Clinical Staging Of Esophageal Cancer Research Articles

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis.

Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. To investigate the benefits and complications of neoadjuvant modalities. To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.

S1125 Utility and Role of Endoscopic Ultrasound for Suspected Early Esophageal Cancer

Introduction: Accurate clinical staging of esophageal cancer is vital in selecting appropriate treatment options. Endoscopic ultrasound (EUS) has been determined to be an accurate imaging modality for esophageal cancer staging, differentiating superficial lesions from deep lesions. Despite being accurate, utilization of EUS in apparent early-stage cancer remains controversial. The current study aims to assess the utility of EUS for early-stage esophageal cancer and whether endoscopic features of esophageal malignancy can help direct the optimal management of the cancer. Methods: This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center. 50 patients met inclusion criteria for this study. Patient clinical data, initial EGD/biopsy, EUS, and final resection pathology reports were extracted from chart review and statistical analysis was performed to determine the accuracy of EUS and associations of endoscopic findings with deeper invasion. Results: EUS T stage was concordant with histological T stage in 74% of patients (37/50). In determining sub-mucosal involvement (T1a vs T1b), EUS had a specificity of 85% and sensitivity of 53.8%. EUS had an overall accuracy of 72.7% in identifying sub-mucosal invasion in T1 cancers. Prominent lymph nodes on EUS and tumor size >2 cm on visual inspection were significantly associated with deeper invasion of cancer on histology with p-values < 0.01. Barrett’s morphology was significantly associated with superficial cancers with a p-value < 0.01. EUS affected management from EMR/ESD to esophagectomy in 9.4% of patient with Barrett’s morphology and 6.7% of patients with tumor size < 2cm. In patients without any endoscopic findings suggestive of deep invasion, EUS identified deeper cancer and changed management in < 7% of cases. Conclusion: For assessing deeper invasion (T2, T3 and T4), EUS has been substantiated as a significantly effective tool. In staging T1b lesions, EUS was reasonably specific in ruling out sub-mucosal invasion; however, it had relatively poor sensitivity in identifying sub-mucosal invasion. Additionally, data validated endoscopic features suggesting superficial cancers including a tumor size < 2cm and the presence of Barrett’s morphology. In patients with these findings suggesting superficial cancer, EUS rarely identified a deep cancer that warranted a change in management.

Normal radiological lymph node appearance in the thorax.

Modern treatment of esophageal cancer is multimodal and highly dependent on a detailed diagnostic assessment of clinical stage, which includes nodal stage. Clinical appraisal of nodal stage is highly dependent on knowledge of normal radiological appearance, information of which is scarce. We aimed to describe lymph node appearance on computed tomography (CT) investigations in a randomly selected cohort of healthy subjects. In a sample of the Swedish Cardiopulmonary bioimage study, which investigates a sample of the Swedish population aged 50-64 years, the CT scans of 426 subjects were studied in detail concerning intrathoracic node stations relevant in clinical staging of esophageal cancer. With stratification for sex, the short axis of visible lymph nodes was measured and the distribution of lymph node sizes was calculated as well as proportion of patients with visible nodes above 5 and 10 millimeters for each station. Probability of having any lymph node station above 5 and 10 millimeters was calculated with a logistic regression model adjusted for age and sex. In the 214 men (aged: 57.3 ± 4.1 years) and 212 women (aged: 57.8 ± 4.4 years) included in this study, a total of 309 (72.5%) had a lymph node with a short axis of 5 mm or above was seen in at least one of the node stations investigated. When using 10 mm as a cutoff, nodes were visible in 29 (6.81%) of the subjects. Men had higher odds of having any lymph node with short axis 5 mm or above (OR 3.03 95% CI 1.89-4.85, P < 0.001) as well as 10 mm or above (OR 2.31 95% CI 1.02-5.23, P = 0.044) compared to women. Higher age was not associated with propensity for lymph nodes above 5 or 10 millimeters in this sample. We conclude that, in a randomly selected cohort of patients between 50 and 64 years, almost 10% of the men and 4% of the women had lymph nodes above 10 millimeters, most frequently in the subcarinal station (station 107). More than half of the patients had nodes above 5 millimeters on CT and men were much more prone to have this finding. The probability of finding lymph nodes in specific stations relevant of esophageal cancer is now described.

RA09.01: NORMAL LYMPH NODE APPEARANCE IN THE THORAX

Abstract Background Modern treatment of esophageal cancer is multimodal and highly dependent on detailed diagnostic assessment of clinical stage which includes nodal stage. Clinical appraisal of nodal stage requires knowledge of normal radiological appearance, information of which is scarce. We aimed to describe lymph node appearance on computed tomography (CT) investigations in a randomly selected cohort of healthy subjects. Methods In a sample of 426 healthy Swedish volunteers aged 50–64 years, CT scans were studied in detail concerning intrathoracic node stations relevant in clinical staging of esophageal cancer. With stratification for sex, the short axis of visible lymph nodes was measured and distribution of lymph node sizes was calculated as well as proportion of patients with visible nodes above 5 and 10 millimeters for each station. Probability of having any lymph node station above 5 and 10 millimeters was calculated with a logistic regression model adjusted for age and sex. Results In the 214 men (age 57.3 ± 4.1 years) and 212 women (57.8 ± 4.4years) included in the study, a total of 309 (72.5%) had a lymph node with a short axis of 5 mm or above was seen in one of the node stations investigated. When using 10 mm as a cutoff, nodes were visible in 29 (6.81%) patients. Men had three times higher odds of having any lymph node with short axis 5 mm or above (OR 3.03 95% CI 1.89–4.85, P &lt; 0.001) as well as 10mm or above (OR 2.31 95% CI 1.02–5.23, P = 0.044) compared to women. Higher age was not associated with propensity for lymph nodes above 5 or 10 millimeters in this sample. Conclusion In a randomly selected cohort of patients between 50 and 64 years, almost ten percent of the men and four percent of the women had lymph nodes above ten millimeters, most frequently in the subcarinal station (station 107). More than half of the patients had nodes above five millimeters on computed tomography and men were much more prone to have this finding. The probability of finding lymph nodes in specific stations relevant of esophageal cancer is now described. Disclosure All authors have declared no conflicts of interest.

Comparison of two major staging systems of esophageal cancer-toward more practical common scale for tumor staging.

The latest 8th edition of TNM Classification of Malignant Tumours by Union for International Cancer Control (UICC) and 11th edition of Japanese Classification of Esophageal Cancer by Japan Esophageal Society (JES) are the two major classifications widely accepted as tools for clinical staging of esophageal cancer. Both systems consist of three main categories, i.e., T, N, and M, but large difference exists between the two. JES system has more detailed sub-classification of T1 tumors reflecting meticulous work by Japanese investigators on superficial esophageal cancer. N-category shows the largest difference. UICC defines the N-category according to only the number of the metastatic regional lymph nodes. The definition of regional nodes in UICC system is static and uniform, and supraclavicular nodes are definitely excluded. In JES system, regional nodes are subgrouped into five different patterns according to the main tumor location, and the supraclavicular nodes are always regional nodes for thoracic esophageal cancer. Japanese surgeons have described the evidence that regional nodes should be dynamically defined according to tumor location and supraclavicular nodes should be included in regional nodes. Compared to the simplified N-category, the staging matrix of UICC system is somewhat complicated. The clinical stage and pathological stage of UICC system are not identical and difference exists also between squamous cell carcinoma (SCC) and adenocarcinoma. It has another system of pathological prognostic grouping. We can imagine several reasons for the difference occurred between the two systems. One is the difference of major pathology. Another reason is the difference of basic concept of cancer treatment. The relative "dependence" on radical surgery in Japan has required the detailed definition of each lymph node station and the evaluation of "efficacy index" of each station. The strict and detailed definition of lymph node stations has been regarded as an obstacle to those who are not familiar with it. Some simplification can be done but maintaining dynamic definition of regional lymph nodes linked to tumor location. If UICC system can accept this concept, I think the two systems can be unified to realize more practical and useful staging system as an international common language.

Significance of miR-145 expression in peripheral blood in short-term efficacy evaluation of radiotherapy for esophageal carcinoma

Objective To investigate the relationship between the expression level of microRNA-145 (miR-145) in peripheral blood and clinicopathological characteristics of esophageal cancer patients and eva-luate its significance in short-term efficacy of radiotherapy. Methods A total of 52 patients with esophageal cancer diagnosed in Affiliated Hospital of Qingdao University were collected, and all of the patients received radiotherapy alone. The relative expression level of miR-145 in peripheral blood was detected by using the method of reverse transcriptase polymerase chain reaction (RT-PCR) before radiotherapy. The correlations between the expression of miR-145 and pathological characteristics as well as short-term efficacy of radiotherapy were analyzed. Results In the 52 patients, the relative expression of miR-145 [M(QR)] in peripheral blood of clinical stage Ⅰ-Ⅱ was 3.14 (1.44), higher than that of stage Ⅲ-Ⅳ [1.71 (0.48)], and the difference was statistically significant (Z=-3.002, P=0.003). The expression level of miR-145 was not related with the age (Z=-0.403, P=0.687), gender (Z=-1.179, P=0.238) and history of drinking (Z=-0.389, P=0.697). The expression levels of miR-145 in complete response (CR), partial response (PR) and no change (NC) groups were 3.27 (1.64), 1.83 (1.26) and 1.40 (2.51), respectively, and the difference was statistically significant (H=6.567, P=0.038). Conclusion The expression level of miR-145 in peri-pheral blood is significantly correlated with the clinical stage of esophageal cancer. Its expression level is positively correlated with the short-term efficacy of esophageal cancer radiotherapy. High expression of miR-145 shows a better short-term efficacy of radiotherapy. Key words: Esophageal neoplasms; Radiotherapy; MicroRNAs; Prognosis

Correlation of overexpression of ATPase Na+/K+ transporting alpha 1 polypeptide with the diagnosis and clinical staging of esophageal cancer: A translational study.

66 Background: This study aims to identify the novel and potential upregulated genes related to secretionary or membranous proteins for the clinical diagnosis and staging of esophageal squamous cell carcinoma (ESCC). Methods: By combining microarray-based screening, which contained at least 25,000 DNA oligonucleotide probes, of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and 17 human ESCC specimens, we further confirmed the potential candidate genes by tissue arrays in 243 cancer tissues and 126 normal tissues of esophagus from Taiwan, Korea, and USA and by ELISA in 78 serum specimens of ESCC patients from Taiwan. Results: Four candidate genes, including ATP1A1, SPINT2, CMTM8, and AGR2, were chosen due to their up-regulation in more than half of 17 paired tissues from 17 ESCC patients in the microarray-based screening. The four genes were verified by RT-PCR and immunohistochemical (IHC) staining in ESCC tissue specimens and only ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) expression was consistent and further studied. Among the 243 cancer tissues and 126 normal tissues of esophagus, we found that the positive expressions of ATP1A1 by IHC staining were 207 (85%) of 243 in cancer tissues and 88 (70%) of 126 in normal tissues. After adjusted for age and sex, ATP1A1 overexpression had a 3.2-time (95% CI = 1.8-5.6) to be likely in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to the tumor stage by IHC staining. Using the median level of 1,465.0 pg/mL of serum ATP1A1 protein expression as the cut-off point, we found that patients with stage III-IV had a 2.91-fold (1.12-7.36) likely to have high serum ATP1A1 levels than those with stage I-II after adjusting for age and sex. Conclusions: ATP1A1 overexpression may serve as a potential noninvasive marker of the clinical diagnosis and staging for ESCC patients.

Tu1597 Outcomes of Salvage Curative Intent Therapy for Recurrences of Esophago-Gastric Adenocarcinoma

difference was seen in total lymph nodes harvested. Conclusion: The findings of this study suggest an important association between esophageal cancer tumor length and regional lymph node metastasis as well as overall survival. Future clinical staging of esophageal cancer may benefit from adding tumor length to current methods relying on depth of invasion (T status) and an estimation of positive lymph nodes from CT or EUS (N status).

Evaluation of the Reliability of Clinical Staging of T2 N0 Esophageal Cancer: A Review of The Society of Thoracic Surgeons Database

Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study demonstrated similar perioperative morbidity and mortality with and without induction therapy, further study is needed to examine the effect of upstaging on long-term survival.

Evaluation of the clinical staging of esophageal cancer by using diffusion-weighted imaging

The purpose of this study was to assess the effectiveness of the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI) for the clinical staging of esophageal cancer. The ADC of the tumors was compared to the standardized uptake value (SUV) of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). A total of 123 consecutive patients with esophageal squamous cell cancer were enrolled. DW images were obtained using a 1.5T whole-body scanner equipped with a phased-array body coil. A single shot spin-echo type of echo-planar sequence that provided diffusion weighting in the direction of the slice selection was used to obtain DW images. There was a negative correlation between the ADC value of the tumors and tumor diameter. A negative correlation was also found between the ADC value/SUV of the FDG-PET and serum levels of the tumor markers squamous cell carcinoma antigen and CYFRA. The ADC value was significantly correlated with clinical T and N stages. The ADC values of advanced-stage tumors were significantly lower than those of early-stage tumors. The ADC value of esophageal cancer decreased as the clinical stage advanced, and was correlated with the clinical findings. This non-invasive modality may be a valid clinical imaging method for the staging of esophageal cancer.

Esophageal Cancer Surgery in Elderly Patients 80 Years of Age or Older

As society ages, the elderly are increasingly affected by esophageal cancer. We reviewed the data of the elderly patients 80 years of age or older, who underwent surgery for esophageal cancer to evaluate the safety of surgery in this particular patient population.Nine patients aged 80 or above who underwent surgery for esophageal cancer in our department between 1999 and 2009 were included in this study. We analyzed their preoperative assessment, concurrent disorders, surgical techniques, postoperative course and complications. The patients' mean age was 82 years. Four patients had concurrent hypertension, two had concurrent diabetes, two had concurrent cerebral infarction, and two had undergone a malignant tumor operation. Three had obstructive pulmonary dysfunction, one had restrictive pulmonary dysfunction, and one had mixed pulmonary dysfunction. Clinical stage of esophageal cancer was graded as Stage I in one, Stage II in five, and Stage III in three patients. Four patients underwent esophagectomy with right thoracotomy and two-field lymph node dissection (LD), one underwent esophagectomy with right thoracotomy and three-field LD, one underwent esophagectomy with left thoracoabdominal incision and two-field LD, one underwent esophagectomy with left thoracotomy and two-field LD and two underwent transhiatal esophagectomy. Postoperative complications occurred in seven patients; however, no severe pneumonia or anastomotic leakage was noted. All patients were discharged with improved conditions. The mean postoperative hospital stay was 33 days. Esophageal cancer surgery can be performed safely in the oldest of elderly patients with appropriate preoperative assessment, selection of the optimal surgical technique, and pre- and postoperative patient management.

Expressions of human telomerase reverse transcriptase gene in cancer and pre-cancer tissues of esophagus

AIM: To investigate the expressions of human telomerase reverse transcriptase (hTERT) gene in cancer and precancer tissues of esophagus and its relation with cellular proliferation antigen Ki-67 and to investigate the value of hTERT in early diagnosis for esophageal cancer as well as predication of prognosis. METHODS: In situ hybridization was adopted to detect the expressions of hTERTmRNA in tissues of esophageal cancer (42 cases), atypical hyperplasia (37 cases), and normal esophagus(12 cases). Ki-67 antigen was detected by immunohistochemical methods. RESULTS: The positive rates of hTERTmRNA in tissues of normal mucosa, atypical hyperplasia and cancers were 0.0%, 48.6%, and 83.3% while rates of Ki-67 antigen were 0%, 56.8%, and 88.1% respectively. The expressions of hTERTmRNA and Ki-67 were significantly increased in tissues of hyperplasia and cancer, compared with those in the normal tissues (P <0.01); Expressions of hTERTmRNA and Ki-67 antigen between hyperplasia and cancer also had significant differences (P <0.01). Expressions of hTERTmRNA and Ki-67 antigen significantly related to clinical staging of esophageal cancer and metastasis of lymph node (P <0.05). Meanwhile, there was significant relation between expression of hTERTmRNA and Ki-67 antigen (P <0.05). CONCLUSION: Over-expression of hTERT gene may play an important role during carcinogenesis and progression of esophageal cancer; Expression of hTERTmRNA is relative to cellular proliferating activity. The detection of hTERT will be helpful for early diagnosis and prognosis evaluation of esophageal cancer. Li J, Wang Q, Rong WD. Expressions of human telomerase reverse transcriptase gene in cancer and pre-cancer tissues of esophagus. Shijie Huaren Xiaohua Zazhi 2004;12(10):2280-2282 http://www.wjgnet.com/1009-3079/12/2280.asp

Staging of esophageal carcinoma

J Thorac Cardiovasc Surg 2003;125:988-91

Esophageal cancer staging: improved accuracy by endoscopic ultrasound of celiac lymph nodes

Background. Clinical staging of esophageal cancer is required for optimal therapy but remains imprecise. Pathologic verification of involved lymph nodes could potentially direct treatment allocation. With the rising incidence of distal and gastroesophageal junction adenocarcinomas, assessment of the celiac axis lymph nodes (CLNs) becomes important because it is a common nodal drainage basin. Endoscopic ultrasound (EUS) permits evaluation of CLNs and biopsy by fine-needle aspiration. This study examined the usefulness of this staging tool. Methods. A consecutive series of 62 patients with esophageal cancer considered resectable by computed tomographic scan underwent EUS for T and N staging and were retrospectively studied. A CLN visualized by EUS as greater than 5 mm was considered positive. Fine-needle aspiration of the CLN was performed routinely. Endoscopic ultrasound and computed tomographic staging were compared on the basis of pathologic verification of CLNs. Results. It was possible to evaluate CLNs by EUS in 59 (95%) of 62 patients: positive in 19, negative in 40. In EUS-positive patients, fine-needle aspiration was positive in 15, falsely negative in 2, and not done in 2. By computed tomographic scan, CLNs were negative in 57 patients and positive in 2. The CLNs were positive in 23 of 54 patients eligible for CLN pathologic verification. All positive CLNs not identified by EUS (7 false-negative EUS) were microscopic foci in one or two nodes and were associated with T3 tumors. Sensitivity and specificity of EUS were 72% and 97%, respectively, compared with 8% and 100% for computed tomographic scan. When EUS identified CLNs, fine-needle aspiration confirmed positivity in 88% of cases. Conclusions. Endoscopic ultrasound with fine-needle aspiration is useful in the detection and confirmation of CLN metastasis. In T3 tumors of the distal esophagus, a negative EUS result does not substantiate absence of CLN disease. Endoscopic ultrasound with fine-needle aspiration may be important in guiding treatment for patients with distal adenocarcinoma and documenting disease before neoadjuvant therapy.

Esophageal carcinoma: pre-operative staging and evaluation of anastomotic recurrence

Survival after surgical resection of esophageal carcinoma is highly related to stage. The latest staging classifications (UICC/AJCC, 1987/1988) use the TNM system. Accumulating data show endoscopic ultrasonography (EUS) to be consistently more accurate than CT in pre-operative staging of depth of tumor invasion. Detailed images of the esophageal wall obtained by EUS allow accurate staging even in early cancer where CT is ineffective. EUS is also more accurate than CT in staging regional lymph nodes, but is less accurate than CT in staging distant metastases due to tumor stenosis in some patients and limited depth of field. EUS has also been shown to be accurate in diagnosing post-operative recurrence of cancer in the area of the surgical anastomosis. EUS represents a major advance in the clinical staging of esophageal cancer.