Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Evaluation and management of symptomatic duodenal diverticula: a single-center retrospective analysis of 647 patients.

Aims: To explore the clinical characteristics of patients with symptomatic duodenal diverticula and to generalize how to make appropriate treatment choices for this group of patients. Materials and methods: From January 2010 to September 2020, a total of 647 patients with duodenal diverticula (DD) were included in this study. 345 of them with relevant symptoms were divided into the symptomatic group and the other 302 patients were in the asymptomatic group. Results: Among all patients, most DD were located in the periampullary area, <1 cm in size, and single in number. The distribution of DD localized in the 2nd portion/periampullary (P = 0.002/P < 0.001) and with a 1 cm size cut-off value (P = 0.003) was significantly different between the symptomatic and asymptomatic groups. Multivariate Logistics analysis further suggests that diverticular size (<1 cm, 1-3 cm) and combined biliary comorbidities (bile duct stones and gallstones, primary bile duct stones, cholangitis without bile duct stones) may be factors influencing the choice of treatment modality. Of all patients undergoing surgical treatment, a total of 7 cases developed various postoperative complications, and no one died. Conclusions: Patients with DD ≥1 cm or located in the periampullary were more likely to be symptomatic. The specific size of the DD and the combination of specific biliary comorbidities may have an impact on the choice of treatment modality.

Prognostic nomogram for primary splenic lymphoma: a SEER database-based study.

This study aimed to establish a nomogram model based on the clinicopathological factors affecting the prognosis of patients with primary splenic lymphoma (PSL) to predict the overall survival (OS) and cancer-specific survival (CSS) of patients. A total of 4074 patients diagnosed with PSL were included in this study. Among them, 4052 cases from the SEER (Surveillance, Epidemiology, and End Results) database were randomized into a training set and an internal validation set in a 7:3 ratio. Another 22 patients from the First Affiliated Hospital of Xi'an Jiaotong University were used as an external validation set. The prognostic factors affecting the OS and CSS of patients were analyzed using univariate and multivariate Cox regression models. Survival analysis was performed using Kaplan-Meier (KM) method and compared by Log-rank test. Then, a nomogram model was established to predict OS and CSS. Finally, the model was validated both internally and externally using the concordance index (C-index), receiver operating characteristic curve (ROC), and calibration curve to evaluate its predictive value, and the decision curve analysis (DCA) was conducted to assess its clinical utility. Our results showed that the model displayed a good prediction ability. In the training set, the OS rates at 1, 3, and 5 years were 85.9%, 75.8% and 70.1%, respectively, while the CSS rates at 1, 3, and 5 years were 91.9%, 86.2% and 82.3%, respectively. Predictors in the prediction model of OS included age, sex, marital status, Ann Arbor stage, histology, surgery, chemotherapy and year at diagnosis. On the other hand, predictors in the model of CSS included age, Ann Arbor stage, histology, chemotherapy, and year at diagnosis. Internal and external validation of the nomogram model showed that the C-index for predicting OS was 0.678 (0.662, 0.694) in the training set, 0.672 (0.648, 0.696) in the internal validation set, and 0.704 (0.565, 0.843) in the external validation set; the C-index for predicting CSS was 0.685 (0.661, 0.709) in the training set, 0.683 (0.650, 0.716) in the internal validation set, and 0.676 (0.488, 0.864) in the external validation set. The calibration curves for several groups showed good consistency, and DCA suggested its clinical usability. In conclusion, the nomogram constructed in this study has a good predictive value for the survival of patients with PSL, and can be a clinically applicable and practical prediction tool, facilitating rapid and accurate individualized predictions of the patient survival.

Infusion of Human Albumin on Acute Pancreatitis Therapy: New Tricks for Old Dog?

Objective: Human serum albumin (HSA) infusion is a common administration on acute pancreatitis therapy in the Intensive Care Unit (ICU), but its actual association with patients' outcomes has not been confirmed. The study is aimed to determine whether the in-hospital prognosis of ICU patients with acute pancreatitis could benefit from HSA. Methods: 950 acute pancreatitis patients diagnosed in 2008-2019 were extracted from the MIMIC-IV database as our primary study cohort. The primary outcome was in-hospital mortality. We also performed an external validation with a cohort of 104 acute pancreatitis patients after PSM matching from the eICU database. Results: In MIMIC-IV, 228 acute pancreatitis patients received HSA infusion (Alb group) during their hospitalization, while 722 patients did not (non-Alb group). Patients in the Alb group presented a poorer survival curve than the non-Alb group, while this difference disappeared after PSM or IPTW matching (log-rank test: PSM: p = 0.660, IPTW: p = 0.760). After including covariates, no association was found between HSA infusion and patients' in-hospital mortality before and after matching (original cohort: HR: 1.00, 95% CI: 0.66-1.52, p = 0.998). HSA infusion also did not benefit patients' 28-days or ICU mortality, while it was significantly associated with a longer duration of hospital and ICU. In addition, the initial serum albumin levels, infections, the total amount, or the initial timing of infusion did not affect the conclusion. Similarly, in the eICU cohort, HSA infusion was still not a beneficial prognostic factor for patients' in-hospital prognosis (p = 0.087). Conclusion: Intravenous human serum albumin infusion could not benefit acute pancreatitis patients' in-hospital prognosis and was associated with prolonged hospital and ICU duration.

Nodal Enhances Perineural Invasion in Pancreatic Cancer by Promoting Tumor-Nerve Convergence.

Perineural invasion (PNI) is a typical feature of pancreatic ductal adenocarcinoma (PDAC), which occurs in most cases. The embryonic protein Nodal plays a critical role in embryonic neural development and is overexpressed in human pancreatic cancer. In this study, we explored the contribution of Nodal to pancreatic cancer PNI and progression. We evaluated the function of Nodal in PNI by coculturing rat dorsal root ganglia and pancreatic cancer cells in vitro and performing cellular and molecular biology assays. The results illustrate that Nodal upregulates NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), and GDNF (glial cell line-derived neurotrophic factor) expression in pancreatic cancer cells and promotes cancer cell migration/invasion. Furthermore, in the in vitro 3D PNI model, Nodal enhances nerve outgrowth to pancreatic cancer cell colonies. Our study indicates that Nodal participates in tumor invasion by mediating neural and tumor cell signaling interactions, and inhibiting the expression of Nodal represents a potential strategy for targeting PNI in pancreatic cancer therapy.

Development and external validation of a dynamic nomogram to predict the survival for adenosquamous carcinoma of the pancreas.

Objective: We aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP). Background: Adenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance. Methods: Histologically confirmed ASCP patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis. Results: A total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8th) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis. Conclusion: The nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans.