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Although total mesorectal excision (TME) has been generally accepted as a principle of rectal cancer surgery, the corresponding laparoscopic approach still needs evaluation in depth, especially the controversial dissection of lateral pelvic areas. At our center, 982 patients with rectal cancers received laparoscopic or laparoscopic-assisted surgery during the past ten years. Short-term results showed an anastomic leakage rate of 4.2% (29/683) in patients with anal sphincter preservation and an average hospitalization of 8.8 days. Sixty-two cases (6.3%) suffered postoperative urinary dysfunction while well-controlled defecation was observed in 87.6% cases that underwent colo-rectal/colo-anal anastomosis. According to our experience, the laparoscope amplifies the local view within the narrow pelvis, thus facilitating the identification of surgical plane and adjacent structures. The radial, proximal and distal distribution of mesorectal micrometastases underline the importance of total mesorectal excision and the sharp dissection between parietal and visceral pelvic fascia is essential for better clearance and nerve protection. Lateral metastasis was more common in lower located cancers while laparoscopic lateral dissection is practical and safe when performed by trained surgeons. Lateral dissection is advised when preoperative imaging or intraoperative exploration suggest the existence of lateral metastasis. [ABSTRACT FROM AUTHOR]

Aim : To investigate the regional spread of microscopic tumor nodules in the mesorectum of patients with low rectal cancer, and to provide further pathological evidence for optimal procedure selection of radical resection for rectal cancer. Methods : Sixty-two patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME). Surgical specimens were sliced transversely on serial embedded blocks at 2.5-mm intervals, and stained with hematoxylin and eosin (HE). On whole-mount sections the mesorectum was divided into 3 regions: the outer region of the mesorectum (ORM), the middle region of the mesorectum (MRM), and the inner region of the mesorectum (IRM). Microscopic metastatic foci were investigated for metastatic mesorectal region, frequency, types, involvement of the lymphatic system, and correlation with the primary tumor. Tumor-suspect nodules previously considered disease free by HE stain on whole-mount section were examined by in situ hybridization (ISH) on tissue microarray (TMA) through detecting mRNAs of CEA and CK20 with non radioactive biotin-tagged oligonucleotide probes. Results : Microscopic spread of the tumor was observed in 50.0 percent of patients (31 out of 62, 24 by HE stain on whole-mount section and 7 by ISH on TMA) and that in the ORM was observed in 38.7 percent of the patients (24 out of 62, 16 observed by HE stain on whole-mount section and 8 by ISH on TMA). Microscopic tumor foci spread in the circumferential resection margin (CRM) occurred in 8.1 percent of the patients (5 out of 62, 4 observed by HE stain on whole-mount section and one by ISH on TMA), and distal mesorectum (DMR) involvement was detected in 6.5 percent (4 out of 62, all observed by HE stain on whole-mount section), with the spread extending to within 3 cm from the lower margin of the tumor. Most (26 of 31) of the patients with microscopic spread in mesorectum had TNM Stage III diseases. Conclusions : The results of the present study support the theory that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin of no less than 4 cm was referenced. Five patients with microscopic tumor nodule spread in the CRM observed in the study suggested that microscopic metastases exist in pelvic lateral areas and in the mesorectum simultaneously, indicating the significance of preoperative and/or postoperative radiochemotherapy. [ABSTRACT FROM AUTHOR]

Background: While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated. Methods: We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta‐analysis. To delve deeper, we employed Weighted Gene Co‐expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis. Results: Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta‐analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis‐related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis‐related network, and IRF1 was identified as a predictive marker for both recurrence‐free and distant metastasis‐free survival across multiple datasets. Conclusion: Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP. [ABSTRACT FROM AUTHOR]

Background: The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA).Methods: Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled.Results: A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881-1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779-1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57-0.96 p < 0.01) and after PS matching cohort (HR: 0.65, 95% CI: 0.46-0.94, p < 0.01).Conclusions: Combined with the results of previous studies, total intravenous anesthesia has been shown to be superior to inhalation anesthesia in terms of overall survival for gastric cancer patients undergoing surgical treatment. The selection of intravenous or inhalation anesthesia for gastric cancer surgery should take into account the long-term prognosis of the patient. [ABSTRACT FROM AUTHOR]

Metastasis is the main culprit of cancer-associated mortality and involves a complex and multistage process termed the metastatic cascade, which requires tumor cells to detach from the primary site, intravasate, disseminate in the circulation, extravasate, adapt to the foreign microenvironment, and form organ-specific colonization. Each of these processes has been already studied extensively for molecular mechanisms focused mainly on protein-coding genes. Recently, increasing evidence is pointing towards RNAs without coding potential for proteins, referred to as non-coding RNAs, as regulators in shaping cellular activity. Since those first reports, the detection and characterization of non-coding RNA have explosively thrived and greatly enriched the understanding of the molecular regulatory networks in metastasis. Moreover, a comprehensive description of ncRNA dysregulation will provide new insights into novel tools for the early detection and treatment of metastatic cancer. In this review, we focus on discussion of the emerging role of ncRNAs in governing cancer metastasis and describe step by step how ncRNAs impinge on cancer metastasis. In particular, we highlight the diagnostic and therapeutic applications of ncRNAs in metastatic cancer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the primary outcomes of traditional laparoscopic cholecystectomy (TLC) compared with laparoendoscopic single-site cholecystectomy (LESSC). Subjects and Methods: Randomized controlled trials (RCTs) comparing TLC with LESSC were included by a systematic literature research. The inclusion and extraction of the data were completed by two authors independently. Meta-analysis was performed using Review Manager version 5.1.4 software. The clinical outcomes were evaluated by odds ratio (OR) and standard mean difference (SMD) according to the different types of data. Sensitivity and heterogeneity analyses were used to account for rationality of pooling data and sources of heterogeneity. Results: Seven RCTs involving 611 patients met the predefined inclusion criteria. The cosmetic score of the LESSC group was significantly higher at 1 week (SMD=0.48; 95% confidence intervals [CI] 0.24, 0.73; P=.0001), 2 weeks (SMD=0.87; 95% CI 0.61, 1.13; P<.00001), and 1 month (SMD=0.88; 95% CI 0.62, 1.44; P<.00001) postoperatively. However, LESSC showed a lesser physical quality of life (PQOL) score at 3 days (SMD=−0.28; 95% CI −0.52, −0.44; P=.02), 1 week (SMD=−0.31; 95% CI −0.55, 0.06; P=.01), and 2 weeks (SMD=−0.30; 95% CI −0.55, −0.05; P=.02) postoperatively. There was no significant difference between the two groups in operating time, perioperative complication, intraoperative blood loss, postoperative hospital stay, Visual Analog Scale pain score, and PQOL on 1 day, 5 days, and 1 month postoperatively. Conclusion: LESSC is associated with a higher cosmetic score and a lesser short-term PQOL score compared with TLC. [ABSTRACT FROM AUTHOR]

Compound amino acid solution (CAAS) is a large class of solution of amino acids' mixture and was widely used in China. Its extensive nutritional treatment was accompanied by a substantial incidence of adverse reactions, especially life-threatening anaphylaxis. However, the adverse reactions were reported in isolated case reports only, and the reasons behind this needed further investigation. The Chinese language papers were searched from China National Knowledge Infrastructure and Wanfang database published in China from 1985 to 2010. The search terms 'anaphylactic', 'anaphylaxis', 'allergic', 'allergy', 'shock', and 'adverse reaction' combined with the term 'amino acid' were used. Totally 71 episodes of anaphylactic shock and seven deaths in 38 articles were analyzed. Chest distress and cool extremities were the most common clinical manifestations. Almost all patients suffered from significant hypotension. The vast majority of patients were not found to be allergic to certain substances. CAAS was inappropriately administrated in more than one-third of patients. The life-threatening anaphylaxis was prominently prevalent in pregnant women, the elderly and patients with hypersensitivity such as asthma, and patients without medicinal indication. Innovation of processing technique and establishment of more strict supervision system are an urgent need for CAAS to control its production quality and thus improve its safety in China. [ABSTRACT FROM AUTHOR]

Background. Several studies have been conducted to investigate the association between the presence of perineural invasion (PNI) and overall survival (OS) of gastric cancer (GC) patients who underwent curative resection, but no consensus has been reached. This study is aimed at determining the prognostic significance of PNI in gastric cancer. Study Design. The data of 2969 patients with gastric cancer and who had undergone curative gastrectomy from 2006 to 2010 in two high-volume hospitals of China and Korea were retrospectively analyzed. PNI positivity was identified when carcinoma cells were found to infiltrate into the perineurium or neural fascicles. The relationships between PNI and other clinicopathological factors were evaluated, and survival analyses were performed. Results. The presence of PNI was detected in 1055 of the 2969 patients (35.5%). Nationality, age, tumor location, size of tumor, differentiation of the tumor, pT stage, pN stage, lymphatic invasion, and vascular invasion had been associated with PNI positivity. The mean survival time of patients with and without PNI was 62.5 months and 87.3 months, respectively (P < 0.001). However, the presence of PNI was not an independent prognostic factor for gastric cancer, except for patients in stage III (P = 0.037 , hazard ratio: 1.21, 95% confidence interval: 1.01-1.44). Conclusion. PNI occurs frequently in patients with gastric cancer, and the incidence of PNI increases with the staging of the tumor. The presence of PNI can provide additional information in predicting the survival outcome for those with stage III tumors. [ABSTRACT FROM AUTHOR]

Background. Several studies have been conducted to investigate the association between the presence of perineural invasion (PNI) and overall survival (OS) of gastric cancer (GC) patients who underwent curative resection, but no consensus has been reached. This study is aimed at determining the prognostic significance of PNI in gastric cancer. Study Design. The data of 2969 patients with gastric cancer and who had undergone curative gastrectomy from 2006 to 2010 in two high-volume hospitals of China and Korea were retrospectively analyzed. PNI positivity was identified when carcinoma cells were found to infiltrate into the perineurium or neural fascicles. The relationships between PNI and other clinicopathological factors were evaluated, and survival analyses were performed. Results. The presence of PNI was detected in 1055 of the 2969 patients (35.5%). Nationality, age, tumor location, size of tumor, differentiation of the tumor, pT stage, pN stage, lymphatic invasion, and vascular invasion had been associated with PNI positivity. The mean survival time of patients with and without PNI was 62.5 months and 87.3 months, respectively (P < 0.001). However, the presence of PNI was not an independent prognostic factor for gastric cancer, except for patients in stage III (P = 0.037 , hazard ratio: 1.21, 95% confidence interval: 1.01-1.44). Conclusion. PNI occurs frequently in patients with gastric cancer, and the incidence of PNI increases with the staging of the tumor. The presence of PNI can provide additional information in predicting the survival outcome for those with stage III tumors. [ABSTRACT FROM AUTHOR]

Purpose: Petersen's hernia (PH) is a serious complication after gastrectomy for gastric cancer. The aim of this study was to investigate whether closure of Petersen's defect (PD) can decrease the rates of PH and suspected Petersen's hernia (SPH). Methods: Patients who underwent gastrectomy with PD were enrolled. From January 2014 to January 2017, we performed gastrectomy without PD closure (non-closure group). From February 2017 to June 2018, we closed PDs during gastrectomy (closure group). The rates of PH and SPH were compared between the two groups. The last follow-up was updated in August 2020. Results: Among a total of 1213 patients, 12 patients (1.0%) developed PH, and 23 patients (1.9%) developed SPH. The rate of PH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 11/828, 1.3%, p = 0.042, log-rank test). The rate of SPH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 22/828, 2.7%, p = 0.008, log-rank test). Non-closure of PD was a risk factor for PH and SPH (odds ratio (OR) 7.72, 95% CI 1.84–32.35, p = 0.006). Conclusions: PD closure is recommended after gastrectomy for gastric cancer, as the rates of PH and SPH were significantly decreased. [ABSTRACT FROM AUTHOR]

Background: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. Methods: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. Results: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28–44.74 vs. 29, IQR 29–39.5, p = 0.002) and no. 9 station nodes (2, IQR 1–5 vs. 2, IQR 1–3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20–80 ml vs. 80, IQR 50–80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220–303.25 min vs. 232, IQR 220–255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7–9 days vs. 8, IQR 7–9 days, p = 0.452) were comparable between the CML and OG groups. Conclusion: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events. [ABSTRACT FROM AUTHOR]

Background: Due to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC. Methods: We retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type. Results: Patients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV. Conclusions: The clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC. [ABSTRACT FROM AUTHOR]

Background: Obesity may impact surgical outcomes of gastrectomy. Whether visceral fat area (VFA) is a better obesity parameter than body mass index (BMI) is still controversial. The aim of this study is to compare the accuracy and effectiveness of VFA and BMI in predicting the short-term surgical outcomes of gastrectomy.Methods: Patients who were diagnosed with gastric cancer were measured for BMI and VFA preoperatively and then divided into a VFA-H (VFA-high) group and VFA-L (VFA-low) group, at the cutoff point of 100 cm2, and a BMI-H (BMI-high) group and BMI-L (BMI-low) group, at the cutoff point of 25 kg/m2. The short-term surgical outcomes were compared between the different groups.Results: In total, 276 patients were enrolled in this study; 55 (19.9%) patients were classified into the BMI-H group, and 122 (44.2%) patients were classified into the VFA-H group. There was a significant correlation between BMI and VFA (r = 0.652, p < 0.001). Compared with the VFA-L group, the VFA-H group had a higher incidence of postoperative complications (31.1% vs. 13.0%; p < 0.001), longer operation duration (270.0 (235.0-305.0) vs. 255.0 (223.8-295.0), p = 0.046), and more blood loss (100.0 (100.0-150.0) vs. 80.0 (80.0-100.0), p < 0.001), while the BMI-H group had more blood loss than the BMI-L group (100.0 (100.0-120.0) vs. 100.0(80.0-100.0), p = 0.006). Logistic regression showed that VFA was an independent risk factor for postoperative complications (odds ratio 2.813, 95% CI 1.523-5.194; p = 0.001).Conclusion: For gastric cancer patients, VFA is superior to BMI in accurately and effectively illuminating the impact of obesity on short-term surgical outcomes.Trial Registration: Clinicaltrials.gov: NCT02800005. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. Methods: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X‐tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. Results: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C‐index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. Conclusions: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction. [ABSTRACT FROM AUTHOR]

Background. The da Vinci robotic system was considered an effectively alternative treatment option for early gastric cancer patients in recent years. The aim of our study was to evaluate the safety and feasibility of robot-assisted gastrectomy in our center. Methods. This study included 33 patients who underwent robot-assisted gastrectomy (RAG) and 88 patients who underwent laparoscopic-assisted gastrectomy (LAG) between January 2016 and April 2018. Clinicopathological characteristics, surgical parameters, postoperative recovery, and the learning curves of RAG were evaluated. Results. Baseline characteristics between two groups were well balanced. The operation time of RAG was longer than that of LAG (333.1±61.4 min vs. 290.6±39.0 min, p=0.001), and the estimated blood loss was 62.4±41.2 ml in the RAG group and 77.7±32.3 ml in the LAG group (p=0.005), respectively. The mean number of examined lymph nodes in RAG was less than that in LAG (30.3±10.2 vs. 37.4±13.7, p=0.008). However, RAG had an advantage in the dissection of No. 9 lymph nodes (3.4±2.1 vs. 2.5±1.6, p=0.039). The incidence of postoperative complications was similar in both groups (p=0.735). There were no significant differences in terms of postoperative recovery between the two groups. The learning curve of RAG showed that the CUSUM value decreased from the 8th case, which suggested a rapid learning curve among experienced surgeons on LAG operations. Conclusions. RAG was safe and feasible for gastric cancer patients, with superiority in the dissection of No. 9 lymph nodes. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to present the clockwise, modularized lymphadenectomy model of laparoscopic gastrectomy for gastric cancer patients, which is based on our clinical practice experience in laparoscopic gastric cancer surgery.Methods: From Jan 2015 to July 2017, 116 patients who underwent laparoscopic gastrectomy were retrospectively collected and analyzed. According to the different resection models, patients were divided into two groups: traditional laparoscopic lymphadenectomy group (63 patients) and clockwise, modularized lymphadenectomy group (53 patients). Operation-related parameters were compared between the two groups.Results: The clockwise, modularized lymphadenectomy group had less dissection time (119.8 ± 19.1 min vs. 135.3 ± 23.8 min, p < 0.001) and less intraoperative blood loss (81.7 ± 42.9 ml vs. 91.4 ± 28.7 ml, p = 0.016) compared with the traditional laparoscopic lymphadenectomy group. Meanwhile, the clockwise, modularized lymphadenectomy group had more numbers of examined lymph nodes (40.5 ± 14.3 vs. 33.9 ± 11.0, p = 0.007) than the traditional laparoscopic lymphadenectomy group. Besides, there was no statistically significant difference in the postoperative complication rates between the two groups. The clockwise, modularized lymphadenectomy group had shorter postoperative hospital stay than the traditional laparoscopic lymphadenectomy group (8.7 ± 3.2 days vs. 10.4 ± 3.9 days, respectively, p < 0.001).Conclusions: Through the adoption of the fixed sequence of lymphadenectomy, requirements and standard of lymphadenectomy of each lymph node station, and specific surgical skills for intraoperative exposure by the clockwise and modularized lymphadenectomy model, we can optimize and facilitate the laparoscopic gastric cancer surgery. [ABSTRACT FROM AUTHOR]

Background: The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. Methods: We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). Results: By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P < 0.001), TNM-EC (P = 0.001) in training cohort and TNM-GC (P < 0.001) TNM-EC (P < 0.001) in the validation cohort were both independent prognostic factors. The C-index value for the TNM-GC scheme was larger than that of TNM-EC system in both training (0.721 vs. 0.690, P < 0.001) and validation (0.721 vs. 0.696, P < 0.001) cohorts. After stratification analysis for Siewert type II, the C-index for TNM-GC scheme was still larger than that of TNM-EC in both training (0.724 vs. 0.694, P = 0.005) and validation (0.723 vs. 0.699, P < 0.001) cohorts. Conclusions: The 8th TNM-GC scheme is superior to TNM-EC in predicting the prognosis of AEG especially for type II among patients underwent transhiatal approaches. [ABSTRACT FROM AUTHOR]

Background: The preoperative work-up has limitations on finding peritoneal dissemination (PD) in gastric cancer patients. Laparoscopic exploration (LE) can discover radiographically occult PD, obtain accurate stage and avert futile laparotomy. The aim of our study was to introduce "Four-Step Procedure" LE in West China Hospital and further evaluate its safety and feasibility.Methods: We conducted a retrospective analysis on 165 patients from July 2016 to December 2017 who underwent "Four-Step Procedure" LE in gastrointestinal surgery department of West China Hospital. All the patients were diagnosed with gastric adenocarcinoma without explicit distant metastasis through Computed Tomography and/or Gastrointestinal Ultrasonography. Peritoneal lavage cytological examination (CY) was routinely performed during LE in our research. The "Four-Step" technical process of LE was introduced comprehensively. The clinicopathologic features and the presence of PD or CY at LE were analyzed, and the stratified analysis by cT and cN stages on the proportion of P1 and/or CY1 was also reported in this study.Results: Total of 165 patients accepted LE in our study, among these patients: 27 (16.4%) patients with P1 and/or CY1: 19 (11.5%) patients were found PD (P1), 17 (10.3%) patients with positive cytological examination (CY1) and 9 (3.6%) patients with P1Cy1. The stratified analysis by cT stage indicated that there was no P1 and/or Cy1 in cT1-cT2 stages, 1 (2.7%) patient with P1 and 1 (2.7%) with Cy1 in cT3 stage, 18 (20.0%) patients with P1 and 16 (17.8%) with Cy1 in cT4 stage. After LE, there were 74 (44.8%) patients underwent laparoscopic assistant gastrectomy, 25 (15.2%) patients with open gastrectomy, 50 (30.3%) patients with neoadjuvant chemotherapy and 16 (9.7%) patients with palliative chemotherapy and/or conversion therapy.Conclusion: "Four-Step Procedure" LE is reliable and feasible for gastric cancer. From our study, LE has unique superiority on ascertaining PD and cytological examination and LE should be recommended in cT4 stage gastric cancer before resection. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Ketoconazole induces apoptosis in HCC cells by triggering excessive mitophagy. • Downregulation of cyclooxygenase 2 (COX-2) is key in the induction of excessive mitophagy via the PINK1/Parkin axis. • HCC characterized by high COX-2 expression may benefit more from ketoconazole treatment than other subtypes. • Ketoconazole acts synergistically with sorafenib in the suppression of HCC growth in vitro and in vivo. Background & Aims Hepatocellular carcinoma (HCC) is a common cancer worldwide and remains a major clinical challenge. Ketoconazole, a traditional antifungal agent, has attracted considerable attention as a therapeutic option for cancer treatment. However, its mechanism of action is still not clearly defined. We aimed to evaluate the effect of ketoconazole on HCC and investigate the underlying mechanisms. Methods We examined the antitumor effect of ketoconazole on HCC cells, cell line-derived xenografts, and a patient-derived xenograft (PDX) model. Ketoconazole-induced mitophagy was quantified by immunofluorescence, immunoblotting and transmission electron microscopy analysis. We used mitophagy inhibitors to study the role of mitophagy on HCC cell death induced by ketoconazole. The role of cyclooxygenase-2 (COX-2 [encoded by PTGS2 ]) on ketoconazole-induced mitophagy was evaluated using gain- and loss-of-function methods. The synergistic effect of ketoconazole with sorafenib on HCC was measured in vivo and in vitro. Results Ketoconazole stimulated apoptosis in HCC cells by triggering mitophagy in vitro and in vivo. Mechanistically, ketoconazole downregulated COX-2, which led to PINK1 accumulation and subsequent mitochondrial translocation of Parkin (PRKN), and thereby promoted mitophagy-mediated mitochondrial dysfunction. Inhibiting mitophagy alleviated ketoconazole-induced mitochondrial dysfunction and apoptosis, supporting a causal role for mitophagy in the antitumor effect of ketoconazole. In the HCC PDX model, ketoconazole demonstrated a marked antitumor effect characterized by COX-2 downregulation, mitophagy activation, and apoptosis induction. Moreover, ketoconazole acted synergistically with sorafenib to suppress HCC xenograft growth in vivo. Conclusion Our results demonstrate a novel link between ketoconazole and mitophagy machinery, providing preclinical proof of concept for the use of ketoconazole in HCC treatment. Lay summary Hepatocellular carcinoma (HCC) is a common malignancy worldwide and remains a major clinical challenge. Our study reveals that ketoconazole, a broad-spectrum antifungal agent, activates PINK1/Parkin-mediated mitophagy by downregulating COX-2, consequently resulting in the acceleration of apoptosis and thereby inhibiting the growth of HCC. Furthermore, ketoconazole acts synergistically with sorafenib in the suppression of HCC growth in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Aim: To evaluate short-term and long-term outcomes of laparoscopic-assisted transhiatal esophagogastrectomy (LTEG) for treatment of adenocarcinoma of the esophagogastric junction (AEG).Methods: Patients with AEG who underwent laparoscopic or open surgery at our department from October 2008 to December 2012 were enrolled in this retrospective study. Patients' demographics, perioperative outcomes, and survival data were collected.Results: A total of 136 patients with AEG were enrolled (103 patients underwent laparoscopic surgery and 33 patients underwent open surgery). Patient characteristics were comparable between two groups in terms of age, gender, tumor-node-metastasis stage, tumor size, preoperative complications, and type of surgery. The median operative time was longer in laparoscopic group (240 versus 210 minutes, P = .048). However, the estimated blood loss was less, and the rate of pleural rupture was lower in laparoscopic group (20 versus 70 mL, P < .001 and 18.4% versus 36.4%, P = .033, respectively). The rate of patients with pleural rupture requiring prolonged use of mechanical ventilation longer than 12 hours (6/31, 19.4%) was higher than that of patients without pleural rupture (6/105, 5.7%) (P = .019). The incidence of reflux symptoms at postoperative month six was similar in two groups (18.4% in laparoscopic group versus 24.2% in open group, P = .468), as well as the use of proton pump inhibitors (12.6% versus 15.2%, P = .709). Furthermore, the number of lymph nodes harvested (22 versus 25), 2-year cumulative overall survival rates (80.4% versus 57.5%), and the median survival times (51.52 months versus 24.24 months) were similar between two groups (P > .05).Conclusion: LTEG is a safe, feasible, and oncologically effective procedure for AEG when performed by an experienced surgeon. Laparoscopic surgery is associated with a lower risk of pleural rupture, but pleural rupture in laparoscopic surgery may cause an adverse effect on the recovery of pulmonary function presumably due to tension pneumothorax. [ABSTRACT FROM AUTHOR]

Aim: To compare the short-term and long-term outcomes of laparoscopic versus open surgery for low rectal cancer.Methods: Patients with low rectal cancer who underwent laparoscopic or open surgery at our department from January 2009 to December 2013 were enrolled in this retrospective study. The primary end points were 3-year local recurrence and overall and disease-free survival (DFS) rates. Secondary end points were intraoperative and postoperative outcomes.Results: Laparoscopic group had longer operative time (165.0 versus 140.0, P < .001), less blood loss (20.0 versus 40.0, P < .001), shorter length of incision (5.0 versus 18.0, P < .001), and more lymph node harvested (11.0 versus 9.0, P = .002). However, time to first flatus (P = .941), postoperative hospital stay (P = .095), postoperative complications (P = .155), and 30-day mortality (P = .683) was similar between two groups. With the median follow-up period of 65 months, the 3-year local recurrence rate was 4.3% in laparoscopic group and 7.5% in open group (P = .077); the 3-year overall and DFS rates were similar in two groups (85.9% versus 88.8%, P = .229 and 76.9% versus 79.2%, P = .448, respectively); and the overall and DFS curves were comparable between two groups (hazard ratio [HR] = 0.858, 95% confidence intervals [CI] 0.709-1.037, P = .112 and HR = 1.076, 95% CI 0.834-1.389, P = .275, respectively).Conclusions: Laparoscopic surgery is safe and has equivalent long-term oncologic outcomes for low rectal cancer when compared to open surgery. Furthermore, large-scale, prospective randomized clinical trials are needed to confirm the present findings. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) is technically feasible, but the long-term effect remains uncertain. This study aims to compare the long-term oncologic outcomes of laparoscopic versus open resection of GISTs by larger cases based on tumor size-location-matched study. Methods: Between 2006 and 2015, 63 consecutive patients with a primary gastric GIST undergoing laparoscopic resection were enrolled in and matched (1:1) to patients undergoing open resection by tumor size and location. Clinical and pathologic parameters and surgical outcomes associated with each surgical type were collected and compared. Results: The operation time, intraoperative blood loss, return of bowel function and oral intake, nasogastric tube retention time and postoperative stay were all shorter/faster in laparoscopic group than those in open group ( P < 0.001). Postoperative complications were comparable except for the higher incidence of abdominal/incision pain in open group (9.52 vs 27%, P = 0.01). There was no statistical difference in recurrence rate (9.52 vs 15.87%, P = 0.29) and long-term recurrence-free survival between the two groups ( P = 0.39). Conclusions: The long-term oncologic outcome of laparoscopic resection of primary gastric GISTs is comparable to that of open procedure, but laparoscopic procedure has the advantage of minimal invasion and is superior in postoperative recovery. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Two-Day Hospital Stay After Laparoscopic Colorectal Surgery Under an Enhanced Recovery After Surgery (ERAS) Pathway" by G. Rossi and colleagues published in the journal in 2013.

Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated.Design: Randomized experiment.Setting: Research laboratory at a university hospital.Subject: Experimental severe acute pancreatitis in rats.Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr).Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-κB and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration.Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications. [ABSTRACT FROM AUTHOR]

Background: The effect of Helicobacter pylori ( H. pylori) eradication on gastric cancer (GC) prevention is controversial. Intestinal metaplasia (IM) seems to be a 'point of no return' in the precancerous cascade. We performed a meta-analysis of randomized controlled trials (RCTs) to illustrate this issue. Materials and Methods: The MEDLINE, EMBASE, Cochrane Library were searched for relevant RCTs that were published in any language up to March 2014. By dividing participants into subgroups based on their baseline diagnoses as group

Background. The impact of perioperative blood transfusion on the prognosis of gastric adenocarcinoma patients is still controversial. The aim of this study was to elucidate the impact of perioperative blood transfusion on postoperative complications and prognosis of patients who underwent gastrectomy for gastric adenocarcinoma with different levels of preoperative hemoglobin value (POHb). Method. From 2003 to 2011, 1199 patients who underwent curative gastrectomy were retrospectively enrolled and followed up to December 2014. Clinicopathological features and survival outcomes were compared between transfused and nontransfused patients. Results. In this study, transfused patients had more postoperative complications than nontransfused ones (P=0.002). In survival analysis, the difference was not significant between transfused and nontransfused patients with POHb between 70 and 100 g/L (P=0.191). However, in patients with POHb >100 g/L, transfused patients had significantly worse prognosis (P<0.001), especially in TNM III stage patients (P=0.002). And intraoperative blood transfusion predicted poor prognosis (P=0.001). Conclusion. Perioperative blood transfusion might lead to poor survival in gastric adenocarcinoma patients with POHb >100 g/L and transfused patients had more postoperative complications; thus it is better to refrain from unnecessary perioperative blood transfusion especially intraoperative transfusion. [ABSTRACT FROM AUTHOR]

Background. To evaluate prognostic value of metastatic No.8p LNs in patients with gastric cancer. Methods. From August 2002 to December 2011, a total of 284 gastric cancer patients who underwent gastrectomy with No.8p LNs dissection were analyzed retrospectively in this study. Patients were divided into two groups according to the status of No.8p LNs. Clinicopathological features were collected to conduct the correlation analysis. Follow-up was carried out up to December 31st, 2014. Overall survival was analyzed. Results. Out of 284 patients, metastatic No.8p LNs were found in 24 (8.5%) patients. Compared with other 260 cases, these patients suffered morphologically larger tumor (P=0.003), node stage (P=0.000), and metastatic stage (P=0.000). The 3-year overall survival rate was 26% in No.8p-positive group and 53% in No.8p-negative group. No significant difference of cumulative survival rates existed between the No.8p-positive group and No.8p-negative stage IV group (26% versus 28%, P=0.923). Patients with other distant metastasis or not in No.8p+ group had similar cumulative survival rates (24% versus 28%, P=0.914). Conclusions. Positive No.8p LNs were a poor but not an independent prognostic factor for patients with GC and should be recognized as distant metastasis. [ABSTRACT FROM AUTHOR]

Background. The studies on risk factors and metastatic rate of retropancreatic (number 13) lymph nodes in gastric adenocarcinoma were few and the results were still controversial. The aim of this study was to elucidate risk factors and prognostic significance of number 13 lymph nodes in gastric adenocarcinoma. Method. From January 2000 to December 2011, 114 patients who underwent gastrectomy with number 13 lymph nodes dissection were enrolled and followed up to January 2014. Patients were grouped according to whether number 13 lymph nodes were positive or negative. Results. The metastatic rate of number 13 lymph nodes was 22.8%. In multivariate analysis, pT stage (P=0.027), pN stage (P=0.005), and number 11p (P=0.015) lymph nodes were independent risk factors of positive number 13 lymph nodes. In all patients (P<0.001) and subpopulation with TNM III stage (P=0.007), positive number 13 lymph nodes had significantly worse prognosis than those of patients with negative number 13 LNs in Kaplan-Meier analysis. Conclusion. Number 13 lymph nodes had relatively high metastatic rate and led to poor prognosis. pT stage, pN stage, and number 11p lymph nodes were independent risk factors of positive number 13 lymph nodes. [ABSTRACT FROM AUTHOR]

Introduction:K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear. Objective:Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence. Method:Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated. Principal Findings:7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49). Conclusions:K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To compare surgical efficacy and postoperative recovery of ultrasonic scalpel (USS) with conventional techniques for the resection of gastric carcinoma. Methods: A systematic search of major medical databases (PubMed, Embase, CCRT and CNKI) was conducted. Both randomized and non-randomized controlled trials (RCTs and nRCTs) were considered eligible. Operation time (OT), intraoperative blood loss (BL) and postoperative complications (POC) rates as well as postoperative hospitalization days, number of dissected lymph nodes, abdominal drainage volume and time for recovery of gastrointestinal functions were synthesized and compared. Results: Nineteen studies were included (7 RCTs and 12 nRCTs), in which 1930 patients were enrolled totally (946 in the USS group and 984 in the conventional group). Monopolar electrocautery and ligation were used as the conventional methods. Comparative meta-analysis showed perioperative outcomes were significantly improved using USS compared with conventional surgical instrumentation. OT was reduced from a weighted mean of 185.3 min in the conventional group to 151.0 min in the USS group (MD = −33.30, 95% CI [−41.75, −24.86], p<0.001) and intraoperative BL was decreased from a weighted mean of 217.9 ml in the conventional group to 111.6 ml in the USS group (MD = −113.42, 95% CI [−142.05, −84.79], p<0.001). Results from RCTs subgroup were consistent with those from nRCTs subgroup. The weighted cumulative risk of POC accounted for 8.9% (0%–25%) and 12.9% (5.5%–45%) in the USS and conventional groups, respectively. Pooled estimated results from nRCTs (OR = 0.54, 95% CI [0.27, 1.06], p = 0.07) and RCTs (RR = 0.75, 95% CI [0.44, 1.26], p = 0.27) showed no significant difference between the USS and control groups. Analysis of secondary outcomes showed the improvements of the USS group over control group regarding the number of dissected lymph nodes, postoperative hospitalization days, abdominal drainage volume and time for recovery of gastrointestinal functions. Conclusion: Compared with conventional electrosurgery, the USS is a safe and effective technique with more short-term advantages in open surgery for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The metastatic rate and risk factors of splenic hilar (No.10) lymph nodes (LNs) in gastric adenocarcinoma were still variable and uncertain, and the prognostic significance of No.10 LNs was also controversial. The aim of this retrospective study was to analyze the metastatic rate, risk factors and prognostic significance of No.10 LNs in gastric adenocarcinoma. Methods: From August 2007 to December 2011, 205 patients who were diagnosed with primary gastric adenocarcinoma and underwent total or proximal gastrectomy plus No.10 LNs dissection in West China Hospital were enrolled. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Mean numbers of harvested LNs and metastatic LNs were 34.8±12.6 (15–73) and 8.7±10.8 (0–67), respectively. The proportion of cases with positive No.10 LNs was 8.8% (18/205). In all 204 dissected No.10 LNs, 47 LNs (23.0%) were metastatic. In 52.2% (107/205) patients, the dissected splenic hilar tissues were histologically determined as only fat tissues but without LNs structure. Histological evidence of LNs structure was found in 98 (47.8%) patients with 18.4% (18/98) metastatic No.10 LNs. In multivariate logistic regression analysis, metastasis of No.10 LNs was significantly correlated with No.4sa LNs (p = 0.010) and pN stage (p = 0.012). Regarding survival analysis, 199 (97.1%) patients were followed up (0.6–74.8 months). In all patients with R0 resection, metastatic No.10 LNs caused significantly worse prognosis both in Kaplan-Meier (p = 0.006) and Cox regression analysis (p = 0.031). Conclusions: Although the metastatic rate of No.10 LNs was 8.8%, dissection of No.10 LNs might be meaningful due to the poor prognosis of positive cases. And attentions should be also paid to its correlated factors including pN stage and No.4sa LNs. [ABSTRACT FROM AUTHOR]

Objective: Currently, little is known regarding the role of peroxisome proliferator-activated receptor-β (PPAR β) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR β expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients.Design: The expression and localization of PPAR β in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients.Results: PPAR β was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR β in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR β in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR β in CRC cells but increased expression in VECs exhibited less favorable prognosis.Conclusions: PPAR β might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs. [ABSTRACT FROM AUTHOR]

Objective: Currently, little is known regarding the role of peroxisome proliferator-activated receptor-β (PPAR β) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR β expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients. Design: The expression and localization of PPAR β in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients. Results: PPAR β was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR β in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR β in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR β in CRC cells but increased expression in VECs exhibited less favorable prognosis. Conclusions: PPAR β might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a potentially lethal disease characterized by inflammation and parenchymal cell death; also, the severity of AP correlates directly with necrosis and inversely with apoptosis. However, mechanisms of regulating cell death in AP remain unclear. The endoplasmic reticulum (ER) chaperone protein GRP78 has anti-apoptotic properties, in addition to modulating ER stress responses. This study used RNA interference (RNAi) approach to investigate the potential role of GRP78 in regulating apoptosis during AP. In vitro models of AP were successfully developed by treating AR42J cells with cerulein or cerulein plus lipoplysaccharide (LPS). There was more pancreatic inflammation and less apoptosis with the cerulein plus LPS treatment. Furthermore, knockdown of GRP78 expression markedly promoted apoptosis and reduced necrosis in pancreatic acinar cells. This was accomplished by enhancing the activation of caspases and inhibiting the activity of X-linked inhibitor of apoptosis protein (XIAP), as well as a receptor interacting protein kinase-1(RIPK1), which is a key mediator of necrosis. This attenuated the severity of pancreatic inflammation, especially after cerulein plus LPS treatment. In conclusion, these findings indicate that GRP78 plays an anti-apoptotic role in regulating the cell death response during AP. Therefore, GRP78 is a potential therapeutic target for AP. [ABSTRACT FROM AUTHOR]

The role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis of colon cancer is not understood thoroughly. Previous studies from our group have shown that the expression levels of MMP-7 were highly elevated in colorectal cancer patient specimens and were correlated with Dukes Staging, histological differentiation grade and CEA level. The goal of this study was to investigate the cellular impact of MMP-7 in colon cancer. In this study, we used the SW480 colon cancer cell lines of MMP-7 knockdown by lentivirus-mediated RNA interference as a model system to investigate the impact of MMP-7 on cell proliferation and sensitivity to 5-Fluorouracil (5-FU) and X-ray irradiation (IR). Cell proliferation and sensitivity to 5-FU and IR were measured by MTT assay and colony formation assay. Cell cycle was evaluated by flow cytometry. We showed that the down regulation of MMP-7 inhibits colon cancer cell proliferation and sensitizes tumour cells to 5-FU and IR ( P < 0.05). Decreased MMP-7 expression in SW480 cells by RNA interference triggered cell cycle arrest at G1 phase ( P < 0.05). Down regulation of MMP-7 may inhibit the cell proliferation of colon cancer cells and increase tumour cells sensitivity to radiotherapy and chemotherapy. RNAi-mediated silencing of MMP-7 may represent a powerful therapeutic approach for controlling human colorectal cancer growth. [ABSTRACT FROM AUTHOR]

Background: Gastric carcinoma (GC) is one of the highest cancer-mortality diseases with a high incidence rate in Asia. For surgically unfit but medically fit patients, palliative chemotherapy is the main treatment. The chemotherapy regimen of docetaxel, cisplatin and 5-fluorouracil (DCF) has been used to treat the advanced stage or metastatic GC. It is necessary to compare effectiveness and toxicities of DCF regimen with non-taxane-containing palliative chemotherapy for GC. Methods: PubMed, EmBase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched to select relative randomized controlled trials (RCTs) comparing DCF to non-taxane-containing chemotherapy for patients with palliatively resected, unresectable, recurrent or metastatic GC. Primary outcome measures were 1-year and 2-year overall survival (OS) rates. Secondary outcome measures were median survival time (MST), median time to progression (TTP), response rate and toxicities. Results: Twelve RCTs were eligible and 1089 patients were analyzed totally (549 in DCF and 540 in control). DCF regimen increased partial response rate (38.8% vs 27.9%, p = 0.0003) and reduced progressive disease rate (18.9% vs 33.3%, p = 0.0005) compared to control regimen. Significant improvement of 2-year OS rate was found in DCF regimen (RR = 2.03, p = 0.006), but not of 1-year OS rate (RR = 1.22, p = 0.08). MST was significantly prolonged by DCF regimen (p = 0.039), but not median TTP (p = 0.054). Both 1-year OS rate and median TTP had a trend of prolongation by DCF regimen. Chemotherapy-related mortality was comparable (RR = 1.23, p = 0.49) in both regimens. In grade I-IV toxicities, DCF regimen showed a major raise of febrile neutropenia (RR = 2.33, p<0.0001) and minor raises of leucopenia (RR = 1.25, p<0.00001), neutropenia (RR = 1.19, p<0.00001), and diarrhea (RR = 1.59, p<0.00001), while in other toxicities there were no significant differences. Conclusion: DCF regimen has better response than non-taxane containing regimen and could potentially improve the survival outcomes. The chemotherapy-related toxicity of DCF regimen is acceptable to some extent. [ABSTRACT FROM AUTHOR]

Background Open splenectomy and devascularization are effective treatments for cirrhotic patients with severe thrombocytopenia and variceal bleeding. However, it remains controversial whether laparoscopic splenectomy ( LS) and devascularization ( LSD) can be indicated and beneficial in these patients. Objectives A systematic review of the efficacy and safety of LS and LSD for patients with liver cirrhosis and portal hypertension was undertaken to clarify controversy about their utilization in such patients. Methods A systematic search strategy was performed to retrieve relevant studies from PubMed and Embase.com. The literature search and data extraction were independently performed by two reviewers. Results Sixteen articles met the inclusion criteria. The methodology of the identified articles was poor. Six hundred and fifty-one patients, including 478 LS patients and 173 LSD patients, were involved in efficacy and safety evaluations. There was wide variability in the outcome measures between studies. There was only one death in the patients underwent LSD. Reported major complications included post-operative bleeding requiring re-surgery, pancreatic leakage and gastric perforation. Seven studies were identified with comparisons between laparoscopic and open procedures. No meta-analysis was possible because of heterogeneity between studies and lack of randomization. Conclusions The publications reviewed revealed LS and LSD to be safe and effective in the setting of liver cirrhosis and portal hypertension. From the comparison articles, laparoscopic procedures appear to be superior to open procedures regarding blood loss, hospital stay, complication rate and liver function impairment. However, it is difficult to draw firm statistical conclusions due to lack of high-quality evidence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between CD133-positive gastric cancer and clinicopathological features and its impact on survival. Methods: A search in the Medline and Chinese CNKI (up to 1 Dec 2011) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1 etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Results: A total of 773 gastric cancer patients from 7 studies were included. The median rate of CD133 expression by immunohistochemistry (IHC) was 44.8% (15.2%–57.4%) from 5 studies, and that by reverse transcription polymerase chain reaction (RT-PCR) was 91.3% (66.7%–100%) from 4 studies. The accumulative 5-year overall survival rates of CD133-positive and CD133-negative patients were 21.4% and 55.7%, respectively. Meta-analysis showed that CD133-positive patients had a significant worse 5-year overall survival compared to the negative ones (OR = 0.20, 95% CI 0.14–0.29, P<0.00001). With respect to clinicopathological features, CD133 overexpression by IHC method was closely correlated with tumor size, N stage, lymphatic/vascular infiltration, as well as TNM stage. Conclusion: CD133-positive gastric cancer patients had worse prognosis, and was associated with common clinicopathological poor prognostic factors. [ABSTRACT FROM AUTHOR]

Purpose: Recently, microRNA-124 (miR-124) has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer. Methods: Quantitative real-time PCR was used to analyze miR-124 expression in 96 colorectal cancers and individual-matched normal mucosa samples. The expression of miR-124 was assessed for associations with clinicopathological characteristics using chi-square test. The survival curves were calculated by the Kaplan-Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis. Results: The miR-124 expression was significantly downregulated in colorectal cancer compared to normal mucosa ( P = 0.001). In colorectal cancer, miR-124 decreased expression correlated significantly with the grade of differentiation ( P = 0.021). Univariate survival analysis showed that the downregulated miR-124 was significantly correlated with worse prognosis, both in terms of overall survival ( P = 0.017) and disease-free survival (DFS) ( P = 0.014). Further, the downregulated miR-124 was demonstrated as a prognostic factor for overall survival (hazard ratio, HR = 4.634; 95 % confidence interval, CI, 1.731-12.404; P = 0.002) and DFS (HR = 4.533, 95 % CI 1.733-11.856, P = 0.002), independently of gender, age, location, maximum tumor size, depth of invasion, differentiation, and TNM stage. Conclusions: MiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31) is obviously up-regulated in colorectal cancer (CRC), there is no study on the functional roles of miR-31 in CRC.Methods: Anti-miR™ miRNA 31 inhibitor (anti-miR-31) is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116p53+/+ and HCT-116p53-/-colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU), cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines.Results: Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116p53+/+ and 67.8% in HCT-116p53-/-cell line (p = 0.042 and 0.046). MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116p53+/+ or HCT-116p53-/-. However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044). Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116p53+/+ and HCT-116p53-/-(p = 0.040 and 0.001). The invasive ability of the cells were increased by 8-fold in HCT-116p53+/+ and 2-fold in HCT-116p53-/- (p = 0.045 and 0.009). Suppression of miR-31 had no effect on cell cycle and colony formation (p > 0.05).Conclusions: Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells. [ABSTRACT FROM AUTHOR]

Background and aims: To date, the association between special AT-rich sequence-binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This study was aimed at investigating the expression and potential role of SATB1 in human rectal cancers. Methods: Ninety-three paired samples of rectal cancer and distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and the correlations between SATB1 expression and clinicopathological parameters were evaluated. The expression profiles of SATB1 were also investigated in a panel of five human colon carcinoma cell lines. Results: The general level of SATB1 mRNA in rectal cancer tissues was statistically significantly higher than that in normal mucosa ( P = 0.043). The rate of positive SATB1 protein expression in rectal cancers (44.1%) was significantly higher than that in normal tissues (25.8%) by IHC analysis ( P = 0.009). Overexpression of SATB1 mRNA was more predominant in patients with earlier onset of rectal cancer ( P = 0.033). SATB1 expression correlated with invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA levels ( P < 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells and higher than the HCT116 and SW480 cells ( P = 0.001). These results were further confirmed by Western blotting. Conclusion: Our results indicate that SATB1 may play an important role in the progression of human rectal cancer, which represents a possible new mechanism underlying CRC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the prevalence and clinical significance of caspase-10 mRNA expression in stage II colorectal cancer. Methods: Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze caspase-10 expression in cancer tissue and corresponding normal mucosa from 120 patients with stage II colorectal cancer. Variables were analyzed by Chi-square test or Fisher's exact test. Survival was evaluated with method of Kaplan-Meier. Multivariate analysis was performed with Cox's proportional hazards model. Results: The expression of caspase-10 mRNA was found to be downregulated in cancer tissue compared to normal mucosa ( P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation ( P = 0.031). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between caspase-10 expression and both overall survival ( P = 0.012) and disease-free survival ( P = 0.021). A multivariate analysis, performed by Cox's proportional hazards regression model, confirmed that a low caspase-10 expression was the only significant factor to predict poor prognosis in patients with stage II colorectal cancer. Conclusion: Our data indicate that caspase-10 expression, measured by quantitative real-time RT-PCR, is a possible prognostic factor in patients with stage II colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective: To compare the perioperative systemic immunity of laparoscopy-assisted and open radical gastrectomy for gastric cancer. Methods: Patients with gastric adenocarcinoma proven by endoscopy and biopsy were eligible, while patients with preoperative staging of T4, N2-3, or M1 were excluded. Eligible patients willing to undertake laparoscopic surgery in the consecutive cohort were assigned to the laparoscopy-assisted gastrectomy (LAG) group, while concurrent patients were assigned to the conventional open gastrectomy (OG) group. All operations were performed with the intention of radical resection. Various immunological parameters were tested in peripheral venous blood collected at preoperative 1st day and postoperative 2nd day (POD2) and 7th day (POD7). SPSS 13.0 software was used for statistical analysis. Results: Thirty patients were included, 15 each in the LAG and OG groups. The general characteristics and short-term outcomes (harvested lymph nodes number, hospital stay, complications, and mortality rate) of the two groups were comparable, but the operation time was significantly longer in LAG (P = 0.001). Moreover, intergroup comparisons indicated no significant differences between the groups in levels of neutrophils, T-lymphocytes, natural killer cells, IgG, IgM, IgA, C3, C4, interleukin-6, or interleukin-10 at any time point (P > 0.05). However, there was a gradual decrease in natural killer cell count in the LAG group up to POD7 (P = 0.008). Conclusion: The changes in systemic immunity markers were comparable between laparoscopy-assisted and open gastrectomy for gastric cancer. However, there was a trend of suppression of natural killer cells in the laparoscopy-assisted gastrectomy group. [ABSTRACT FROM AUTHOR]

Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients. Methods: Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed. Results: A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p < 0.001). Conclusions: Patients with no. 6 lymph node metastasis have poor survival outcomes. Complete infra-pyloric lymphadenectomy is necessary and crucial for gastric cancer patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The elderly patients with colorectal cancer need careful multidisciplinary evaluation and optimizing comprehensive management" in the October 22, 2014 issue.