The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression.

Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified via cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study's findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.

Improving the diagnosis of AUS/FLUS thyroid nodules using an algorithm with combination of BRAFV600E mutation analysis and ultrasound pattern-based risk stratification.

PURPOSE: To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. METHODS: This study retrospectively enrolled 77 consecutive patients with 81 AUS/FLUS nodules who underwent preoperative BRAFV600E mutation analysis. A new diagnostic algorithm was proposed that BRAFV600E mutation analysis for the Fine-needle aspiration cytology specimen was firstly carried out, in which positive BRAFV600E mutation indicated malignancy and classification of the nodules with negative BRAFV600E mutation was further performed based on ultrasound pattern-based risk stratification of American Thyroid Association Guidelines. The diagnostic performance of the new diagnostic algorithm was evaluated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve (AUROC) of new diagnostic algorithm were 94.6%, 84.0%, 91.4%, 86.9%, 90.1%, and 0.893, respectively. The proposed diagnostic algorithm significantly increased the diagnostic performances (AUROC: 0.893 vs. 0.837 and 0.795), sensitivity (94.6% vs. 71.4% and 75.0%), and accuracy (90.1% vs. 79.0% and 77.8%) compared with BRAFV600E mutation analysis alone and ultrasound pattern-based risk stratification alone (all P < 0.05). CONCLUSION: The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach.

Ultrasound Biomicroscopy and High-Frequency Ultrasound for Evaluating Extramammary Paget Disease With Pathologic Correlation.

OBJECTIVES: The purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high-frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings. METHODS: In this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS. RESULTS: Ultrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P < .001). Additionally, the layer involvement of 15 lesions (88.2%) on UBM was consistent with the pathologic results (κ = 0.746). High-frequency ultrasound revealed profuse blood flow in most lesions (64.7% [11 of 17]), and 1 case showed inguinal lymph node metastasis. CONCLUSIONS: Combined use of UBM and HFUS can provide key information on EMPD based on ultrasound features. Comparatively, UBM provides clearer morphologic information, whereas HFUS provides information on lymph node metastasis and blood flow.

G59S mutation in the GJB2 gene in a Chinese family with classic Vohwinkel syndrome.

Vohwinkel syndrome (VS) is a rare autosomal dominant condition, also known as mutilating palmoplantar keratoderma accompanied by sensorineural deafness. The LOR and GJB2 genes are reported to be responsible for VS. The GJB2 gene encodes connexin 26, a component of intercellular gap junctions expressed in various tissues. We report the case of a 31-year-old Chinese woman with classic VS characterized by sensorineural deafness and mutilating palmoplantar keratoderma. Further genetic studies demonstrated a nucleotide change (c.175G>A) in the GJB2 gene, leading to an amino acid alteration (G59S). This identical missense mutation (G59S) has also been reported in a patient with Bart-Pumphrey syndrome. Together with our findings and previous studies, we conclude that the identical mutation (G59S) in the GJB2 gene contributes to various manifestations.

[Effects of FBI-1 silencing on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231].

This work aimed to observe the effects of short hairpin RNA (shRNA)-silenced FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) on proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231. qRT-PCR and Western blot analysis were applied to detect the mRNA and/or protein expression of FBI-1, Bcl-2, Bax, cleaved-Caspase 3 and Survivin. RNA interference method was used to silence FBI-1 expression in MDA-MB-231 cells. CCK-8 and colony formation assay were employed to detect the cell proliferation. Flow cytometry was employed for examining cell apoptosis. In vivo tumorigenicity of MDA-MB-231 cells was detected by tumor transplantation in nude mice. The results showed that the mRNA and protein expressions of FBI-1 were higher in MDA-MB-231 cells compared with those in normal human mammary epithelial cells MCF-10A. FBI-1 gene silencing inhibited proliferation and induced apoptosis of MDA-MB-231 cells in vitro, together with decreased Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Moreover, FBI-1 gene silencing inhibited the tumorigenesis of MDA-MB-231 cells in vivo. These results suggest that silencing of FBI-1 gene inhibits proliferation, induces apoptosis and suppresses the tumorigenesis of MDA-MB-231 cells.

Involvement of p53 and Bcl-2 in sensory cell degeneration in aging rat cochleae.

CONCLUSION: p53 and Bcl-2 (B-cell lymphoma 2) are involved in the process of sensory cell degeneration in aging cochleae. OBJECTIVE: To determine molecular players in age-related hair cell degeneration, this study examined the changes in p53 and Bcl-2 expression at different stages of apoptotic and necrotic death of hair cells in aging rat cochleae. METHODS: Young (3-4 months) and aging (23-24 months) Fisher 344/NHsd rats were used. The thresholds of the auditory brainstem response (ABR) were measured to determine the auditory function. Immunolabeling was performed to determine the expression of p53 and Bcl-2 proteins in the sensory epithelium. Propidium iodide staining was performed to determine the morphologic changes in hair cell nuclei. RESULTS: Aging rats exhibited a significant elevation in ABR thresholds at all tested frequencies (p < 0.001). The p53 and Bcl-2 immunoreactivity was increased in aging hair cells showing the early signs of apoptotic changes in their nuclei. The Bcl-2 expression increase was also observed in hair cells displaying early signs of necrosis. As the hair cell degenerative process advanced, p53 and Bcl-2 immunoreactivity became reduced or absent. In the areas where no detectable nuclear staining was present, p53 and Bcl-2 immunoreactivity was absent.

[Optimization on Preparation of Total Saponins of Aralia taibaiensis Phospholipid Complex by Central Composite Design-Response Surface Method].

Objective: To optimize the preparation of total saponins of Aralia taibaiensis phospholipid complex( TSAT-PC) by the central composite design-response surface method. Methods: Total saponins of Aralia taibaiensis phospholipid complex was prepared by using solvent evaporation method, five factors including reaction solvent, reaction time, reaction temperature, ratio of reactants on this reaction, and the concentration of the drug were investigated, then to optimize the preparation of TSAT-PC by the central composite design response surface method, and to study its physicochemical properties. Results: The optimal process conditions were as follows, the reaction time was 1 h, the reaction temperature was 45 ℃,the ratio of soya lecithine ( SL) and TSAT was 3∶ 1, the reaction concentration was16 mg / m L, the complexing rate was 97. 23%,it was less than 5% with the predicted deviation; IR analysis proved the formation of TSAT-PC, and the solubility in the octyl alcohol was higher than the original drug. Conclusion: TSAT-PC was successfully developed by the optimized process, enhance the solubility in octyl alcohol, which provide the reference for the further development and utilization of Chinese materia medica preparation.

[In vivo intestinal absorption characteristics of phloridzin in rats].

To study the in vivo intestinal absorption kinetics of phloridzin in rats. The absorption of phloridzin in the small intestines and colon of rats was investigated using an in vivo single-pass perfusion method and the drug concentration was measured by HPLC. The effects on intestinal absorption of different drug concentration and P-glycoprotein (P-gp) inhibitor were conducted. The results showed that the phloridzin could be absorbed in whole intestine, but more fully in the jejunum and colon segment,poorly absorbed in the duodenum and ileum. The absorption rate constant (Ka) and the apparent absorption coefficient（Papp）of phloridzin decreased following the sequence of jejunum> colon > duodenum > ileum. Absorption parameters of phloridzin had no significant difference at different concentration (5.14, 10.28, 20.56 mg•L⁻¹) . The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport.There had a significant difference in Ka and Papp values between P-gp inhibitor and no P-gp inhibitor groups. Phloridzin may be the substrate of P-gp.

New variation of right recurrent laryngeal nerve: cases report.

The recognition of variation in recurrent laryngeal nerves is important for both surgeons and the prognosis of patients undergoing surgery of the neck. Here, we reported a new variation of the right recurrent laryngeal nerves in five patients with thyroid surgery. The new variation is characterized by the additional ascending intracranial branches after division of laryngeal branches.

[Investigation on endemic situation of schistosomiasis in infection-controlled regions in Anhui Province].

OBJECTIVE: To understand the epidemic situation of schistosomiasis in 27 counties (cities, districts) that reached the criteria of schistosomiasis infection controlled in Anhui Province. METHODS: According to the requirement of The National Assessment Scheme of Schistosomiasis, 81 administrative villages where the schistosomiasis epidemic situation was relatively heaver in above-mentioned 27 counties (1 village per town, 3 towns per county) were sampled and investigated. RESULTS: From 2012 to 2014, 81 villages were investigated, and 34,293 residents received the serum examinations, and 1,086 were positive with a positive rate of 3.17% (0.65%-9.58%), and the positives received stool examinations and the average stool positive rate was 0.37% (0-4.0%). The calculated prevalence of human infection was 0.01%. A total of 3 057 domestic animals were investigated including 438 cattle, 2,550 sheep, and 69 other animals, and no infections were detected. A total of 11,261 living Oncomelania hupensis snails were collected and detected, but no schistosome infected snails were found. Before this investigation, no infected snails were detected for more than 2 years [average 2.3 (2-6) years], and no acute schistosome infection cases were found for more than 2 years [average 4.9 (2-9) years]. CONCLUSION: The infection rates of schistosomiasis in residents and domestic animals are relatively low, and no schistosome infected snails are found in the regions.

Consistency analysis of contrast-enhanced ultrasound and contrast-enhanced CT in diagnosis of small hepatocellular carcinoma.

UNLABELLED: To compare the consistency of contrast-enhanced ultrasound (CEUS) and contrast-enhance CT (CECT) in diagnosis of 1~2 cm and 2.1~3 cm small hepatocellular carcinoma (HCC) and evaluate the value of CEUS in diagnosis of HCC. METHODS: A total of 74 patients (89 lesions) with small HCC and cirrhosis background were retrospectively analyzed. All of the eighty-nine lesions were confirmed by histopathological examination of surgical samples or needle biopsy. All the cases were divided into 1~2 cm group and 2.1~3 cm group. The CEUS and CECT enhanced pattern and diagnosis results of the two groups were compared and the consistency between the two imaging methods were statistically analyzed. RESULTS: In the diagnosis of 1.0-2.0 cm HCC, CEUS and CECT had a moderate consistency in arterial phase, CEUS showed a tolerable consistency with CECT in portal venous and delayphase. The two imaging methods have a better consistency for the diagnosis in 2.1-3.0 cm HCC. CONCLUSION: CEUS can be used as a supplement to provide important diagnostic information in clinical practice when positive results or definite diagnoses cannot obtain.

Expression of CDKN1A/p21 and TGFBR2 in breast cancer and their prognostic significance.

BACKGROUND: A new diagnostic and prognostic biomarker may be of value in cancer diseases. Our study aimed to evaluate the CDKN1A/p21 and TGFBR2 level measurable in a cohort of patients with breast cancer after mastectomy, and to confirm their suitability to serve as prognostic biomarkers of the cancer. METHODS: The expression levels of CDKN1A/p21 and TGFBR2 were detected by reverse transcription-PCR (RT-PCR), western blot assay and immunohistochemical staining for 65 primary tumor samples and paired adjacent noncancerous breast tissues. Their relations to clinicopathologic parameters and to the prognosis of patients with breast cancer were analyzed. RESULTS: We found the mRNA and protein expression levels of CDKN1A/p21 were significantly upregulated in breast cancer tissues compared with adjacent nontumorous breast tissues. Increased CDKN1A/p21 expression showed a significant correlation with larger tumor size (P=0.014), higher tumor dedifferentiation grade (P=0.021), lymph node metastasis (P=0.019) and a shorter disease-free survival (P=0.044). Contrarily, the expression levels of TGFBR2 mRNA and protein were significantly decreased in breast cancer tissues compared with adjacent nontumorous breast tissues. Underexpression of TGFBR2 in breast cancer was correlated with larger tumor size (P=0.034), lymph node metastasis (P=0.039) and a shorter disease-free survival (P=0.035). Statistical analysis suggested that there was no significant association between CDKN1A/p21 and TGFBR2 expression. CONCLUSIONS: in summary, our results suggested that high CDKN1A/p21 and low TGFBR2 expression was closely correlated with adverse pathological parameters and poor prognosis in breast cancer. Both CDKN1A/p21 and TGFBR2 are presented as possible candidates for breast cancer biomarkers.

Prognostic value of Ki67 expression in HR-negative breast cancer before and after neoadjuvant chemotherapy.

BACKGROUND: Immunohistochemical (IHC) expression of Ki67 has been identified as a prognostic and predictive marker in hormone receptor (HR)-positive breast cancer, however, there is little evidence of the association of Ki67 with prognosis in HR-negative patients. We aimed to assess the benefit of Ki67 assessment in HR-negative breast cancers after neoadjuvant chemotherapy (NAC). METHODS: In the present study, a total of 183 HR-negative breast cancer patients with Stage II to III that treated with anthracycline and/or taxane-based neoadjuvant chemotherapy between 2004 and 2011 were retrospectively analyzed. Endocrine therapy and trastuzumab was not administered to any patients in this study. Clinical and pathological features of the patients with breast cancer were retrieved from the hospital records. Predictive factors for NAC response and survival were analyzed. RESULTS: Of the 183 patients, 122 (66.6%) were HR- HER2+, and 61 (33.3%) were triple-negative. The clinical response rates were similar across breast cancer subtype. Patients whose tumors contained high Ki67 expression effectively responded to NAC. Ki67 labeling index was a predictive marker for pathologic complete response (pCR). Ki67 expression showed a positive correlation with HER2 status, tumor size, lymph node status, lymphovascular invasion and tumor grade. Furthermore, high Ki67 expression in post-treatment tumors was strongly correlated with poor disease-free survival (DFS), but no correlation of Ki-67 expression with overall survival (OS) was observed. CONCLUSIONS: Our results suggest that Ki67 expression in HR-negative breast cancer may improve the assessment of pathological response after NAC, and Ki67 score in residual tumor was an independent prognosticator for DFS in the HR-negative breast cancer patients.

Prognostic value of hormone receptor status conversion following neoadjuvant chemotherapy in a series of operable breast cancer patients.

BACKGROUND: To investigate the prognostic value of hormone receptor (HR) status conversion after neoadjuvant chemotherapy (NAC) in patients with primary breast cancer. METHODS: 267 stage II-III breast cancer patients treated with NAC who had residual disease in the breast after NAC were retrospectively studied. The patients were divided into four groups based on the HR status: Group A, patients with HR-positive both before and after NAC; Group B, patients with HR status positive-to-negative change; Group C, patients with HR status negative-to-positive change; Group D, patients with HR-negative both before and after NAC. Patients with positive HR status (regardless of before or after NAC) were treated with adjuvant endocrine therapy, and a survival analysis was performed. RESULTS: In total, 15.7% of patients had HR status change after NAC. progression-free survival (PFS) in Group A was similar to that in Group C (hazard ratio, 1.16; P = 0.652), but that in Group B was significantly lesser than that in Group A (hazard ratio, 6.88; P = 0.001), and that in Group C was significantly longer than that in Group D (hazard ratio, 6.88; P = 0.001). A similar pattern of results was obtained for overall survival (OS). CONCLUSIONS: The switch of HR status after NAC is remarkable for breast cancer. An HR switch may identify patients who would benefit from adjuvant endocrine therapy and impact the long-term outcome.

Sorafenib-based therapy in HER2-negative advanced breast cancer: Results from a retrospective pooled analysis of randomized controlled trials.

A standard systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) is yet to be identified. Sorafenib has been developed for the treatment of solid tumors, including breast cancer, as an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. The aim of the present study was to assess the efficacy and safety of sorafenib in patients with HER2-negative ABC by performing a meta-analysis. A literature search was applied to databases, including PubMed, EMBASE, the Cochrane Library Databases, American Society of Clinical Oncology and the European Society for Medical Oncology, with the search terms 'advanced breast cancer' and 'sorafenib' and relevant studies were selected for analysis. The data extracted from the selected studies included progression-free survival (PFS), time to progression (TTP), overall survival (OS) and overall response rate (ORR). Major adverse events (AEs) were also analyzed. A total of four randomized controlled trials containing 844 cases were identified. Combined results revealed that when compared with chemotherapy (or with anti-hormone receptor therapy) alone, sorafenib-based therapy significantly increased the PFS [hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.54-1.02] and TTP (HR, 0.74; 95% CI, 0.50-0.97), but not the OS (HR, 0.95; 95% CI, 0.75-1.15) and ORR (relative risk, 1.19; 95% CI, 1.01-1.39). In addition, the incidence of grade 3/4 AEs, including hand-foot skin syndrome, anemia, fatigue, rash and stomatitis, were significantly increased in patients that received sorafenib-based therapy. Therefore, the results from the current meta-analysis indicated that sorafenib-based therapy improved the PFS and TTP in patients with HER2-negative ABC, but not the OS and ORR. In addition, combination treatment was associated with increased toxicities and frequently required dose reductions.

Radiobiological effect induced by different activities of (125)I seed brachytherapy in a hepatocellular carcinoma model.

BACKGROUND: Iodine 125 ((125)I) seed irradiation is an effective non-surgical treatment for unresectable hepatocellular carcinoma (HCC) patients. However, the safety and tolerability of (125)I seed sequential irradiation therapy remain unclear, there is no unified standard of brachytherapy radiation dose, and further study on the basic radiobiology of continuous rate irradiation is necessary. METHODS: Forty Kunming-mice (KM-mice, China) were injected with suspensions of human hepatocellular carcinoma cells (H22) to create an animal model and mimic (125)I seed implantation. The survival rates of mice, curative effect, pathological impairments including apoptosis and necrosis were investigated. The mice were randomly divided into four groups, A, B, C and D. In group A, 0.78 mCi (125)I seeds were implanted into the tumor focus. In groups B and C, 0.58 mCi and 0.38 mCi (125)I seeds were inserted at the same location, respectively. Group D was a control group, without any treatment. After 28 days of therapy, the survival rates and the tumor size were measured, and pathological impairments was measured by light or electron microscopy. RESULTS: The tumor volume inhibition rate was 68.21% ± 3.21%, 51.38% ± 4.96%, and 35.71% ± 2.79% after 0.78 mCi, 0.58 mCi, and 0.38 mCi (125)I seeds irradiation, respectively. However, radiation-related side effects were also observed in the high-dose group. Pathological results showed that radiation effect was closely associated with radiation dose, as the increase of radiation dose, an increase in apoptosis and necrosis was detected. Significant cellular impairments were noted by pathological analysis under electron microscopy. CONCLUSIONS: Our results demonstrate that the Kunming-mouse is an ideal animal to study (125)I brachytherapy, and the curative effect was closely associated with radiation dose. High-dose of brachytherapy may effectively increase apoptosis and necrosis in liver cells in KM-mice. A dose of 0.58 mCi (125)I radioactive particles may be a safe, effective and minimally invasive therapeutic option for liver cancer.

Primary adenosquamous carcinoma of the esophagus.

AIM: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary adenosquamous carcinoma (ASC) of the esophagus. METHODS: A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College. In 37 cases, the histological diagnosis was primary ASC. Clinical data were retrospectively analyzed from these 37 patients, who underwent transthoracic esophagectomy with lymphadenectomy. The χ(2) or Fisher's exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma (SCC). The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates. A Cox proportional hazard regression model was used to identify independent prognostic factors. RESULTS: Primary esophageal ASC accounted for 0.92% of all primary esophageal carcinoma cases (37/4015). The clinical manifestations were identical to those of other types of esophageal cancer. All of the 24 patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC. The median survival time (MST) was 21.0 mo (95%CI: 12.6-29.4), and the 1-, 3-, and 5-year overall survival rates were 67.5%, 29.4%, and 22.9%, respectively. In multivariate analysis, only adjuvant radiotherapy (HR = 0.317, 95%CI: 0.114-0.885, P = 0.028) was found to be an independent prognostic factor. The MST for ASC patients was significantly lower than that for SCC patients [21.0 mo (95%CI: 12.6-29.4) vs 46.0 mo (95%CI: 40.8-51.2), P = 0.001]. In subgroup analyses, the MST for ASC patients was similar to that for poorly differentiated SCC patients. CONCLUSION: Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.

Surgical treatment for early esophageal squamous cell carcinoma.

More studies are needed to clarify treatments and prognosis of early esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to review the outcome of surgical treatment for early ESCC, evaluate the results of a left thoracotomy for selected patients with early ESCC, and identify factors affecting lymph node metastases and survival. The clinicopathological data of 228 patients with early ESCC who underwent transthoracic esophagectomy with lymphadenectomy without preoperative adjuvant treatment were reviewed. The χ(2) test or Fisher's exact test were used to detect factors related to lymph node metastasis. Univariate and multivariate analyses were performed to identify prognostic factors. There were 152 males and 76 females with a median age of 55 years. Two hundred and eight patients underwent a left thoracotomy, and the remaining 20 patients with lymph nodes in the upper mediastinum more than 5 mm in short-axis diameter by computed tomography scan underwent a right thoracotomy. No lymph node metastasis was found in the 18 patients with carcinoma in situ, while lymph node metastases were detected in 1.6% (1/62) of patients with mucosal tumours and 18.2% (27/148) of patients with submucosal tumours. Only 7 patients showed upper mediastinal lymph node metastases in the follow-up. The 5- and 10-year overall survival rates were 81.4% and 70.1%, respectively. Only histologic grade (P<0.001) and pT category (P=0.001) significantly correlated with the presence of lymph node metastases. In multivariate analysis, only histologic grade (P=0.026) and pT category (P=0.008) were independent prognostic factors. A left thoracotomy is acceptable for selected patients with early ESCC. Histologic grade and pT category affected the presence of lymph node metastases and were independent prognostic factors for early ESCC.