Thrombosis and survival in essential thrombocythemia: A regional study of 1,144 patients

To identify prognostic factors affecting thrombosis‐free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real‐life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow‐up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years (P < 0.0054, 95% CI 1.18–2.6), previous thrombosis (P < 0.0001, 95% CI 1.58–4.52) and the presence of at least one cardiovascular risk factor (P = 0.036, 95% CI 1.15–3.13). Patients with a previous thrombosis occurred ≥24 months before ET diagnosis had a shorter TFS compared to patients with a previous thrombosis occurred <24 months (P = 0.0029, 95% CI 1.5–6.1); furthermore, patients with previous thrombosis occurred <24 months did not show a shorter TFS compared with patients without previous thrombosis (P = 0.303, 95% CI 0.64–3.21). At multivariate analysis for TFS, only the occurrence of a previous thrombosis maintained its prognostic impact (P = 0.0004, 95% CI 1.48–3.79, RR 2.36). The 10‐year OS was 89.9% (95% CI 87.3–92.5): at multivariate analysis for OS, age >60 years (P < 0.0001), anemia (P < 0.0001), male gender (P = 0.0019), previous thromboses (P = 0.0344), and white blood cell >15 × 10⁹/l (P = 0.0370) were independent risk factors. Previous thrombotic events in ET patients are crucial for TFS but their importance seems related not to the occurrence per se but mainly to the interval between the event and the diagnosis. Am. J. Hematol. 89:542–546, 2014. © 2014 Wiley Periodicals, Inc.     

High circulating VEGF level predicts poor overall survival in lung cancer

Purpose

Vascular endothelial growth factor (VEGF) is considered as the best-validated key regulator of angiogenesis, while the prognostic role of circulating VEGF in lung cancer remains controversial. We conducted a meta-analysis to evaluate the prognostic role of circulating VEGF.

Methods

Nineteen studies with a total number of 2,890 patients were analyzed in our meta-analysis. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) were used to quantify the predictive ability of circulating VEGF on survival.

Results

The pooled HR of all 17 studies evaluating overall survival (OS) was 1.29 (95 % CI 1.19–1.40, p < 0.001), indicating high circulating VEGF predicted poor OS. When grouped by disease stages, the pooled HRs were 0.97 (95 % CI 0.47–1.47, p < 0.001) for operable stage and 1.34 (95 % CI 1.18–1.49, p < 0.001) for inoperable stage. The pooled HRs were 1.28 (95 % CI 1.15–1.42, p < 0.001) for serum and 1.31 (95 % CI 1.13–1.49, p < 0.001) for plasma, when categorized by blood sample. Meta-analysis of circulating VEGF related to progression-free survival (PFS) was performed in 7 studies, and the pooled HR was 1.03 (95 % CI 0.96–1.09).

Conclusions

Our results indicate that high level of circulating VEGF predicts poor OS in lung cancer, yet it does not predict poor PFS.     

Maternal adiposity as an independent risk factor for pre‐eclampsia: a meta‐analysis of prospective cohort studies

Studies investigating the association between maternal adiposity and risk of pre‐eclampsia showed contradictory results. Therefore, we performed a meta‐analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre‐eclampsia. We reviewed 1,286 abstracts and finally included 29 prospective cohort studies with 1,980,761 participants and 67,075 pre‐eclampsia events. We pooled data with a random‐effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal‐weight (reference), overweight, obese and severely obese. In the cohort studies that unadjusted for pre‐eclampsia risk factors, the pooled unadjusted relative risks (RR) with 95% confidence intervals (95%CI) for pre‐eclampsia of overweight, obese and severely obese women were 1.58 (95% CI 1.44–1.72, P < 0.001), 2.68 (95% CI 2.39–3.01, P < 0.001) and 3.12 (95% CI 2.24–4.36, P < 0.001), respectively. In those cohorts that adjusted for pre‐eclampsia risk factors, the pooled unadjusted RRs for pre‐eclampsia of overweight, obese and severely obese women were 1.70 (95% CI 1.60–1.81, P < 0.001), 2.93 (95% CI 2.58–3.33, P < 0.001) and 4.14 (95% CI 3.61–4.75, P < 0.001), respectively. Sensitivity analysis showed maternal adiposity was associated with increased risk of pre‐eclampsia in both nulliparous and multiparas women. In conclusion, overweight or obese pregnant women have a substantially increased risk of pre‐eclampsia, and maternal adiposity is an independent risk factor of pre‐eclampsia.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

Hormonal and reproductive factors and risk of esophageal cancer in women: a meta‐analysis

Currently published studies on the relationship between hormonal and reproductive factors and esophageal cancer (EC) risk in women have yielded contradictory findings. For a better understanding of this relationship, we first performed this meta‐analysis by pooling all available publications. Sixteen independent studies were retrieved after a comprehensive search in PubMed and Embase databases. The pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were calculated. The pooled RRs implicated that hormone replacement therapy was negatively associated with the risk of EC (RR = 0.72, 95% CI 0.60–0.86, P < 0.001) and esophageal squamous cell carcinoma (RR = 0.68, 95% CI 0.48–0.97, P = 0.031). Menopausal women were at an increased risk of EC (RR = 1.47, 95% CI 1.07–2.03, P = 0.018), particularly esophageal squamous cell carcinoma (RR = 1.66, 95% CI 1.12–2.48, P = 0.012). Additionally, decreased risk of EC (RR = 0.79, 95% CI 0.68–0.92, P = 0.003) and esophageal adenocarcinoma (RR = 0.66, 95% CI 0.53–0.82, P < 0.001) was demonstrated among women with breast‐feeding history. Moreover, such associations were more significant among Caucasians, but not Asians. Our study suggests that menopause is an independent risk factor for EC, while hormone replacement therapy and breast‐feeding history play a protective role against EC, particularly among Caucasians. All results are consistent with the hypothesis that effects of estrogen may lower the risk of EC in women.     

Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis

The current meta-analysis analyzed the prognostic impact of elevated platelet count before the treatment of malignant mesothelioma (MM). We performed a search for articles published up to April 15, 2016 in PubMed, MEDLINE, EMBASE, and Web of Science, which evaluated elevated platelet count and survival outcome of MM. STATA version 12 was used for statistical analysis. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were combined to calculate overall effects. The assessment of heterogeneity was tested by the Cochran Q and I² statistics. The sensitivity and meta-regression analyses were performed to explore the origin of heterogeneity. We analyzed 18 eligible studies (3602 patients) that evaluated the correlation between pretreatment platelet count and overall survival (OS). Elevated platelet count was a prognostic factor of poor OS, with a pooled HR of 1.56 (95% CI = 1.36–1.77). However, significant heterogeneity was observed in the included studies (I² = 86.0%, p < 0.001). Sensitivity and meta-regression analyses were performed to trace the origin of heterogeneity. Only the variable type (multivariable or univariate model) was traced as the origin of heterogeneity. Hence, we conducted a subgroup analysis of variable type. The HR was 1.66 (95% CI = 1.41–1.91) in the multivariable group and no significant heterogeneity was observed (I² = 0.0%, p = 0.476). In conclusion, high pretreatment platelet count resulted in poor OS in MM. Therefore, platelet count could be an adequate and useful factor of prognosis for MM.     

Death decoy receptor overexpression and increased malignancy risk in colorectal cancer

AIM:To evaluate human epidermal growth factor receptor 2(HER2)and death decoy receptor(DcR3)as colorectal cancer prognostic indicators.METHODS:Colorectal carcinoma specimens from 300patients were analyzed by immunohistochemistry to detect the staining patterns of HER2 and DcR3.Classification of HER2 staining was carried out using the United States Food and Drug Administration semi-quantitative scoring system,with scores of 0 or 1+indicating a tumor-negative(normal expression)status and scores of 2+and 3+indicating a tumor-positive(overexpression)status.Classification of DcR3 was carried out by quantitating the percentage of positive cells within the stained section,with<10%indicating a tumor-negative status and≥10%indicating a tumor-positive status.Correlation of the HER2 and DcR3 staining status with clinicopathological parameters[age,sex,tumor size,differentiation,and the tumor,node,metastasis(pTNM)classification]and survival was statistically assessed.RESULTS:Tumor-positive status for HER2 and DcR3was found in 18.33%and 58.33%of the 300 colorectal carcinoma specimens,respectively.HER2 tumorpositive status showed a significant correlation with tumor size(P=0.003)but not with other clinicopathological parameters.DcR3 tumor-positive status showed a significant correlation with tumor differentiation(P<0.001),pTNM stage(P<0.001),and lymph node metastasis(P<0.001).However,correlation coefficient analysis did not indicate that a statistically significant correlation exists between tumor-positive status for the HER2 and DcR3 overexpression(P=0.236).Patients with specimens classified as DcR3-overexpressing had a significantly worse overall survival(OS)rate than those without DcR3 overexpression(median OS:42.11vs 61.21 mo;HR=50.27,95%CI:44.90-55.64,P<0.001).HER2 overexpression had no significant impact on median OS(35.10 mo vs 45.25 mo;HR=44.40,95%CI:39.32-49.48,P=0.344).However,patients with specimens classified as both HER2-and DcR3-overexpressing had a significantly poorer median OS than those with only HER2 overexpression(31.80 mo vs 52.20 mo;HR=35.10,95%CI:22.04-48.16,P=0.006).CONCLUSION:HER2 overexpression is not an independent prognostic marker of colorectal cancer,but DcR3 overexpression is highly correlated with lymph node metastasis and poor OS.     

Bendamustine in chronic lymphocytic leukemia: Outcome according to different clinical and biological prognostic factors in the everyday clinical practice

Bendamustine proved to be effective for the treatment of chronic lymphocytic leukemia (CLL). However, the relationship between its activity with clinico‐biological prognosticators has been addressed only in few studies. We retrospectively evaluated the efficacy of bendamustine, in a real‐life contest, on 142 patients, median age 70 years, median number of previous regimens 2 (0–8, 13% previously untreated). Bendamustine was administered for a median number of 4 cycles, in 84% of cases with rituximab. Overall (ORR) and complete response (CRR) rates were 68 and 16.5%, respectively. Multivariate analysis demonstrated a relationship between ORR and number of prior treatments (OR 0.25, 95% CI 0.08–0.71; P = 0.009), del(17p) (OR 0.10, 95% CI 0.03–0.32; P < 0.001) and concomitant rituximab (OR 4.37, 95% CI 1.12–17.04; P = 0.033). The estimated 1‐ and 2‐years overall survival (OS) and progression free survival (PFS) rates were 76, 61, 51, and 26%, respectively. Previous sensitivity to fludarabine (HR 0.36, 95% CI 0.16–0.82), response to bendamustine (HR 0.21, 95% CI 0.10–0.45), and del(17p) (HR 2.18, 95% CI 1.002–4.74) had a prognostic significance in multivariate analysis for PFS, while the number of previous therapies (HR 3.48, 95% CI 1.29–9.38; P = 0.014), concomitant use of rituximab (HR 0.32, 95% CI 0.11–0.93) and response to bendamustine (HR 0.22, 95% CI 0.07–0.66) were significant for OS. Side effects included grade 3–4 neutropenia, infections, thrombocytopenia and anemia which occurred in 40, 14, 14, and 10% of patients, respectively. These results confirm the activity and safety of bendamustine and rituximab combination even in patients with unfavorable clinical and biological features excluding del(17p). Am. J. Heamtol. 88:955–960, 2013. © 2013 Wiley Periodicals, Inc.     

Reduced intensity conditioned allograft yields favorable survival for older adults with B‐cell acute lymphoblastic leukemia

Older adults with B‐cell acute lymphoblastic leukemia (B‐ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B‐ALL age 55 years and older and explored prognostic factors associated with long‐term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55–72) with B‐ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA‐matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3‐year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20–31%) and 47% (95% CI: 41–53%), respectively. Three‐year overall survival (OS) was 38% (95% CI: 33–44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25–43%) versus KPS ≥90 (18%; 95% CI: 12–24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55–60: Relative Risk [RR] 1.51 95% CI: 1.00–2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36–3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38–52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B‐ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42–49, 2017. © 2016 Wiley Periodicals, Inc.     

Development of sorafenib-related side effects in patients diagnosed with advanced hepatocellular carcinoma treated with sorafenib: a systematic-review and meta-analysis of the impact on survival

?Introduction: Clinical markers to predict the benefit from sorafenib in patients diagnosed with hepatocellular carcinoma (HCC) are lacking. A meta-analysis exploring the impact of development of sorafenib-related side effects on survival was conducted.

Areas covered: Eligible studies included all clinical studies reporting on the survival/toxicity relationship in sorafenib-treated HCC patients. Data sources included Pub-Med, the Cochrane Controlled Trials Register, and Google scholar. After exclusion of ineligible studies, 16 studies were included in the analysis. Pooled hazard ratio (HR) for overall survival (OS) for patients developing diarrhoea vs. patients who did not was 0.42 (95% confidence interval (CI): 0.30–0.60; p < 0.00001); pooled HR for patients developing hypertension vs. those who did not was 0.46 (95% CI: 0.30–0.70; p = 0.0003); pooled HR for patients developing hand foot skin reaction vs. those who did not was 0.47 (95% CI: 0.35–0.62; p < 0.00001); pooled HR for OS for all types of skin toxicities was 0.51 (95% CI: 0.36–0.72; p = 0.0002); while pooled HR for OS for a combination of selected side effects (hypertension, HFS and diarrhoea) was 0.38 (95% CI: 0.30–0.48; p < 0.00001). No information was available regarding the impact of thyroid dysfunction or proteinuria.

Expert commentary: This analysis of data demonstrated that the occurrence of sorafenib-related side effects (such as diarrhoea, hypertension and skin toxicities) is associated with a better OS in sorafenib-treated HCC patients.     

Is obesity an indicator of complications and mortality in acute pancreatitis? An updated meta‐analysis

OBJECTIVE: To provide a meta‐analyisis on whether obesity could be a prognostic indicator on the severity, development of complications and mortality of acute pancreatitis (AP). METHODS: Eligible articles were retrieved using electronic databases. Clinical studies evaluating the association between obesity and disease course of patients with AP were included. Weighted mean difference (WMD) and 95% confidence interval (CI) were estimated and pooled using RevMan 4.2.8. RESULTS: In all, 12 clinical studies with a total of 1483 patients were included in the analysis. Obese patients had a significantly increased risk of severe acute pancreatitis (SAP; RR = 2.20, 95% CI 1.82–2.66, P < 0.05), local complication (RR = 2.68, 95% CI 2.09–3.43, P < 0.05), systemic complication (RR = 2.14, 95% CI 1.42–3.21, P < 0.05) and in‐hospital mortality (RR = 2.59, 95% CI 1.66–4.03, P < 0.05) compared with non‐obese patients. CONCLUSIONS: Obesity is a definite risk factor of morbidity and in‐hospital mortality for AP and may serve as a prognostic indicator.     

A systematic review comparing outcomes of surgical resection and non-surgical treatments for patients with hepatocellular carcinoma and portal vein tumor thrombus

Background

The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is very poor. According to most HCC guidelines, sorafenib, transarterial chemoembolization (TACE) or other non-surgical treatments are recommended as the first-line therapy for these patients. However, selected patients with HCC and PVTT can undergo surgical resection (SR). The aim of this meta-analysis was to compare the outcomes of SR with Non-SR for such patients.

Clinical effect of E‐series of prostaglandin receptor 2 and epidermal growth factor receptor signal pathways in the development of esophageal squamous cell carcinoma

Signal pathways mediated by epidermal growth factor receptor (EGFR) and E‐series of prostaglandin receptors (EPs) are closely correlated to the pathogenesis of tumor. This experiment was designed to investigate the expression and clinical significance of EP2 and EGFR in esophageal squamous cell carcinoma (ESCC). Tissue samples were collected reterospectively from 87 patients with ESCC (first diagnosed). The patients were followed up for 5 years after radical surgery. The expression of EP‐2 and EGFR were examined by tissue chip technology and immunohistochemistry methods. Clinicopathological and prognostic impact were evaluated. Overexpression of EGFR and EP‐2 was more observed in ESCC than the control group (58.6% vs. 13.9%; 52.9% vs. 4.88%, P < 0.001, respectively); which correlated with tumor infiltration depth, lymph node metastasis, and tumor‐lymph node‐metastasis staging. Both the EP‐2 and EGFR overexpression were detected in 39 specimens and exhibited the positive correlation (P < 0.001, r = 0.404). Overexpression of EP2 and EGFR exhibited significant correlation with worse 5‐year overall survival than those with negative result (17.6% vs. 27.8%, P = 0.011; 10.9% vs. 34.1%, P < 0.001, respectively). Cox proportional hazard model showed that the T‐staging, lymph node metastasis, and EGFR overexpression were the independent risk factors of the prognosis. The present study exhibited that the overexpression of EP2 and EGFR in ESCC tissues might play an important role in carcinogenesis and the progression of ESCC.     

High doses of β‐blockers and alcohol abstinence improve long‐term rebleeding and mortality in cirrhotic patients after an acute variceal bleeding

Background & aim: We analysed prognostic indicators of long‐term outcome in cirrhotic patients surviving the critical 6‐week period after an episode of acute variceal bleeding. Methods: All patients with oesophageal variceal bleeding from 2001–2007 were prospectively registered. Follow‐up extended from day 42 after index bleeding to last visit, death or liver transplantation (LT). Multivariate Cox regression analysis was performed. Results: Two hundred and fifty variceal bleeding episodes were registered. Fifty‐four patients (26%) died before day 42, and 123 patients were finally included. Median follow‐up was 23.5 months. Nadolol±nitrates alone or combined with variceal ligation were used as prophylaxis in 93% of patients. During follow‐up, 43 patients (35%) experienced rebleeding, 34 (27.5%) died and 10 (8%) were transplanted. Follow‐up β‐blocker dose (HR 0.993, 95% CI 0.987–0.998, P=0.027) and alcohol abstinence (HR 0.324, 95% CI 0.152–0.691, P=0.004) were independent rebleeding predictors. The Cox analysis disclosed the Child–Pugh score (HR 1.24, 95% CI 1.08–1.43, P=0.002), creatinine (HR 1.82, 95% CI 1.17–2.82, P=0.008), β‐blocker dose (HR 0.992, 95% CI 0.987–0.997, P=0.003), viral cirrhosis (HR 2.72, 95% CI 1.31–5.67, P=0.008), hepatocellular carcinoma (HR 9.44, 95% CI 3.54–25.20, P<0.001) and alcohol abstinence (HR 0.29, 95% CI 0.13–0.62, P=0.002) to be independent prognostic markers for mortality/LT. Conclusion: High doses of β‐blockers and alcohol abstinence decrease rebleeding and mortality in cirrhotic patients surviving the 6‐week period after acute variceal bleeding.     

Prognostic significance of ASXL1 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: A meta-analysis

Objectives: Although additional sex comb-like 1 (ASXL1) gene mutations have long been reported in myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML), the prognostic significance has been controversial. Therefore, a meta-analysis to study the impact of ASXL1 mutations on patients with MDS and CMML is useful.

Methods: The identified articles were retrieved from some common databases. We extracted hazard ratios (HRs) for overall survival (OS) and leukemic-free survival (LFS) and P-value of some clinical parameters, which compared AXSL1 mutations to those without from the available studies. Each individual HR and P-value was used to calculate the pooled HR and P-value.

Results: Six studies covering 1689 patients were selected for this meta-analysis. The pooled HRs for OS and LFS were 1.45 (95% confidential interval (CI), 1.24–1.70) and 2.20 (95% CI, 1.53–3.17), respectively. When considering CMML patients alone the HR for OS was 1.50 (95% CI, 1.18–1.90). Additionally, ASXL1 mutations were more frequently found in male (P?=?0.008), older (P?=?0.019), and patients with lower platelets (P?=?0.009) or hemoglobin level (P?=?0.0015) and associated with other mutations such as EZH2, IDH1/2, RUNX1, and TET2.

Discussion: Although our analysis has its limitation, it showed that ASXL1 mutations had significant inferior impact on OS and LFS for French–American–British-defined MDS patients. However, the influence of different types of ASXL1 mutations on patients with MDS still needs illustrating.

Conclusion: ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.     

The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis

Purpose

The prognostic role of matrix metalloproteinase 2 (MMP-2) in gastric cancer remains controversial. We systematically reviewed the evidence for assessment of MMP-2 expression in gastric cancer to elucidate this issue.

Method

Pubmed, Embase and Web of Science were searched to identify eligible studies to evaluate the association of MMP-2 expression and overall survival and clinicopathological features of gastric cancer.

Results

MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients (HR 1.92, 95 % CI 1.48–2.48). Subgroup analysis indicated that MMP-2 overexpression had an unfavorable impact on OS in Asian countries (HR 2.23, 95 % CI 1.57–3.17) and European countries (HR 1.43, 95 % CI 1.13–1.80). Furthermore, MMP-2 overexpression was significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 2.17, 95 % CI 1.64–2.87), the depth of invasion (T3/T4 vs T1/T2: OR 2.59, 95 % CI 1.63–4.12), lymph node metastasis (positive vs negative: OR 2.21, 95 % CI 1.69–2.88), and distant metastasis (positive vs negative: OR 4.44, 95 % CI 1.24–15.94).

Conclusion

This meta-analysis indicated that MMP-2 overexpression might be a predictive factor for poor prognosis for gastric cancer.     

Factors associated with access to antiviral treatment in a multicentre cross‐sectional study of patients with chronic hepatitis B in Italy

Summary. A multicentre cross‐sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg‐positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1–2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2–6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02–2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4–10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5–0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5–0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5–0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3–0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.     

Ki‐67 expression as a prognostic factor in diffuse large B‐cell lymphoma patients treated with rituximab plus CHOP

Background: Assessment of tumor cell proliferation based on Ki‐67 expression yielded conflicting prognostic predictions of patients with diffuse large B‐cell lymphoma (DLBCL). The introduction of rituximab to the DLBCL treatment regime has led to alterations in the significance of previous prognostic factors. Methods: We analyzed Ki‐67 expression and its correlation with prognosis in 144 patients with DLBCL treated with rituximab plus CHOP (R‐CHOP) between July 2003 and January 2008. Results: The complete response (CR) rates following R‐CHOP administration were not significantly different, based on Ki‐67 expression status (P = 0.104). However, higher rates of relapse were observed in the high Ki‐67 expression group (Ki‐67 ≥ 85%, n = 46) with 25.0%, compared to 10.0% in the low Ki‐67 expression group (Ki‐67 < 85%, n = 88) (P = 0.040). The 2‐yr event‐free survival (EFS) rates were 44.3% and 74.1% in the high and low Ki‐67 expression groups, respectively (P = 0.011). The 2‐yr overall survival (OS) rate was 66.4% in the high Ki‐67 expression group and 82.2% in the low Ki‐67 expression group (P = 0.016). In multivariate analysis, Ki‐67 expression was a significant prognostic factor for EFS [hazard ratio (HR) = 2.909; 95% confidence interval (CI) 1.261–6.708; P = 0.012]. Ki‐67 was associated with OS but with borderline significance (HR = 2.876; 95% CI, 0.972–8.508; P = 0.056). Conclusion: Elevated Ki‐67 expression seems to be associated with higher relapse after CR and inferior EFS in patients with DLBCL treated with R‐CHOP.     

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I² = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I² = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010     

Efficacy and safety of cold versus hot snare polypectomy for resecting small colorectal polyps: Systematic review and meta‐analysis

Background and Aim

Safety and effectiveness of cold snare polypectomy (CSP) compared with hot snare polypectomy (HSP) has been reported. The aim of the present study is to carry out a meta‐analysis of the efficacy and safety of HSP and CSP.

Methods

Randomized controlled trials were reviewed to compare HSP with CSP for resecting small colorectal polyps. Outcomes reviewed include complete resection rate, polyp retrieval, delayed bleeding, perforation and procedure time. Outcomes were documented by pooled risk ratios (RR) with 95% confidence intervals (CI) using the Mantel‐Haenszel random effect model.

Results

Eight studies were reviewed in this meta‐analysis, including 1665 patients with 3195 polyps. Complete resection rate using HSP was similar to CSP (RR: 1.02, 95% CI: 0.98–1.07, P = 0.31). Polyp retrieval after HSP was similar to CSP (RR: 1.00, 95% CI: 1.00–1.01, P = 0.60). Delayed bleeding rate after HSP was higher than after CSP, although not significantly (patient basis: RR: 7.53, 95% CI: 0.94–60.24, P = 0.06; polyp basis: RR: 7.35, 95% CI: 0.91–59.33, P = 0.06). Perforation was not reported in all eight studies. Total colonoscopy time for HSP was significantly longer than CSP (mean difference 7.13 min, 95% CI: 5.32–8.94, P < 0.001). Specific polypectomy time for HSP was significantly longer than CSP (mean difference 30.92 s, 95% CI: 9.15–52.68, P = 0.005).

Conclusion

This meta‐analysis shows significantly shorter procedure time using CSP compared with HSP. CSP tends toward less delayed bleeding compared with HSP. We recommend CSP as the standard treatment for resecting small benign colorectal polyps.