in the tibial fixation site during ACL reconstruction. Two different tibial tunnel groups were established: in group A, the tunnel external aperture was placed at the 25° angle of coronal section; in group B, the tunnel external aperture was placed at the 45° angle of coronal section. The guide was placed at the plane 0.5 mm below articular facet through the tibial tunnel, with three rotation positions set at 0°, 30°, and 60° slopes. The incidences of iatrogenic injuries at tibial plateau cartilage (TPC), medial collateral ligament (MCL), and patellar tendon in three different slope angles were calculated in groups A and B and the results were analyzed by using chi square test. RESULTS: The iatrogenic injuries at MCL, TPC, and patellar tendon could occur after the Rigidfix cross-pin system was placed 5 mm below tibial plateau cartilage for ACL reconstruction. The incidences of TPC injury (χ2 = 5.662, P = 0.017) and MCL injury (P = 0.048, Fisher exact probability method) were significantly lower in group A than in group B. However, the incidence of patellar tendon injury showed no significant difference between these two groups (χ2 = 0.120, P = 0.729). CONCLUSIONS: When the Rigidfix cross-pin system is used for ACL reconstruction at the tibial fixation site, the external aperture of tibial tunnel should not be placed at the excessively posterosuperior site, to avoid MCL and TPC injuries.

9.
Aging (Albany NY) ; 12(19): 18982-19011, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052878

RESUMO

The effect of POC1 centriolar protein A (POC1A) on gastric cancer (GC) has not been clearly defined. In this study, POC1A expression and clinical information in patients with GC were analyzed. Multiple databases were used to investigate the genes that were co-expressed with POC1A and genes whose changes co-occurred with genetic alternations of POC1A. Moreover, the TISIDB and TIMER databases were used to analyze immune infiltration. The GSE54129 GC dataset and LASSO regression model (tumor vs. normal) were employed, and 6 significant differentially expressed genes (LAMP5, CEBPB, ARMC9, PAOX, VMP1, POC1A) were identified. POC1A was selected for its high expression in adjacent tissues, which was confirmed with IHC. High POC1A expression was related to better overall and recurrence-free survival. GO and KEGG analyses demonstrated that POC1A may regulate the cell cycle, DNA replication and cell growth. Furthermore, POC1A was found to be correlated with immune infiltration levels in GC according to the TISIDB and TIMER databases. These findings indicate that POC1A acts as a tumor suppressor in GC by regulating the cell cycle and cell growth. In addition, POC1A preferentially regulates the immune infiltration of GC via several immune genes. However, the specific mechanism requires further study.

10.
BMC Cancer ; 20(1): 1002, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059606

RESUMO

BACKGROUND: The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. METHODS: This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). RESULTS: In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p < 0.05). CONCLUSIONS: Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

11.
Ann Surg ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889876

RESUMO

OBJECTIVE: To evaluate the short-term outcomes of patients with gastric cancer (GC) who received robotic distal gastrectomy (RDG) or laparoscopic distal gastrectomy (LDG). SUMMARY BACKGROUND DATA: Despite the increasing use of RDG in patients with GC, its safety and efficacy compared to those of LDG have not been elucidated in a randomized controlled trial (RCT). METHODS: Three hundred patients with cT1-4a and N0/+ between September 2017 and January 2020 were enrolled in this RCT at a high-volume hospital in China. The short-term outcomes were compared between the groups. RESULTS: The modified intention-to-treat analysis included data from 283 patients (RDG group: n = 141) and (LDG group: n = 142). Patients in the RDG group exhibited faster postoperative recovery, milder inflammatory responses, and reduced postoperative morbidity (9.2% vs. 17.6%, respectively, p = 0.039). Higher extraperigastric lymph nodes (LNs) were retrieved in the RDG group (17.6 ±â€Š5.8 vs. 15.8 ±â€Š6.6, p = 0.018) with lower noncompliance rate (7.7% vs. 16.9%, respectively, p = 0.006). Additionally, patients in the RDG group were more likely to initiate adjuvant chemotherapy earlier (median [interquartile range] postoperative days: 28 [24-32] vs. 32 [26-42], p = 0.003). Although total hospital costs were higher in the robotic group than in the laparoscopic group, the direct cost was lower for RDG than for LDG (all p < 0.001). CONCLUSIONS: RDG is associated with a lower morbidity rate, faster recovery, milder inflammatory responses, and improved lymphadenectomy. Additionally, faster postoperative recovery in the RDG group enables early initiation of adjuvant chemotherapy. Our results provide evidence for the application of RDG in patients with GC.

12.
Eur J Surg Oncol ; 46(12): 2221-2228, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32859432

RESUMO

OBJECTIVE: To investigate a reasonable lymph node (N) staging system for gastric cancer patients with ≤15 retrieved lymph nodes (LNs). METHODS: The clinicopathological and follow-up data of patients with ≤15 LNs were obtained from the US Surveillance, Epidemiology, and End Results (SEER) database to analyze the impact of the number of retrieved LNs and metastatic status on the prognosis. In addition, external validation was achieved with data from two medical centers in China. RESULTS: A total of 18,139 gastric cancer patients with 1-15 retrieved LNs from the SEER database were enrolled and randomly divided into the training group and the internal validation group. A new LN staging system, mNr staging (mNr0-4; 5 stages), was established according to the number of retrieved LNs and the metastatic rate. Compared with the TNM and TNrM staging systems (established by Wang J; misclassification rates of 50.4% and 62.5%, respectively), the mTNrM staging system had a lower misclassification rate (23.4%). Furthermore, there was a significant difference in the 5-year overall survival (OS) rate between the mTNrM staging subgroups (p < 0.05); however, no significant difference was found in the 5-year OS rate of partial adjacent stages in the TNM (8th edition) and TNrM (p > 0.05) staging systems. Similar results were obtained in the external validation cohort. CONCLUSION: mNr and mTNrM staging systems can efficiently distinguish a survival difference in patients who undergo gastrectomy with ≤15 retrieved LNs, with more accurate predictions of the 5-year OS rate of patients compared with the TNM and TNrM staging systems.

13.
BMC Cancer ; 20(1): 638, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646396

RESUMO

BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers. For colorectal cancer, a benefit that was associated with postdiagnosis aspirin use was observed for overall survival and cancer-specific survival [HR = 0.83, 95%CI(0.75, 0.9.);HR = 0.78, 95%CI(0.66, 0.92), respectively. However, a prediagnosis of aspirin use did not provide a benefit for overall or cancer-specific survival in colorectal cancer. HR values for overall and cancer-specific survival benefits for colorectal cancer associated with both prediagnosis and postdiagnosis aspirin were as follows: HR = 0.75, 95%CI(0.61, 0.92) and HR = 0.78, 95%CI(0.73, 0.85), respectively. In addition, the survival benefit of postdiagnosis aspirin use appeared to be confined to patients with mutated PIK3CA tumors [HR = 0.78, 95%CI(0.50, 0.99)] and was positive for PTGS2 (COX-2) expression [HR = 0.75, 95%CI(0.43, 1.30)]. CONCLUSIONS: These findings provide further indications that postdiagnosis aspirin use improves overall survival and cancer-specific survival in colorectal cancer, especially for patients who are positive for PTGS2 (COX-2) expression and PIK3CA-mutated tumors. However, aspirin therapy does not improve overall survival in esophageal and gastric cancers, although the meta-analysis was mainly limited to retrospective studies.

14.
Mol Cancer ; 19(1): 114, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650804

RESUMO

BACKGROUND: BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. METHODS: We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. RESULTS: BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. CONCLUSIONS: Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.

15.
J Dermatol ; 47(9): 1046-1049, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32613680

RESUMO

We retrospectively analyzed 66 patients with palmoplantar pustulosis (PPP) from January 1994 to September 2019 in our department. Interleukin-36 receptor antagonist gene (IL36RN) intron 3 c.115+6T>C mutation was present in two out of 27 patients (7.4%). Both cases developed generalized pustular psoriasis and/or acrodermatitis continua of Hallopeau later. Topical medications and phototherapy were used in 93.9% and 28.8% of patients, respectively, while 60.6% received systemic agents. The majority of patients (60.6%) responded to treatment, but episodes of flare-up existed. The demographic data of our patients with PPP showed female predominance (59.1%), middle-age onset (44.2 years old) and current smokers (62.1%). Generalized pustular psoriasis initially presenting as palmoplantar lesions may be misdiagnosed as PPP, and the presence of IL36RN mutation may serve to predict or confirm the diagnosis of future generalized pustular psoriasis or acrodermatitis continua of Hallopeau. To our knowledge, this is the largest demographic study of PPP in Taiwan.

16.
Eur J Surg Oncol ; 46(10 Pt B): e7-e13, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32709375

RESUMO

Most gastric cancer (GC) cases are diagnosed at an advanced stage in China. Because of its high morbidity and mortality, GC remains a major health crisis in China. Surgical resection is the only potentially curative treatment for GC. Owing to being minimally invasive, laparoscopic radical gastrectomy has been widely used in various countries, especially in East Asia, since Kitano first reported the feasibility and safety of this technique. Although laparoscopic gastric surgery was introduced relatively late in China, Chinese surgeons have made unique contributions to the research and clinical practice of laparoscopic gastric surgery due to the large number of clinical cases. This review focuses on the progress in laparoscopic gastrectomy for advanced stage GC in China, including reasonable approaches in different areas and oncologic efficacy of laparoscopic surgery, and introduce advanced technology to facilitate surgeons to rapidly overcome the learning curve in clinical practice.

17.
Br J Cancer ; 123(7): 1131-1144, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32606358

RESUMO

BACKGROUND: Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. METHODS: We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. RESULTS: We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. CONCLUSIONS: Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

18.
J Gastrointest Surg ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410176

RESUMO

PURPOSE: We have shown that activation of the receptor tyrosine kinase (RTK)-RAS pathway in gastric adenocarcinoma (GA) promotes acquisition of cancer stem-like cell (CSC) phenotypes including metastasis and chemotherapy resistance. Here, we evaluated the prognostic value of the CSC marker CD44 and the RTK-RAS activation marker phosphorylated MEK (p-MEK) in patients with resectable GA. METHODS: CD44 and p-MEK were measured in tumors from GA patients who underwent curative-intent gastrectomy at Fujian Medical University Union Hospital (FMUUH, n = 134) and Memorial Sloan Kettering Cancer Center (MSKCC, n = 56). Overall survival (OS) was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling. RESULTS: Despite multiple significant differences in clinicopathologic characteristics between the FMUUH and MSKCC cohorts, high CD44 and high p-MEK expression were both independent negative prognostic factors for OS on univariate analysis in both cohorts (p < 0.05). Both factors were also significant on multivariate analysis when the cohorts were combined (p ≤ 0.003). On subgroup analysis, the 5-year OS of patients with both high CD44 and high p-MEK was 39.5-41.6% compared with 55.4-66.4% for patients with low CD44. High CD44 expression was associated with more advanced TNM stage in the FMUUH cohort and larger tumor size and undifferentiated histology in the MSKCC cohort. High p-MEK was associated with undifferentiated histology in the FMUUH cohort and larger tumor size in the MSKCC cohort. CONCLUSIONS: Increased CD44 and p-MEK expression are predictive of worse OS in GA patients. Thus, targeting the RTK-RAS pathway may benefit patients with CD44-positive, RAS-activated GA by inhibiting metastasis and reversing chemotherapy resistance.

19.
Br J Cancer ; 123(3): 418-425, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32451469

RESUMO

BACKGROUND: In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear. METHODS: Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated. RESULTS: A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P < 0.001). Multivariable analysis revealed that the number of pre-operative positive tumour markers was an independent prognostic factor (P < 0.05). For patients with abnormal pre-operative tumour markers, normalisation of tumour markers after surgery is an independent prognostic protective factor (hazard ratio (HR) = 0.618; 95% confidence interval (CI) = 0.414-0.921), and patients with both positive post-operative tumour markers had double the risk of overall death (HR = 2.338; 95% CI = 1.071-5.101). Similar results were observed in the internal validation and external validation cohorts. CONCLUSION: Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival.

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