Search

Background: The aim of this systematic review and meta-analysis is to assess the efficacy of adjuvant chemotherapy in patients with stage IIB/C CRC and defective mismatch repair (dMMr) status, and to evaluate what is the determinant risk factor for adjuvant chemotherapy in those patients., Method: A systematic search of PubMed, EMBASE, Web of science, Cochrane Library databases will be performed. All RCTs published in electronic databases from inception to March 19, 2020, with language restricted in English will be included in this review study. Two reviewers will independently perform the Study selection, data extraction, quality assessment, and assessment of risk bias and will be supervised by third party. Outcomes consisted of overall survival, progression-free survival and sufficient information to extract hazard ratios and their 95% confidence intervals and it will be calculated to present the prognostic role of adjuvant chemotherapy in patients with stage IIB/C CRC and dMMR status using Review Manager version 5.3 when there is sufficient available data., Results: The results of this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication., Conclusion: This study will summarize up-to-date evidence to assess the efficacy of adjuvant chemotherapy in patients with stage IIB/C CRC and dMMR status and provide a scientific and practical suggestions for treatment decision-making., Registration: This protocol has been registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) with a registration number of INPLASY202050019.

Laparoscopy-assisted distal gastrectomy (LADG) is widely used for gastric cancer (GC) patients nowadays. This study aimed to investigate the time trend of outcomes so as to describe the learning curve for GC patients with LADG at a single medical institution in western China over a 6-year period.A total of 246 consecutive GC patients with LADG were divided into 5 groups (group A: 46 patients from 2006 to 2007; group B: 47 patients in 2008; group C: 49 patients in 2009; group D: 73 patients in 2010; and group E: 31 patients in 2011). All surgeries were conducted by the same surgeon. Comparative analyses were successively performed by Mann-Whitney U test or Student t test among the 5 different groups for the clinical data, including clinicopathologic characteristics, surgical parameters, postoperative course, and survival outcomes, through which the learning curve was described.There were no differences in the baseline information among the 5 groups (P > 0.05), and the proportion of advanced GC patients with LADG slightly increased from 58.7% to 77.4% during the 6 years. Besides, the proportion of D2/D2+ lymphadenectomy and the number of retrieved lymph nodes gradually grew from 60.9% to 80.6% and from 20.0 to 28.8, respectively. In addition, the operation time decreased from 299.2 to 267.8 minutes, while the estimated blood loss dropped from 175.2 to 146.8 mL. Furthermore, some surgical parameters (surgical duration and blood loss) and postoperative course (such as postoperative complications, the time to ambulation, to first flatus, and to first liquid intake as well as the length of hospital stay) were all observed to be significantly different between group A and other groups (P < 0.05), illustrating a similar downward trend and remaining stable to form a plateau after 46 cases in group A. However, no difference on overall survival was found among these 5 groups, and multivariate analysis indicated that factors, such as age, tumor differentiation, tumor size, and T stage as well as N stage, were independent prognostic factors for patients with LADG.Improvement on surgical parameters and postoperative course can be seen over the past years, and the cutoff value of the learning curve of LADG for surgeons with rich experience in open operation might be 46 cases.

Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin lymphoma. This retrospective study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in patients with PGL.From January 2003 to November 2014, 165 patients who were diagnosed with PGL at West China Hospital were enrolled in this study. The clinical features, treatment, and follow-up information were analyzed.In this study, diffuse large B-cell lymphoma (DLBCL) (108, 65.5%) and mucosa-associated lymphoid tissue (MALT) lymphoma (52, 31.5%) were two predominant histological subtypes. One-year and 5-year overall survival (OS) rates of all patients were 95.2% and 79.5%, respectively; in whom 110 (66.7%) underwent surgery, 110 (66.7%) received chemotherapy, 12 (7.3%) received radiotherapy, and 10 (6.1%) received Helicobacter pylori eradication. And 75 patients (45.5%) were treated with at least 2 different types of therapies. Elevated lactic dehydrogenase (LDH) levels, poor performance status (PS), advanced stage, International Prognostic Index (IPI) score ≥3, conservative treatment, and high-grade histological subtype were associated with worse prognosis in univariate analysis. Cox regression analysis showed that LDH levels, PS, staging, and histological subtype were independent predictors of survival outcomes. In the DLBCL type, 5-year OS was significantly better in the surgically treated group (80.1%) than that of patients conservatively treated (49.8%) (P = 0.001). Surgical treatment had almost no impact on OS in the MALT type than conservative treatment (P = 0.597). The proportion of patients received conservative treatment increased from 4.5% in period 1 to 51.7% in period 4.High LDH levels, poor PS, advanced staging, and malignant pathological type at diagnosis are significantly associated with poor OS. Our data suggest that surgery is superior in prognosis over conservative treatment in the DLBCL type, but not in the MALT type. Recently, conservative treatment is becoming more preferred approach in patients with PGL.

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.

This study aimed to investigate the clinicopathological characteristics and survival outcomes of the subclassification of pT2 gastric cancers according to the depth of tumor involvement. We retrospectively collected clinicopathological data and survival outcomes for pT2 gastric cancer patients from 2006 to 2011. Patients were classified into the superficial muscularis propria (sMP) and deep muscularis propria (dMP) groups. Eighty-nine patients had sMP gastric cancers and 90 patients had dMP gastric cancers. The rates of lymph node metastasis for the sMP and dMP groups were 55.1% and 64.4%, respectively, P = 0.202. The 5-year overall survival (OS) of patients in the sMP group was significantly better than patients in the dMP group (76% vs 61%, P = 0.018). Multivariate analysis demonstrated that the depth of tumor invasion, lymph node metastasis, and postoperative chemotherapy were prognostic risk factors for the OS. For patients with pN0 stage tumor(s), the sMP group had a significantly better 5-year OS rate than the dMP group (92% vs 62%, P = 0.004); for patients with pN1-N3 stages, the 5-year OS rates were comparable between the sMP and dMP groups (64% vs 61%, P = 0.540). The subclassification of pT2 gastric cancer into the sMP and dMP groups can demonstrate different survival outcomes according to the lymph node status. However, the pT2 stage subclassification in the next tumor, node, metastasis (TNM) staging system is pending and requires more large sample size studies to confirm its importance., Competing Interests: The authors have no conflicts of interest to disclose.

Objectives: The aim of the study was to explore the potential role of myeloid differentiation factor 88 (MyD88), which acts as an adaptor in the TLR4 signalling pathway, in immune responses of the pancreatic duct during acute pancreatitis., Methods: Primary cultures of pancreatic duct epithelial cells from Wistar rats and cultures of the pancreatic ductal ARIP cell line were treated with lipopolysaccharide (LPS), and expression of toll-like receptor 4 mRNA was determined using real-time PCR, expression of MyD88 protein using Western blot, and levels of inflammatory cytokines using enzyme-linked immunosorbent assay. These experiments were repeated using ARIP cells in which MyD88 expression was stably knocked down., Results: Toll-like receptor 4 and MyD88 expression were similar between pancreatic duct epithelial cells and ARIP cells after LPS stimulation. Myeloid differentiation factor 88 knockdown led to significantly lower levels of inflammatory cytokines after LPS induction in ARIP cells., Conclusions: Myeloid differentiation factor 88 knockdown attenuates LPS-induced inflammatory responses in pancreatic ductal cells, suggesting that the MyD88 pathway plays a critical role in their immune defense activity.

The clinical prognostic significance of tumor size (Ts) in gastric cancer remains under debate. This study aims to evaluate the prognostic value of Ts in gastric cancer patients undergoing gastrectomy. A total of 2405 patients with gastric cancer, all having received radical resection, were enrolled in this retrospective study from 2000 to 2011. Patients were categorized by minimum P value from log-rank χ2 statistics using X-tile. The relationships between Ts and other clinicopathologic characteristics were analyzed, and the survival prediction accuracy was also compared between Ts and T stage. Patients were divided into 5 groups, according to which Ts stage and TsNM stage system were proposed. Ts, an independent prognostic factor identified by univariate and multivariate survival analysis, was significantly associated with sex, age, tumor location, macroscopic type, tumor diffferentiation, vessel invasion, perineural invasion, T stage, N stage, and TNM stage. Compared with T stage system, Ts stage system was found no superiorities in survival prediction. However, for patients with lymph node metastasis and patients with age ≥60, Ts stage system revealed a significant improvement of predictive accuracy in subgroup survival analysis. Furthermore, TsNM stage (c-index = 0.783) system was found to be superior to TNM stage (c-index = 0.743) system in prognostic prediction accuracy (P < 0.05). Ts is significantly correlated with gastric cancer progression, which can be regarded as a reliable prognostic factor, and the TsNM stage system may improve the prognostic prediction accuracy in gastric cancer patients., Competing Interests: The authors have no conflicts of interest to disclose.

Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973-2011), and Linköping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106-1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

Nonislet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia in different tumor types of mesochymal or epithelial origin; however, NICTH is infrequently induced by sarcomatoid carcinoma (SC). Despite some sarcomatoid and epithelioid characteristics in few cases of malignancies from epithelium, NICTH induced by recurrent SC in pelvic cavity in this report is extremely rare.We report a case in which NICTH caused by recurrence and pulmonary metastases from SC in the pelvic cavity, and the computed tomography scan revealed multiple pelvic masses and multiple large masses in the pulmonary fields. During the treatment of intestinal obstruction, the patient presented paroxysmal loss of consciousness and sweating. Her glucose even reached 1.22 mmol/L while the serum glycosylated hemoglobin was normal and previous history of diabetes or use of oral hypoglycemic agents and insulin denied.The laboratory examination showed that the low level of insulin, C-peptide, and growth hormone levels in the course of hypoglycemic episodes suggesting to the diagnosis of hypoglycemia induced by nonislet cell tumor, and the decreased levels of insulin-like growth factor (IGF)-I and IGFBP3 and the high expression of big IGF-II in the serum further confirmed the diagnosis of NICTH. Because of the widely pelvic recurrence and pulmonary metastases were unresected, the patient was discharged from the hospital after 2 weeks treatment with dexamethasone and glucose and unfortunately died 1 week later.NICTH caused by SC in the pelvic cavity is extremely rare case in clinical. The aim of this report was to present the importance to examine big IGF-II expression in patient's serum in order to reach the diagnosis of NICTH in cases of intractable cancer-associated hypoglycemia.

Intestinal necrosis is a life-threatening disease, and its prompt and accurate diagnosis is very important. This study aimed to evaluate the value of D-dimer as a marker for early diagnosis of bowel necrosis. From 2009 to 2013, patients undergoing operation due to acute intestinal obstruction were retrospectively analyzed. Clinicopathologic characteristics were compared among no ischemia group, reversible ischemia group, and bowel necrosis group. There were totally 274 patients being included for analyses. Patients with bowel necrosis had a significant highest level of D-dimer compared with other 2 groups (P =  .007) when FEU unit was applied. The optimal cutoff value of D-dimer levels as an indicator in diagnosing bowel necrosis was projected to be 1.965 mg/L, which yielded a sensitivity of 84.0%, a specificity of 45.6%, a positive predictive value of 60.7%, and a negative predictive value of 74.0%. And the sensitivity of 84.0% and specificity of 70.0% were detected, when 1.65 mg/L of D-dimer was set as the cutoff value to distinguish the reversible ischemia and bowel necrosis. The corresponding results in patients with no or slight peritoneal irritation signs were 85.2%, 44.7%, 35.4% and 89.5% respectively. The sensitivity and negative predictive value were 96.0% and 91.7%, respectively, when D-dimer and peritoneal irritation signs were combined to perform the parallel analysis. The combination of D-dimer and peritoneal irritation signs could generate a reliable negative predictive value, which is helpful to exclude the diagnosis of intestinal necrosis. However, it should also be proved in well-designed large-scale prospective study.

This study aimed to investigate the impact of body mass index (BMI) on the short-term and long-term results of a large cohort of gastric cancer (GC) patients undergoing gastrectomy.Recently, the "obesity paradox" has been proposed, referring to the paradoxically "better" outcomes of overweight and obese patients compared with nonoverweight patients. The associations between BMI and surgical outcomes among patients with GC remain controversial.A single-institution cohort of 1249 GC patients undergoing gastrectomy between 2000 and 2010 were categorized to low-BMI (<18.49 kg/m), normal-BMI (18.50-24.99 kg/m), and high-BMI (≥25.00 kg/m) groups. The postoperative complications were classified according to the Clavien-Dindo system, and their severity was assessed by using the Comprehensive Complication Index (CCI). The impact of BMI on the postoperative complications and overall survival was analyzed.There were 908, 158, and 182 patients in the normal-BMI, low-BMI, and high-BMI groups, respectively. The overall morbidity in the high-BMI group (24.7%) was higher than that in either the low-BMI or the normal-BMI group (20.9% and 15.5%, respectively; P = 0.006), but the mean CCI in the low-BMI group was significantly higher (8.32 ± 19.97) than the mean CCI in the normal-BMI and high-BMI groups (3.76 ± 11.98 and 5.58 ± 13.07, respectively; P < 0.001). The Kaplan-Meier curve and the log-rank test demonstrated that the low-BMI group exhibited the worst survival outcomes compared with the normal-BMI group, whereas the high-BMI group exhibited the best survival outcomes (P < 0.001). In multivariate analysis, BMI was identified as an independent prognostic factor. In the stage-specific subgroup analysis, a low BMI was associated with poorer survival in the cases of stage III-IV diseases.Low BMI was associated with more severe postoperative complications and poorer prognosis. Despite a higher risk of mild postoperative complications, the high-BMI patients exhibited paradoxically "superior" survival outcomes compared with the normal-BMI patients. These findings confirm the "obesity paradox" in GC patients undergoing gastrectomy.

Over the past decades, immunohistochemistry has gained significance and already taken a crucial position in diagnosis of diseases and prognosis of patients. However, manual interpretation of immunohistochemistry and reproducibility of the scoring systems can be highly subjective. In the article, the immunohistochemical staining of survivin in 98 rectal cancers was analyzed by using Image Pro-Plus (IPP) [3 parameters: density mean, area sum, and integrated optical density (IOD)] and the results were compared with visual assessment (2 parameters: intensity and percentage). The correlations between the 2 methods were examined, significant correlations were observed between density mean and staining intensity (Spearman correlation coefficient, rs=0.806, P<0.001), IOD and staining intensity (rs=0.914, P<0.001), area sum and staining percentage (rs=0.883, P<0.001), IOD and staining percentage (rs=0.884, P<0.001). There was no significant difference between survivin expression and clinicopathologic variables (P>0.05) by visual assessment. However, by IPP analysis, both the density mean and IOD were higher in better-differentiated cancers than in worse differentiated ones (P=0.02 and 0.03). There was a substantial agreement between the 2 methods. Density mean and IOD of IPP were representative parameters to assess the immunostaining quantification, and increased sensitivity in scoring and provided a more reliable and reproducible analysis of protein expression, especially, more information of the protein expression in relation to clinicopathologic variables can be provided by IPP analysis.

Objectives: To detect Toll-like receptor 4 (TLR4) expression and distribution in rat pancreas and the change of TLR4 expression in cerulein-induced pancreatitis (CIP)., Methods: Acute pancreatitis was induced by subcutaneous injections of cerulein at a total dose of 20 microg/kg. Immunohistochemistry (IHC) was used to detect and localize TLR4 in rat pancreas, and real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitatively determine the expression of TLR4 mRNA in CIP., Results: IHC showed the presence of TLR4 in rat pancreas, and its distribution was specifically localized to pancreatic ductal epithelium, vascular endothelium, and islet. No TLR4 staining was detected in exocrine acinar cells. Real-time RT-PCR results revealed low-level TLR4 mRNA expression in the rat pancreas, and the change of TLR4 in CIP only developed within the first 4 hours, which is a rapid up-regulation process that peaks at the first hour. TLR4 mRNA was sustained at baseline level from 4 to 24 hours., Conclusions: TLR4 protein was expressed in pancreas and localized to epithelial (pancreatic duct) or endothelial (vessels) tissues; TLR4 responded favorably to the inflammatory process, and the change of expression was characterized as a rapid up-regulation in the early stage of CIP.

Introduction: Severe acute pancreatitis (SAP) remains a serious disease state difficult to manage. Laparoscopic surgery represents a relatively new solution to this problem. This study was aimed to investigate the feasibility of laparoscopic treatment of SAP and the selection of laparoscopic procedures in various stages of SAP according to different pathologic alterations., Methods: Thirteen patients, 9 men and 4 women with an average age of 46 years old, were diagnosed with SAP. Laparoscopic necrosectomy followed by external drainage were performed on 7 patients with massive fluid collections and/or infected necrosis in acute reaction phase of SAP. For 2 cases in subacute phase characterized by fresh-formed adhesions and encapsulation, laparoscopic intracavitary debridement experienced difficulty. For the other 4 patients in late phase with well-defined pancreatic or peripancreatic pseudocyst/abscess, ultrasound-guided, directly visualized laparoscopic intracavitary debridement, and external drainage were carried out with ease and efficiency., Results: Laparoscopic procedures were accomplished successfully on 12 patients (92.3%), except for 1 conversion (7.7%) to open laparotomy owing to poor exposure and hard maneuvers in subacute phase. There was no mortality in this group. Patients were witnessed to have accelerated recovery following laparoscopic surgery., Conclusion: Laparoscopic technique offers new hope for the treatment of SAP. It is recommended as a feasible, effective, and less traumatic therapeutic means on condition that the strategy of individualization is followed.