Long-term outcomes of laparoscopic versus open distal gastrectomy for patients with advanced gastric cancer in North China: a multicenter randomized controlled trial.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) has become a common procedure for treating advanced gastric cancer (AGC) in China. However, there is uncertainty regarding its oncological outcomes compared to open distal gastrectomy (ODG). This study aims to compare the 3-year disease-free survival (DFS) rates among patients who underwent surgery for AGC in northern China. METHODS: A multicenter, non-inferiority, open-label, parallel, randomized clinical trial was conducted to evaluate patients with AGC who were eligible for distal gastrectomy at five tertiary hospitals in North China. In this trial, patients were randomly assigned preoperatively to receive either LDG or ODG in a 1:1 allocation ratio. The primary endpoint was postoperative morbidity and mortality within 30 days and the secondary endpoint was the 3-year DFS rate. This trial has been registered at ClinicalTrials.gov (Identifier: NCT02464215). RESULTS: A total of 446 patients were randomly allocated to LDG (n = 223) or ODG group (n = 223) between March 2014 and August 2017. After screening, a total of 214 patients underwent the open surgical approach, while 216 patients underwent laparoscopic surgery. The 3-year DFS rate was 85.9% for the LDG group and 84.72% for the ODG group, with no significant statistical difference (Hazard ratio 1.12; 95% CI 0.68-1.84, P = 0.65). Body mass index (BMI) < 25 kg/m2, advanced pathologic T4, and pathologic N2-3 category were confirmed as independent risk factors for DFS in the Cox regression. CONCLUSIONS: In comparison to ODG, LDG with D2 lymphadenectomy yielded similar outcomes in terms of 3-year DFS rates among patients diagnosed with AGC.

Characteristics and Incidence of Colon Complication in Necrotizing pancreatitis: A Propensity Score-Matched Study.

Objective: To clarify the incidence of colonic complications in patients with NP and their impact on prognosis. Methods: The clinical data of NP patients admitted to the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of colonic complications, and the clinical prognosis of the two groups was analyzed after matching using a 1:1 propensity score, The primary study endpoint was patient mortality during hospitalization. Data are reported as median (range) or percentage of patients (%). Results: A total of 306 patients with NP were included in this study, and the incidence of colonic complications was 12.4%, including 15 cases of colonic obstruction, 17 cases of colonic fistula, and 9 cases of colonic hemorrhage. Before matching, patients in the colonic group had severe admissions and poor clinical outcomes (P<0.05). After matching, the baseline data and clinical characteristics at admission were comparable between the two groups of patients. In terms of clinical outcomes, although the mortality was similar in the two groups (P>0.05), but patients in the colonic group were more likely to have multiorgan failure, length of nutrition support, number of minimally invasive interventions, number of extra-pancreatic infections, length of ICU stay and total length of stay were significantly higher than those of patients in the group without colonic complications (P<0.05). During long-term follow-up, patients in the colonic group were more likely to develop recurrent pancreatitis. Conclusion: About 12.4% of NP patients developed colonic complications, and after PSM it was found that colonic complications only led to a longer hospital stay and an increased number of clinical interventions in NP patients and did not increase the mortality.

Risk Factors and Outcomes of Multidrug-Resistant Bacteria Infection in Infected Pancreatic Necrosis Patients.

Objective: The incidence of acute pancreatitis (AP) is increasing. Twenty percent of AP patients with developing necrotizing pancreatitis (NP), while ~40-70% of NP patients develop potentially fatal infectious complications. When patients are suspected or confirmed infected pancreatic necrosis (IPN), antibiotics should be administered timeously to control the infection, but long-term use of antibiotics can lead to multidrug-resistant bacteria (MDRB) infection and eventually to increased mortality. Our study aimed to determine the incidence of MDRB infection and evaluate the risk factors for MDRB infection in IPN patients. Methods: Clinical data of IPN patients admitted to the general surgery department of Xuanwu Hospital of Capital Medical University between January 1, 2014, and December 31, 2021, were retrospectively analyzed. Results: IPN patients (n = 267) were assigned to MDRB infection (n = 124) and non-MDRB infection (n = 143) groups. On admission, patients in the MDRB group had a higher modified computer tomography severity index (CTSI) score (P < 0.05), pancreatic necrosis degree, and PCT level (P < 0.05) than those in the non-MDRB group, and the prognosis of patients in MDRB group was poor. The most common gram-negative bacteria were Acinetobacter baumannii (n = 117), the most common gram-positive bacteria were Enterococcus faecium (n = 98), and the most common fungal infection was Candida albicans (n = 47). Multivariable analysis showed that complications of EPI (OR: 4.116, 95% CI: 1.381-12.271, P = 0.011), procalcitonin (PCT) level at admission (OR: 2.728, 95% CI: 1.502-4.954, P = 0.001), and degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109-6.775, P = 0.029) were independent risk factors for MDRB infection in IPN patients. Conclusion: We identified common infectious strains and risk factors for MDRB infection in IPN patients.

Predicting infected pancreatic necrosis based on influential factors among the most common types of acute pancreatitis: a retrospective cohort study.

BACKGROUND: Biliary and hypertriglyceridemic acute pancreatitis (BAP and HTGAP) are two of the leading etiologies in China. Infected pancreatic necrosis (IPN) is a particular and noticeable condition in the late stage of these diseases; however, the influential correlated factors on IPN and how to predict IPN are unclear. METHODS: In this retrospective study, 1,116 patients whose diagnosis was BAP or HTGAP met the inclusion criteria among 1,746 enrolled cases. Clinical characteristics were carefully recorded for further investigation of the factors influencing IPN. During a 6-month follow-up, we analyzed bacterial spectra and postoperative indicators related to minimally invasive necrosectomy. RESULTS: Gallstones and hypertriglyceridemia were the most prevalent causes (52.6% vs. 11.3%). The participants with HTGAP were younger (40 vs. 52 years, P<0.001), had a higher rate of severe acute pancreatitis (SAP) (51.8% vs. 32.0%, P<0.001), and had a higher prevalence of multiple organ dysfunction syndrome (MODS) (26.4% vs. 19.0%, P=0.020) than BAP patients. More IPN cases were noted in the BAP group than in the HTGAP group [20.2% vs. 13.7%; odds ratio (OR): 1.598, 95% confidence interval (CI): 1.027 to 2.451; P=0.034]. Etiologies, C-reactive protein (CRP) levels, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and MODS were the factors influencing IPN. The bacterial spectra and the rates of major postoperative complications were not significantly different. CONCLUSIONS: Patients with BAP more frequently developed IPN. Etiology was independently related to the occurrence of IPN. The APACHE II score, MODS, etiology, and CRP contributed to predicting IPN occurrence. Management of IPN substantially improved the prognosis.

Laparoscopic transgastric necrosectomy in treatment of walled-off pancreatic necrosis with sinistral portal hypertension.

BACKGROUND: Laparoscopic transgastric necrosectomy (LTGN) has been used in treatment of walled-off pancreatic necrosis (WON) for more than a decade. However, the safety and effectiveness of LTGN for WON with sinistral portal hypertension was still unclear. METHODS: WON patients with sinistral portal hypertension treated in our department between January 2011 and December 2018 were included and retrospectively analyzed in this study. Patients were divided into two groups according to different surgical approaches, LTNG or laparoscopic assisted trans-lesser sac necrosectomy (LATLSN). Perioperative and long-term outcomes were compared between two groups. RESULTS: 312 cases diagnosed with WON were screened and 53 were finally included in this study. Of the included patients, 21 and 32 cases were received LTGN and LATLSN, respectively. LTGN was associated with significantly lower morbidity than LATLSN (19.0% vs 46.9%, p = 0.04) and similar severe complication (Clavien-Dindo ≥ III) rate (12.5% vs 19.0%, p = 0.70). LTGN did not increase the rate of postoperative hemorrhage (9.5% vs 6.3%, p = 1.00) and mortality (9.5% vs 9.4%, p = 1.00). After 39 (11-108) months follow-up, the recurrence rate of WON and long-term complications were also comparable between groups. CONCLUSION: From current data, LTGN was safe and effective in treatment of WON patients with sinistral portal hypertension in terms of short- and long-term outcomes.

Infection recurrence following minimally invasive treatment in patients with infectious pancreatic necrosis.

BACKGROUND: In recent decades, an increasing number of patients have received minimally invasive intervention for infected pancreatic necrosis (IPN) because of the benefits in reducing postoperative multiple organ failure and mortality. However, there are limited published data regarding infection recurrence after treatment of this patient population. AIM: To investigate the incidence and prediction of infection recurrence following successful minimally invasive treatment in IPN patients. METHODS: Medical records for 193 IPN patients, who underwent minimally invasive treatment between February 2014 and October 2018, were retrospectively reviewed. Patients, who survived after the treatment, were divided into two groups: one group with infection after drainage catheter removal and another group without infection. The morphological and clinical data were compared between the two groups. Significantly different variables were introduced into the correlation and multivariate logistic analysis to identify independent predictors for infection recurrence. Sensitivity and specificity for diagnostic performance were determined. RESULTS: Of the 193 IPN patients, 178 were recruited into the study. Of them, 9 (5.06%) patients died and 169 patients survived but infection recurred in 13 of 178 patients (7.30%) at 7 (4-10) d after drainage catheters were removed. White blood cell (WBC) count, serum C-reactive protein (CRP), interleukin-6, and procalcitonin levels measured at the time of catheter removal were significantly higher in patients with infection than in those without (all P < 0.05). In addition, drainage duration and length of the catheter measured by computerized tomography scan were significantly longer in patients with infection (P = 0.025 and P < 0.0001, respectively). Although these parameters all correlated positively with the incidence of infection (all P < 0.05), only WBC, CRP, procalcitonin levels, and catheter length were identified as independent predictors for infection recurrence. The sensitivity and specificity for infection prediction were high in WBC count (≥ 9.95 × 109/L) and serum procalcitonin level (≥ 0.05 ng/mL) but moderate in serum CRP level (cut-off point ≥ 7.37 mg/L). The catheter length (cut-off value ≥ 8.05 cm) had a high sensitivity but low specificity to predict the infection recurrence. CONCLUSION: WBC count, serum procalcitonin, and CRP levels may be valuable for predicting infection recurrence following minimally invasive intervention in IPN patients. These biomarkers should be considered before removing the drainage catheters.

One-Step verse Step-Up Laparoscopic-Assisted Necrosectomy for Infected Pancreatic Necrosis.

BACKGROUND: Percutaneous or endoscopic drainage was usually performed as the first step in step-up approach for infected pancreatic necrosis (IPN). However, drainage was unnecessary or unavailable in some patients. OBJECTIVE: To estimate the safety and effect of one-step laparoscopic-assisted necrosectomy in IPN patients. METHODS: A retrospective analysis of IPN patients received surgical therapy in our center between January 2015 and December 2017 was performed. Patients were assigned to either one-step or step-up groups according to the received therapeutic approach. Incidence of complications, death, total number of interventions, and total hospital stay were compared. Logistic regression and nomogram were used to explore the risk factors and probability for patients undergoing interventions ≥3 times. RESULTS: There were 45 and 49 patients included in one-step and step-up groups, respectively. No significant difference between groups in terms of new organ failure (14.29 vs. 14.33%, p = 0.832), death (8.89 vs.8.17%, p = 0.949), and long-term complications (18.37 vs. 15.56%, p = 0.717). However, the number of interventions in one-step group was significantly less than in step-up group with shorter hospital stay. After multivariate analysis, C-reactive protein, interleukin-6, and surgical approach were independent predicators for patients undergoing interventions ≥3. A nomogram was built with area under ROC curve 0.891. CONCLUSION: Compared with step-up approach, one-step surgery was safe and effective in selected IPN patients with less interventions and shorter hospital stay.

The effect of technical details of percutaneous catheter drainage on the clinical outcomes of infected necrotizing pancreatitis patients

Background/aim: This study aimed to investigate the effect of technical details of percutaneous catheter drainage (PCD) on the clinical outcomes of patients with infected necrotizing pancreatitis (INP). Materials and methods: A total of 44 INP patients treated in our hospital from October 2013 to October 2015 were included. The correlations of the first PCD treatment data and the clinical outcomes were analyzed. Results: The number of catheters was positively correlated with hospital readmission (r = 0.335, P = 0.032). Receiver operating characteristic curve analysis showed that patients with ≥ 3 catheters were more likely to have hospital readmission. Patients with pleural effusion undergoing thoracentesis were more likely to have new intensive care unit admission (P = 0.025) and bleeding in need of intervention (P = 0.032). Patients with more effusion regions had higher incidences of mortality (P = 0.012) and new intensive care unit admissions (2.44 ± 1.03 vs. 1.88 ± 0.80; P = 0.059). Patients with PCD only were less likely to have new intensive care unit admissions (22.22% vs. 54.55%; P = 0.038) than those with PCD + small incision or/and videoscopic assisted retroperitoneal debridement. Conclusion: Number of catheters greater than three was associated with unfavorable outcomes of PCD treatment in INP patients. Patients that received PCD treatment only had better outcomes.

Short-term surgical outcomes of laparoscopy-assisted versus open D2 distal gastrectomy for locally advanced gastric cancer in North China: a multicenter randomized controlled trial.

BACKGROUND: Although laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China. METHODS: In this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215. RESULTS: Between March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms. CONCLUSIONS: This trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.

A meta-analysis and systematic review of percutaneous catheter drainage in treating infected pancreatitis necrosis.

BACKGROUND: In the current meta-analysis, we focus on the exploration of percutaneous catheter drainage (PCD) in terms of its overall safety as well as efficacy in the treatment of infected pancreatitis necrosis based on qualified studies. METHODS: The following electronic databases were searched to identify eligible studies through the use of index words updated to May 2018: PubMed, Cochrane, and Embase. Relative risk (RR) or mean difference (MD) along with 95% confidence interval (95% CI) were utilized for the main outcomes. RESULTS: A total of 622 patients in the PCD group and 650 patients in the control group from 13 studies were included in the present meta-analysis. The aggregated results indicated that the incidence of bleeding was decreased significantly (RR: 0.42, 95% CI: 0.25-0.70) in the PCD group as compared with the control group. In addition, PCD decreased the mortality (RR: 0.76, 95% CI: 0.41-1.42), hospital duration (SMD: -0.22, 95% CI: -0.77 to -0.33), duration in intensive care unit (ICU) (SMD: -0.13, 95% CI: -0.30 to -0.04), pancreatic fistula (RR: 0.73, 95% CI: 0.46-1.17), and organ failure (RR: 0.91, 95% CI: 0.45-1.82) in comparison with the control group, but without statistical significance. CONCLUSION: Our findings provide evidence for the treatment effect of PCD in the decrease of bleeding, mortality, duration in hospital and ICU, pancreatic fistula, organ failure as compared with the surgical treatment. In conclusion, further studies based on high-quality RCTs with larger sample size and long-term follow-ups are warranted for the confirmation of PCD efficacy in treating infected pancreatitis necrosis.

Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine.

Pancreatic adenocarcinoma upregulated factor (PAUF) is a new oncogene that activates signaling pathways that play a critical role in resistance to gemcitabine. We thus speculated that PAUF also plays a role in resistance to gemcitabine of pancreatic cancer cells. We established BxPC-3 cell lines with stable PAUF knockdown (BxPC-3_shPAUF) and controls (BxPC-3_shCtrl) and evaluated sensitivity to gemcitabine in vitro by MTT and flow cytometry. We established a xenograft model of human pancreatic cancer to examine PAUF function in gemcitabine resistance in vivo. Gene chip microarrays were performed to identify differentially expressed genes in BxPC-3_shPAUF and BxPC-3_shCtrl cells. Silencing PAUF increased the sensitivity of BxPC-3 cells to gemcitabine in vitro and in vivo. PAUF-knockdown BxPC-3 cell lines treated with gemcitabine showed increased proliferation inhibition and apoptosis compared with controls. Gemcitabine exhibited a more pronounced effect on reduction of BxPC-3_shPAUF tumors than BxPC-3_shCtrl tumors. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assays confirmed a significantly higher apoptotic rate of BXPC-3_shPAUF tumors compared with BXPC-3_shCtrl tumors. Gene array showed that PAUF function in gemcitabine sensitivity might involve MRP2, MRP3, MDR1, PIK3R1, and NFkB2 genes. PAUF could be considered as a key molecular target for sensitizing pancreatic cancer cells to gemcitabine.

Indoleamine 2,3-dioxygenase is upregulated in the brain of rats with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) has an effect on both inflammatory/autoimmune processes and psychological states, but the pathophysiological causes of pancreatic encephalopathy in the brain are unclear. We hypothesized that the peripheral immune/inflammatory response during AP can affect indolamine 2,3-dioxygenase (IDO) expression and serotonin content in the brain. METHODS: About 210 male Sprague Dawley rats were randomly divided into five groups: control (0 h) and 6 h, 24 h, 48 h and 72 h experimental groups. Acute pancreatitis was induced by an injection of a sodium taurocholate solution via a cannulated bile-pancreatic duct. We measured the plasma TNF-α and IL-6 levels; serotonin, 5-HIAA and the protein concentration levels of IDO and monoamine oxidase A (MAO-A) were evaluated in the striatum, hippocampus and left prefrontal cortex. RESULTS: The IL-6 and the TNF-α levels increased in the 24 h, 48 h and 72 h groups. The IDO concentrations of both the 72 h group in the hippocampus and 48 h, 72 h groups in the prefrontal cortex increased; in the corpus striatum, the IDO concentrations fluctuated without statistical significance. The MAO-A protein concentration of the 6 h and 24 h groups decreased in the striatum, hippocampus and prefrontal cortex. There were no statistically significant differences found in the serotonin and 5-HIAA concentrations. CONCLUSIONS: During the process of AP, cytokines, such as IL-6 and TNF-α, may play a role in activation of neuronal pathways utilizing the metabolic enzyme IDO, which may play an important role in determining the mental symptomatology accompanying AP.

MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer.

MMI-166 is a third-generation selective matrix metalloproteinase (MMP) inhibitor that prevents tumor invasion and metastasis by downregulating the activity of MMP-2 and MMP-9. However, MMI-166's effect in pancreatic cancer cells has not been widely studied. Initially, we treated SW1990, human pancreatic cancer cells, with 0, 50 or 100 µg/ml of MMI-166 for 24 h. Apoptosis in the cells was then observed by inverted fluorescence microscope and flow cytometry; the apoptosis rate was dependent on MMI-166 concentration. We then injected nude mice with SW1990 cells. Volume of the resulting xenograft tumors in nude mice treated with MMI-166 was far less than that of the control group, whereas their apoptotic index was much greater. Expression of MMP-2, MMP-9, c-myc and survivin were markedly lower in tumors from the treated mice than in the control group. In cell experiments, MMP-2 and MMP-9 activities were downregulated by MMI-166 compared with controls, as were both mRNA and protein levels of MMP-2, MMP-9 and c-myc, although survivin expression did not differ. These results show that MMI-166 can induce apoptosis of pancreatic cancer cells in vitro and in vivo. The mechanism may be related to downregulation of c-myc by MMI-166.