[Advances in study of surgical approaches and MRI evaluation of total hip arthroplasty].

Objective: To review the research on different surgical approaches and MRI evaluation of total hip arthroplasty (THA), to clarify the possible muscle damage caused by different approaches, and to help clinicians avoid intraoperative muscle damage and identify the causes of certain muscle-related complications after operation. Methods: The research literature on different surgical approaches and MRI evaluation of THA at home and abroad was extensively reviewed to summarize the MRI performance of the posterior approach, modified direct lateral approach, direct anterior approach, and minimally invasive anterolateral approach (also called Orthopadische Chirurgie Munchen approach). Results: The traditional posterior approach mainly damages the short external rotator muscle group and increases the incidence of postoperative dislocation; the piriformis-keeping posterior approach significantly improves the quality of the pyriformis tendon in the postoperative period, but it may lead to damage to the intrapelvic portion of the piriformis muscle. The modified direct lateral approach mainly damages the gluteus medius muscle, which increases the risk of postoperative claudication. The direct anterior approach mainly damages the vastus tensoris muscle and may result in damage to the short external rotator muscle group and the muscles around the incision. The minimally invasive anterolateral approach primarily damages the superior gluteal nerve, which subsequently leads to denervation of the broad fascial tensor fasciae latae, and this approach may also result in injury to the gluteus medius and gluteus minimus muscles. The muscle damage status significantly affects prognosis, and the minimally invasive approach is more suitable for elderly patients. Conclusion: MRI can clarify the different types of muscle damage caused by different surgical approaches. Minimally invasive approaches can reduce muscle damage and improve postoperative function compared with traditional approaches, and can benefit elderly patients more, but due to the small field, forcing to expand the surgical field will lead to unintended muscle damage and reduce postoperative function.

Considerations for multidisciplinary management of synchronous primary breast cancer and primary lung cancer - Analysis of thirty-one patients.

BACKGROUND: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. METHODS: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. RESULTS: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)-CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. CONCLUSION: Routine chest CT is needed for breast cancer patients before surgery, and PET-CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Feasibility analysis of rapid gene detection using intraoperative frozen tissues: comparison of intraoperative frozen tissues with paraffin-embedded tissues in epidermal growth factor receptor gene mutation detection of lung adenocarcinoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) is the driver gene with the highest frequency of mutations in lung adenocarcinoma and can guide the development of targeted therapies. The detection of routine gene mutations must be performed after the preparation of paraffin samples in a standard polymerase chain reaction (PCR) laboratory, which is time-consuming. The Idylla™ EGFR fully automatic PCR system for rapid detection requires no special detection environment and completes the process in only 2.5 h. It has been applied to tissues embedded in paraffin. METHODS: The Idylla™ EGFR automated PCR system was used to detect EGFR gene mutations in intraoperative frozen fresh tissues and paraffin-embedded tissues from 47 enrolled patients with lung adenocarcinoma. The gold standard amplification refractory mutation system (ARMS) method for gene mutation detection was used for verification, and the concordance between the three detection results was compared, to investigate the feasibility of detecting rapid gene mutations in intraoperative frozen samples. RESULTS: The EGFR mutation rate in 47 fresh samples of lung adenocarcinoma was 61.7% (29/47), which is consistent with the mutation level of lung adenocarcinoma in the Asian population (38.8-64.0%). The concordance rate between the Idylla™ frozen tissues and paraffin-embedded tissues was 91.4% (43/47) when compared to the ARMS method, while the coincidence rate between the two methods was 93.6% (44/47). The three methods had a total consistency rate of 89.4% (42/47). CONCLUSIONS: The Idylla™ EGFR fully automatic PCR system directly detects EGFR mutations in fresh tissues. The operation is simple, the detection time is short, and the accuracy is high. The detection time is reduced to 1/4-1/3 of the original time while meeting clinical standards for detecting the gene status of patients, thus saving crucial time for individualized and accurate treatment of patients. The method has promising clinical application prospects.

Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial.

EMERGING-CTONG 1103 showed improved progression-free survival (PFS) with neoadjuvant erlotinib vs. chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) (NCT01407822). Herein, we report the final results. Recruited patients were randomly allocated 1:1 to the erlotinib group (150 mg/day orally; neoadjuvant phase for 42 days and adjuvant phase to 12 months) or to the GC group (gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously; 2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase). Objective response rate (ORR), complete pathologic response (pCR), PFS, and overall survival (OS) were assessed along with safety. Post hoc analysis was performed for subsequent treatments after disease recurrence. Among investigated 72 patients (erlotinib, n = 37; GC, n = 35), the median follow-up was 62.5 months. The median OS was 42.2 months (erlotinib) and 36.9 months (GC) (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.47-1.47; p = 0.513). The 3- and 5-year OS rates were 58.6% and 40.8% with erlotinib and 55.9% and 27.6% with GC (p3-y = 0.819, p5-y = 0.252). Subsequent treatment was administered in 71.9% and 81.8% of patients receiving erlotinib and GC, respectively; targeted therapy contributed mostly to OS (HR, 0.35; 95% CI, 0.18-0.70). After disease progression, the ORR was 53.3%, and the median PFS was 10.9 months during the EGFR-TKI rechallenge. During postoperative therapy, grade 3 or 4 adverse events (AEs) were 13.5% in the erlotinib group and 29.4% in the GC group. No serious adverse events were observed. Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.

Pre-operative oil ingestion reduces the probability of thoracic duct trunk ligation during esophagectomy.

Chylothorax is an important complication after esophagectomy. Ligation of the injured thoracic duct is the main method to prevent chylothorax after esophagectomy, but may be associated with adverse effects. Whether ligation of the injured tributary alone, keeping the main trunk intact, may suffice to prevent post-operative chylothorax is not well known. Since March 2017, 40 mL of olive oil was administered to patients posted for esophagectomy. We compared patients admitted between March 2017 and December 2019 with patients admitted between July 2014 and February 2017, who had not received pre-operative oil. The outcome measures were the need for thoracic duct main trunk or tributary ligation, development of chylothorax and missed ligation. There were 371 patients in the oil ingestion group and 308 patients in the standard control group. Chylothorax in the oil ingestion group was significantly lower than that in the standard control group (1.3% vs. 4.5%, P = 0.012). Chyle leak from thoracic duct tributaries was diagnosed in a significantly higher percentage (5.7% vs. 0.0%, P < 0.001) and missed ligation of the injured thoracic duct was significantly lower (0.3% vs. 3.9%, P = 0.002) in the oil ingestion group compared with the standard control group. The incidence of post-operative chylothorax was not statistically different (6.3% vs. 10.0%, P = 1.000) between the tributary and the trunk ligation group. Pre-operative oil ingestion can help visualize the thoracic duct trunk and its tributaries during esophagectomy. Thus, non-selected thoracic duct trunk ligation and missed ligation during esophagectomy can be reduced. Precise ligation of the injured tributary while the main trunk is intact can also prevent post-operative chylothorax.

Malignant transformation of heterotopic pancreas as middle esophagus adenocarcinoma-A rare case report and comprehensive literature review.

Heterotopic pancreas is a rare congenital abnormality that occurs during the growth and development process. It can be found in any part of the digestive tract, but the most common sites are the stomach, duodenum, and jejunum. Malignant transformation especially in the esophagus is rare. Here, we aim to report an unusual case of mid-esophageal adenocarcinoma that originated from a heterotopic pancreas.

A comparison of capillary electrophoresis and next-generation sequencing in the detection of immunoglobulin heavy chain H and light chain κ gene rearrangements in the diagnosis of classic hodgkin's lymphoma.

This study aimed to compare the application value of capillary electrophoresis and next-generation sequencing for immunoglobulin (IG) gene rearrangement in the diagnosis of classic Hodgkin's lymphoma. Twenty paraffin-embedded specimens from patients with classic Hodgkin's lymphoma were screened. For gene rearrangement detection, the ABI 3500 Genetic Analyzer and ABI Ion GeneStudio S5 Plus sequencing system were used, respectively, and the results were compared. Five cases with monoclonal rearrangements (25%, 5/20) were detected by Capillary Electrophoresis, and positivity for the FR1, FR2, FR3, and IGк loci was 5%, 10%, 10%, and 15%, respectively; 12 cases with monoclonal rearrangements (60%, 12/20) were detected by Next-generation Sequencing where the positivity of the above corresponding loci were 35%, 45%, 50%, and 30%, respectively. Among the 20 samples, 6 IGк clonal rearrangements were detected, and the usage frequency (66.7%) of IGкJ4 was the highest in the IGкJ subgroup. The usage frequency of IGкV1 and IGкV3 in the GкV sub-group was 33.3% and 33.3%, respectively. Twelve immunoglobulin heavy chain (IGH) clonal rearrangements were detected among the 20 samples, and the order of usage frequency in the IGH joining region J (IGHJ) subgroup was IGHJ4 > IGHJ5 > IGHJ6 > IGHJ3. The gene with the highest usage frequency in the IGH variable (IGHV) subgroup was IGHV3 (50%) and the percentage of IGHV mutations ranged from 0% ± 11.45% with an average frequency of 3.34%. Compared with Capillary Electrophoresis, Next-generation Sequencing showed a higher positivity in the detection of gene clonal rearrangements, was more accurate in the interpretation of results.

Risk factors for early local lymph node recurrence of thoracic ESCC after McKeown esophagectomy.

Objectives: Even underwent radical resection, some patients of thoracic esophageal squamous cell carcinoma (ESCC) are still exposed to local recurrence in a short time. To this end, the present study sought to differentiate patient subgroups by assessing risk factors for postoperative early (within one year) local lymph node recurrence (PELLNR). Methods: ESCC patients were selected from a prospective database, and divided into high- and low-risk groups according to the time of their local lymphatic recurrence (within one year or later). Survival analysis was conducted by the Cox regression model to evaluate the overall survival (OS) between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) of different variables were also calculated. Logistic regression analysis was used to explore the high-risk factors for PELLNR with the odds ratio (OR) and 95% CI calculated. Results: A total of 432 cases were included. The survival of patients in the high-risk group (n = 47) was significantly inferior to the low-risk group (n = 385) (HR = 11.331, 95% CI: 6.870-16.688, P < 0.001). The 1-year, 3-year, and 5-year OS rate of the patients in high/low-risk groups were 74.5% vs. 100%, 17% vs. 88.8%, and 11.3% vs. 79.2%, respectively (P < 0.001). Risk factors for local lymph node recurrence within one year included upper thoracic location (OR = 4.071, 95% CI: 1.499-11.055, P = 0.006), advanced T staging (pT3-4, OR = 3.258, 95% CI: 1.547-6.861, P = 0.002), advanced N staging (pN2-3, OR = 5.195, 95% CI: 2.269-11.894, P < 0.001), and neoadjuvant treatment (OR = 3.609, 95% CI: 1.716-7.589, P = 0.001). In neoadjuvant therapy subgroup, high-risk group still had unfavorable survival (Log-rank P < 0.001). Multivariate analysis demonstrated that upper thoracic location (OR = 5.064, 95% CI: 1.485-17.261, P = 0.010) and advanced N staging (pN2-3) (OR = 5.999, 95% CI: 1.986-18.115, P = 0.001) were independent risk factors for early local lymphatic recurrence. However, the cT downstaging (OR = 0.862, 95% CI: 0.241-3.086, P = 0.819) and cN downstaging (OR = 0.937, 95% CI: 0.372-2.360, P = 0.890) for patients in the neoadjuvant subgroup failed to lower PELLNR. The predominant recurrence field type was single-field. Conclusions: Thoracic ESCC patients with lymph node recurrence within one year delivered poor outcomes, with advanced stages (pT3-4/pN2-3) and upper thoracic location considered risk factors for early recurrence.

Genome-scale CRISPR activation screening identifies a role of ELAVL2-CDKN1A axis in paclitaxel resistance in esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) may provide survival benefits for patients with advanced esophageal squamous cell carcinoma. However, tumor cells can display primary or secondary resistance to paclitaxel (PTX), a primary component of induction chemotherapy regimen. To identify genes capable of conveying PTX resistance, we performed a genome-wide CRISPR transcriptional activation library in human KYSE-180 cells. High throughput next generation sequencing was further applied to establish the phenotype-to-genotype relationship. Our highest-ranking hits are CDKN1A, TSPAN4, ELAVL2, JUNB and PAAF1. We generated evidence that esophageal tumors with high CDKN1A, ELAVL2 and TSPAN4 levels, quantified using qRT-PCR and Western blot assays, showed poorer chemotherapy response. Higher expression levels of TSPAN4 and ELAVL2 protein are independent risk factors for poor chemotherapy response in ESCC patients. We then found that overexpression of CDKN1A, ELAVL2 or TSPAN4 in ESCC cell lines significantly promoted the resistance to PTX by inhibiting cell apoptosis. Interestingly, ESCC cells overexpressed CDKN1A, ELAVL2 or TSPAN4 also acquired resistance to cisplatin (DDP). This phenomenon may be explained by cross-resistance of chemotherapy. We additionally found an association between ELAVL2 and CDKN1A, which may be regarded as the upstream and downstream factors that synergistically involved in the regulation of chemo-resistance in ESCC. Therefore, our study demonstrated that the genome-wide CRISPR activation library is a powerful strategy for the discovery of chemo-resistant genes critical for ESCC and we reported the first evidence that the ELAVL2-CDKN1A axis may be an important mechanism involved in chemo-resistance in ESCC.

The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma.

Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. The endogenous DNA damage response confers chemoresistance to these agents by repairing DNA damage. The initiation and transduction of the DNA damage response (DDR) signaling pathway, which is dependent on the activation of ATM (ataxia-telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), is essential for DNA damage repair, the maintenance of genomic stability and cell survival. Therefore, ATM or ATR inhibition is considered as a promising strategy for sensitizing cancer cells to chemotherapy. This study is aimed to explore the effect of ATR inhibitor on sensitizing ESCC (esophageal squamous cell carcinoma) cells to cisplatin, and whether ATM deficiency could impact the sensitization. We found that 21.5% of ESCC cases had ATM deficiency and that patients with ATR activation after neoadjuvant chemotherapy had worse chemotherapy response and poorer overall survival than that without ATR activation (32 mons vs. >140mons). Then, it was shown that VE-822 inhibited ATR-CHK1 pathway activation, leading to the accumulation of cisplatin-modified DNA. And it inhibited cell proliferation, induced cell cycle arrest in G1 phase and enhanced cell apoptosis. Moreover, VE-822 significantly sensitized ESCC cells to cisplatin, and these two drugs had synergistic effects, especially in ATM-deficient cells, in vitro and in vivo. Our results suggest that ATR inhibition combining with cisplatin is a new strategy for managing patients with ESCC, especially those with ATM-deficiency. However, this is an idea that requires further validation.

Discrimination of Malignant versus Benign Mediastinal Lymph Nodes Using Diffusion MRI with an IVIM Model.

OBJECTIVES: To investigate the value of an intravoxel incoherent motion (IVIM) diffusion model for discriminating malignant versus benign mediastinal lymph nodes (MLN). METHODS: Thirty-five subjects with enlarged MLN were scanned at 1.5 Tesla. Diffusion-weighted imaging was performed with eight b-values. IVIM parameters D, D*, and f, as well as apparent diffusion coefficient (ADC) from a mono-exponential model were obtained. 91 nodes (49 malignant and 42 benign) were analysed with pathologic (n=90) or radiologic (n=1) confirmations. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance. RESULTS: The mean values of D, ADC, and f for the malignant group were significantly lower than those for the benign group (p<0.001), while D* showed no significant difference (p=0.281). In the ROC analysis, the combination of D and f produced the largest area under the curve (0.953) compared to ADC or other individual IVIM parameters, leading to the best specificity (92.9%) and diagnostic accuracy (90.1%). CONCLUSION: This study demonstrates that the combination of IVIM parameters can improve differentiation between malignant and benign MLN as compared to using ADC alone. KEY POINTS: • Diffusion MRI is useful for non-invasively discriminating malignant versus benign lymph nodes. • A mono-exponential model is not adequate to characterise diffusion process in lymph nodes. • IVIM model is advantageous over mono-exponential model for assessing lymph node malignancy. • Combination of IVIM parameters improves differentiation of malignant versus benign lymph nodes.

Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma.

Increased expression of homeobox C6 (HOXC6) predicts poor prognosis of patients with esophageal squamous cell carcinoma (ESCC) and promotes ESCC cell proliferation. Additionally, the expression of HOXC6 was upregulated in chemosensitive ESCC cell lines. Therefore, it was hypothesized that HOXC6 may be associated with chemosensitivity of ESCC. Patients with ESCC who underwent neoadjuvant chemotherapy followed by surgery by a single-surgeon team between January 2000 and December 2012 were enrolled in the present study. Pretreatment biopsy specimens and postoperative resection samples were collected. Immunohistochemistry was performed to examine HOXC6 expression, and the association between HOXC6 expression and tumor regression grade (TRG) was analyzed. In cell lines exhibiting stable knockdown of HOXC6, Cell Counting Kit-8 assays were used to evaluate the chemosensitivity of cells to various concentrations of cisplatin and paclitaxel. A total of 51 pretreatment biopsy specimens were assessed, and patients with increased expression of HOXC6 in pretreatment biopsy specimens exhibited higher TRGs. A total of 186 surgical samples were evaluated; HOXC6 was expressed at a decreased level in patients with higher TRG and at a high level in patients with lower TRG. In addition, downregulation of HOXC6 decreased the sensitivity of ESCC cell lines to cisplatin and paclitaxel, resulting in an increased half-maximal inhibitory concentration. Increased expression of HOXC6 prior to treatment was associated with chemosensitivity in ESCC tissues.

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future.

The equivalent efficacy of multiple operations for multiple primary lung cancer and a single operation for single primary lung cancer.

BACKGROUND: The incidence of synchronous and metachronous multiple primary lung cancers (MPLCs) has been increasing recently. The new multidisciplinary classification of lung adenocarcinoma and TNM Classification of Lung Cancer (7(th) edition, 2009), have improved the understanding of MPLC. Most researchers recommend that surgical therapy should be actively pursued if the patient's physical condition and lung function permit it and if a complete cure can be achieved. However, few studies have reported the long-term efficacy of surgical treatment for MPLC, which we explored in this study. METHODS: A total of 1,290 Lung cancer patients from a prospectively maintained database, treated by a single surgeon group between January 2000 and July 2013, at Beijing Cancer Hospital, Peking University, were reviewed. We retrospectively analyzed the clinical data of 31 patients diagnosed with MPLC out of 1290 lung cancer patients, focusing on long-term survival. RESULTS: MPLC patients accounted for 2.4% (31/1,290) of the patient cohort: 27 had synchronous MPLC (87.1%) and 4 had metachronous MPLC (12.9%). The 1-, 3- and 5-year postoperative survival rates were 100%, 75.8% and 75.8%. On stratification according to TNM stage, the 1-, 3- and 5-year of patients with stage I cancer (20 patients) were 100%, 77.2% and 77.2%, not statistically significant with those for the entire cohort (1,290 patients; 95.4%, 80.5% and 66.2%, P=0.455). CONCLUSIONS: When the patient's physical condition and tumor-related factors permit it, surgery should be the first choice of treatment for MPLC; it is associated with an equivalent efficacy to that of surgery for single primary lung cancer.

Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling.

BACKGROUND: Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling. METHODS: CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo-responsiveness. RESULTS: EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively. CONCLUSIONS: MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo.

BACKGROUND: We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism. METHODS: Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo. RESULTS: Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341-0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350-0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably. CONCLUSIONS: HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.

CT Signs Can Predict Treatment Response and Long-Term Survival: A Study in Locally Advanced Esophageal Cancer with Preoperative Chemotherapy.

BACKGROUND: Accurate prediction of treatment response and prognosis before surgery allows prompt therapy adjustment. This study aimed to evaluate the efficacy of computed tomography (CT) signs in predicting treatment response and survival for advanced esophageal squamous cell carcinoma patients who received preoperative chemotherapy. METHODS: This study retrospectively enrolled 135 consecutive patients with preoperative chemotherapy from September 2005 to December 2011. A logistic regression model was used to evaluate the association between pathologic response and CT signs. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and a Cox proportional hazards model was constructed to determine associations between CT signs after neoadjuvant chemotherapy and survival outcomes. RESULTS: Logistic regression showed that the significant predictors of a poor response were the total number of lymph nodes (LNs) (>6) at baseline [odds ratio (OR) 5.07; 95 % confidence interval (CI) 1.86-13.81; P = 0.002] and the CT value change rate (≤17 %) (OR 2.35; 95 % CI 1.05-5.23; P = 0.037). In the Cox analyses, the significant predictors of OS were preoperative tumor thickness (>10 mm) [hazard ratio (HR) 2.33; 95 % CI 1.36-4; P = 0.002), total number of LNs (>6) (HR 1.88; 95 % CI 1.12-3.17; P = 0.017), and short diameter of the largest LN (>10 mm) (HR 1.87; 95 % CI 1.07-3.28; P = 0.028), whereas only the short diameter of the largest LN was a significant predictor of DFS (HR 2.36; 95 % CI 1.23-4.54; P = 0.01). CONCLUSIONS: CT signs can predict therapeutic efficacy and survival outcomes and provide an opportunity to offer additional treatment options before surgery.

A retrospective analysis of the clinicopathological characteristics of large cell carcinoma of the lung.

The aim of the present study was to analyze and summarize the clinicopathological characteristics of large-cell lung carcinoma (LCLC) of the lung, in order to improve the definite diagnosis rate of LCLC. Clinicopathological data of 174 patients with LCLC, confirmed pathologically, were retrospectively reviewed. The 174 cases of LCLC accounted for 5.7% of the total lung cancer cases during the corresponding time period at the Affiliated Cancer Hospital of Tianjin Medical University (Tianjin, China), among which there were 131 males and 43 females with an average age of 61.4 years. The postoperative pathological diagnosis of the 174 cases showed 80 cases of classic LCLC, 64 cases of large cell neuroendocrine carcinoma (LCNEC), six cases of combined LCNEC, 19 cases of basaloid carcinoma, three cases of clear cell carcinoma and two cases of lymphoepithelioma-like carcinoma. Of the total 174 LCLC cases, 96 patients exhibited lymph node metastasis. LCLC is a highly aggressive malignancy with a high tendency of invasion and metastasis, although the incidence rate is low. A definite diagnosis of LCLC primarily relies on the pathological diagnosis. Each subtype of LCLC has its own pathomorphological and immunohistochemical characteristics.

Dopaminergic neuron-like cells derived from bone marrow mesenchymal stem cells by Lmx1α and neurturin overexpression for autologous cytotherapy in hemiparkinsonian rhesus monkeys.

Bone marrow-derived mesenchymal stem cells hold great potential for cytotherapeutics of neurodegenerative disorders, including Parkinson's disease. The neurotrophic factor neurturin can rescue dopaminergic neurons damaged during the disease process. Lmx1α can promote mesencephalic dopaminergic differentiation during embryogenesis. In this study, we tested a cytotherapeutic strategy combining NTN/Lmx1α gene therapy and cell transplantation to ameliorate disease progression in hemiparkinsonian rhesus. Rhesus BMSCs were prepared for autologous grafting by transfection with recombinant adenoviral vectors expressing secreted NTN and Lmx1α,and cultured in the presence of induce factors, particularly the Lmx1α regulatory factor sonic hedgehog, to guide dopaminergic differentiation. These induced rh-BMSCs exhibited gene/protein expression phenotypes resembling nigral dopaminergic neurons. They survived and retained dopaminergic function following stereotaxic injection into the MPTP-lesioned right-side substantia nigra as indicated by SPECT measurement of DAT activity. Injected cells preserved and supplemented the remaining endogenous population of dopamine neurons (TH-positive cell ipsilateral/contralateral ratio was 56.81% ± 7.28% vs. 3.86%±1.22% in vehicle-injected controls; p<0.05). Cell injection also partially restored motor function and reduce apomorphine-evoked rotation (p<0.05). Moreover, function recovery occurred earlier than in previous studies on injected BMSCs. Our findings demonstrate a promising strategy for restoration of PD-associated motor dysfunction by transplantation of autologous BMSCs overexpressing NTN/Lmx1α.