Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer.

BACKGROUND: The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC. METHODS: This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status. RESULTS: We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules. CONCLUSION: CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Efficacy of nab­paclitaxel vs. Gemcitabine in combination with S­1 for advanced pancreatic cancer: A multicenter phase II randomized trial.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

Tumor Microenvironment Responsive CD8+ T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer.

CD73 plays a critical role in the pathogenesis and immune escape in pancreatic ductal adenocarcinoma (PDAC). AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti-PD-1 therapy, for the treatment of PDAC. Nevertheless, the specific therapeutic efficacy and immunoregulation within the microenvironment of AB680 monotherapy in PDAC have yet to be fully elucidated. In this study, AB680 exhibits a significant effect in augmenting the infiltration of responsive CD8+ T cells and prolongs the survival in both subcutaneous and orthotopic murine PDAC models. In parallel, it also facilitates chemotaxis of myeloid-derived suppressor cells (MDSCs) by tumor-derived CXCL5 in an AMP-dependent manner, which may potentially contribute to enhanced immunosuppression. The concurrent administration of AB680 and PD-1 blockade, rather than gemcitabine, synergistically restrain tumor growth. Notably, gemcitabine weakened the efficacy of AB680, which is dependent on CD8+ T cells. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD-1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC.

Serum Interleukin-6 as a Biomarker for Early Prediction of Post-Operative Infectious Complications After Elective Pancreatectomy.

Background: To investigate whether interleukin (IL)-6 could predict the post-operative complications of elective pancreatectomy early. Patients and Methods: Overall, 122 patients who underwent elective pancreatectomy from June 2020 to May 2021 in our hospital were enrolled. Interleukin-6 was measured on the day before and at six hours after surgery, and on post-operative day one, three, and five. The associations between IL-6 level and post-operative complications were analyzed, and the predictive value of IL-6 for complications was assessed. Results: Sixty-three patients developed post-operative complications. Higher IL-6 was observed in patients with post-operative complications on post-operative day one, post-operative day three, and post-operative day five, with odd ratios of 1.43, 1.68, and 2.54 (p = 0.01, p = 0.01, and p = 0.01), respectively. These trends were also observed in patients with infectious complications preoperatively, on post-operative day one, post-operative day three, and post-operative day five, with ORs of 2.46, 1.95, 2.01, and 2.49 (p = 0.00, 0.00, 0.01, 0.00) respectively. Multivariate regression revealed that IL-6 is the only predictor for infectious complications on post-operative day one (p = 0.016). Based on the optimal cutoffs, pre-operative IL-6, IL-6 on post-operative day one and post-operative day three for predicting infectious complications yielded area under the curve (AUC) of 0.73, 0.70, and 0.70, with high negative predictive value of 82.7%, 92.2%, and of 91.3%, respectively. Conclusions: This study validated the early predictive value of IL-6 on infectious complications after pancreatectomy. Because of the performance of serum IL-6 in predicting infectious complications and high NPV, we endorse that IL-6 could be a potential biomarker for early prediction and antibiotic optimization after pancreatectomy.

The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications.

Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.

Additional adjuvant radiotherapy improves survival at 1 year after surgical treatment for pancreatic cancer patients with T4, N2 disease, positive resection margin, and receiving adjuvant chemotherapy.

Background: While adjuvant chemotherapy has been established as standard practice following radical resection of pancreatic ductal adenocarcinoma (PDAC), the role of adjuvant radiation therapy (RT) and which patients may benefit remains unclear. Methods: This retrospective study included PDAC patients who received pancreatic surgery from April 2012 to December 2019 in Zhongshan Hospital Fudan University. Patients with carcinoma in situ, distant metastasis, and without adjuvant chemotherapy were excluded. Cox proportional hazards modeling of survival were constructed to find potential prognostic factors. Propensity score matching (PSM) and exploratory subgroup analyses were used to create a balanced covariate distribution between groups and to investigate therapeutic effect of radiotherapy in certain subgroups. Results: A total of 399 patients were finally included, 93 of them receiving adjuvant chemoradiotherapy (C+R+) and 306 of them receiving chemotherapy only. Patients in C+R+ group were more likely to be male patients with T3-4 disease. Lymph node metastases was the only negative prognostic factor associated with overall survival (OS). Additional adjuvant RT was not associated with an OS benefit both before and after PSM. Surprisingly, a trend towards improved OS with RT among patients with either T4, N2 disease or R1 resection becomes significant in patients alive more than 1 year after surgery. Conclusion: Adjuvant RT was not associated with an OS benefit across all patients, though did show a possible OS benefit for the subgroup with T4N2 disease or R1 resection at 1 year after surgery.

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. METHODS: Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. RESULTS: The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P =0.002) and CSS (33.0 vs. 27.0 months, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95% CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95% CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. CONCLUSION: Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.

BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting. METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 µm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 µm in CRT. RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: - 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (- 127.6 ± 104.2 µm and - 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (- 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005). CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Circulating cytokines allow for identification of malignant intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF-α, IL-2R, IL-6, and IL-8, then build a novel predictive model to improve the diagnostic accuracy. METHOD: A total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed. RESULT: The circulating levels of TNF-α, IL-2R, IL-6, and IL-8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p < 0.05). Then, a novel score, the circulating cytokine score (CCS), was calculated and demonstrated as an independent predictive indicator with a higher area under the curve (AUC) than each cytokine alone (p < 0.001). Besides the CCS, two high-risk stigmata features, the presence of solid component (PSC), and main pancreatic duct (MPD) dilation ≥10 mm were also demonstrated as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating the CCS and these two high-risk stigmata features presented a remarkable diagnostic performance, both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively. CONCLUSION: The CCS can be considered a novel independent predictive indicator for malignant IPMNs. Additionally, the formulated nomogram model integrating the CCS, PSC, and MPD ≥10 mm can be a valuable and promising tool for predicting the malignant transformation of IPMNs during long-term follow-ups to assist in timely and accurate surgical decisions.

GFAT1 is highly expressed in cancer stem cells of pancreatic cancer.

Background: Cancer stem cells (CSCs) play pivotal roles in the growth, invasion, metastasis, and chemoresistance of pancreatic cancer (PC). The current characterization of CSCs in PC is not complete. Glutamine-fructose-6-phosphate transaminase 1 (GFAT1) is a key enzyme that regulates the hexosamine pathway (HP), in which it not only controls glucose influx but also catalyzes the reaction to form glucosamine 6-phosphate. Recently, it was reported that GFAT1 is highly expressed in PC. However, the relevance of this high expression of GFAT1, especially its association with cancer stemness, has not been well defined and is thus addressed in the current study. Methods: GFAT1 levels were determined in PC from a public database and assessed by bioinformatics tools. GFAT1 expression in CD133+ and CD44+ CSCs in PC was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunostaining on cytospun cells after flow cytometry-based cell sorting. GFAT1+ cells were separated from GFAT1- cells by transfection of PC cell lines with a designed plasmid that expressed red fluorescent protein (RFP) under a GFAT1 promoter. Tumor sphere formation, tumor growth, tumor cell invasion, cell migration, and the resistance to gemcitabine-induced apoptosis were determined in GFAT1+ vs. GFAT1- PC cells. Results: GFAT1 levels were significantly upregulated in PC compared to the adjacent non-PC tissue. There were significantly more GFAT1+ cells in the CD133+ population than in the CD133- population, and similarly, there were significantly more GFAT1+ cells in the CD44+ population than in the CD44- population. Compared to GFAT1- PC cells, GFAT1+ PC cells generated significantly more tumor spheres in culture, appeared to be more invasive and migratory, and were significantly more resistant to gemcitabine-induced cell apoptosis. Conclusions: GFAT1 is highly expressed in CSCs among PC cells and may be crucial for PC growth, metastasis, and chemoresistance.

MR quantitative 3D shape analysis helps to distinguish mucinous cystic neoplasm from serous oligocystic adenoma.

PURPOSE We aimed to assess the performance of quantitative 3D shape analysis in the differential diagno- sis of pancreatic serous oligocystic adenoma (SOA) and mucinous cystic neoplasm (MCN). METHODS Four hundred thirty-two patients diagnosed with serous cystic neoplasms (SCNs) or MCNs were retrospectively reviewed from August 2014 to July 2019 and finally 87 patients with MCNs (n = 45) and SOAs (n = 42) were included. Clinical data and magnetic resonance morphologic fea- tures with 3D shape analysis of lesions (shape sphericity, compacity, and volume) were recorded and compared between MCNs and SOAs according to the pathology. Univariable and multivari- able regression analyses were used to identify independent impact factors for differentiating MCN from SOA. RESULTS The age of MCN patients was younger than SOAs (43.02 ± 10.83 years vs. 52.78 ± 12.31 years; OR = 0.275; 95% CI: 0.098-0.768; P = .014). MCN has a higher female/male ratio than SOA (43/2 vs. 27/15; OR = 40.418; 95% CI: 2.704-604.171; P = .007) and was more often located in the distal of pancreas (OR = 31.403; 95% CI: 2.985-330.342; P = .004). Shape_Sphericity derived from 3D shape analysis was a significant independent factor in the multivariable analysis and the value of MCN was closer to 1 than SOA (OR = 35.153; 95% CI: 5.301-237.585; P < .001). Area under the receiver operating characteristic curve (AUC) of Shape_Sphericity was 0.923 (optimal cutoff value was 0.964876). CONCLUSION Shape_Sphericity in combination with age, sex, and location could help to distinguish MCN from SOA.

Long-Term Follow-Up of Refractory Large Macular Hole with Autologous Neurosensory Retinal Free Flap Transplantation.

Purpose: To evaluate the long-term anatomic and functional outcomes of autologous neurosensory retinal free flap transplantation (ART) for patients with refractory large macular hole (MH). Design: Retrospective interventional case series. Methods: We reviewed 9 patients who underwent ART for their refractory large MH. In this extended follow-up study, postoperative assessment including spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) were recorded at 12, 15, 18, 21, and 24 months after surgery. Results: The macular hole of all patients appeared successfully closed during the whole follow-up period. The mean logMAR BCVA improved from 1.61 ± 0.44 (preoperative) to 0.72 ± 0.30 (12 months after surgery) (p < 0.001). Thereafter, the mean BCVA remained stable at each follow-up. At the mean 16.0 ± 0.8 months postoperatively, inner retinal cystic changes were observed in 4 eyes (44.4%), but these did not significantly affect vision. Conclusion: ART is a good alternative technique for closing large refractory macular holes. Although inner retinal cystic changes were observed in 4 eyes (44.4%), this phenomenon did not significantly affect visual acuity. It provides long-term good anatomical and functional results, especially in cases where insufficient ILM or lens capsule are left.

Prognostic Effect of Age in Resected Pancreatic Cancer Patients: A Propensity Score Matching Analysis.

Background: While the elderly population account for an indispensable proportion in pancreatic ductal adenocarcinoma (PDAC), these patients are underrepresented in clinical trials. Whether surgery offered the same benefit for elderly patients as that for younger cohort and which factors affected long-term outcome of elderly population remained unclear. Aims: This study aims to evaluate long-term prognosis of elderly PDAC patients (≥70 years old) after surgery and to investigate potential prognostic factors. Methods: This retrospective study included PDAC patients receiving radical resection from January 2012 to July 2019 in Zhongshan Hospital Fudan University. Patients were divided into young (<70) and old groups (≥70). Propensity score matching (PSM) was conducted to eliminate the confounding factors. We investigated potential prognostic factors via Cox proportional hazards model and Kaplan-Meier estimator. Nomogram model and forest plot were constructed to illustrate the prognostic value of age. Results: A total of 552 PDAC patients who received radical resection were included in this research. Elderly patients showed poorer nutritional status and were less likely to received adjuvant treatment. After matching, although age [hazard ratio (HR)=1.025, 95%CI 0.997-1.054; p=0.083] was not statistically significant in the multivariate cox regression analysis, further survival analysis showed that patients in the old group had poorer overall survival (OS) when compared with young group (p=0.039). Furthermore, reception of adjuvant chemotherapy (HR=0.411, 95%CI 0.201-0.837; p=0.014) was the only independent prognostic factor among elderly patients and could significantly improve OS. Subgroup analysis indicated that age had better prognostic value in PDAC patients with good preoperative nutritional status and relative low tumor burden. Finally, a prognostic prediction model contained age, reception of adjuvant chemotherapy, American Joint Committee on Cancer (AJCC) 8th T and N stage was constructed and presented in nomogram, whose Harrell's concordance index was 0.7478 (95%CI, 0.6960-0.7996). The calibration curves at 1 and 3 years indicated an optimal conformity between actual and nomogram-predicted survival probability in the PDAC patient who received surgery. Conclusion: The elderly PDAC patients were associated with worse OS survival after radical resection, and the noticeable negative effect of age was observed among PDAC patients with better preoperative nutritional status and less aggressive tumor biology. Adjuvant chemotherapy was essential to improve survival outcome of elderly PDAC patients following radical resection.

Comparison of Choroidal Thickness, Foveal Avascular Zone, and Macular Capillary Density in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Ranibizumab or Aflibercept-A Prospective Study.

This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA). Ten patients were enrolled with macular capillary density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ) measured in both eyes before and after treatment. Final central retinal thickness and BCVA improved significantly (p < 0.05), and densities of SCP and DCP of BRVO sectors were significantly lower at baseline than fellow eye counterparts and remained persistently lower during treatment, particularly in the aflibercept group (p < 0.05). SCP density, DCP density of both BRVO sectors (p = 0.0001, p < 0.0001), and non-BRVO sectors (p < 0.0001, p < 0.0001) were significantly correlated with final BCVA for diseased eyes. Using multivariate general linear model analysis, and including OCTA parameters only, but not all of the available clinical data, DCP density of BRVO sectors in both eyes was the most predictive factor for final visual outcome (probability p < 0.0001). OCTA offered further qualitative and quantitative evaluation of treatment-naïve BRVO. Judging by OCTA parameters, not only in the diseased eye but also in the fellow eye, DCP density of BRVO sectors was the most predictive factor of final visual outcome.

PYCR1: A Potential Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor with an extremely poor prognosis in digestive tumors. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays an important role in tumor development. Therefore, we aimed to explore the effect of PYCR1 on the growth of PDAC cells. Methods: Tumor tissues and adjacent normal pancreatic tissues were collected from 89 patients with PDAC. And immunohistochemistry (IHC) was used to analyze the expression level of PYCR1 in both. RNA interference was used to inhibit the expression of PYCR1 in PANC- 1 and AsPC-1 cells. After infection, the expression of PYCR1 protein was detected by Western blot. The proliferation and growth of PDAC cells were detected by Celigo analysis, MTT, and clone formation assay. Cell apoptosis was analyzed by flow cytometry. Furthermore, the effect of PYCR1 interference on tumor growth was evaluated in vivo through injecting tumor cells subcutaneously into nude mice. Results: The expression of PYCR1 in pancreatic cancer tissues was significantly higher than in paired adjacent normal pancreatic tissues (P <0.01). In vitro, the downregulation of PYCR1 expression significantly inhibited the cell proliferation and colony formation, and increased apoptosis in PANC-1 cells and AsPC-1 cells compared with the shCtrl group (P <0.01). And in vivo, PYCR1 interference also significantly inhibited tumor growth both in the tumor volume and weight. Conclusion: PYCR1 interference was able to inhibit cell proliferation and promote cell apoptosis of pancreatic cancer. The PYCR1 may serve as a potential therapeutic and prognostic biomarker for the treatment of pancreatic cancer.