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RESUMEN Antecedentes: la duodenopancreatectomía cefálica (DPC) con resección vascular venosa está indicada para el tratamiento del adenocarcinoma ductal y de tumores neuroendocrinos de páncreas, tanto por laparoscopia como por laparotomía. Objetivo: describir los resultados de una serie de pacientes operados de DPC con resección vascular venosa y comparar la morbimortalidad entre los abordados por laparoscopia y por laparotomía. Material y métodos: se realizó un estudio observacional, comparativo, retrospectivo de pacientes con DPC con resección vascular entre enero de 2022 y agosto de 2023. El abordaje laparoscópico fue determinado en menores de 80 años, invasión venosa tumoral igual a 180° o menor en la tomografía, buen performance status, y no haber realizado tratamiento neoadyuvante. Resultados: fueron realizadas 23 DPC con resección vascular venosa: 11 por laparoscopia y 12 por laparotomía. Las 11 realizadas por laparoscopia fueron resecciones laterales, y, en los 12 abordados por laparotomía, se realizó resección total de vena porta en 5 y en el resto, resección lateral. El tiempo de "clampeo" (pinzamiento) portal y la necesidad de transfusiones fue similar en ambos grupos. El estudio patológico reveló R0 en el 78,2% de los pacientes e invasión venosa en el 40.9%. La morbilidad con laparoscopia y con laparotomía consistió, respectivamente, en: fístula pancreática en 7 (4 y 3), vaciamiento gástrico retardado en 4 (1 y 4), fístula biliar en uno (1 y 0), neumonía en dos (1 y 1) e infección de herida en uno (0 y 1). La mortalidad fue de 8,6% por el fallecimiento de dos pacientes, uno en cada grupo. Conclusión: de acuerdo con los criterios empleados, la morbimortalidad de la DPC con resección vascular fue similar por laparoscopia y por laparotomía.
ABSTRACT Background: Cephalic pancreaticoduodenectomy (CPD) with venous resection is indicated for the treatment of ductal adenocarcinoma and neuroendocrine tumors of the pancreas, either through laparoscopy or laparotomy. Objective: The aim of this study was to describe the results of a series of patients undergoing CPD with venous vascular resection and compare morbidity and mortality between the laparoscopic approach and open surgery. Material and methods: We conducted a retrospective, comparative and observational study of patients who underwent CPD with venous vascular resection between January 2022 and July 2023. Criteria for laparoscopic surgery were age < 80 years, interface between tumor and vein of 180° of the circumference of the vessel wall or less on computed tomography, good performance status, and no previous neoadjuvant treatment. Results: A total of 23 CPD procedures with venous vascular resection were performed: 11 by laparoscopy and 12 by laparotomy. The 11 laparoscopic procedures were lateral resections, and in the 12 patients approached by laparotomy, 5 were total portal vein resections and 7 were lateral resections. Portal vein clamping time and need for transfusion was similar in both groups. The pathological examination reported R0 resections in 78.2% and venous invasion in 40.9%. The complications associated with laparoscopy and laparotomy were pancreatic fistula in 4 and 3 patients, respectively, delayed gastric emptying in 1 and 4 patients, respectively, biliary fistula in 1 and 0 patients, respectively, aspiration pneumonia i 1 and 1 patients, respectively and surgical site infection in 0 and 1 patients, respectively. Mortality was 8.6% (n =2), one in each group. Conclusion: According to the criteria used, the morbidity and mortality of CPD with vascular resection were similar for laparoscopy and laparotomy.
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Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.
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Objective To study the effect of carboxyamidotriazole-orotate(CTO)on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells.Methods Human pancreatic cancer cell lines AsPC-1,AsPC-1/GEM(AR),PANC-1 and MiaPaCa-2 were used as the study subjects;cell survival rate was detected by sulfo-nylrhodamine B(SRB);the mRNA level of key genes for fatty acid synthesis was detected by qPCR;the protein level of the AMPK/ACC pathway was detected by Western blot;intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS).Results Comparing to control group,CTO significantly de-creased the cell viability of AsPC-1,AR,PANC-1,and MiaPaCa-2(P＜0.05).CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05).CTO significantly reduced the protein expression of AMPK,ACC and c-Myc(P＜0.05),while increasing the protein expression of p-AMPK and p-ACC(P＜0.05).CTO decreased lipid metabolite content in AR cells(P＜0.05).Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway,down-regulates the expression of fatty acid synthesis-related genes,and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1,AR,PANC-1 and MiaPaCa-2.
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Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.
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Objective To study the expression of kynureninase(KYNU)in pancreatic cancer tissue and its relationship with immune invasion and prognosis.Methods A total of 49 patients with resectable pancreatic cancer who underwent surgical treatment in Department of General Surgery,Wuxi Fifth People's Hospital from January 2019 to June 2021 were selected as the study subjects.All patients were diagnosed with resectable pancreatic cancer by pathology and imaging,and their TNM stagings of tumors were stages Ⅰ-Ⅲ,which received neoadjuvant therapy before surgery.Cancer tissue and corresponding paracancer tissue samples(≥4cm from the cancer focus)of all patients were collected.Immunohistochemical staining was used to detect the expression of KYNU protein in pancreatic cancer tissues and corresponding adjacent tissues,and the infiltration of CD8+TILs,CD103+TILs,CD68+TAMs,CD204+TAMs,and CD11c+DCs in cancer tissues.Real-time fluorescence quantitative PCR was used to detect the relative expression of KYNU mRNA.The relationship between KYNU mRNA expression and immune infiltration and prognosis was analyzed by Pearson correlation analysis,Kaplan Meier survival curve,and COX proportional hazards regression model.Results The positive rate of KYNU protein(77.6%)and mRNA expression(2.9±0.7)in pancreatic cancer tissues were higher than those in adjacent normal tissues(38.8%,0.8±0.5),and the differences were significant(χ2=15.138,t=17.088,all P<0.05).The infiltration number of CD8+TILs,CD103+TILs,CD68+TAMs,CD204+TAMs and CD11c+DCs in KYNU high expression group was higher than those in KYNU low expression group,and the differences were significant(t=2.533～5.806,all P<0.05).The expression of KYNU in pancreatic cancer was positively correlated with the invasion numbers of CD8+TILs,CD103+TILs,CD68+TAMs,CD204+TAMs and CD11c+DCs(r=0.514,0.502,0.319,0.415,0.438,all P<0.05).The cumulative OS and DFS of high KYNU expression group were lower than those of low KYNU expression group(20.0%vs 42.9%,14.3%vs 35.7%),and the differences were significant(Log Rank χ2=4.358,4.273,P = 0.039,0.042).Multivariate COX regression analysis showed that TNM stageⅢ(HR:1.653,95%CI:1.294～1.937),low differentiation(HR:1.671,95%CI:1.284～2.003),lymph node metastasis(HR:1.582,95%CI:1.117～1.896)and KYNU high expression(HR:1.591,95%CI:1.106～1.902)were independent risk factors for pancreatic cancer prognosis(all P<0.05).Conclusion KYNU was highly expressed in pancreatic cancer tissues,which was closely related to immune infiltration and clinical prognosis of pancreatic cancer.It may be a potential biomarker for predicting prognosis of pancreatic cancer.
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Objective To explore the role of long non-coding RNA smad7(Linc-smad7)in invasion and migration of pancreatic cancer(PC)cells and its mechanisms.Methods The expression level of Linc-smad7 in PC tissues and cell lines was detected by qRT-PCR assays.Transwell assays were performed to observe the effect of Linc-smad7 overexpression on the migration and invasion abilities of PaCa-2 cells.Luciferase reporter analysis was made to detect the direct binding effect of Linc-smad7 on miR-125b and miR-125b on Sirtuin1(SIRT1).qRT-PCR assays were used to detect the regulatory effect of Linc-smad7 on miR-125b expression in PaCa-2 cells.qRT-PCR and Western blotting assays were used to detect the regulatory effect of miR-125b on SIRT1 expression.Results Linc-smad7 was significantly increased in PC tissues and cell lines.Paca-2 cells with overexpressed Linc-smad7 showed higher migration and invasion abilities,while miR-125b expression was decreased.After the expression of miR-125b was increased,the expression of SIRT1 was decreased significantly.Luciferase reporter assays results suggested that Linc-smad7 directly targeted with miR-125b,and miR-125b directly bound with SIRT1.Increased Linc-Smad7 or decreased miR-125b could reverse the effect of SIRT1 inhibition on invasion and migration of PaCa-2 cells.Conclusion Linc-smad7 promotes invasion and migration of PaCa-2 cells through miR-125b/SIRT1 axis.
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Objective:To construct pancreatic cancer cell lines expressing luciferase and mesothelin (MSLN), and evaluate the feasibility of using them as target cells in analyzing the cytotoxicity activity of immune cells.Methods:Lentiviral vectors expressing luciferase and MSLN genes were constructed, and pancreatic cancer cell lines were infected after lentivirus packaging. Single-cell clones were obtained by limited dilution following antibiotic screening, and the stable expression of the target genes were verified. These cells were used as target cells to detect the cytotoxicity of immune cells by real-time cell analysis (RTCA) and luciferase activity. Besides, these luciferase-expressing cells were transplanted into B-NDG mice to establish the animal models of pancreatic cancer, and in vivo optical imaging technology was used to detect the expression of luciferase and monitor the tumor growth in mice. The cytotoxicity of chimeric antigen receptor T (CAR-T) cells was verified in these animal models. Results:Three pancreatic cancer cell lines, panc-1-luc, panc-1-luc-MSLN and capan-2-luc, that could stably express luciferase and MSLN genes were successfully constructed. The expression of the reporter gene in these cells were high, and positively correlated with the number of cells. There were 95.6% of panc-1-luc-MSLN cells expressing MSLN. MSLN-CAR-T cells had specific killing effect on MSLN-positive panc-1-luc-MSLN cells and capan-2-luc cells, with the minimum killing rates of (70.00±18.19)% and (57.00±5.29)%, respectively. But they had no cytotoxicity to MSLN-negative panc-1-luc cells. RTCA results showed that MSLN-CAR-T cells were able to lyse all three pancreatic cancer cell lines, and the minimum killing rates were (56.33±7.64)%, (93.00±2.65)% and (26.33±28.15)%, respectively. The killing of target cells by NK-92MI cells was not depended on MSLN expression. The cytotoxicity in the mice models of pancreatic cancer was consistent with the results in vitro. The in vivo and in vitro test results suggested that the expression of luciferase by target cells could reflect the cytotoxicity of immune cells. Conclusions:This study establishes three pancreatic cancer cell lines stably expressing luciferase, which can be used to evaluate the cytotoxicity of immunotherapy products targeting tumor cells in vitro and in vivo.
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Objective To investigate the short-term efficacy of celiac plexus block combined with the interstitial permanent implantation of 125I seeds in the treatment of advanced pancreatic cancer (inoperable locally advanced and metastatic pancreatic cancers). Methods A total of 100 patients with advanced pancreatic cancer were selected and treated with celiac plexus block combined with the interstitial permanent implantation of 125I seeds under CT guidance. Pain relief and changes in the tumor marker CA19-9 were assessed on the seventh day, the first and third months after surgery. In the third month after surgery, tumor size was assessed by CT. Results Among the 100 patients with advanced pancreatic cancer, complete response (CR) was found in 12 cases, partial response (PR) in 78 cases, stable disease in five cases, and progression of disease in five cases three months after surgery. The CA19-9 level and the sum of short and long tumor diameters were significantly decreased (both P<0.01). A total of 100 patients had severe pain before treatment (visual analogue scale (VAS)): 7–10 points), 59 patients reported pain disappearance (VAS: 0 points), 35 patients had mild pain (VAS: 1–3 points), and six patients experienced moderate pain (VAS: 4–6 points) in the third month after treatment. The pain relief rate was 100%. Conclusion Celiac plexus block combined with the interstitial permanent implantation of 125I seeds has good short-term efficacy and can effectively improve short-term pain in patients with advanced pancreatic cancer.
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Introduction: Pancreatic cancer often recurs as local recurrence or peritoneal dissemination, causing severe abdominal and back pain. We report a case of postoperative skull metastasis of pancreatic cancer that caused headache and was treated effectively with radiotherapy. Case: A 67-year-old woman underwent surgery for pancreatic cancer. She had epigastric pain due to local recurrence and peritoneal dissemination, which was controlled with loxoprofen and fentanyl transdermal patch. She had right-sided headache, which gradually increased in intensity, but lacked intracranial hypertension and focal neurological symptoms. Acetaminophen and Goreisan did not provide adequate pain relief. Although CT showed no brain or bone metastasis, MRI showed metastasis in the right frontal bone. Palliative radiotherapy was administered. Subsequently, headache decreased from 7–8/10 to 2–3/10 on the Numerical Rating Scale. Conclusion: Skull metastases in cancer patients may be diagnosed using MRI, even when they remain undetectable by CT.
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Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
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Humans , Glycosylation , Pancreatic Neoplasms/pathology , Adenocarcinoma , Proto-Oncogene Proteins p21(ras)/metabolism , Glycoproteins , Mass Spectrometry , Biomarkers/metabolism , PolysaccharidesABSTRACT
Objective:To analyze the safety and therapeutic efficacy of laparoscopic pancreaticoduodenectomy (LPD) and laparoscopic total pancreatectomy (LTP) in the treatment of pancreatic cancer.Methods:Clinical data of 87 patients with pancreatic head and neck cancer who underwent LPD or LTP in the Department of General Surgery at Peking Union Medical College Hospital from December 2018 to August 2023 were retrospectively analyzed. The surgical approach, operative time, intraoperative blood loss volume, conversion rate to open surgery, perioperative mortality, re-operative rate, rate of major postoperative complications, postoperative hospital stay, number of lymph nodes harvested, tumor pathological stage, R 0 resection rate, initiation of postoperative chemotherapy and survival outcomes were recorded. The follow-up period extended until September 2023. Results:Among the 87 patients, 78(89.7%) underwent LPD and 9(10.3%) underwent LTP. PV-SMV vascular resection and reconstruction was performed in 16 cases (18.4%), and 11 cases totally underwent laparoscopy. Five cases (5.7%) required conversion to open surgery. The mean operative time was 279.8±74.0 minutes, and the mean intraoperative blood loss volume was 520.1±743.2 ml. The overall length of hospital stay was 15.9±6.3 days, with a mean postoperative hospital stay of 11.5±6.0 days. The rate of major postoperative complications was 19.5%, including 4 cases (4.6%) of postoperative bile leakage, 6 cases (6.9%) of postoperative gastric emptying disorders, and 3 cases (3.4%) of postoperative bleeding. There was one case (1.1%) with secondary surgery and one case (1.1%) with perioperative death. Among LPD patients, 5 cases (6.4%) had postoperative grade B or higher pancreatic fistula. Advanced age (≥70 years) did not increase the incidence of perioperative complications. All patients achieved R 0 resection. The mean number of lymph nodes harvested was 25.9±11.4. The median time to initiation of postoperative chemotherapy was 2.13±1.43 months. The median overall survival was 16 months. Conclusions:In a high-volume center for pancreatic diseases, LPD and LTP are safe and feasible for the treatment of pancreatic cancer, which could achieve satisfactory anti-tumor efficacy and improve patients' prognosis.
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Objective To explore the effect and potential mechanisms of melatonin combined with gemcitabine on the chemosensitivity of human pancreatic cancer cell line PANC-1.Methods Human pancreatic cancer cell line PANC-1 was trea-ted with gemcitabine alone or in combination with melatonin.Cell viability was assessed using CCK-8.Effect of melatonin and gem-citabine alone or in combination on the clonogenic capacity of PANC-1 cells were observed through colony formation experiments.Scratch assays and transwell experiments were conducted to evaluate cell migration ability.Reactive oxygen species(ROS)and mitochondrial membrane point JC-1 assay kit were used to determine reactive oxygen species synthesis and membrane potential levels.Intracellular Fe2+level was measured using ferrous ion fluorescent probe.The protein expression levels of LC3,P62,GPX4 and SLC7A11 in different treatment groups were detected by immunofluorescence and Western blotting.Results CCK-8 results showed that the viability of PANC-1 cells was inhibited by gemcitabine alone after 48 h and 72 h of treatment in a time-and dose-dependent manner.The cell viability of gemcitabine combined with melatonin group was significantly lower than that of gemcitabine group,and the cell viability decreased with the increase of melatonin concentration.Scratch assays,transwell experiments,and plate colony formation assay results demonstrated that the proliferation and migration of cells in the gemcitabine combined with the me-latonin group were significantly inhibited compared with the gemcitabine group.The levels of reactive oxygen species and Fe2+in PANC-1 in gemcitabine combined with the melatonin group were higher than those in the gemcitabine group,and the mitochondri-al membrane potential was significantly decreased(P＜0.01).Western blotting and immunofluorescence results showed that the ra-tio of autophagy-related protein LC3-Ⅱ/LC3-Ⅰ in gemcitabine combined with the melatonin group was lower than that in the gem-citabine group,and the expression of P62 was up-regulated,and the expression of anti-iron death-related protein GPX4 and SLC7A11 was significantly inhibited(P＜0.05),suggesting that melatonin combined with gemcitabine can inhibit autophagy and promote ferroptosis in PANC-1 cells.Conclusion Melatonin enhances the chemosensitivity of pancreatic cancer cell PANC-1 to gemcitabine by inhibiting autophagy and promoting ferroptosis of tumor cells.
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Pancreatic cancer is a highly malignant digestive tract tumor with hidden symptoms,limited treatment options and rapid progression.With an increasing incidence rate year by year,pancreatic cancer has increasingly become a prominent issue endangering public health,causing a huge social burden.Although there was no significant improvement in survival rates for pancreatic cancer patients in the past two decades,recent progress in epidemiology,basic research and clinical research of pancreatic cancer has accelerated significantly compared to the past.Some findings have already enabled a small proportion of pancreatic cancer patients to achieve better survival.This article provided a review of the significant progress made in research,diagnosis and treatment of pancreatic cancer in 2023.
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Objective To establish an orthotopic transplantation tumor model of pancreatic cancer derived from transgenic LSL-KrasG12D/+ LSL-Trp53R172H/+ Pdx1-Cre(KPC)mice.To provide a stable and reliable drug preclinical research animal model to study the developmental mechanism and treatment strategies of pancreatic cancer.Methods Tumor tissue derived from KPC transgenic mice with spontaneous pancreatic cancer was transplanted into the C57BL/6J mouse pancreas.Ultrasound was used to monitor tumor growth.HE and immunofluorescence staining was used to evaluate the pathological characteristics of this model.Results The tumor derived from KPC mice grew steadily on the pancreas of C57BL/6J mice.Tumor cell proliferation index Ki67,matrix fibrosis marker αSMA,and immune cell markers CD45 and CD206 were all stably expressed in the tumor.The model stably retained the pathological features of primary pancreatic cancer.Widespread tumor metastases,which were similar to those observed in patients with pancreatic cancer,developed in this model.Conclusions An orthotopic transplantation model derived from a transgenic mouse with spontaneous pancreatic cancer was established successfully.The model simulates the stromal environment and immune cell infiltration of pancreatic cancer and retains strong stability and uniformity with the original tumor.It can be used as an effective drug preclinical research model to study pancreatic cancer progression and treatment strategies.
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Objective To screen long non-coding RNA(lncRNA)associated with disulfidptosis and investigate the immune landscape between lncRNA and pancreatic cancer,for effective guidance in clinical practice.Methods The normal and pancreatic cancer tissue samples were obtained from The Cancer Genome Atlas database,and the lncRNA associated with disulfidptosis was identified based on the Cox and LASSO regression analyses.A risk prognosis model was constructed,and its predictive performance was verified using comprehensive methods.An accurate nomogram was construted to predict the prognosis of patients with pancreatic cancer.The biological differences were analyzed via Gene Ontology,Gene Set Enrichment Analysis,and an immunoassay.The immunotherapy response was estimated using the tumor mutational burden(TMB)score.Results A total of 251 disulfidptosis-related lncRNAs were successfully identified,and three groups of lncRNAs were selected as the reference for the risk model.Pathway analysis showed that immune-related pathways were associated with disulfidptosis-related lncRNA risk models.The risk score was significantly correlated with immune cell infiltration and the ESTIMATE score.Patients with higher risk scores had elevated TMB,indicating that high-risk patients exhibited a better immune checkpoint blockade response.Conclusion The findings of this study contribute to a deeper understanding of disulfidpto-sis-related lncRNA and provide a potential therapeutic strategy for pancreatic cancer.
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Objective To calculate the absorbed dose of 90Y TheraSphere in the pancreas and the surrounding sensitive organs after the administration in the treatment of pancreatic cancer through the establishment of an individual voxel model, and to provide technical support for the clinical application of 90Y TheraSphere in the treatment of pancreatic cancer. Methods An individualized voxel model was constructed in Geant4 software based on the CT images of the patient. 12 monoenergetic electron specific absorption fractions (SAFs) in the range of 0.01 to 1 MeV were calculated and validated against the ICRP data. The model and method were used to calculate the absorbed doses in the target organs under uniform and nonuniform distribution of 90Y microspheres in the pancreas. Results The relative errors between the SAF values calculated based on the individualized voxel model and the ICRP data after mass calibration were less than 3.89%. When 90Y was uniformly distributed in the pancreas, the absorbed dose in the pancreas was 4.69 × 10−7 Gy/Bq; the absorbed doses in the liver, kidneys, and spleen were 6.15 × 10−12, 6 × 10−12, and 1.65 × 10−11 Gy/Bq, respectively. When 90Y was distributed within the tumor, the absorbed dose in the tumor was 6.69 × 10−6 Gy/Bq and the absorbed dose in normal pancreas was 5.72 × 10−8 Gy/Bq. The fitted relationship between tumor volume V and administered activity A at the prescribed dose of 120 Gy was quadratic, with relatively low activity required for concentrated administration in the center of the tumor. Conclusion The Monte Carlo dose calculation method based on individual voxel model accurately predicted the absorbed doses in the surrounding sensitive organs (liver, kidneys, and spleen) when 90Y TheraSphere was used to treat pancreatic cancer. These results and the analysis of the factors affecting the drug delivery activity will provide data support for the clinical research of 90Y TheraSphere in pancreatic cancer.
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Objective To evaluate the effects of radioactive impurity nuclides in 90Y glass microsphere on therapeutic dose during radioembolization of pancreatic cancer. To provide a reference for correction of the dose calculated for individuals with different pancreatic tumors. Methods In this study, the radioactive impurity nuclide composition of 90Y glass microsphere samples was analyzed to determine the source term of Monte Carlo calculation. Then, according to the PET/CT medical imaging data of pancreatic cancer patients, the three-dimensional modeling software Solidworks 2020 was used to construct the real and personalized digital human digestive system model of pancreatic cancer patients at a resolution showing the vascular distribution in pancreas and tumor. Finally, the Monte Carlo program GATE 8.2 was used to simulate the three-dimensional radiation dose fields of radioactive impurity nuclides 91Y and 65Zn from 90Y glass microspheres in various tissues and organs. The three-dimensional dose fields were visualized to analyze the influence of radioactive impurity nuclides on therapeutic dose. Results The three-dimensional radiation dose fields of 91Y and 65Zn from 90Y glass microspheres demonstrated two dose extreme points. The maximum dose value of 91Y to tissue was 0.272 mGy and the maximum dose value of 65Zn to tissue was 9.34 μGy, with average statistical errors of less than 3.2%. Conclusion The impact of radioactive impurity nuclides 91Y and 65Zn in 90Y glass microsphere sample on therapeutic dose is minimal and can be neglected.
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Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.
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Objective To systematically evaluate the diversity of oral flora in patients with pancreatic cancer. Methods A cross-sectional study was conducted, focusing on the oral flora diversity profiles of patients with pancreatic cancer. The studies were retrieved from PubMed, Web of science, EMbase, The Cochrane Library, CBM, CNKI, Wanfang, and VIP databases, and the search period was from the establishment of the database to July 15, 2023. According to the inclusion and exclusion criteria, two researchers screened intensive review literature, extracted data and information, and carried out Meta-analysis using qualitative systematic review and Review Manager 5.4. Results Seven cross-sectional studies were reviewed, including 187 patients with pancreatic cancer and 440 healthy controls. The results of meta-analysis showed that the oral microbiota diversity Simpson index of patients with pancreatic cancer was reduced compared with that of healthy controls. Qualitative analysis showed that the relative abundance of Firmicute, Prevotella, Roseburia, and Streptococcus in patients with pancreatic cancer was higher than that in healthy people. The relative abundance of Proteobacteria, Neisseria, Haemophilus, porphyromonas, and Haemophilus parainfluenza in patients with pancreatic cancer was lower than that in healthy people. Conclusion Patients with pancreatic cancer have distinct oral flora, which has high relative abundance of Firmicutes, Prevotella etc. and low relative abundance of Proteobacteria, Neisseria, etc.
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Abstract Objective: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. Methods: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. Results It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. Conclusion: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.