Single-center retrospective study of the diagnostic value of double-balloon enteroscopy in Meckel's diverticulum with bleeding.

BACKGROUND: The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel's diverticulum (MD) complicated by digestive tract hemorrhage. Moreover, we aimed to evaluate the value of double-balloon enteroscopy (DBE) in MD diagnosis and the prognosis after laparoscopic diverticula resection. AIM: To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding. METHODS: The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations, auxiliary examination, and follow-up after laparoscopic resection of diverticula. RESULTS: (1) Among 84 MD patients complicated with hemorrhage, 77 were male, and 7 were female with an average age of 31.31 ± 10.75 years. The incidence was higher in men than in women of different ages; (2) Among the 84 MD patients, 65 (78.40%) had defecated dark red stools, and 50 (58.80%) had no accompanying symptoms during bleeding, indicating that most MD bleeding appeared a dark red stool without accompanying symptoms; (3) The shock index of 71 patients (85.20%) was < 1, suggesting that the blood loss of most MD patients was less than 20%-30%, and only a few patients had a blood loss of > 30%; (4) The DBE-positive rate was 100% (54/54), 99mTc-pertechnetate-positive scanning rate was 78% (35/45) compared with capsule endoscopy (36%) and small intestine computed tomography (19%). These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding, especially DBE was a highly precise examination method in MD diagnosis; (5) A total of 54 MD patients with hemorrhage underwent DBE examination before surgery. DBE endoscopy revealed many mucosal manifestations including normal appearance, inflammatory changes, ulcerative changes, diverticulum inversion, and nodular hyperplasia, with ulcerative changes being the most common (53.70%). This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding; and (6) Laparoscopic dissection of diverticulae was performed in 76 patients, The patients who underwent postoperative follow-up did not experience any further bleeding. Additionally, follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding. These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis. CONCLUSION: Bleeding associated with MD was predominantly observed in male adolescents, particularly at a young age. DBE was a highly precise examination method in MD diagnosis. Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.

CTRP3 acts as a novel regulator in depressive-like behavior associated inflammation and apoptosis by meditating p38 and JNK MAPK signaling.

Depression is a complicated etiological pattern, and its pathology and effective treatments are highly limited.C1q-tumor necrosis factor-related protein-3 (CTRP3) is an adipokine, playing crucial roles in metabolic regulatory properties. However, the effects of CTRP3 on depression are largely unknown. In the present study, we found that CTRP3 expression levels were markedly reduced in hippocampus of mice with depression induced by chronic unpredictable mild stress (CUMS). In mouse model with depression, CTRP3-deficient mice aggravated depression-associated behaviors, as evidenced by the reduced locomotor activity and sucrose consumption, while the elevated immobility time in the tail suspension test (TST) and forced swimming test (FST). Moreover, CUMS-induced neuron death and increased expression of cleaved Caspase-3 were significantly accelerated by CTRP3 knockout. Furthermore, CTRP3 deletion intensified pro-inflammatory response in CUMS-exposed mice, which was associated with the activation of nuclear factor-κB(NF-κB) signaling. The activity of mitogen-activated protein kinases (MAPKs), including p38 and JNK, was further promoted in hippocampus of CTRP3-knockout mice with CUMS exposure. In contrast,CTRP3 over-expression showed anti-apoptotic and anti-inflammatory effects in lipopolysaccharide (LPS)-treated microglial cells. Importantly, the in vitro experiments demonstrated that CTRP3 knockdown-exacerbated apoptosis and inflammatory responsewere remarkably abrogated by the blockage of p38 and JNK signaling pathways in microglia stimulated by LPS. Next, in CUMS-exposed mice with CTRP3 deficiency, suppressing p38 and JNK markedly alleviated depressive-like behavior,hippocampal neuron death, apoptosis and inflammation. Therefore, CTRP3 may be an innovative therapeutic target for treating patients with depression through regulating p38 and JNK signaling.

Comparative Outcomes of Induction Chemotherapy Followed By Definitive Chemoradiotherapy versus Chemoradiotherapy Alone In Esophageal Squamous Cell Carcinoma.

Purpose: To compare the clinical outcomes of induction chemotherapy (IC) followed by chemoradiotherapy (CRT) versus chemoradiotherapy alone in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Patients and methods: Between 2002 and 2015, 267 ESCC patients who received definitive CRT with docetaxel and cisplatin were enrolled in this study. Through a matched case-control study, 85 patients receiving IC before CRT were matched 1:1 to patients who received CRT alone, according to age, gender, performance status, tumor location, tumor length, and pretreatment TNM stage. Results: The median overall survival (OS) in the IC group was significantly better than that in the CRT group (26.0 vs. 22.0 months), with 3-year OS rates of 30.6% vs. 25.9%, respectively (P = 0.028). However, IC plus CRT was associated with a significantly higher rate of grade 3-4 leukopenia than CRT alone (P = 0.048). The overall clinical response rate was 50.6% after IC in the IC group. The IC responder group showed significantly more favorable OS (P=0.002) and progression-free survival (P=0.001) compared with the IC non-responder group and the CRT group. Multivariate analysis revealed that age ≥ 60 (P = 0.003) and the addition of IC (P=0.016) were independent prognostic factors that affected survival positively. Conclusions: The addition of IC before CRT yielded satisfactory clinical outcomes and manageable toxicities. The combination of IC with CRT might be a promising treatment strategy to further improve systemic control and survival in ESCC. Prospective randomized trials are required to confirm the role of IC.

Concurrent cisplatin and 5-fluorouracil versus concurrent cisplatin and docetaxel with radiotherapy for esophageal squamous cell carcinoma: a propensity score-matched analysis.

The optimal concurrent chemotherapy regimen with radiotherapy for esophageal cancer is unknown. Here, we compared the survival outcomes and toxicity of definitive chemoradiotherapy with either cisplatin/5-fluorouracil (PF) or docetaxel/cisplatin (DP) in patients with unresectable esophageal squamous cell carcinoma (ESCC). In this study, we identified 317 patients with ESCC who received PF or DP concurrently with definitive radiotherapy. PF group patients received two cycles of cisplatin (60 mg/m2) and 5-fluorouracil (300 mg/m2) at 4-week intervals during radiotherapy. DP group patients received a concurrent three-weekly schedule of docetaxel (60 mg/m2) and cisplatin (80 mg/m2) or cisplatin (25 mg/m2) and docetaxel (25 mg/m2) weekly. The overall survival (OS) and progression-free survival (PFS) were compared using propensity score (-adjusted, -weighted, -stratified, and -matched) analyses. A sensitivity analysis was performed to examine the impact of unmeasured confounders. Inverse probability of treatment weighting for propensity score demonstrated an improvement in OS and PFS with DP group in comparison with PF group (hazard ratio, 0.700; 95% CI, 0.577-0.851) and similar results were achieved with propensity score matching and stratification. Grade 3-4 esophagitis was more common (16/102 vs. 4/102) and grade 3-4 thrombopenia and skin toxicity were less common (3/102 vs. 10/102; 7/102 vs. 19/102; respectively) in the PF group than the DP group. In conclusion, concurrent chemoradiotherapy with the DP regimen resulted in better OS and PFS compared to concurrent PF regimen with tolerable toxicities in ESCC patients. Prospective randomized trials are required to confirm the efficacy of the DP regimen.

Is There a Correlation Between Clinical Complete Response and Pathological Complete Response After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Cancer?

OBJECTIVE: The aim of this study was to investigate the correlation between clinical complete response (cCR) and pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) for esophageal squamous cell cancer (ESCC). METHODS: Between May 2001 and April 2013, a total of 158 patients with thoracic ESCC treated with neoadjuvant CRT followed by surgery were analyzed. Of these patients, 31 had stage IIb disease and 127 had stage III disease. All patients received concurrent platinum-based chemotherapy with conformal radiotherapy (40 Gy in 20 fractions, five fractions per week for 4 weeks). RESULTS: A total of 65 patients (41.1 %) achieved pCR. Of 44 patients (27.8 %) who achieved cCR after neoadjuvant CRT, 32 (72.7 %) also achieved pCR. On the other hand, only 33 (28.9 %) of 114 patients with non-cCR had pCR. The sensitivity, specificity, positive predictive value, and negative predictive value of cCR for predicting pCR was 87.1, 49.2, 71.1, and 72.7 %, respectively. The median follow-up period was 28.9 months, and overall survival (OS) for the entire group was 38.1 months. Patients who achieved cCR had significantly better 3-year OS than those with non-cCR (71.6 % vs. 46.9 %; p = 0.012). CONCLUSIONS: Our results indicate that cCR after neoadjuvant CRT is significantly correlated with pCR and survival of patients with ESCC. Further studies are required to confirm the prognostic value of cCR after neoadjuvant CRT.

Insulin-like growth factor binding protein-3 is a new predictor of radiosensitivity on esophageal squamous cell carcinoma.

Insulin-like growth factor binding protein-3 (IGFBP-3) plays an essential role in radiosensitivity of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism is not completely understood. Here, we observed that IGFBP-3 had favorable impact on the tumorigenicity of ESCC cells in nude mice by using an in vivo imaging system (IVIS) to monitor tumor growth treated with ionizing radiation (IR). Downregulation of IGFBP-3 expression enhanced tumor growth, inhibited anti-proliferative and apoptotic activity and result in IR resistance in vivo. Cell cycle antibody array suggested that silencing IGFBP-3 promoted transition from G0/G1 to S phase, perhaps though influencing Smad3 dephosphorylation and retinoblastoma protein (Rb) phosphorylation. Downregulation of P21 and P27, and upregulation of p-P27 (phospho-Thr187), cyclin-dependent kinase 2 (CDK2), and cyclin E1 might contribute to the G0/G1 to S phase transition promoted by IGFBP-3. Our results suggest that Smad3-P27/P21-cyclin E1/CDK2-phosphorylated retinoblastoma protein pathways might be involved in this IGFBP-3 mediated radiosensitivity transition in ESCC.

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC. METHODS: IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001). CONCLUSIONS: High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.

Neoadjuvant chemoradiotherapy with cisplatin plus vinorelbine versus cisplatin plus fluorouracil for esophageal squamous cell carcinoma: A matched case-control study.

BACKGROUND: To compare the clinical outcomes of neoadjuvant chemoradiotherapy (CRT) with cisplatin/vinorelbine versus cisplatin/fluorouracil in patients with locally advanced esophageal cancer. METHODS: Between 2000 and 2012, 279 patients with thoracic esophageal squamous cell carcinoma (SCC) undergoing neoadjuvant CRT followed by surgery were reviewed. Through a matched case-control study, 57 patients treated with cisplatin/vinorelbine were matched 1:1 to patients who received cisplatin/fluorouracil according to age, sex, performance status, tumor location, tumor length, and pretreatment TNM stage. RESULTS: Patient and disease-related characteristics were comparable between the two groups. The pathologic complete response (pCR) rate was 47.4% for the cisplatin/vinorelbine group and 28.1% for the cisplatin/fluorouracil group (P=0.034). Median overall survival (OS) in the cisplatin/vinorelbine group was significantly better compared with the cisplatin/fluorouracil group (52.8 vs. 25.2 months), with 3-year OS rates of 64.3% vs. 31.3%, respectively (P=0.001). However, cisplatin/vinorelbine was associated with a significantly higher rate of grade 3-4 leukopenia than cisplatin/fluorouracil (P=0.03). Multivariate analysis showed that being female, age ⩾55 years, pCR after CRT, and chemotherapy with cisplatin/vinorelbine were independent positive prognostic factors for survival. CONCLUSIONS: Cisplatin/vinorelbine might lead to a higher pCR rate and better survival outcomes than cisplatin/fluorouracil in esophageal SCC. The incidence of hematologic toxicity is increased with cisplatin/vinorelbine, but is tolerable and manageable. Prospective controlled studies are required to confirm the efficacy of this regimen.

Association between E-cadherin (CDH1) polymorphisms and pancreatic cancer risk in Han Chinese population.

This study was designed to investigate the associations between E-cadherin (CDH1) gene polymorphisms and pancreatic cancer (PC) risk predisposition. We undertook a case-control study to analyze three E-cadherin polymorphisms (+54T>C, -160C>A and -347G→GA) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 368 patients with PC and 376 control participants and performed E-cadherin genotyping using DNA sequencing. Overall, no statistically significant association was observed in +54T>C. Nevertheless, -347G→GA genotype was at increased risk of PC (P=0.022; odds ratio (OR)=1.128, CI 95%: 1.017-1.251). Furthermore, -347GA/GA genotype pancreatic cancers were more significantly common in cases of advanced T stage, lymph node metastasis and clinical pathological stage than G or G/GA genotypes PC. However, -160C>A genotype demonstrated a protective effect in PCs (P=0.017; OR=0.883, CI 95%: 0.798-0.977). In conclusion, polymorphism in -347G→GA was observed to be associated with susceptibility of PC. However, -160C>A polymorphism indicated to play a protective role in susceptibility to PC. Nevertheless, further investigation with a larger sample size is needed to support our results.

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to be a critical role in cancer progression and prognosis. However, little is known about the pathological role of lncRNA HOXA transcript at the distal tip (HOTTIP) in tongue squamous cell carcinoma (TSCC) patients. The aim of this study is to measure the expression of lncRNA HOTTIP in TSCC patients and to explore the clinical significance of the lncRNA HOTTIP. The expression of lncRNA HOTTIP was measured in 86 TSCC tissues and 14 adjacent non-malignant tissues using qRT-PCR. In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues (P < 0.001) and positively correlated with T stage (T1-2 vs. T3-4, P = 0.023), clinical stage (I-II stages vs. III-IV stages, P = 0.018), and distant metastasis (absent vs. present, P = 0.031) in TSCC patients. Furthermore, we also found that lncRNA HOTTIP overexpression was an unfavorable prognostic factor in TSCC patients (P < 0.001), regardless of T stage, distant metastasis, and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for TSCC patients through multivariate analysis (P = 0.023). In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for TSCC patients. Nevertheless, further investigation with a larger sample size is needed to support our results.