Adjuvant chemotherapy versus surgery alone for esophageal squamous cell carcinoma: a meta‐analysis of randomized controlled trials and nonrandomized studies

The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who will most likely benefit from the adjuvant chemotherapy on long‐term survival has not yet been identified clearly. Studies published from 1995 to May 2012 were searched in Medline, Embase, PubMed, Cancerlit, the Cochrane Library, CNKI and major scientific meetings. Randomized controlled trials and nonrandomized studies comparing surgery plus adjuvant chemotherapy with surgery alone in patients with resectable thoracic esophageal squamous cell carcinomas were included. Eleven studies with a total of 2047 patients were identified, consisting of the adjuvant chemotherapy arm (n = 887) and surgery‐alone arm (n = 1160). There was not statistically significant benefit on 3‐year overall survival for adjuvant chemotherapy (risk ratio [RR] = 0.89, 95% confidence interval [CI], 0.72 to 1.09; P = 0.25). Adjuvant chemotherapy could significantly prolong the 1‐year disease‐free survival (DFS) (RR = 0.68, 95%CI, 0.51 to 0.89; P = 0.006), but not 3‐year DFS (RR = 0.97, 95%CI, 0.73 to 1.29; P = 0.84). Further analysis showed that patients with stage III‐IV diseases could benefit from adjuvant chemotherapy on 3‐year overall survival (RR = 0.43, 95%CI, 0.31 to 0.61; P = 0.00001), but not in the case of patients with stageI‐IIdiseases (RR = 1.12, 95%CI, 0.65 to 1.93; P = 0.68). Additionally, patients with positive lymph node could benefit on 5‐year DFS from adjuvant chemotherapy (RR = 0.79, 95%CI, 0.64 to 0.99; P = 0.04). The modality treatment with adjuvant chemotherapy for patients with squamous cell carcinoma of thoracic esophagus might be determined according to pathological stage or the status of lymph node metastasis.     

Primary esophageal adenosquamous carcinoma: a retrospective analysis of 24 cases

Primary adenosquamous carcinoma (ASC) of the esophagus is a rare kind of malignancy characterized by mixed glandular and squamous differentiation as well as a propensity for aggressive clinical behavior. Data on the evaluation of the clinicopathological features and the prognosis of patients suffering from this malignancy are few because of the rarity of this disease. We conducted a retrospective review of 24 patients with primary esophageal ASC among 6546 esophageal cancer patients who underwent transthoracic esophagectomy in our hospital. The clinicopathological presentation, diagnosis, treatment, and prognostic factors of the patients were respectively investigated. The Kaplan–Meier method and the log rank test were used to calculate and compare overall survival (OS). The Cox proportional hazards model was employed to identify independent prognostic factors. There were 18 males and 6 females with a median age of 60 years (range: 40–78 years). The clinical symptoms, macroscopic type, as well as the radiological and endoscopic features of esophageal ASC were similar to those of esophageal squamous cell carcinoma. Sixteen (88.9%) of the 18 cases who underwent preoperative esophagoscopic biopsy were misdiagnosed as adenocarcinoma or squamous cell carcinoma. The overall median follow‐up period was 36 months, and the median survival time was 32 months. The 1, 3, 5‐year OS rates were 75.0%, 48.5%, and 19.4%, respectively. Univariate analysis showed that gender (P = 0.047), lymph node metastasis (P = 0.007), and TNM stage (P = 0.037) were important factors associated with OS of the 22 patients who underwent radical resection. Multivariate analysis showed that the pathological N stage was the only independent prognostic factor (P = 0.031, hazard ratio [HR], 5.369, 95% confidence interval [CI], 1.167–24.700). These results suggest that esophageal ASC is an uncommon disease prone to be misdiagnosed by endoscopic biopsy. Surgical resection is the primary treatment, but the prognosis of ASC is usually poorer than conventional squamous cell carcinoma. Lymph node metastasis is an independent prognostic factor after radical resection.     

Cyclooxygenase-2 expression in squamous cell carcinoma of the esophagus

Increased cyclooxygenase-2 expression has been reported to be a poor prognostic indicator in a number of cancers. In this study we investigated the relationship between COX-2 expression in squamous cell carcinoma of the esophagus and tumor characteristics and patient survival. The study group consisted of 90 men and 48 women who underwent esophagectomy for squamous cell carcinoma of the esophagus between October 1984 and May 1985. COX-2 expression was measured by immunohistochemistry in 138 primary cancers, 23 metastatic lymph nodes and 21 normal esophageal stumps. The relationship between the extent of staining for COX-2 and clinicopathological features and survival was determined. The extent of staining for COX-2 in both primary and metastatic cancers was higher than in normal squamous epithelia (P = 0.002 and P < 0.0001 respectively), and the grade of staining in the primary tumor correlated positively with the finding of lymph node metastases (P = 0.03). The 5-year survival rate in patients with less than 10% COX-2 positive cells was 47.5% compared to 23.2% in patients with more than 10% COX-2 positive cells (P = 0.0036). The relationship between survival and COX-2 staining was not due to COX-2 being a surrogate marker for TNM stage. Our results show that the expression of COX-2 is elevated in squamous cell carcinoma of the esophagus compared to normal epithelium and correlates with lymph node metastases. Survival was longer in those patients whose tumors expressed lower levels of COX-2.     

Original article: Upregulation of caspase‐3 expression in esophageal cancer correlates with favorable prognosis: an immunohistochemical study from a high incidence area in northern China

Caspase‐3 plays an important role as the key effector during apoptosis, but there are very few studies of caspase‐3 in esophageal squamous cell carcinoma (ESCC). The purpose of this study was to investigate the expression and prognostic significance of caspase‐3 in ESCC from Linzhou City, a high incidence area in northern China. All 64 patients underwent esophagectomy for ESCC between January 2002 and December were enrolled in this study. Caspase‐3 expression was assessed by immunohistochemistry (IHC) in primary ESCC and paired normal esophageal epithelium. The positive rate of caspase‐3 expression was higher in ESCC than in normal esophageal epithelium (79.7% vs. 50.0%, Chi‐square = 12.372, P= 0.001). Caspase‐3 expression was correlated with tumor cell differentiation (Phi = 0.717, P < 0.001), tumor infiltration depth (Phi =?0.334, P= 0.008), and pathologic TNM (pTNM) staging (rs =?0.268, P= 0.032). Patients in caspase‐3 positive group had a significantly better 5‐year overall survival than those in the negative group (77.4% vs. 35.9%, χ²= 7.344, P= 0.007). Our results showed that caspase‐3 expression was upregulated in ESCC compared with normal esophageal epithelium in population of Chinese high incidence area, and patients with caspase‐3 positive expression had better prognosis. Therefore, caspase‐3 immunostaining could be a simple and useful tool for predicting survival in ESCC patients.     

Comparison of the prognostic value of the 6th and 7th editions of the Union for International Cancer Control TNM staging system in patients with lower esophageal cancer undergoing neoadjuvant chemotherapy followed by surgery

Carcinoma of the esophagus is classified according to the Union for International Cancer Control (UICC) TNM staging system. The 7th edition of the UICC TNM staging system was published in 2009. This is the first study to compare the prognostic value of the TNM 6th and 7th editions in patients with esophageal carcinoma treated with chemotherapy followed by surgery. Two hundred forty‐three patients with esophageal carcinoma were retrospectively selected from two referral centers. All patients received chemotherapy before surgery. Histopathologic data from the resection specimens were retrieved and restaged according to the TNM 7th edition. Disease‐specific survival curves were plotted for depth of tumor invasion (ypT), lymph node status (ypN), and ypTNM stage and then compared. Median follow‐up after surgery was 2.5 years (range 0.2–9 years). Survival analysis using the log‐rank method revealed that there was a significant difference in survival between ypT4 disease and ypT3 disease (P= 0.003), but no difference between ypT0, ypT1, ypT2, and ypT3 categories irrespective of TNM edition used. Survival probability was significantly different between ypN0 and ypN1 (P= 0.001 for TNM 6th and 7th edition), as well as ypN2 and ypN3 (TNM 7th edition, P= 0.004), but not between ypN1 and ypN2 (TNM 7th edition, P= 0.89). Neither the TNM 6th nor 7th edition T staging provides accurate survival probability stratification. However, the advantage of the 7th edition is the introduction of a third tier in survival stratification for patients with nodal involvement.     

Neoadjuvant chemoradiotherapy followed by esophagectomy versus definitive chemoradiotherapy in resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma

Background There are two intensive modalities for the treatment of resectable esophageal carcinoma: esophagectomy and definitive chemoradiotherapy (CRT). Esophagectomy with preoperative CRT was retrospectively compared with CRT alone in resectable stage II/III esophageal squamous cell carcinoma. Methods Seventy-four patients with resectable stage II/III (T1-3N0, 1M0) esophageal squamous cell carcinoma were treated with preoperative CRT by 5-fluorouracil (5-FU) 700 mg/m² on days 1 to 5, nedaplatin 80 mg/m² on day 1, and concurrent radiation for a total of 30 Gy in 3 weeks. If patients decided to undergo surgery, esophagectomy from the thoracoabdominal approach was carried out 6 weeks after the completion of CRT (CRT + Surg group, n = 51). If patients decided not to undergo surgery, they were treated with one more course of CRT (CRT-alone group, n = 23). Results There was no significant difference in overall survival between the two groups (P = 0.1006), whereas the disease-free survival in the CRT + Surg group was improved compared with the CRT-alone group (P = 0.0186). In the patients with clinical stage III carcinoma or with regional lymph node metastasis, the overall survival rate was significantly improved in the CRT + Surg group compared with the CRT-alone group. The rate of local failures in the CRT + Surg group was significantly lower compared with the CRT-alone group (P = 0.0011). Conclusions Preoperative CRT followed by esophagectomy provides better local control, but does not prolong overall survival, compared with definitive CRT. However, in clinical stage III or N1, esophagectomy with preoperative CRT could contribute to the improvement of survival in esophageal squamous cell carcinoma.     

Therapeutic strategy for the treatment of postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy of radiotherapy

We investigated the effectiveness of chemoradiotherapy for the treatment of lymph node recurrence and hematogenous metastasis after esophagectomy for esophageal squamous cell carcinoma. Between 2001 and 2006, 216 patients with thoracic esophageal squamous cell carcinoma had curative esophagectomy. Of those, 23 with lymph node recurrence received chemoradiotherapy (50.0–68.8 Gy). In addition, five patients had isolated recurrences in a distant organ and received chemoradiotherapy (50.0–60.0 Gy). We analyzed outcomes from the radiotherapy for recurrent esophageal cancer. The 1‐, 2‐, and 5‐year survival rates after recurrence for the 23 patients whose lymph node recurrence was treated with chemoradiotherapy were 52, 31, and 24%, respectively, and the median survival time was 13 months. Among the five patients with recurrent tumors in a distant organ, chemoradiotherapy produced a complete response in two patients, a partial response in one patient, and stable disease in two patients, giving an effectiveness rate of 60% (complete response + partial response). Chemoradiotherapy has a beneficial prognostic effect in patients with lymph node recurrence of esophageal squamous cell carcinoma. Chemoradiotherapy for a metastatic tumor in a distant organ may be the treatment of choice in cases where systemic chemotherapy has proven ineffective.     

Systematic review and meta‐analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy

The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. ‘Second‐line’ chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment‐related mortality in patients submitted to salvage esophagectomy or second‐line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment‐related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta‐analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21–0.86, P = 0.017) compared with second‐line CRT. A treatment‐related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta‐analysis comparing treatment‐related mortality between the groups. Salvage esophagectomy offers significant gain in long‐term survival compared with second‐line CRT, although the surgery is potentially at a price of a high treatment‐related mortality.     

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.     

Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis

Esophageal squamous cell cancer (ESCC) is a high‐grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5‐Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time‐to‐event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan–Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long‐term outcomes compared with FP‐based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.     

Serum soluble E‐cadherin is a potential prognostic marker in esophageal squamous cell carcinoma

E‐cadherin is a well‐documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80‐kDa degradation fragment, known as soluble E‐cadherin (s‐Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s‐Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre‐ and post‐CRT treatment (CRT group) for measurement of s‐Ecad protein by enzyme linked immunosorbent assay. Serum s‐Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s‐Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s‐Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s‐Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s‐Ecad was 1.104 (95% CI: 1.026–1.187) and P= 0.008. Serum s‐Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation.     

Comparison of anatomic and non‐anatomic hepatic resection for hepatocellular carcinoma

Background

The aim of the present study was to compare the prognostic impact of anatomic resection (AR) versus non‐anatomic resection (NAR) on patient survival after resection of a single hepatocellular carcinoma (HCC).

Methods

To control for confounding variable distributions, a 1‐to‐1 propensity score match was applied to compare the outcomes of AR and NAR. Among 710 patients with a primary, solitary HCC of <5.0 cm in diameter that was resectable by either AR or NAR from 2003 to 2007 in Japan and Korea, 355 patients underwent NAR and 355 underwent AR of at least one section with complete removal of the portal territory containing the tumor.

Results

Overall survival (OS) was better in the AR than NAR group (hazard ratio 1.67, 95% confidence interval 1.28–2.19, P < 0.001) while disease‐free survival showed no significant difference. Significantly fewer patients in the AR than NAR group developed intrahepatic HCC recurrence and multiple intrahepatic recurrences. Patients with poorly differentiated HCC who underwent AR had improved disease‐free survival and OS.

Conclusions

Anatomic resection decreases the risk of tumor recurrence and improves OS in patients with a primary, solitary HCC of <5.0 cm in diameter.     

Esophageal cancer with distant lymph node metastasis: prognostic significance of metastatic lymph node ratio

The cervical and celiac lymph node metastases are defined as distant metastasis (Mlym) from thoracic esophageal carcinoma by TNM (primary tumor, regional lymph nodes, and distant metastasis) classification. The prognostic factors, however, of such distant node metastases are not fully understood. Of 85 patients with node-positive thoracic esophageal carcinoma who were treated with the same modalities of treatment, 31 (37%) had Mlym. Prognostic factors for long-term survival were analyzed by univariate and multivariate analyzes. Three patients are alive and free of cancer, and two patients survived over 5 years. Fifteen patients died of recurrent esophageal cancer and 11 patients succumbed to causes unrelated to esophageal cancer. Two patients with a single Mlym died without recurrence of esophageal cancer at 1.4 years and after more than 5 years, respectively. The 1-, 2-, 3-, and 5-year overall survival rates of all 31 patients were 64.5%, 24.8%, 17.0%, and 12.8%, respectively. The factors influencing survival rate were depth of invasion (pT1,2 vs. pT3,4) and metastatic lymph node ratio (< or =0.104 vs. > or =0.105). The survival rates were not influenced by number of lymph node metastasis, number of Mlym, or by metastatic lymph node ratio of Mlym. Among those two significant variables verified by univariate analysis, independent prognostic factor for survival determined by multivariate analysis was the metastatic lymph node ratio (risk ratio = 3.4, p = 0.0345). The results of this study indicate that a significant number of patients can be cured of esophageal carcinoma by extensive resection along with extended lymph node dissection even when the disease metastasizes to distant nodes.     

Clinicopathological significance of cyclooxygenase‐2 and cell cycle‐regulatory proteins expression in patients with esophageal squamous cell carcinoma

The aim of this study was to examine the expression of the molecular markers cyclooxygenase‐2 (COX‐2), Ki‐67, cyclin A, and p27 in patients with esophageal squamous cell carcinoma (ESCC), to ascertain the relationship of these makers with the clinicopathological significance of the patients, and to assess the additional prognostic value of the expression profile of these proteins for ESCC patients. The expression levels of COX‐2, Ki‐67, cyclin A, and p27 proteins of a series of primarily resected ESCC samples were determined by immunohistochemistry method. Clinicopathological and molecular factors affecting survival were analyzed by multivariate analysis. A total of 78 specimens were included in this study. Expression of COX‐2 was observed in 43 (55.1%) cases, and high levels of expression of Ki‐67, p27, and cyclin A were observed in 57 (73.0%), 33 (42.3%), 43 (55.1%) cases, respectively. The results of univariate survival analysis indicated that more advanced tumor stage, lymph node involvement, systemic dissemination, the levels of expression of COX‐2, Ki‐67, cyclin A, and p27 were associated with survival (all P‐value < 0.05). Multifactorial survival analysis revealed that only lymph node involvement, over‐expression of cyclin A, and low p27 expression were associated with the survival of the patients (hazard ratios = 2.83, 4.7, 2.9, respectively; P= 0.025, 0.042, 0.005, respectively). Among the molecular markers assessed, the expression of cell proliferation markers cyclin A and p27 are independent prognostic factors in patients with ESCC, whereas neither COX‐2 nor Ki‐67 is of independent prognostic value.     

Clinical tools do not predict pathological complete response in patients with esophageal squamous cell cancer treated with definitive chemoradiotherapy

Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rates of pathological complete response. A pathological complete response is recognized to be an important predictor of improved survival, to the extent that observation rather than surgery is advocated by some in patients with presumed pathological complete response based on their clinical response. The goal of this study was to look at the ability of clinical variables to predict pathological complete response after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients with locally advanced esophageal squamous cell carcinoma who underwent chemoradiotherapy followed by surgery and compared those with pathological complete response to patients with residual disease. Between January 1996 and December 2010, 116 patients met inclusion criteria. Fifty‐six percent of patients had a pathological complete response and a median survival of 128.1 months versus 28.4 months in patients with residual disease. When compared with patients with residual disease, patients with a pathological complete response had a lower post‐neoadjuvant positron emission tomography (PET) maximum standardized uptake value (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post‐chemoradiotherapy computed tomography and a higher rate of normal appearing post‐chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of these characteristics alone was able to correctly identify patients with a pathological complete response, and none has significant specificity. Although the rate of pathological complete response after chemoradiotherapy is high in patients with esophageal squamous cell carcinoma, the ability of identifying patients with pathological complete response is limited. A reduction of the PET SUVmax by >70%, a normal appearing endoscopic examination, and no residual disease on biopsy all were seen in >65% of the patients with a pathological complete response. Even if these findings were unable to confirm the absence of residual disease in the primary tumor, they can help guide expectant management in high‐risk patients.     

Maté consumption and the risk of esophageal squamous cell carcinoma: a meta‐analysis

Maté, a tea‐like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta‐analysis on the subject has been performed to date. A meta‐analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever‐ vs. never‐drinkers), as well as for the dose‐dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66–3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33–5.73 vs. OR 1.84, 95% CI 1.12–3.00). Heterogeneity was observed in the ever versus never and the high‐consumption analyses but not in the low‐consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.     

The number of lymph node metastases influences survival and International Union Against Cancer tumor–node–metastasis classification for esophageal squamous cell carcinoma

To study the influence of the number of metastatic lymph nodes (LNs) on survival and International Union Against Cancer tumor–node–metastasis (TNM) classification for esophageal carcinoma. The clinicopathological data on 1146 patients with esophageal squamous cell carcinoma who had undergone an esophagectomy were retrospectively studied. Survival was analyzed by the Kaplan–Meier method. By subclassifying the nodes (N) category according to the number of metastatic LNs as: N₀ for no LN metastases; N₁₍₁₎ for only one positive node; and N₁₍₂₎ for ≥2 positive nodes. TNM staging was refined as stage II_a (T_2‐3N₀M₀), stage II_b (T₁N₁M₀ and T₂N₁₍₁₎M₀), stage IIIa (T₂N₁₍₂₎M₀ and T₃N₁₍₁₎M₀), and stage III_b (T₃N₁₍₂₎M₀ and T₄N_anyM₀), and the survival was analyzed. LN metastases was found in 380 of 1146 (33.2%) treated esophageal cancer patients. In 4270 LNs harvested, metastases was detected in 807 (18.9%). The 5‐year survival rates of the patients with 0, 1, and ≥2 positive nodes were 59.8, 33.4, and 9.4%, respectively. There was statistically significant difference among these three groups. The 5‐year survival of the patients in stages T₂N₁M₀ and T₃N₁M₀ was significantly higher in the N₁₍₁₎ group than in the N₁₍₂₎ group (41.5 vs 24.1%, and 31.2 vs 6.8%, P < 0.001). The 5‐year survival rates of the patients in refined stage II_a, II_b, III_a, and III_b were 57.1, 42.2, 28.6, and 8.5%, with significant difference existing in each stage groups. The number of positive LNs significantly influenced survival of the patients with esophageal cancer. Three grade classification (0, 1, ≥2 positive nodes) could quite well demonstrate the effect of the number of LN metastases and the survival. The refined TNM classification based on the number of LN metastases could better reflect the prognosis of esophageal cancer. Our results offer a strong rationale for refining the International Union Against Cancer TNM classification for esophageal carcinoma.     

Tumor length assessed by miniprobe endosonography can predict the survival of the advanced esophageal squamous cell carcinoma with stricture receiving concurrent chemoradiation

There were tumor strictures commonly encountered in the esophageal squamous cell carcinoma (ESCC) to limit the conventional echoendoscope for exact tumor staging and size measurements. This study evaluated the role of miniprobe endosonography (EUS) to predict the survival of ESCC patients after concurrent chemoradiation therapy (CCRT). This study prospectively enrolled ESCC patients to receive high‐frequency miniprobe EUS for the assessments of the tumor size and tumor–node–metastasis (TNM) stage. For the patients defined with advanced stages to receive CCRT as initial therapy, the tumor size parameters assessed by EUS were analyzed for their correlation with the treatment response and the patients' survivals. Fifty‐four patients, >96% with advanced TNM stage III or IV, were enrolled with a medium follow‐up of 320.5 days. Almost all of the 54 cases had partial or complete stricture of the esophageal lumens due to the tumor obstructions at enrollment. The overall median survival was 18.6 months, and the 1‐ and the 2‐year survival rates were 64.9 and 45.2%, respectively. Patients with initial tumor length <6 cm assessed by the pre‐CCRT EUS had a better survival than those with length ≥6 cm (median survival: >56.5 months vs. 11.5 months, P= 0.006). The patients with initial tumor length <6 cm had a higher rate of downstage than those with tumor length ≥6 cm after the first course of CCRT (80.0% vs. 16.7%, P= 0.035). Multivariate Cox regression confirmed the initial tumor length (hazard ratio [HR]= 1.21, P= 0.034) as well as the presence of distal metastasis are both independent predictors of the survival in ESCC patients receiving CCRT. For the ESCC patients, commonly with tumor stricture, the miniprobe EUS to assess tumor length before CCRT can predict the treatment response and the survivals.     

肌动蛋白凝胶蛋白在食管鳞癌中的表达及其与临床病理因素的关系

目的探讨肌动蛋白凝胶蛋白(Transgelin)在食管鳞癌组织中的表达及其与临床病理因素间的关系。方法采用免疫组化法检测Transgelin在食管鳞癌组织、癌旁不典型增生组织及正常食管黏膜组织中的表达,并分析Transgelin的表达与患者临床病理因素特征的关系及其对预后的影响。结果Transgelin在食管鳞癌中的阳性率明显高于癌旁不典型增生组和正常食管黏膜组织,其差异有统计学意义(P<0.05)。Transgelin在食管癌中的表达与患者的的TNM分期(P<0.05)、淋巴结转移(P<0.05)、远处转移(P<0.05)有关;与患者的性别、年龄、肿瘤直径无关(P>0.05)。在随访的210例患者中,Transgelin的生存曲线显示,高表达组Transgelin的5年生存率明显低于低表达组(P<0.05)。单因素生存分析显示,Transgelin的表达水平、TNM分期、淋巴结转移、远处转移与食管鳞癌患者术后生存时间相关。同时,多因素Cox比例风险回归模型分析显示,Transgelin的表达水平、TNM分期、淋巴结转移和远处转移为食管鳞癌患者预后的独立危险因素。结论Transgelin在食管鳞癌组织中呈高表达,其表达与食管鳞癌的发生发展和侵袭转移相关,Transgelin对于术后食管鳞癌患者的预后评估具有参考价值。