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Background: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). Methods: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. Results: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien–Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256–20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059–0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). Conclusions: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications. [ABSTRACT FROM AUTHOR]

Purpose: Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [68 Ga]Ga–FAPI-04 and [18F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images. Methods: Patients with suspected localized PDAC on CE-CT were recruited for static [68 Ga]Ga-FAPI-04 and 18[F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic 68 Ga-FAPI-04 PET/CT. The diagnostic and staging performances of the static PET/CT results were evaluated by delineating regions of interest in the primary tumor, whole pancreas, and distal pancreas in both types of scans and then evaluating correlations between the PET/CT findings and clinicopathological characteristics. Furthermore, Kaplan–Meier and hazard ratio (log-rank) methods were used to evaluate the prognostic value of the combined dynamic [68 Ga]Ga-FAPI-04 and static [18F]F-FDG PET/CT method. Results: We included 49 patients with histologically confirmed PDAC adenocarcinomas; 32 underwent 60-min dynamic [68 Ga]Ga-FAPI-04 PET/CT imaging simultaneously. The static [68 Ga]Ga-FAPI-04 method had significantly higher accuracy and uptake values than the static [18F]F-FDG method for primary PDAC lesions, metastatic lymph nodes, and distal metastases. Furthermore, 18.4% and 10.2% of the patients' stages changed after using the [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT methodologies, respectively, compared to the CE-CT-designated stage. The Ki values obtained from dynamic [68 Ga]Ga-FAPI-04 PET/CT did not differ between PDAC and distal obstructive pancreatitis lesions. Pathologically enlarged tumor size, poor differentiation, and perineural invasion were associated with increased [68 Ga]Ga-FAPI-04 uptake but not with [18F]F-FDG uptake. The preoperative prognostic performance of [68 Ga]Ga-FAPI-04 was better than that of [18F]F-FDG. Interestingly, combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG uptake results in the whole pancreas could further stratify patients based on their postoperative prognosis. Conclusion: 6[68 Ga]Ga-FAPI-04 PET/CT was more sensitive and accurate than [18F]F-FDG PET/CT for tumor, node, and metastasis staging of PDAC identified on CE-CT. Additionally, [68 Ga]Ga-FAPI-04 uptake was significantly associated with pathologically aggressive tumor features. Combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT findings improved the prognostic value, potentially providing a non-invasive guide for clinical management. Finally, increased fibroblast activity in PDAC-induced obstructive pancreatitis may be associated with poor patient survival rates. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to assess the prognostic value of [68 Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC). Methods: We retrospectively analyzed treatment‐naïve PDAC patients who underwent preoperative [68 Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUVmax), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUVmax), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [68 Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan–Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [68 Ga]Ga-FAPI-04 PET/CT and clinicopathological factors. Results: Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUVmax and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUVmax or TLF and pancreatic TSUVmax or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUVmax had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [68 Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05). Conclusion: The in vivo [68 Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [68 Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the preoperative factors predicting the surgical difficulty of robotic distal pancreatectomy (RDP). This study aims to explore such factors and provide guidance on the selection of suitable patients to aid surgeons lacking extensive experience in RDP. Methods: A retrospective study was conducted on consecutive patients who underwent RDP to identify preoperative factors predicting surgical difficulty. High surgical difficulty was defined by both operation time and intraoperative estimated blood loss exceeding their median, or by conversion to laparotomy. Results: A total of 161 patients were ultimately enrolled, including 51 patients with high levels of surgical difficulty. Multivariate analysis revealed that male sex [OR (95% CI): 4.07 (1.77,9.40), p = 0.001], body mass index (BMI) ≥ 25 kg/m2 OR (95% CI): 2.27 (1.03,5.00), p = 0.042], tumors located at the neck of the pancreas [OR (95% CI): 4.15 (1.49,11.56), p = 0.006] and splenic artery type B [OR (95% CI): 3.28 (1.09,9.91), p = 0.035] were independent risk factors for surgical difficulty. Regarding postoperative complications, high surgical difficulty was associated with the risk of overall complications and pancreatic fistula (grade B/C) (49.0% vs. 22.7%, p < 0.001; 39.2% vs. 19.1%, p = 0.006). Conclusion: Male sex, body mass index ≥ 25 kg/m2, tumor located at the neck of the pancreas and splenic artery type B are associated with a high RDP difficulty level. These factors can be used preoperatively to assess the difficulty level of surgery, to help surgeons choose patients suitable for them and ensure surgical safety. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is an inflammatory malignancy, and tumor-associated macrophages (TAMs) are the predominant inflammatory cells in tumor tissue. TAMs have complicated interactions with pancreatic cancer cells, however, the details and mechanisms remain largely unknown. In this study, transcriptomics and proteomics analyses were performed to explore the interactions between murine pancreatic cancer cells and TAMs. Dopamine (DA) has been reported to suppress inflammations. However, its roles in TAMs of pancreatic cancer have not been reported. Herein, the roles and mechanisms of DA to affect the chemotherapeutic efficacy for pancreatic cancer were studied. Multi-omics results revealed that there was a tumor-promoting vicious cycle involving murine pancreatic cancer cells and TAMs. DA substantially improved the chemotherapeutic efficacy both in vitro study and in immunocompetent murine pancreatic cancer models by suppression of the M2 characters of TAMs. Further studies found that activation of DRD4 by DA led to the decrease of cAMP, and then inhibited the activation of PKA/p38 signal pathway, which suppressed the tumor-promoting inflammation of TAMs. This study uncovers the reciprocal interactions between TAMs and pancreatic cancer cells using multi-omics techniques and presents that DA has synergistic roles with chemotherapy for pancreatic cancer by suppressing of TAM-derived inflammations. [ABSTRACT FROM AUTHOR]

Purpose: The insufficient clearance of regional lymph nodes and unsatisfactory R0 resection rate may result in the metastasis of left-sided pancreatic ductal adenocarcinoma (PDAC) after conventional distal pancreatosplenectomy (CDPS). Radical antegrade modular pancreatosplenectomy (RAMPS) was designed to achieve R0 resection more successfully with better lymph-node clearance; however, there is still insufficient evidence of its short- and long-term results to confirm its superiority. We conducted this study to compare the efficiency of these two procedures. Methods: The subjects of this retrospective analysis were 103 patients with left-sided PDAC who underwent either RAMPS (n = 46) or CDPS (n = 57). We assessed perioperative data and surgical information and used univariate and multivariate analyses to identify prognostic factors for survival. Results: There were no significant differences in baseline data between the groups. RAMPS was associated with a significantly shorter hospital stay (12.11 days vs. 22.98 days; P < 0.001), and significantly less blood loss (451.09 ml vs. 764.04 ml, P = 0.002), as well as a significantly lower rate of blood transfusion (15.22% vs. 33.33%, P = 0.035). RAMPS and CDPS had comparable perioperative complication rates. Moreover, RAMPS achieved more effective lymph-node retrieval (17.87 vs. 10.23; P < 0.001). The RAMPS group had a higher overall survival (OS) rate (28.73 months vs. 18.30 months; P = 0.003) and a higher disease-free survival (DFS) rate (21.97 months vs. 9.40 months; P < 0.001). Conclusion: RAMPS achieved better survival and surgical outcomes than CDPS for patients with left-sided PDAC. [ABSTRACT FROM AUTHOR]

The interactions between tumor immune microenvironment (TIME) and pancreatic cancer cells can affect chemotherapeutic efficacy; however, the mechanisms still remain largely unknown. Thirty items in TIME were comprehensively screened by using tissue microarray from pancreatic cancer patients. Their expressions, interconnections and predictive roles for survival were analyzed. Twenty-one of 30 items could stratify the survival of the patients; however, multivariate analysis found that only 5 independent risk factors could predict worse survival (M2-polarized tumor-associated macrophages (TAMs), IgG4 positive cells, TGF-β1, GM-CSF and lymphangiogenesis). They had a much higher expression levels in tumoral tissue, compared to peritumoral tissue. The Spearman analysis showed that M2-polarized TAM, TGF-β1 and GM-CSF were positively correlated with pancreatic cancer stem cells (PCSC), angiogenesis and lymphangiogenesis. Both human and murine pancreatic cancer cells could induce M2-polarized TAM, which showed substantial roles to decease chemotherapeutic effects. After treated by gemcitabine, both human and murine pancreatic cancer cell lines expressed higher level of immune check points, PCSC markers and varieties of immunosuppressive factors; however, TGF-β1 and GM-CSF had the highest increase. Based on the above results, TGF-β1 and GM-CSF were proposed to be the optimal potential targets to improve chemotherapeutic effects. In immunocompetent murine models, we demonstrated that combined blockade of TGF-β1 and GM-CSF improved the chemotherapeutic effects by inhibition of M2-polarized TAM and induction of CD8 positive T cells. This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples ( P = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade ( P = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis ( P = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells. [ABSTRACT FROM AUTHOR]