Nomogram model for predicting early recurrence for resectable pancreatic cancer: A multicenter study.

Pancreatic cancer is a highly aggressive malignancy that is characterized by early metastasis, high recurrence, and therapy resistance. Early recurrence after surgery is one of the important reasons affecting the prognosis of pancreatic cancer. This study aimed to establish an accurate preoperative nomogram model for predicting early recurrence (ER) for resectable pancreatic adenocarcinoma. We retrospectively analyzed patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2011 and December 2020. The training set consisted of 604 patients, while the validation set included 222 patients. Survival was estimated using Kaplan-Meier curves. The factors influencing early recurrence of resectable pancreatic cancer after surgery were investigated, then the predictive model for early recurrence was established, and subsequently the predictive model was validated based on the data of the validation group. The preoperative risk factors for ER included a Charlson age-comorbidity index ≥ 4 (odds ratio [OR]: 0.628), tumor size > 3.0 cm on computed tomography (OR: 0.628), presence of clinical symptoms (OR: 0.515), carbohydrate antigen 19-9 > 181.3 U/mL (OR 0.396), and carcinoembryonic antigen > 6.01 (OR: 0.440). The area under the curve (AUC) of the predictive model in the training group was 0.711 (95% confidence interval: 0.669-0.752), while it reached 0.730 (95% CI: 0.663-0.797) in the validation group. The predictive model may enable the prediction of the risk of postoperative ER in patients with resectable pancreatic ductal adenocarcinoma, thereby optimizing preoperative decision-making for effective treatment.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma.

OBJECTIVE: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. METHODS: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. RESULTS: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. CONCLUSIONS: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Comparison of adjuvant nab-paclitaxel plus gemcitabine, S-1 and gemcitabine chemotherapy for resectable pancreatic cancer: a real-world study.

Background: A survival benefit has been seen for both adjuvant nab-paclitaxel plus gemcitabine (AG) and S-1 chemotherapy compared to gemcitabine (GEM) for resectable pancreatic cancer in the APACT (2019) and JASPAC01 trials (2016), respectively. However, supporting evidence regarding the effectiveness of AG or S-1 compared to gemcitabine in real-world clinical practice remains lacking. Methods: Our study included all 246 pancreatic cancer patients who underwent surgical treatment and received postoperative adjuvant chemotherapy with AG, S-1, or GEM except for those meeting exclusion criteria (R2 resection, neoadjuvant therapy, or synchronous malignancy) at Tianjin Medical University Cancer Institute and Hospital from June 2015 to July 2021. The primary outcome was overall survival (OS) and recurrence-free survival (RFS). Results: In total, 246 patients were included, of whom 54(22%) received adjuvant AG, 103(41%) received adjuvant S-1, and 89(37%) received adjuvant GEM. Adjuvant S-1 was associated with a prolonged OS compared to GEM (median OS S-1 vs GEM: 27.0 vs 20.0 months; HR: 0.65, P = .016) and a significantly prolonged RFS compared to GEM (median RFS S-1 vs GEM: 20.0 vs 8.2 months; HR: 0.58, P = .002). After adjusting for known prognostic factors in multivariate Cox regression analysis, this survival benefit persists and is consistent in most subgroups in our subgroup analysis. However, no statistically significant differences in OS or RFS were seen between patients treated with AG and patients treated with GEM. Conclusions: In this retrospective real-world study, adjuvant S-1 chemotherapy was associated with improved survival compared to GEM while no differences in OS or RFS were observed for AG compared to GEM.

Biological risk based on preoperative serum CA19-9 and histological grade predicts prognosis and improves accuracy of classification in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Carbohydrate antigen (CA) 19-9 and histological grade can serve as indicators of the biological characteristics of pancreatic ductal adenocarcinoma (PDAC). AIMS: The aim of this study was to investigate the combined impact of preoperative CA19-9 levels and histological grade on prognosis and classification accuracy in PDAC patients. METHODS AND RESULTS: A retrospective cohort study was conducted on 612 patients with PDAC who underwent curative pancreatectomy, and a biological risk model based on preoperative CA19-9 levels and histology grade was established. The prognostic importance of the biological risk model was evaluated, and its validity was confirmed through a validation cohort of 218 patients. The survival of patients with PDAC was independently associated with preoperative CA19-9 levels and histology grade, indicating a biological risk. This biological risk was incorporated into the eighth edition of the TNM staging system, leading to the development of a modified TNM (mTNM) staging system. Receiver operating characteristic (ROC) curves demonstrated that the mTNM staging system had a significantly larger area under the curve (AUC) than the TNM staging system. The discriminatory capacity of the mTNM staging system was further validated in an independent cohort. CONCLUSION: Biological risk based on preoperative CA19-9 and histological grade could predict the survival of patients with PDAC. The incorporation of biological risk into the TNM staging system has the potential to enhance the accuracy of patient classification in PDAC, predicting patient survival and enabling the development of individualized treatment plans.

Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma.

PURPOSE: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains. EXPERIMENTAL DESIGN: Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC. Protein expression and their regulation were measured by Western blot and immunoprecipitation analyses. Protein interactions were determined using gain- and loss-of-function assays and molecular methods, including chromatin immunoprecipitation, co-immunoprecipitation, and dual luciferase reporter. RESULTS: There was concomitant overexpression of both GRP78 and HIF-1α in human and mouse PDA tissues and cells. Glucose deprivation increased the expression of GRP78 and HIF-1α, particularly colocalization in nucleus. Induction of HIF-1α expression by glucose deprivation in PDA cells depended on the expression of and its own interaction with GRP78. Mechanistically, increased expression of both HIF-1α and LDHA under glucose deprivation was caused by the direct binding of GRP78 and HIF-1α protein complexes to the promoters of HIF-1α and LDHA genes and transactivation of their transcriptional activity. CONCLUSIONS: Protein complex of GRP78 and HIF-1α directly binds to HIF-1α own promoter and LDHA promoter, enhances the transcription of both HIF-1α and LDHA, whereas glucose deprivation increases GRP78 expression and further enhances HIF-1α and LDHA transcription. Therefore, crosstalk and integration of hypoxia- and hypoglycemia-responsive signaling critically impact PDA metabolic reprogramming and therapeutic resistance.

A new staging system for postoperative prognostication in pancreatic ductal adenocarcinoma.

The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies validating these modifications have yielded inconsistent results. The existing TNM staging system in prognostic prediction remains unsatisfactory. The prognosis of PDAC is closely associated with pathological and biological factors. Herein, we propose a new staging system incorporating distant metastasis, postoperative serum levels of CA19-9 and CEA, tumor size, lymph node metastasis, lymphovascular involvement, and perineural invasion to enhance the accuracy of prognosis assessment. The proposed staging system exhibited a strong correlation with both overall survival and recurrence-free survival, effectively stratifying survival into five distinct tiers. Additionally, it had favorable discrimination and calibration. Thus, the proposed staging system demonstrates superior prognostic performance compared to the TNM staging system, and can serve as a valuable complementary tool to address the limitations of TNM staging in prognostication.

Bi's purse-string suture: an effective method for presacral venous bleeding.

Presacral venous bleeding (PSVB) is an intractable situation during rectal mobilization. Till now, various methods for PSVB are introduced, but each of them has limitations. This article aims to introduce an effective approach for PSVB, which is created by Professor Xiaogang Bi. In the case of PSVB, a purse-string suture which highlighted each stitch penetrates periosteum of sacrum was performed around the bleeding site. After that, the branches of presacral venous plexus around the bleeding site were compressed to the sacrum when the stitches were tightened, the blood flow of the venous branches was blocked by the thread across them, the bleeding was controlled, and then, the knot was tied. From April 24th 2017 to November 6th 2022, ten patients who suffered PSVB during surgery accepted Bi's suture. With Bi's suture, all of the ten cases of PSVB were controlled effectively. Nine of ten cases were controlled immediately only by Bi's suture, one case which accompanied with blood oozing of sacrum wound was controlled by Bi's suture, bone wax, and pelvic gauze packing. Bi's suture is an effective approach for PSVB. It could be easily performed without the need of special materials.

Presence of tumor deposits is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma.

Tumor deposits (TDs) are associated with poor prognosis in several malignancies and have been incorporated into the tumor-node-metastasis (TNM) staging system for colorectal cancer. This study aims to explore the significance of TDs in pancreatic ductal adenocarcinoma (PDAC). All patients who underwent pancreatectomy with a curative intent for PDAC were retrospectively enrolled. Patients were categorized into 2 groups according to the status of TDs: the positive group, in which TDs were present, and the negative group, in which TDs were absent. The prognostic significance of TDs was evaluated. In addition, a modified staging system was developed by incorporating TDs into the eighth edition of the TNM staging system. One hundred nine (17.8%) patients had TDs. Patients with TDs demonstrated significantly lower 5-year overall survival (OS) and recurrence-free survival (RFS) rates than those without TDs (OS: 9.1% vs. 21.5%, P=0.001; RFS: 6.1% vs. 16.7%, P<0.001). Even after matching, patients with TDs still had significantly worse OS and RFS than those without TDs. In the multivariate analysis, the presence of TDs was an independent prognostic factor in patients with PDAC. The survival of patients with TDs was similar to that of patients with N2 stage disease. The modified staging system had a greater Harrell's C-index than the TNM staging system, which indicates better performance in predicting survival. The presence of TDs was an independent prognostic factor for PDAC. Categorizing patients with TDs into N2 stage improved the accuracy of the TNM staging system in predicting prognosis.

Prognostic nutritional score based on pretreatment lymphocyte, platelet, and prealbumin predicts prognosis in patients with pancreatic cancer.

BACKGROUND AND OBJECTIVES: Pretreatment immunological indicators and nutritional factors are associated with survival of many malignancies. This study aims to develop a prognostic nutritional score based on a combination of pretreatment lymphocyte, platelet, and prealbumin (Co-LPPa) in patients with pancreatic cancer (PC) and to investigate the prognostic significance of this score. METHODS: Patients who underwent pancreatectomy with a curative intent for PC were retrospectively enrolled. A pretreatment prognostic score was established by immunological indicators and nutritional factors that were independently associated with survival. RESULTS: Pretreatment lymphocyte (<1.6 × 109 /L), platelet (<160 × 109 /L) and prealbumin (<0.23 g/L) were independently associated with poorer overall survival (OS) and recurrence-free survival (RFS), and were used to create the Co-LPPa score. The Co-LPPa scores were inversely related to OS and RFS, and were able to stratify survival into four groups. The survival differences among the four groups were all significant. Besides, the Co-LPPa scores could stratify survival independently of pathological prognostic factors. The Co-LPPa score was superior to prognostic nutritional index and carbohydrate antigen 19-9 in predicting OS and RFS. CONCLUSION: The Co-LPPa score could accurately predict the prognosis of PC patients who underwent curative resection. The score may be helpful for preoperative therapeutic strategies.