Protocadherin-1 serves as a prognostic biomarker and promotes pancreatic cancer progression by suppressing CD8+ T cell infiltration through CCL5-CCR5 axis.

Previous studies have shown that Protocadherins (PCDHs) enhance tumor proliferation, invasion, and metastasis; yet their role in pancreatic cancer (PC) progression and the tumor immune microenvironment remains unclear. This study aims to elucidate the role of PCDH1 in different cancer types, with a particular focus on its impact on immune suppression in PC. Utilizing data from TCGA, GTEx, and Gent2 databases, we assessed the expression of PCDH1 across various cancer types. The prognostic value of PCDH1 was demonstrated through Cox regression, Kaplan-Meier analysis, and ROC curve, while its relationship with gene mutations, tumor mutational burden (TMB), immune cell infiltration, and other clinical factors was investigated using Spearman correlation. Furthermore, the effect of PCDH1 on PC malignancy was experimentally validated by a series of in vitro and in vivo assays. Our results show a significant upregulation of PCDH1 in various tumor types, which is associated with poor prognosis, suggesting its potential application as an independent prognostic biomarker. Notably, in PC, PCDH1 exhibited significant associations with gene mutations, TMB, and immune cell infiltration. Clinical validations revealed a correlation between high PCDH1 expression and poor prognosis, coupled with a low level of CD8+ T cell infiltration. Furthermore, both in vitro and in vivo experiments confirmed the role of PCDH1 in promoting PC cell proliferation and migration while inhibiting CD8+ T cell recruitment through its modulation of CCL5-CCR5 axis. In conclusion, PCDH1 regulates the proliferation and migration of PC cells as well as CD8+ T cell infiltration in PC. PCDH1 may serve as a prognostic biomarker in multiple tumor types.

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges.

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

Development and validation of a novel nomogram to predict postoperative pancreatic fistula after pancreatoduodenectomy using lasso-logistic regression: an international multi-institutional observational study.

BACKGROUND: Existing prediction models for clinically relevant postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) lack discriminatory power or are too complex. This study aimed to develop a simple nomogram that could accurately predict clinically relevant POPF after PD. METHODS: A high-volume, multicenter cohort of patients who underwent PD from the American College of Surgeons-National Surgical Quality Improvement Program database in the United States during 2014-2017 was used as the model training cohort ( n =3609), and patients who underwent PD from the Pancreatic Center of the National Cancer Center Hospital in China during 2014-2019 were used as the external validation cohort ( n =1347). The study used lasso penalized regression to screen large-scale variables, then logistic regression was performed to screen the variables and build a model. Finally, a prediction nomogram for clinically relevant POPF was established based on the logistic model, and polynomial equations were extracted. The performance of the nomogram was evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: In the training and validation cohorts, there were 16.7% (601/3609) and 16.6% (224/1347) of patients who developed clinically relevant POPF, respectively. After screening using lasso and logistic regression, only six predictors were independently associated with clinically relevant POPF, including two preoperative indicators (weight and pancreatic duct size), one intraoperative indicator (pancreatic texture), and three postoperative indicators (deep surgical site infection, delayed gastric emptying, and pathology). The prediction of the new nomogram was accurate, with an area under the curve of 0.855 (95% CI: 0.702-0.853) in the external validation cohort, and the predictive performance was superior to three previously proposed POPF risk score models (all P <0.001, likelihood ratio test). CONCLUSIONS: A reliable lasso-logistic method was applied to establish a novel nomogram based on six readily available indicators, achieving a sustained, dynamic, and precise POPF prediction for PD patients. With a limited number of variables and easy clinical application, this new model will enable surgeons to proactively predict, identify, and manage pancreatic fistulas to obtain better outcomes from this daunting postoperative complication.

An improvement in the reconstruction of digestive tract after total gastrectomy: ultra-short cecum.

Aim: This study aimed to evaluate the utility and complications of ultra-short cecum (USC) in the reconstruction of digestive tract after total gastrectomy (TG) for the alleviation of reflux esophagitis and to determine its effect on long-term nutritional status. Methods: Patients who underwent TG with USC or normal cecum (NC) at a single institution between June 2018 and December 2020 were included in this study. The inclusion and exclusion criteria were defined, and the primary endpoints were reflux esophagitis, anastomotic leakage and postoperative nutritional status. The long-term nutritional status was evaluated by the change trend of laboratory blood tests, including total protein, prealbumin, hemoglobin, and total leukocytes. Results: Totally 240 cases were included in the final analysis out of 496 patients who received TG with USC or NC. Postoperative reflux esophagitis was significantly higher in the NC group than in the USC group (24.7% versus 7.7%, P = 0.001), and the NC group had a higher incidence of severe esophagitis symptoms compared to the USC group (13.6% versus 0.00%, P < 0.001), and the incidence of anastomotic leakage in the USC group was similar to that in the NC group (9.0% versus 6.2%, P = 0.6). There was no significant difference in long-term nutritional status between the USC and NC groups in the two years following the surgery (P > 0.05). Conclusion: Ultra-short cecum after total gastrectomy should be more actively recommended due to its significant reduction in reflux esophagitis and similar incidence of anastomotic leakage and nutritional status compared with normal cecum after total gastrectomy.

Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.

ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis.

Contribution of integrin superfamily genes to treatment resistance remains uncertain. Genome patterns of thirty integrin superfamily genes were analyzed of using bulk and single-cell RNA sequencing, mutation, copy number, methylation, clinical information, immune cell infiltration, and drug sensitivity data. To select the integrins that are most strongly associated with treatment resistance in pancreatic cancer, a purity-independent RNA regulation network including integrins were constructed using machine learning. The integrin superfamily genes exhibit extensive dysregulated expression, genome alterations, epigenetic modifications, immune cell infiltration, and drug sensitivity, as evidenced by multi-omics data. However, their heterogeneity varies among different cancers. After constructing a three-gene (TMEM80, EIF4EBP1, and ITGA3) purity-independent Cox regression model using machine learning, ITGA3 was identified as a critical integrin subunit gene in pancreatic cancer. ITGA3 is involved in the molecular transformation from the classical to the basal subtype in pancreatic cancer. Elevated ITGA3 expression correlated with a malignant phenotype characterized by higher PD-L1 expression and reduced CD8+ T cell infiltration, resulting in unfavorable outcomes in patients receiving either chemotherapy or immunotherapy. Our findings suggest that ITGA3 is an important integrin in pancreatic cancer, contributing to chemotherapy resistance and immune checkpoint blockade therapy resistance.

Prognostic value, immune signature and molecular mechanisms of the APOBEC family members APOBEC1, APOBEC3A, APOBEC3G and APOBEC3H in pancreatic adenocarcinoma.

Background: Increasing evidence supports that the APOBEC family is associated with development of a variety of cancers. However, the function of APOBEC1/3A/3G/3H in pancreatic adenocarcinoma (PAAD) is still unclear. Methods: Comprehensive bioinformatic analysis using R (version 3.6.3), TISIDB, Metascape etc. were performed to study the clinicopathological characteristics, prognostic value, immune features and functional mechanisms of the APOBEC1/3A/3G/3H in PAAD. Results: APOBEC1/3A/3G/3H showed significantly elevated expression in PAAD than para-cancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of APOBEC1/3A/3G/3H in the immune regulation is diverse and complex, the high expression of APOBEC1 may inhibit the infiltration level of many kinds of immunoreactive tumor-infiltrating cells, which may be an important factor leading to immune escape of PAAD cells. Mechanistically, APOBEC1/3A/3G/3H played an activating role in multiple oncogenic pathways, including the EMT, RAS/MAPK and TSC/mTOR pathways. Moreover, we found that the expression level of APOBEC3G was positively correlated with the sensitivity of gemcitabine and doxorubicin. Conclusion: APOBEC1/3A/3G/3H play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets.

Long-term nutritional status after total gastrectomy was comparable to proximal gastrectomy but with much less reflux esophagitis and anastomotic stenosis.

Aim: To compare the long-term nutritional status, reflux esophagitis and anastomotic stenosis, between total gastrectomy (TG) and proximal gastrectomy (PG). Methods: Patients who underwent PG or TG in this single institution between January 2014 and December 2016 were included in this study. The inclusion and exclusion criteria were defined. One-to-one propensity score matching (PSM) by the demographic and pathological characteristics was performed to compare the long-term outcomes between the two groups. The primary endpoint was long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes. Results: Totally 460 patients received PG or TG in our institution for the treatment between January 2014 and December 2016 and according to the inclusion and exclusion criteria 226 cases were included in this study finally. There was no significant difference as to nutritional status in the end of first 5 years after PG or TG. While reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group (54.4% versus 26.8%, p < 0.001; 14.9% versus 4.5%, p=0.015; respectively). Overall survival rates were similar between the two groups after PSM (5-year survival rates: 65.4% versus 61.5% in the PG and TG groups, respectively; p = 0.54). The rate of carcinoma of remnant stomach after PG was 3.5% in this group of patients. Conclusions: TG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages II and III gastric cancer.

BACKGROUND: The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated. AIM: To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients. METHODS: Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients. RESULTS: In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate (P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival. CONCLUSION: Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Hyperthermic intraperitoneal chemotherapy for patients with gastric cancer based on laboratory tests is safe: a single Chinese center analysis.

PURPOSE: About 15%-40% of gastric cancer patients have peritoneal metastasis, which leads to poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is considered to be an effective treatment for these patients. This study evaluated the efficacy and safety of HIPEC in patients with gastric cancer diagnosed from laboratory tests. METHODS: The clinical and pathological data of 63 patients with gastric cancer who underwent HIPEC in 2017-2021 were prospectively recorded. Fifty-five patients underwent cytoreductive surgery + HIPEC, and eight patients received HIPEC alone. The factors associated with HIPEC safety and efficacy were analyzed. The primary endpoint was overall survival. RESULTS: The average patient age was 54.84 years and 68.3% of patients were male. Moreover, 79.4% of patients had a peritoneal carcinoma index (PCI) score of ≤ 7 and 61.9% had a completeness of cytoreduction score of 0. Because of peritoneal metastasis, 29 patients (46.03%) were classified as stage IV. Laboratory tests showed no differences in pre-HIPEC blood test results compared to post-HIPEC results after removing the effects of surgery. HIPEC treatment did not cause obvious liver or kidney damage. Serum calcium levels decreased significantly after HIPEC (P = 0.0018). The Karnofsky performance status (KPS) score correlated with the patient's physical function and improved after HIPEC (P = 0.0045). In coagulation tests, FDP (P < 0.0001) and D-dimer (P < 0.0001) levels increased significantly and CA242 (P = 0.0159), CA724 (P < 0.0001), and CEA (P < 0.0014) levels decreased significantly after HIPEC. Completeness of cytoreduction score was an independent prognostic factor. HIPEC did not show a survival benefit in patients with gastric cancer (P = 0.5505). CONCLUSION: HIPEC is a safe treatment for patients with gastric cancer with peritoneal metastasis based on the laboratory tests. However, the efficacy of this treatment on gastric-derived peritoneal metastases requires further confirmation.

Dynamic monitoring revealed a slightly prolonged waiting time for total gastrectomy during the COVID-19 pandemic without increasing the short-term complications.

We aimed to determine the pattern of delay and its effect on the short-term outcomes of total gastrectomy before and during the coronavirus disease 2019 (COVID-19) pandemic. Overlaid line graphs were used to visualize the dynamic changes in the severity of the pandemic, number of gastric cancer patients, and waiting time for a total gastrectomy. We observed a slightly longer waiting time during the pandemic (median: 28.00 days, interquartile range: 22.00-34.75) than before the pandemic (median: 25.00 days, interquartile range: 18.00-34.00; p = 0.0071). Moreover, we study the effect of delayed surgery (waiting time > 30 days) on short-term outcomes using postoperative complications, extreme value of laboratory results, and postoperative stay. In patients who had longer waiting times, we did not observe worse short-term complication rates (grade II-IV: 15% vs. 19%, p = 0.27; grade III-IV: 7.3% vs. 9.2%, p = 0.51, the short waiting group vs. the prolonged waiting group) or a higher risk of a longer POD (univariable: OR 1.09, 95% CI 0.80-1.49, p = 0.59; multivariable: OR 1.10, 95% CI 0.78-1.55, p = 0.59). Patients in the short waiting group, rather than in the delayed surgery group, had an increased risk of bleeding in analyses of laboratory results (plasma prothrombin activity, hemoglobin, and hematocrit). A slightly prolonged preoperative waiting time during COVID-19 pandemic might not influence the short-term outcomes of patients who underwent total gastrectomy.

Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma.

BACKGROUND: Increasing evidence supports the belief that the pleckstrin homology domain family A (PHLDA) family is associated with the development of a variety of cancers. However, the function of the PHLDA family members in PAAD is still unclear. METHODS: Comprehensive bioinformatic analyses using R (version 3.6.3), Cytoscape (version 3.9.1), UALCAN, etc., were performed to study the clinicopathological characteristics, prognostic value, immune features, and functional mechanisms of the PHLDA family members in PAAD. RESULTS: The PHLDA family members showed significantly elevated expression in PAAD compared with paracancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of the PHLDA family members in the immune regulation is diverse and complex. Mechanistically, TP53 mutations were significantly associated with the promoter methylation and expression levels of the PHLDA family members, which were activated in multiple oncogenic pathways, including the EMT, RAS/MAPK, and TSC/mTOR pathways. Moreover, we found that their expression levels were significantly correlated with the sensitivity of multiple traditional chemotherapeutic drugs and novel targeted MEK1/2 inhibitors. CONCLUSION: The PHLDA family members play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets.

A Female With Synchronous Multiple Primary Malignant Tumors in the Esophagogastric Junction, Duodenum and Pancreas: Case Report and Review of the Literature.

The incidence of multiple primary carcinomas (MPCs), which are defined as two or more malignancies detected in an individual person, is gradually increasing around the world. According to the timing of diagnosis for each constituent tumor, MPCs are classified into 2 categories: synchronous MPCs if constituent tumors emerge simultaneously or within 6 months or metachronous MPCs otherwise. In this report, we describe our recent observation and treatment of a female patient with synchronous primary esophagogastric junction adenocarcinoma, duodenal adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, this combination has not yet been reported in the literature. A crucial aspect is the decision regarding which tumor to treat initially and how to schedule further treatments according to individual tumor hazards. Our multidisciplinary team devised an individualized treatment regimen for this patient. The patient ultimately achieved an overall survival time of 18 months, which was much longer than the median survival time (6~11 months) of patients with locally advanced pancreatic cancer. Moreover, treating this rare combination raised a series of diagnostic, etiological and therapeutic questions, motivating us to carry out a critical review of the literature. In summary, an individualized treatment strategy with input from a dedicated multidisciplinary team and consideration of all options at different points along the disease trajectory is essential to optimize outcomes for patients with MPC.

Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer.

Structural variations (SVs) are the greatest source of variations in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human cancer remain technologically challenging. Here, long-read sequencing is first employed to depict the signatures of structural variations in carcinogenesis of human pancreatic ductal epithelium. Then widespread reprogramming of the 3D chromatin architecture is revealed by an in situ Hi-C technique. Integrative analyses indicate that the distribution pattern of SVs among the 3D genome is highly cell-type specific and the bulk remodeling effects of SVs in the chromatin organization partly depend on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability. Notably, complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4 are identified, and their influence on the expression of oncogenes MIR31HG, MYO5B, etc., are further elucidated from both a linear view and 3D perspective. Overall, this work provides a genome-wide resource and highlights the impact, complexity, and dynamicity of the interplay between structural variations and high-order chromatin organization, which expands the current understanding of the pathogenesis of SVs in human cancer.

Expression, Prognostic Value, and Functional Mechanism of the KDM5 Family in Pancreatic Cancer.

Background: The histone lysine demethylase KDM5 family is an important epigenetic state-modifying enzyme family. Increasing evidence supports that epigenetic abnormalities in the KDM5 family are related to multiple cancers in humans. However, the role of the KDM5 family in pancreatic cancer is not clear, and related research is very scarce. Methods: R software, Kaplan-Meier Plotter, cBioPortal, TIMER, LinkedOmics, STRING, Metascape, TISIDB, and the GSCA Lite online tool were utilized for bioinformatics analysis. Results: KDM5A/B/C was significantly overexpressed in many kinds of tumor tissues, including pancreatic adenocarcinoma (PAAD), while the expression of KDM5D was significantly downregulated. The high expression of KDM5A/B/C was related to poor clinical features, such as worse treatment efficacy, higher tumor grade, and more advanced clinical stage. Patients with a family history of breast cancer and melanoma, history of drinking or history chronic pancreatitis were more likely to have KDM5A/B/C gene abnormalities, which were related to a variety of adverse clinical features. The results of gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses of the KDM5 family and its 800 co-expressed genes showed that many gene terms related to cell proliferation, migration and many carcinogenic pathways. Notably, we found that the expression level of KDM5A/B/C was positively correlated with the expression of multiple key driver genes such as KRAS, BRCA1, and BRCA2 etc. In addition, PPI network analysis showed KDM5 family proteins have strong interactions with histone deacetylase family 1 (HDAC1), which could modify the lysines of histone H3, and co-act on many pathways, including the "longevity-regulating pathway" and "Notch signaling pathway". Moreover, the upregulation of KDM5A/B/C expression was associated with an increase in the infiltration of B cells, CD8+ T cells and other infiltrating immune lymphocytes and the expression levels of immune molecules such as NT5E and CD274. Interestingly, the overexpression of KDM5A/C was also corelated with reduced sensitivity of pancreatic cancer cells to many kinds of pancreatic cancer-targeting or chemotherapeutic drugs, including axitinib and gemcitabine. Conclusion: KDM5 family members may be prognostic markers and new therapeutic targets for patients with pancreatic cancer.

Both the serum AFP test and AFP/GPC3/SALL4 immunohistochemistry are beneficial for predicting the prognosis of gastric adenocarcinoma.

BACKGROUND: Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared. METHODS: We collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients' clinicopathological characteristics and prognoses. RESULTS: Seventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P < 0.001), perineural spread (P = 0.008), and metastases or recurrence (P < 0.001). For immunohistochemistry, 34 (8.08%) cases were GAPEP, and GAPEP cases also had later pT categories than nGAPEP cases (P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%). CONCLUSION: Both the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.

Investigation of the factors influencing surgical treatment of duodenal gastrointestinal stromal tumors.

BACKGROUND: Duodenal gastrointestinal stromal tumor (DGIST) is a rare tumor with a specific anatomic site and biological characteristics. As the incidence of lymph node metastasis is very low, the main treatment method is surgery. Two main surgical techniques (local resection and Whipple) are performed in patients with DGISTs. The critical question is which surgical technique to choose. AIM: To identify factors influencing the choice of surgery for DGISTs. METHODS: The clinicopathological data of patients with DGISTs who underwent surgery between January 1999 and January 2021 were analyzed. We used the Student's t-test or Mann-Whitney U-test and the χ 2 test or Fisher's exact test to determine the differences between the two groups of patients. Furthermore, we used logistic analysis to identify the relevant factors and independent factors related to the type of surgery. The Kaplan-Meier method was used to analyze the patient's survival information and Cox regression analysis was performed to determine prognostic risk factors. RESULTS: Overall, 86 patients were analyzed, including 43 men (50%) and 43 women (50%). We divided the patients into two groups based on surgical technique (local resection or Whipple surgery). There were no differences in the age, mitotic figures, and complications between the two groups; however, the tumor size, tumor location, risk grade, postoperative hospital stay, and abdominal drainage time were significantly different. Based on univariate logistic analysis, the Whipple procedure was chosen if the tumor size was ≥ 5.0 cm, the tumor was located in the descending part of the duodenum, or the risk grade was medium or high. In our research, the five-year overall survival rate of patients was more than 90%. We also describe two DGIST patients with liver metastases at first diagnosis and analyzed their management in order to provide advice on complicated cases. CONCLUSION: The Whipple procedure was performed if the primary tumor was in the descending part of the duodenum, tumor size was ≥ 5.0 cm, or the tumor risk grade was medium or high.

Disease-Specific Survival of AJCC 8th Stage II Gastric Cancer Patients After D2 Gastrectomy.

The association between the risk factors and long-term prognosis in patients with stage II gastric cancer after radical gastrectomy has been fully revealed. The purpose of this study was to investigate the independent risk factors for treatment failure in stage II gastric cancer. Demographic, clinical, and pathological information of 247 stage II gastric cancer patients who underwent radical D2 gastrectomy in our department between January 2011 and December 2014 were collected and retrospectively analyzed. The relationship between and long-term clinical outcomes of stage II gastric cancer was analyzed using t-tests, chi-square tests, receiver operating characteristic (ROC) analysis, time-dependent ROC analysis, K-M curves, and a Cox regression model. The median follow-up of 247 stage II gastric cancer patients was 5.49 years (range: 0.12-8.62 years). The Kaplan-Meier estimated 3-year and 5-year DSS rates of the study group were 92.7% (95% CI 89.4-95.9) and 88.7% (95% CI 84.7-92.7), respectively. Higher age (>70 vs. ≤70, log-rank p = 0.0406), nerve invasion (positive vs. negative, log-rank p = 0.0133), and non-distal gastrectomy (distal partial gastrectomy vs. other surgical methods, log-rank p = 0.00235) had worse prognoses compared to controls. Univariate and multivariate analyses of disease-specific survival showed that these three factors were independent prognostic factors for patients with stage II disease. The area under time-dependent ROC curve (AUC) is 0.748 of 5-year survival and c-index is 0.696 based on the three-marker model drawn for stage II patients. Subgroup analyses showed an interaction between tumor location and nerve invasion. The age, perineural invasion, and surgical approach are independent prognostic factors for disease-specific survival after radical gastrectomy. Tumor location may be an important confounding factor for outcomes by affecting surgical methods and the hazards of nerve invasion.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.