Research progress and challenges of neoadjuvant therapy for esophageal squamous cell carcinoma / 中华胃肠外科杂志

Surgery is the main treatment for resectable esophageal squamous cell carcinoma. However, for patients with locally advanced lesions, surgery-based comprehensive treatment is the best treatment strategy. According to the results of some randomized controlled clinical studies and meta-analysis, preoperative neoadjuvant therapy is recommended to improve the survival rate of patients. Neoadjuvant therapy includes neoadjuvant chemotherapy, chemoradiotherapy, targeted therapy and immunotherapy. Great progress has been made in neoadjuvant therapy, but there are still many clinical problems that need to be solved urgently, including the efficacy and safety of neoadjuvant therapy, the choice of neoadjuvant regimen and treatment cycle, the best combination and advantages of multimodal treatment, and the selection of responders to treatment, etc. This article provides a systematic review of the latest developments and existing controversies in neoadjuvant therapy for esophageal squamous cell carcinoma.

Clinical significance of serum high-mobility group box 1 detection in esophageal squamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the level of serum high-mobility group box 1 (HMGB1) in patients with esophageal squamous cell carcinoma (ESCC) and the feasibility of HMGB1 as a tumor marker.</p><p><b>METHODS</b>Serum HMGB1, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (Cyfra21-1) and squamous cell carcinoma antigen (SCC) were measured by enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA) and microparticle enzyme immunoassay (MEIA) respectively in 78 patients with ESCC preoperatively as well as a month after esophagectomy. At the same time, serum HMGB1, CEA, Cyfra21-1 and SCC of 60 healthy adult volunteers were detected with the same method. The unilateral P95 value of serum HMGB1 (>96 μg/L) was defined as positive. According to the Roche kit diagnostic criteria, CEA>5.0 μg/L, Cyfra21-1>3.3 μg/L and SCC>1.5 μg/L were defined as positive.</p><p><b>RESULTS</b>The preoperative positive ratio of serum HMGB1 in 78 patients with ESCC was 84.6%, and the level of serum HMGB1 was associated with the tumor size, infiltration depth, lymph node metastasis and tumor stage (P<0.01 or P<0.05). One month after esophagectomy, the level of serum HMGB1 in ESCC declined significantly compared with the preoperative level (P<0.01), and the level of serum HMGB1 in T4, N1, stage III was higher compared to corresponding T, N and tumor stage (P<0.01 or P<0.05). The positive ratio of CEA, Cyfra21-1 and SCC was 10.3%, 25.6% and 42.3% respectively in 78 ESCC patients preoperatively, so the sensitivity of these tumor markers was lower. One month after esophagectomy, serum Cyfra21-1 and serum SCC were significantly decreased compared to the preoperative level (P<0.01). However, there was no significant difference of preoperative serum CEA compared to a month after esophagectomy in ESCC (P>0.05). The specificity of HMGB1, CEA, Cyfra21-1 and SCC were 93.3%, 88.3%, 90.0% and 93.3% respectively.</p><p><b>CONCLUSION</b>Compared to CEA, Cyfra21-1 and SCC, serum HMGB1 in ESCC patients is easier for detection and its sensitivity and specificity are higher, which may be used as a marker in diagnosis, prediction of prognosis and monitor of postoperative recurrence of ESCC.</p>

Application of sentinel lymph node biopsy in esophageal cancer / 中华胃肠外科杂志

The sentinel lymph node (SLN) is defined as the lymph node(s) first receiving lymphatic drainage from the site of primary tumor. The application of SLN navigation surgery has been widely confirmed in both melanoma and breast cancer. In recent years, the concept of SLN has gained high attention in gastrointestinal tumors. However, the validity and feasibility of the SLN concept remains controversial for esophageal cancer due to its special anatomical sites and lymphatic drainage pathways. Lymph node micrometastasis is an important prognostic factor in esophageal cancer patients without lymph node metastasis. Detection of micrometastases in SLN of esophageal cancer plays an important role in determining the treatment options. In this article, we make a brief discussion on the application of SLN biopsy in esophageal surgery and explain its clinical significance.

Prognostic value of metastatic lymph node ratio in adenocarcinoma of the gastroesophageal junction / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the prognostic value of AJCC/UICC pN stage with metastatic lymph node ratio (MLR) and the prognostic difference between the tumor-node-metastasis (TNM) stage and tumor-ratio-metastasis (TRM) stage in patients with adenocarcinoma of the gastroesophageal junction.</p><p><b>METHODS</b>Clinical data of 414 patients with adenocarcinoma of the gastroesophageal junction undergoing curative resection at the Tianjin Medical University Cancer Institute and Hospital from January 2000 to June 2007 were retrospectively reviewed. Spearman correlation analysis was performed to examine the correlations between pN, MLR and retrieved nodes. Univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis were performed to analyze the effects of pN, MLR, TNM and TRM stage on the prognosis of these patients. The area under the ROC curve (AUC) was plotted to compare the value of these stages and to predict the 5-year survival rate.</p><p><b>RESULTS</b>The median number of retrieved nodes was 17 (4-71) per patient, and the median number of positive nodes was 4 (0-67) per patient. The number of metastatic lymph node was positively correlated with that of retrieved nodes (P<0.01), but MLR was not correlated with the number of retrieved nodes (P>0.05). Univariate and multivariate survival analysis showed that either pN or MLR could be used as an independent risk factor for survival (P<0.01) and the hazard ratio of MLR stage was larger than that of pN stage (1.573 vs 1.382). While pN and MLR were entered into the Cox hazard ratio model as covariates at the same time, MLR remained as the independent prognostic factor (P<0.01), but pN lost significance (P>0.05). The AUC of MLR and pN staging was 0.726 and 0.714, and of TRM and TNM staging was 0.747 and 0.736, respectively, however the differences were not statistically significant (all P>0.05).</p><p><b>CONCLUSIONS</b>MLR is an independent prognostic factor for patients with adenocarcinoma of the gastroesophageal junction. The value of MLR and TRM staging systems may be superior to pN and TNM staging systems in evaluating the prognosis of these patients.</p>

Analysis of the clinicopathologic characters and prognostic impact of extranodal metastasis in gastric cardia patients / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the correlation between extranodal metastasis (EM) and clinicopathologic features as well as the effect of EM on the prognosis in gastric cardia patients.</p><p><b>METHODS</b>Retrospective analysis was performed for the 323 cases with histologically proven adenocarcinoma of gastric cardia who underwent curative resection from January 2000 to January 2007. There were 272 male patients and 51 female patients with their median age of 63 (22 to 85) years. The relationship between clinicopathological features and extranodal metastasis was studied. The effects of the EM on the recurrence and survival of these patients were also analyzed.</p><p><b>RESULTS</b>EM positive was detected in 67 (20.7%) of the 323 patients. The incidence of EM was correlated with tumor Lauren typing, differentiation degree, invasive depth and lymph node metastasis (χ(2) = 4.647-27.216, P < 0.05). The 5-year survival rate and media survival time between patients with EM and those without EM were 12.3%, 34.1% and 20, 39 months, there was a statistically significantly difference (χ(2) = 23.936, P = 0.000) in 5-year survival rate. Multivariate analysis identified that invasive depth, lymph node metustasis and EM as an independent prognostic factor of all the patients. To the last follow up, the cumulative probability of recurrence of EM-positive patients was significant higher than EM-negative patients (59.7% vs. 35.9%; χ(2) = 12.409, P = 0.000). To study furthermore, stratified analysis showed that, in the node-positive patients, the cumulative recurrence rate of EM-positive patients was higher than EM-negative patients (60.9% vs. 40.0%; χ(2) = 8.410, P = 0.004) and the 5-year survival rate of EM-positive patients was less than the EM-negative patients (12.9% vs. 30.1%; χ(2) = 12.939, P = 0.000), the differences were statistically significant.</p><p><b>CONCLUSIONS</b>EM positive is determined to be an independent prognosis factor of gastric cardia after curative resection. EM-positive patients have a high risk for recurrence and a short time to live.</p>

Effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells as well as its possible mechanism.</p><p><b>METHODS</b>A cassette encoding siRNA targeting HMGB1 mediated by rAAV was constructed, the rAAV-siHMGB1-hrGFP, and a vector encoding siRNA mismatching HMGB1 was constructed, the rAAV-miHMGB1-hrGFP. This experiment in vitro included three groups, namely, the blank control group (group A) of KYSE150 cells transfected by rAAV-hrGFP, negative mismatch control group (group B) of KYSE150 cells transfected with rAAV-miHMGB1-hrGFP, and RNA interference group (group C) of KYSE150 cells transfected with rAAV-siHMGB1-hrGFP. We examined the expression of HMGB1 mRNA and protein in the three group cells by real-time PCR and Western blot after 24 h and 48 h, respectively. Then, VEGF-C expression and cell proliferation in the three group cells with or without sRAGE, as an inhibitor of RAGE signal pathway, were assayed by ELISA and MTT after 24 h.</p><p><b>RESULTS</b>The expression of HMGB1 mRNA and protein in KYSE150 cells in vitro in the group C transfected with rAAV-siHMGB1-hrGFP at the final concentration of 2×10(6) v.g/cell was significantly lower than that of the group A or B after 24 h and 48 h (P < 0.01). The VEGF-C expression of KYSE150 cells was (502.43 ± 13.10) pg/ml in the group C, significantly reduced in comparison with that of the group A (686.40 ± 10.94) pg/ml or group B (682.31 ± 9.61) pg/ml after 24 h (P < 0.05). At the same time, the proliferation of KYSE150 cells in the group C was significantly inhibited compared with that of groups A and B after 24 h (P < 0.01). Moreover, sRAGE at the final concentration of 0.2 µg/ml inhibited the VEGF-C expression and proliferation of KYSE150 cells compared with the corresponding group without sRAGE after 24 h (P < 0.01 or P < 0.05). However, there was no significant difference of the VEGF-C expression and proliferation of KYSE150 cells with sRAGE in the group C compared with that of cells with sRAGE of the group A or group B after 24 h (P > 0.05).</p><p><b>CONCLUSIONS</b>In esophageal squamous cell carcinoma, HMGB1 can promote the VEGF-C expression and proliferation of the cancer cells through RAGE signal pathway, and HMGB1-RAGE may become a potential target for cell proliferation and lymph node metastasis of this cancer.</p>

Application of Ivor-Lewis esophagectomy in elderly patients with carcinoma in middle and lower esophagus / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety of Ivor-Lewis procedure for middle and lower esophageal carcinoma in the elderly.</p><p><b>METHODS</b>From June 2009 to June 2010, 232 cases aged over 60 years were diagnosed as esophageal carcinoma. These cases were randomly divided into two groups using table of random digits. One group underwent abdominal and right chest approaches for middle and lower esophageal carcinoma (Ivor-Lewis procedure, n=116). The other group underwent posterolateral left thoracal incisions(Sweet procedure, n=116). Intraoperative and postoperative parameters were compared.</p><p><b>RESULTS</b>The radical resection rates in Ivor-Lewis and Sweet procedure were 95.7% and 92.2% respectively(P>0.05). The time required for opening the thorax was(47.2 ± 5.2) min and (105.4 ± 9.3) min(P=0.000), respectively. The respiratory failure rates were 1.7% and 6.9%(P=0.049). The incidences of supraventricular tachyarrhythmia were 3.4% and 10.3%, respectively. The overall complication rates were 22.4% and 34.5%(P=0.004). The perioperative mortalities were 1.7% and 3.4%(P>0.05). The postoperative ambulation time was (4.0 ± 2.0)d and (4.8 ± 3.7)d(P=0.046). The postoperative time in hospital was (11.5 ± 4.7)d and (13.7 ± 7.8)d(P=0.008).</p><p><b>CONCLUSIONS</b>Ivor-Lewis procedure is associated with little damage to diaphragm, shorter intrathoracic operative time, minimal influence on cardiopulmonary function, less postoperative complications, and quicker recovery. This procedure should be considered as the first choice for middle and lower esophageal carcinoma in the elderly.</p>

Studying the biocompatibility of implant titanium alloy after surface treatment by sandblasting and etching / 华西口腔医学杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the in vitro effect of cell behavior on a new titanium alloy and coarsening surface with sandblasting and duplicate treated by sandblasting and acid etching (SLA), including cell proliferation, morphology as well as alkaline phosphatase expression.</p><p><b>METHODS</b>The cell derived from calvarial bone of neonate and co-cultured with the surface treated titanium alloys in vitro. The samples were treated by mechanical polishing, the sandblasting and the SLA. Cell proliferation on samples for 3 d was examined by MTT assay and cell morphology was observed by scan electron microscope. Alkaline phosphatase activity was measured at 5 d by ALP-special assay.</p><p><b>RESULTS</b>The sandblasting and the SLA surface showed a significant different to smooth surface in the proliferation osteoblasts. The cells were elongated and spread well and having plentiful filopods on the coarse surface. The basal ALP activity indicated that optical density value of osteoblasts was not significant difference between coarse surface and smooth surface.</p><p><b>CONCLUSION</b>The observed effects are attributed to coarsening surface and support the concept that roughness can enhance the differentiation, good morphology and alkaline phosphatase expression of the cells. These results suggest that the good biological performance evaluation of sandblasting and etching surface is merited.</p>