Remission of organ failure in patients with predicted severe acute pancreatitis treated by somatostation, octreotide and cyclooxygenase-2 inhibitors.

BACKGROUND: /Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world. METHODS: Clinical data of patients with predicted SAP from 2010 to 2017 were retrospectively reviewed. Cases were divided into conventional support (C), C+ somatostatin/octreotide (C + S/O), and C + S/O + Cyclooxygenase-2-inhibitors (C + S/O + COX-2-I). The occurrence of SAP, OF, changes of proportion for three strategies, length of hospital stay, meperidine injection, and cytokine levels were compared. The constituent ratios of the three schemes over eight years were evaluated. RESULTS: A total of 580 cases (C = 124, C + S/O = 290, C + S/O + COX-2-I = 166) were included. The occurrences of SAP in the C + S/O (28.3 %) and C + S/O + COX-2-I (18.1 %) groups were significantly lower than that in C group (60.5 %, P < 0.001), mainly by reducing persistent respiratory failure (P < 0.001) and renal failure (P = 0.002). C + S/O and C + S/O + COX-2-I regimens significantly decreased new onset OF and enhanced OF amelioration within 48 h when compared with C treatment (P < 0.001) in patients with OF score <2 and ≥ 2 on admission, respectively. C + S/O and C + S/O + COX-2-I as compared with C group significantly decrease OF occurrences in a multivariate logistic regression analysis (P < 0.05). CONCLUSIONS: Somatostatin or its analogs and cyclooxygenase-2 inhibitors are promising for OF prevention and remission in patients with predicted SAP. The acceptance of combined strategies in the real world has increased, and the occurrence of SAP has decreased annually.

Metastasis Prevalence and Survival of Patients with T1-2 Gastric Neuroendocrine Tumor Treated with Endoscopic Therapy and Surgery.

BACKGROUND AND AIM: The selection criteria and long-term outcomes of endoscopic therapy (ET) for gastric neuroendocrine tumors (G-NETs) remain controversial. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) Program database, we assessed the prevalence of metastasis of early G-NETs and long-term outcomes of ET in G-NET patients with good/moderate differentiation and no muscularis propria (MP) involvement. RESULTS: A total of 2207 patients with stage T1 and T2 G-NETs were included. The depth of invasion into MP [odds ratio (OR) 4.581, 95% confidence interval (CI) 2.571-8.162; P < 0.001] and size of > 20 mm (OR 5.656, 95% CI 2.002-15.975; P = 0.001) were significantly associated with metastasis. The 5-year overall survival (OS) and cancer-specific survival (CSS) of the ET group were similar to the surgery group (91.11% vs. 91.09%, P = 0.750; 99.26% vs. 99.01%, P = 0.173). In the multivariable Cox proportional hazards regression models adjusting for age, gender, race, year of diagnosis, SEER region, depth of tumor invasion, site of cancer, tumor size, and chemotherapy, procedures employed (ET or surgery) had no significant impact on the OS [hazard ratio (HR) 1.189; 95%CI 0.721-1.961; P = 0.498] and CSS (HR 0.684; 95% CI 0.021-22.727; P = 0.832). CONCLUSIONS: The long-term outcome of survival did not appear to differ between ET and surgery in G-NETs with good/moderate differentiation, ≤ 20 mm size, and no MP involvement.

Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis.

BACKGROUND/OBJECTIVES: Obesity is an independent risk factor for severe acute pancreatitis (AP). Leptin plays an important role in energy homeostasis. It has been reported that leptin might also participate in the regulation of the intestinal mucosal barrier and inflammatory response. This study aimed to evaluate the effects of leptin on the intestinal mucosal barrier and inflammatory injury in obese mice with AP. SUBJECTS/METHODS: AP was induced in leptin-deficient (ob/ob) or wild type (WT) mice by peritoneal injection of caerulein. The animals were divided into 4 groups: WT mice with or without exogenous leptin injection and ob/ob mice with or without leptin treatment. The inflammatory scoring of the pancreas and intestine were evaluated. Intestinal permeability, ileal interleukin (IL)-6 and IL-1ß, proliferation, apoptosis and intestinal expression levels of claudin-1 and occludin were measured. RESULTS: Pancreatic pathologic scores (8.50 ± 0.96 vs. 3.78 ± 1.35, p < 0.001), pancreatic levels of IL-6 (8.34 ± 3.21 ng/mg vs. 4.99 ± 0.53 ng/mg, p = 0.022), intestinal oedema scores (2.25 ± 0.46 vs. 1.14 ± 0.69, p = 0.001) and intestinal permeability to FD4 (0.78 ± 0.06 µg/ml vs. 0.53 ± 0.11 µg/ml, p < 0.001) were significantly higher in ob/ob mice than those in WT mice. Leptin replacement in ob/ob mice greatly improved the intestinal permeability (FD4 0.66 ± 0.03 µg/ml, vs. 0.78 ± 0.06 µg/ml, p = 0.012), increased the ileal expression of claudin-1(1.07 ± 0.08 vs. 0.83 ± 0.07 relative densitometry, p = 0.001) and reduced intestinal IL-6 and IL-1ß to levels comparable to those in WT mice. The pancreatic level of IL-6 in ob/ob mice treated with leptin was also significantly decreased relative to that of untreated ob/ob mice (4.45 ± 1.71 ng/mg vs. 8.34 ± 3.21 ng/mg, p = 0.010). CONCLUSIONS: Obesity may aggravate intestinal inflammation and increase intestinal permeability under the condition of acute pancreatitis. Exogenous leptin supplementation was in favour of anti-inflammation and improvement of intestinal mucosal barrier.

Spigelian hernia in the right upper abdominal wall: a case report.

BACKGROUND: Spigelian hernia (SH) is rare and constitutes less than 2% of all hernias. It is reported that more than 90% of SHs lie in the "Spigelian belt", but SH in the upper abdominal wall is extremely uncommon. Here, we report a case of SH in the right upper quadrant of abdomen. CASE PRESENTATION: A 38-year-old female was admitted to hospital with complaints of abdominal pain and right upper quadrant mass for 10 days. Contrast-enhanced computed tomography (CECT) of abdomen revealed the dilated small intestine between the swelling ventral muscles in the right upper abdominal wall which suggested a ventral hernia. The surgeons considered it was a spontaneous hernia because there was no history of surgery or trauma in the upper abdomen. About two hours later, the patient underwent emergency surgery. According to laparotomy, a diagnosis of SH with ileum herniation in the right upper abdominal wall was confirmed. The necrotic ileum segment was resected. Meanwhile the abdominal wall defect was repaired by suturing the internal oblique and transverse muscles to the rectus sheath. The patient had a favorable outcome for 1 year without recurrence. CONCLUSION: A mass and pain in the upper abdominal wall may suggest an atypical SH. SH occurring in the upper abdominal wall is a rare condition with possibility of dire outcome if not managed early.

PKA RIα/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer.

BACKGROUND AND AIM: Previously study showed that the loss of the control of cAMP-dependent protein kinase A RIα (PKA RIα)/ A-kinase anchoring proteins 10 (AKAP10) signaling pathway initiate dysregulation of cellular healthy physiology leading to tumorigenesis. The aim of this study was to investigate the role of PKA RIα/AKAP10 signaling pathway in colorectal cancer (CRC). METHODS: The AKAP10 expression at the mRNA and protein level have been analyzed in colon cancer cell lines, primary CRCs and matched normal mucosa samples, and compared in accordance with specific clinicopathological features of CRC. The correlation between expression of AKAP10 and PKA RIα were also analyzed. RESULTS: Compared with HCT116 and SW480 cells, the AKAP10 was significantly upregulated in the colon cell line KM12C and its metastatic counterparts, KM12SM and KM12L4A. Moreover, the KM12SM and KM12L4A having high metastatic potentials displayed the elevated levels of AKAP10 compared with KM12C having poor metastatic potential. A notably higher level of AKAP10 expression was found in CRC tissues at both mRNA and protein levels. Increased expression of AKAP10 in CRC patients was positively associated with the depth of invasion and the grade of differentiation. Univariate survival analysis showed that the increased expression of AKAP10 was related to poorer survival. Cox multivariate regression analysis confirmed that AKAP10 was an independent predictor of the overall survival of CRC patients. PKA RIα mRNA was also expressed at high levels in CRC. The correlation coefficient between mRNA expression of AKAP10 and PKA RIα in CRC was 0.417. AKAP10 mRNA overexpression was correlated significantly with PKA RIα. CONCLUSIONS: Our data indicated that PKA RIα/AKAP10 signaling pathway is associated with the progression and prognosis of CRC.

Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer.

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.

A Narrative Review of Nutritional Therapy for Gastrointestinal Cancer Patients Underwent Surgery.

Background: Patients with gastrointestinal cancer often suffer from malnutrition during tumor progression. Malnutrition is associated with postoperative complications and decreased quality of life. Supporting cancer patients with proper nutrition is vital for improving their prognoses.Method: Google scholar and PubMed database searches were performed. Selection criteria included gastrointestinal cancer, surgery, ω - 3 fatty acids, randomized clinical trials from 2007 to August 2022.Conclusion: Nutritional therapy includes nutritional counseling, enteral nutrition, parenteral nutrition, and oral nutritional supplements. Immune nutrients like glutamine and ω-3 fatty acid have been demonstrated with benefits in reducing inflammatory responses and postoperative complications, regulating immune function and improving prognosis.

Mechanisms of microRNA action in rectal cancer radiotherapy.

ABSTRACT: Preoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.

Effects of Preoperative Oral Nutritional Supplements on Improving Postoperative Early Enteral Feeding Intolerance and Short-Term Prognosis for Gastric Cancer: A Prospective, Single-Center, Single-Blind, Randomized Controlled Trial.

BACKGROUND: Early enteral nutrition (EN) after abdominal surgery can improve the prognosis of patients. However, the high feeding intolerance (FI) rate is the primary factor impeding postoperative EN. METHODS: Sixty-seven patients who underwent radical subtotal or total gastrectomy for gastric cancer (GC) were randomly allocated to the preoperative oral nutritional supplement group (ONS group) or dietary advice alone (DA group). Both groups were fed via nasojejunal tubes (NJs) from the first day after surgery to the fifth day. The primary endpoint is the FI rate. RESULTS: Of the patients, 66 completed the trial (31 in the ONS group, 35 in the DA group). The FI rate in the ONS group was lower than that in the DA group (25.8% vs. 31.4%, p = 0.249). The postoperative five-day 50% energy compliance rate in the ONS group was higher than that in the DA group (54.8% vs. 48.6%, p = 0.465). The main gastrointestinal intolerance symptoms were distension (ONS vs. DA: 45.2% vs. 62.9, p = 0.150) and abdominal pain (ONS vs. DA: 29.0% vs. 45.7%, p = 0.226). Postoperative nausea/vomiting rate and heartburn/reflux rate were similar between the two groups. We noted no difference in perioperative serum indices, short-term prognosis or postoperative complication rates between the two groups. CONCLUSIONS: The study shows that short-term preoperative ONS cannot significantly improve FI and the energy compliance rate in the early stage after radical gastrectomy.

Clinicopathological Features and Survival of Signet-Ring Cell Carcinoma and Mucinous Adenocarcinoma of Right Colon, Left Colon, and Rectum.

Histological subtype plays an important role in the different clinical characteristics and survival outcomes of patients with colorectal carcinoma (CRC). However, in previous studies, the influences of tumor locations and tumor stages have not been strictly controlled. This study focused on the assessment of the prognostic value of each histological subtype in different tumor locations and tumor stages of CRC. We used the Surveillance, Epidemiology, and End Results (SEER) database (1973-2011) to analyze 818,229 CRC patients with different clinical and pathological features, and analyzed the prognostic value of each histological subtype. Under the condition of stratification by tumor stage, signet-ring cell carcinoma (SRCC) presented the worst survival in each stage of right colon cancer (stage I, log-rank, p = 0.002, stages II, III, and IV, log-rank, p < 0.001), rectal cancer (RC) (log-rank, p < 0.001), and in stages II, III, and IV of left colon cancer (log-rank, p < 0.001). Multivariate survival analysis suggested SRCC subtype, male gender, age ≥ 70 years, tumor size ≥ 5 cm, stage progression, and poor differentiation were all significant factors worsening survival in CRC (p < 0.001, respectively). Mucinous adenocarcinoma (MC) histological subtype proved to be an independent protective factor for the prognosis of right colon cancer (p = 0.003). Overall, in our study, the results suggested SRCC had the worst survival among the three histological subtypes of CRC. MC was associated with favorable prognosis in right colon cancer but not with other tumor locations.

Prognostic impact of lymph node status in patients after total pancreatectomy for pancreatic ductal adenocarcinoma: A strobe-compliant study.

The optimal number of examined lymph nodes (ELN) for staging and impact of nodal status on survival following total pancreatectomy (TP) for pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of this study was to evaluate the prognostic impact of different lymph node status after TP for PDAC.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients who underwent TP for PDAC from 2004 to 2015. We calculated overall survival (OS) of these patients using Kaplan-Meier analysis and Cox proportional hazards model.Overall, 1291 patients were included in the study, with 869 node-positive patients (49.5%). A cut-off points analysis revealed that 19, 19, and 13 lymph nodes best discriminated OS for all patients, node-negative patients, and node-positive patients, respectively. Higher number of ELN than the corresponding cut-off points was an independent predictor for better prognosis [all patients: hazard ratios (HR) 0.786, P = .002; node-negative patients: HR 0.714, P = .043; node-positive patients: HR 0.678, P < .001]. For node-positive patients, 1 to 3 positive lymph nodes (PLN) correlated independently with better survival compared with those with 4 or more PLN (HR 1.433, P = .002). Moreover, when analyzed in node-positive patients with less than 13 ELN, neither the number of PLN nor lymph node ratio (LNR) was associated with survival. However, when limited node-positive patients with at least 13 ELN, univariate analyses showed that both the number of PLN and LNR were associated with survival, whereas multivariate analyses demonstrated that only number of PLN was consistently associated with survival (HR 1.556, P = .004).Evaluation at least 19 lymph nodes should be considered as quality metric of surgery in patients who underwent TP for PDAC. For node-negative patients, a minimal number of 19 lymph nodes is adequate to avoid stage migration. For node-positive patients, PLN is superior to LNR in predicting survival after TP, predominantly for those with high number of ELN.

miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer.

Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU]+leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR-124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC.

The Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 and the risk of colorectal cancer.

OBJECTIVE: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. METHODS: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. RESULTS: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01-2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94-2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08-3.05, p = 0.01) among young subjects (age <57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08-2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. CONCLUSIONS: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.

[Genotyping of AKAP10 gene 2073A/G single nucleotide polymorphism by TaqMan probe real-time PCR].

OBJECTIVE: To detect AKAP10 gene 2073A/G single nucleotide polymorphism (SNP) genotyping by TaqMan probe real-time PCR. METHODS: The genotype of AKAP10 gene 2073A/G was detected by real-time PCR with a pair of new-designed TaqMan probes. The PCR products also were subjected to gene sequence analysis to validate the results of TaqMan probe real-time PCR. RESULTS: The TaqMan probe real-time PCR method was successfully developed to detect AKAP10 gene 2073A/G SNP. The results were accordant with those achieved by DNA sequencing. The distribution of AKAP10 gene 2073A/G among population had no relationship with gender, age (P > 0.05). Unconditional logistic regression analysis revealed that the variant genotypes (AG + GG) had a 52% increased risk of colorectal cancer, compared with the AA genotype (P = 0.019). CONCLUSION: A detection platform for SNP genotyping by TaqMan probe was set up successfully. There was a significant association between AKAP10 gene 2073A/G and colorectal cancer.

A unique case of ectopic pancreas presenting as jejunal malignance.

Ectopic pancreas is defined as pancreatic tissues having no anatomic or vascular connections with the orthotopic pancreas. It is difficult for clinicians to diagnose this disease without performing a histopathological examination because it lacks specific clinical manifestations. This case report is of a 46-year-old woman who presented with epigastric pain. She had elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4). Abdominal contrast-enhanced computed tomography (CT) revealed a persistently enhanced mass in the proximal jejunum, which was confirmed as ectopic pancreas via histopathological examination. Her serum CEA and CA72-4 levels were restored to normal ranges after resecting the jejunal ectopic pancreas. This is the first reported case of ectopic pancreas causing an elevation in serum CEA and CA-724 levels; this report supports the metaplasia theory and suggests that jejunal masses should be cautiously diagnosed for avoiding unnecessary concerns among patients and their families.

Impact of different surgical procedures on survival outcomes of patients with adenocarcinoma of pancreatic neck.

BACKGROUND: The only curative treatment for pancreatic adenocarcinoma is radical surgical resection. Because of the special anatomic features of pancreatic neck, the selection of optimal surgical procedure for treatment of adenocarcinoma of pancreatic neck has always been a dilemma for surgeons. In this paper, we aim to investigate whether different surgical procedures can affect prognosis in the patient with adenocarcinoma of pancreatic neck. METHODS: We used the surveillance, epidemiology, and end results database to review patients with adenocarcinoma of pancreatic neck diagnosed between 1998 and 2015. We calculated overall survival (OS) and cancer-specific survival (CSS) of these patients using Kaplan-Meier analysis and Cox regression model. RESULTS: Overall, 1443 patients were included in the study, with 12.5% treated with surgical resection. Among them, 30 (18.8%) patients underwent distal pancreatectomy (DP), 105 (65.6%) patients underwent pancreatoduodenectomy (PD), and 25 (15.6%) patients underwent total pancreatectomy (TP). Patients underwent DP were older than these underwent TP (70.5±10.7 vs. 62.2±14.1, P = 0.027). Patients underwent TP had higher percentages of nodal metastasis (N1 stage) than these underwent DP (68.0% vs. 34.5%, P = 0.014). The surgical procedures did not significantly affect either OS times (P = 0.924) or CSS times (P = 0.786) in Kaplan-Meier analysis, even if in any subgroup of AJCC stage. The multivariate Cox regression model showed that types of surgery were not associated with OS and CSS. Higher tumor grade and AJCC stage are independent prognostic factors for OS and CSS. No radiotherapy was associated with a worse CSS (HR 1.610, 95% CI 1.016-2.554, P = 0.043). CONCLUSION: Different surgical procedures did not affect prognosis in the patients with adenocarcinoma of pancreatic neck. TP should be performed in carefully selective patients in high-volume pancreatic centers.