Potential drug targets for gastroesophageal reflux disease and Barrett's esophagus identified through Mendelian randomization analysis.

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

Mapping and ablation of ventricular arrhythmias arising from the left ventricular summit.

The left ventricular summit (LVS) refers to the highest portion of the left ventricular outflow tract (LVOT). It is an epicardially delimited triangular area by the left coronary arteries and the coronary venous circulation. Its deep myocardium correlates closely with the left coronary cusp, aortic-mitral continuity, and right ventricular outflow tract (RVOT), complicating the anatomical relationship. Ventricular arrhythmias (VAs) originating from this area are common, accounting for 14.5% of all VAs origin from left ventricle. Specific electrocardiogram (ECG) characteristics may assist in locating LVS-VAs pre-procedure and facilitate procedure planning. However, catheter ablation of LVS-VAs remains challenging because of anatomical constraints. This paper reviews the recent understanding of LVS anatomy, concludes ECG characteristics, and summarizes current mapping and ablation methods for LVS-VAs.

The role of adipose tissue-derived hydrogen sulfide in inhibiting atherosclerosis.

Hydrogen sulfide (H2S) is the third gaseous signaling molecule discovered in the body after NO and CO and plays an important organismal protective role in various diseases. Within adipose tissue, related catalytic enzymes (cystathionine-ß-synthetase, cystathionine-γ-lyase, and 3-mercaptopyruvate transsulfuration enzyme) can produce and release endogenous H2S. Atherosclerosis (As) is a pathological change in arterial vessels that is closely related to abnormal glucose and lipid metabolism and a chronic inflammatory response. Previous studies have shown that H2S can act on the cardiovascular system, exerting effects such as improving disorders of glycolipid metabolism, alleviating insulin resistance, protecting the function of vascular endothelial cells, inhibiting vascular smooth muscle cell proliferation and migration, regulating vascular tone, inhibiting the inflammatory response, and antagonizing the occurrence and development of As.

A Distal Resection Margin of ≤1 mm and Rectal Cancer Recurrence After Sphincter-Preserving Surgery: The Role of a Positive Distal Margin in Rectal Cancer Surgery.

BACKGROUND: There is little information about the prognostic value of a microscopically positive distal margin in patients who have rectal cancer. OBJECTIVE: We aimed to investigate the influence of a distal margin of ≤1 mm on oncologic outcomes after sphincter-preserving resection for rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: The study was conducted at 2 hospitals. PATIENTS: A total of 6574 patients underwent anterior resection for rectal cancer from January 1999 to December 2014; 97 (1.5%) patients with a distal margin of ≤1 mm were included in this study. For comparative analyses, patients were matched with 194 patients with a negative distal margin (>1 mm) according to sex, age, BMI, ASA score, neoadjuvant treatment, tumor location, and stage. MAIN OUTCOME MEASURES: The oncologic outcomes of the 2 groups were compared. RESULTS: Perineural and lymphovascular invasion rates were significantly higher in patients with a positive distal margin (54.6% vs 28.9%; 67.0% vs 42.8%; both p < 0.001) compared with to patients with negative distal margin. Comparison between microscopically positive and negative distal margin showed worse oncologic outcomes in patients with a microscopically positive distal margin, including 5-year local recurrence rate (24.1% vs 12.0%, p = 0.005); 5-year distant recurrence rate (35.5% vs 20.2%, p = 0.011); 5-year disease-free survival (45.5% vs 69.5%, p < 0.001); and 5-year OS (69.2% vs 79.7%, p = 0.004). Among the 97 patients with a microscopically positive distal margin, the 5-year disease-free survival rate was higher in patients who received adjuvant therapy (52.0% vs 30.7%, p = 0.089). LIMITATIONS: This is a retrospective study; bias may exist. CONCLUSIONS: A distal margin of 1 mm is associated with worse oncologic results. Our data indicate the importance of achieving a clear distal margin in the surgical treatment of rectal cancer. Adjuvant therapy should be used in these patients to reduce recurrence. See Video Abstract at http://links.lww.com/DCR/A408.

Outcome of laparoscopic versus open resection for rectal cancer in elderly patients.

BACKGROUND: Laparoscopic colorectal resection has been gaining popularity over the past two decades. However, studies about laparoscopic rectal surgery in elderly patients with long-term oncologic outcomes are limited. In this study, we evaluated the short-term and long-term outcomes of laparoscopic and open resection in patients with rectal cancer aged ≥ 70 y. METHODS: From 2007-2012, a total of 294 consecutive patients with rectal cancer from a single institution were included, 112 patients undergoing laparoscopic rectal resection were compared with 182 patients undergoing open rectal resection. RESULTS: Seven (6.3%) patients in the laparoscopic group required conversion to open surgery. The two groups were well balanced in terms of age, gender, body mass index, American society of anesthesiologists scores, site, and stage of the tumors. Laparoscopic surgery was associated with significantly longer median operating time (220 versus 200 min; P = 0.005), less estimated blood loss (100 versus 150 mL; P < 0.001), a shorter postoperative hospital stay (8 versus 11 d), lower overall postoperative complication rate (15.2% versus 26.4%; P = 0.025), wound-related complication rate (7.14% versus 17.03%; P = 0.015), less need of blood transfusion (8.04% versus 16.5%; P = 0.038), and surgical intensive care unit after surgery (12.5% versus 22.0%; P = 0.042) when compared with open surgery. Mortality, quality of surgical specimen, lymph nodes harvested, positive distal, and circumferential margin rate were not significantly different between two groups. The estimated 3-y survival rates were similar between two groups. CONCLUSIONS: Laparoscopic rectal surgery is safe and feasible in patients >70 y and is associated with better short-term outcomes when compared with open surgery.

Impact of previous abdominal surgery on the outcome of laparoscopic resection for colorectal cancer: a case-control study in 756 patients.

BACKGROUND: A history of previous abdominal surgery (PAS) may increase the complexity of laparoscopic colorectal surgery. The aim of this study was to investigate the impact of PAS on the outcomes of laparoscopic colorectal resection for colorectal cancer. METHODS: A total of 378 colorectal cancer patients (group A) with a history of PAS were 1:1 matched to 378 controls (group B) without PAS from our prospective laparoscopic colorectal surgery database. The two groups were matched for age, gender, body mass index, American Society of Anesthesiology score, tumor location, type of surgical procedure, and tumor stage. RESULTS: Patients in the two groups were well balanced with respect to baseline demographic and clinical characteristics. Group A was associated with significantly longer median operating time (220 versus 200 min; P = 0.002). Conversion rate in group A (63/378, 16.67%) was almost twice as high as that in group B (36/378, 9.55%; P = 0.004). Conversions caused by adhesion were more common in patients with a history of PAS (55.56% [35/63] versus 27.78% [10/36], P = 0.008). Postoperative recovery time, length of postoperative hospital stay, perioperative mortality and morbidity rate, lymph nodes harvested, circumferential resection margin positive rate, 3-y disease-free survival, and overall survival rate were not significantly different between the two groups. CONCLUSIONS: Laparoscopic colorectal surgery for colorectal cancer patients with PAS is time consuming, but the incidence of a successfully completed laparoscopic colorectal resection remains high, and the short- and long-term outcomes are not affected by PAS.

Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer.

INTRODUCTION: Preoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer. METHODS: A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable. RESULTS: Of the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of ≤ 5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195-3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484-4.512, P = 0.001) were significantly associated with an increased rate of pCR. CONCLUSIONS: The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.

Prognostic factors for desmoid tumor: a surgical series of 233 patients at a single institution.

Desmoid tumors are rare soft tissue tumors with limited data on their management and prognosis. We sought to determine the rates of recurrence after surgery for desmoid tumors and analyze factors predictive of recurrence-free survival (RFS). From February 1976 to October 2011, 233 consecutive patients with desmoid tumors who underwent macroscopically complete resection were included in this study. Clinicopathologic and treatment characteristics were evaluated to determine predictors of recurrence. Patterns of presentation included primary (n = 156, 67.0 %) and locally recurrent (n = 77, 33.0 %) disease initially treated elsewhere. Most patients had a R0 resection (n = 169, 72.5 %). In addition to surgery, 43 (18.5 %) patients received radiotherapy and 10 (4.3 %) patients received systemic therapy. Median follow-up was 54 months; recurrence disease was observed in 62 (26.6 %) patients. The estimated 5- and 10-year RFS was 74.2 % (95 % confidence interval (CI), 68.3-80.1) and 70.7 % (95 % CI, 64.2-77.2), respectively. Factors associated with worse RFS were tumor size larger than 5 cm (hazard ratio (HR) = 3.757; 95 % CI, 1.945-7.259; p < 0.001), extra-abdominal tumor location (abdominal wall referent; HR = 3.373; 95 % CI, 1.425-7.984; p = 0.006), and R1 resection status (HR = 1.901; 95 % CI, 1.140-3.171; p = 0.014). Patients were grouped according to the number of unfavorable prognostic factors; the 10-year RFS rates of patients with zero, one, two, and three prognostic factors were 100, 86.9, 48.5, and 34.4 %, respectively (p < 0.001). Regardless of primary or recurrent disease, surgical resection remains central to the management of patients with desmoid tumors. However, there are clearly different prognostic subgroups that could benefit from different therapeutic strategies, and a wait-and-see policy is a possible option for a subset of patients.

Short-term outcomes of laparoscopically assisted surgery for rectal cancer following neoadjuvant chemoradiotherapy: a single-center experience.

OBJECTIVE: The efficacy of laparoscopic treatment of rectal cancer remains unclear, and little is known about its effect on sphincter preservation. We compared short-term outcomes of laparoscopically assisted and open surgeries following neoadjuvant chemoradiotherapy (CRT) for mid and low rectal cancer. METHODS: This study enrolled 137 patients with mid-low rectal cancer who underwent curative resection, 51 by laparoscopically assisted (Lap group) and 86 by conventional open (Open group) surgeries, following neoadjuvant CRT from July 2007 to July 2012. The clinical and surgical findings of the two groups of patients were prospectively collected and analyzed. RESULTS: Three patients (5.9%) in the Lap group were converted to an open procedure. The mean operating times were similar in both groups. The Lap group had a significantly higher rate of sphincter preservation (62.7% versus 41.9%, P = 0.018) and significantly lower mean blood loss than the Open group. Mean times to first flatus, start of a normal diet, and overall postoperative hospitalization were longer for open surgery. The complication rate (11.8% versus 31.4%, P = 0.009) was significantly lower in the Lap group. Mean distal resection margin, involvement of the circumferential resection margin (2.0% versus 3.5%, P = 1.000), and mean lymph nodes harvested (12 versus 11; P = 0.242) were equivalent in the two groups. CONCLUSIONS: Laparoscopically assisted surgery following neoadjuvant CRT is safe for patients with rectal cancer and provides favorable short-term benefits but without compromising oncologic outcomes. This sphincter-preserving procedure may be a treatment of choice for patients with lower rectal cancer.

Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome.

BACKGROUND: The aim of this study was to evaluate the effect of a longer interval between long-course neoadjuvant chemoradiotherapy and surgery on surgical and oncologic outcome. METHODS: A total of 233 consecutive patients with clinical stage II and III rectal cancer were divided into 2 groups according to the neoadjuvant-surgery interval: short-interval group (≤ 7 weeks, n = 111), and long-interval group (>7 weeks, n = 122). Data on neoadjuvant-surgery interval, operative time, perioperative complications, final pathology, disease recurrence, and mortality were prospectively collected and analyzed. RESULTS: The two groups were comparable in terms of demographics, tumor, and treatment characteristics. Operative time and perioperative complications were not influenced by a longer interval. Patients in the long-interval group had a significantly higher pathologic complete response (pCR) rate (27.1% vs. 15.3%, P = 0.029), and a decreased rate of circumferential resection margin involvement (1.6% vs. 8.1%, P = 0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year local recurrence rate was 12.9% in the short-interval group versus 4.8% in the long-interval group (P = 0.025). CONCLUSIONS: A neoadjuvant-surgery interval >7 weeks is safe and is associated with a higher rate of pCR and R0 resection, and decreased local recurrence.

Mini-invasive surgery for colorectal cancer.

Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer.

Effects of the recombinant allergen rDer f 2 on neuro-endocrino-immune network in asthmatic mice.

Severe and life-threatening side effects can occur in patients receiving allergen-specific immunotherapy (SIT), and recombinant allergens made from cDNA have been used in clinical trials for ten years and appear promising for SIT. The aim of this study is to explore the effects of the recombinant allergen Der f 2 (the group 2 allergen from Dermatophagoides farinae) on the neuro-endocrino-immune network in asthmatic mice. Twenty-eight mice were divided into four groups - A, B, C and D. To induce asthma, a crude extract of D. farinae was injected intraperitoneally into the mice in groups B, C and D. Later, the crude extract or recombinant allergen rDer f 2 was given to groups C and D, respectively. Normal saline was given to groups A and B. Serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), interleukin 4 (IL-4), and interferon γ (IFN-γ) were detected by immunoassay and the pathological change of lung tissue was observed by hematoxylin and eosin (HE) staining. Serum CRH, ACTH, CORT, and IFN-γ were highest in healthy group A but lowest in asthma group B. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no difference between the two treatments (p > 0.05). Serum IL-4 was elevated in asthma group B but lowest in healthy group A. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no significant difference between the two treatments (p > 0.05). However, lung pathology as measured histologically (Underwood Score) showed that rDer f 2-treatment was significantly better than crude extract treatment (p < 0.05). In brief, recombinant allergen Der f 2 can strengthen the function of hypothalamus-pituitary-adrenal (HPA) axis, affect the balance of Th1 and Th2 cytokines, and reduce pulmonary inflammation in asthmatic mice.

Multifaceted Nature of HuR in Atherosclerosis Development.

HuR (Human antigen R) is an RNA binding protein (RBP) that specifically binds to certain RNA sequences, influencing post-transcriptional regulation. HuR is primarily involved in tumor regulation, as well as cell growth, proliferation, inflammation, and angiogenesis. HuR is implicated in endothelial activation, smooth muscle proliferation, inflammatory response, macrophage apoptosis, lipid regulation, and autophagy, playing a crucial regulatory role in atherosclerosis. Accumulating evidence suggests that HuR has dual roles in AS. On the one hand, HuR expedites the development of AS by facilitating endothelial activation, smooth muscle proliferation, and inflammation. On the contrary, it exerts beneficial effects by reducing macrophage apoptosis, regulating lipid efflux, and increasing autophagy. In this review, we aim to provide a comprehensive summary of the role of HuR in the development of AS by examining its involvement in cellular mechanisms, inflammation, autophagy, and apoptosis. Additionally, we discuss the mechanisms of drugs that target HuR, with the goal of offering new perspectives for the treatment of AS.

Bilirubin Elevation During Hospitalization Post Radiofrequency Catheter Ablation of Persistent Atrial Fibrillation: Variation Trend, Related Factors, and Relevance to 1-Year Recurrence.

Background: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA). Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (ß=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (ß=0.153, P=0.042) and left atrial diameter (LAD) (ß=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%). Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.

LncRNA-mediated Modulation of Endothelial Cells: Novel Progress in the Pathogenesis of Coronary Atherosclerotic Disease.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

[Outcome analysis of simultaneous liver resection for synchronous liver metastases from colorectal cancer].

OBJECTIVE: To analyze the outcomes of simultaneous liver resection for patients who have primary colorectal cancer with synchronous hepatic metastases to see if there is any advantage for doing so. METHODS: We retrospectively analyzed the medical records (1999 - 2009) of 53 consecutive patients with synchronously recognized primary colorectal carcinoma and hepatic metastases who underwent simultaneous (40 patients) or two-stage (13 patients) colonic and hepatic resections performed at our hospital. RESULTS: There was no thirty-day mortality in both groups. The two groups had significant differences in mean operation duration [(212.9 ± 72.3) min vs. (326.5 ± 140.2) min, P = 0.014], mean blood loss [(337.5 ± 298.0) ml vs. (594.6 ± 430.5) ml, P = 0.020], post-operative hospital stay [(16.2 ± 8.1) day vs. (25.8 ± 8.5) day, P = 0.001]. The incidence rates of post-operative complications were 25.0% (10/40) and 53.8% (7/13), respectively, in the two groups (P = 0.053). The 1-, 3-, 5-year survival rates in the simultaneous resection group were 95.0%, 57.0% and 37.4%, respectively, with a median overall survival of 40.0 months and median disease-free survival of 14.0 months. The 1-, 3-, 5-year survival rates in the two-stage resection group were 92.3%, 58.7% and 36.7%, respectively, with a median overall survival of 38.0 months and median disease-free survival of 13.0 months. There were no significant differences between the two groups in respect of their survivals (P > 0.05). CONCLUSIONS: Simultaneous colectomy and hepatectomy are safe and efficient for colorectal cancer patients who have synchronous colorectal liver metastases, with less complications and blood loss, and shorter hospital stay compared with the two-stage resection.

[Clinical analysis of 17 cases of gastric small cell carcinoma].

OBJECTIVE: To analyze the clinical data and prognosis of gastric small cell carcinoma (GSCC), summarize recent progress in diagnosis and therapy of this disease reported in the literature, and to provide the theoretical basis for its appropriate treatment. METHODS: Clinicopathological data of 17 patients with pathologically confirmed GSCC, treated in our hospital between 1999 to 2012, were retrospectively reviewed. RESULTS: There were 16 males and 1 female, ranged from 46 to 75 years (mean 64.6 years). The tumor was located in the gastric cardia in 13 cases, three in the gastric fundus, and one in the gastric body. All the 17 patients received surgery and 10 of them received postoperative adjuvant chemotherapy, one received preoperative adjuvant chemotherapy. Thirteen patients were followed up. Among them, two 1ived for 40 months all along, the other 3 cases died of recurrence and extensive metastasis in 6 month after operation. The median survival was 13.0 months. The median survival of the patients with and without lymph node metastasis were 42 months and 13 months, respectively. The median survival time of stage II and III patients were 24 months and 14 months, respectively. CONCLUSIONS: It is difficult to make a definite diagnosis before or during the operation for GSCC. Radical operation could be done according to other gastric cancers and lymph node dissection could be simplified. Postoperative chemotherapy with the same scheme as lung small cell carcinoma may help to improve the outcome and prolong the survival of the patients.

[Analysis of 21 cases treated by total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction].

OBJECTIVE: To evaluate the feasibility, safety and short-term outcomes of total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction. METHODS: From July 2012 to February 2013, 21 patients underwent total laparoscopic surgery with transanal natural orifice specimen extraction. There were 12 males and 9 females with a median age of 53 (48-77) years.Rectal cancer (n = 11) and sigmoid cancer (n = 10) were diagnosed. The clinical data such as bowel function recovery time, number of lymph nodes harvested and an incidence of anastomotic leakage was collected and retrospectively analyzed to assess the value of this technique. RESULTS: Operation was successfully accomplished without conversion into open surgery or conventional laparoscopic-assisted surgery. The median operative duration was 105 (80-165) min, the median volume of blood loss 50 (20-300) ml, the median number of lymph nodes harvested 16(8-29) and the time of first bowl movement was 48 (24-72) h. The postoperative hospitalization stay was 9 (6-12) d. There were abdominal hemorrhage (n = 1) and anastomotic leakage (n = 1). CONCLUSION: Total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction appears to be feasible, and oncologically acceptable for selected patients.

Biological functions of CRTC2 and its role in metabolism-related diseases.

CREB-regulated transcription coactivator2 (CRTC2 or TORC2) is a transcriptional coactivator of CREB(cAMP response element binding protein), which affects human energy metabolism through cyclic adenosine phosphate pathway, Mammalian target of rapamycin (mTOR) pathway, Sterol regulatory element binding protein 1(SREBP1), Sterol regulatory element binding protein 2 (SREBP2) and other substances Current studies on CRTC2 mainly focus on glucose and lipid metabolism, relevant studies show that CRTC2 can participate in the occurrence and development of related diseases by affecting metabolic homeostasis. It has been found that Crtc2 acts as a signaling regulator for cAMP and Ca2 + signaling pathways in many cell types, and phosphorylation at ser171 and ser275 can regulate downstream biological functions by controlling CRTC2 shuttling between cytoplasm and nucleus.