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Oncology Letters Aug 2024Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for...
Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for recurrent PDAC involves systemic chemotherapy, with gemcitabine (GEM) monotherapy historically serving as the standard of care. The present study describes the case of a patient with PDAC and postoperative liver metastases that maintained clinical complete remission (cCR) for >7 years following GEM monotherapy. A 63-year-old woman with upper abdominal pain was diagnosed with resectable PDAC and underwent pancreaticoduodenectomy. The patient was treated with GEM + S-1 as adjuvant chemotherapy for 6 months. Multiple liver metastases were detected 15 months post-operation and the patient was administered GEM alone. After 12 cycles, computed tomography showed cCR and GEM monotherapy was discontinued after 15 cycles. The patient has had no signs or symptoms of recurrence >7 years after the first recurrence. In addition, the present study analyzed PDAC resection specimens from four patients, including this case, to determine the expression levels of hENT1 protein in the tumor tissues. hENT1 is a transmembrane protein that acts as a nucleoside transporter and is a major mediator of GEM uptake into human cells. In the present case, hENT1 staining exhibited low frequency and weak positivity in the central region, whereas a strong positive reaction was observed in nearly all cell membranes at the invasive front of the cancer. The location, intensity, and frequency of hENT1 staining varied among cases. In conclusion, the efficacy of GEM may be predicted prior to treatment by evaluating hENT1 expression.
PubMed: 38933809
DOI: 10.3892/ol.2024.14503 -
Frontiers in Surgery 2024Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and...
BACKGROUND
Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP).
METHODS
A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed.
RESULTS
Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy.
CONCLUSION
This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).
PubMed: 38933652
DOI: 10.3389/fsurg.2024.1369169 -
Cureus May 2024Cystic echinococcosis, a zoonotic disease caused by the larval form of , predominantly affects the liver and lungs, with humans acting as accidental hosts.
INTRODUCTION
Cystic echinococcosis, a zoonotic disease caused by the larval form of , predominantly affects the liver and lungs, with humans acting as accidental hosts.
METHODS
Our retrospective study at the Department of Radiology and Imageology, Nizam's Institute of Medical Sciences, included 187 histopathologically or serologically proven cases. The mean age of presentation was 49.4 years.
RESULTS
Liver involvement was most prevalent, accounting for 83.4% (n=156) of cases, followed by sporadic involvement of other organs such as the mesentery, spleen, pancreas, thalamus, kidney, lung, spine, and omentum. Characteristic diagnostic features observed on imaging included peripheral calcifications in 33% of cases, internal septations in 25% (n=47), dense calcifications in 15% (n=29), daughter cysts in 6% (n=11), and floating membranes in 5% (n=10). Among hepatic lesions, 90% (n=141) were showing involvement of a single lobe. Notably, 78% (n=110) of lesions were limited to the right lobe, 21% (n=30) to the left lobe, and 1% (n=1) to the caudate lobe. The most affected hepatic segment was segment VIII, while the least common was segment I (caudate lobe). Complications were identified in 13% (n=25) of cases of hepatic hydatidosis.
CONCLUSIONS
The findings of our study emphasize the systemic nature of infection which can affect various organs in the body. It also illustrates the invaluable insights imaging provides for timely and accurate diagnosis of hydatid disease.
PubMed: 38933644
DOI: 10.7759/cureus.61180 -
Cureus May 2024A serous cystic tumor is a rare entity that has a benign course. Its imaging characteristics, such as the presence of multiple cysts with or without nodular enhancement,...
A serous cystic tumor is a rare entity that has a benign course. Its imaging characteristics, such as the presence of multiple cysts with or without nodular enhancement, can simulate other cystic or solid lesions of the pancreas. Identification of the enhancing scar with punctate calcifications on computed tomography (CT) or magnetic resonance imaging (MRI) may be a distinctive finding suggesting this diagnosis. Neuroendocrine tumors of the pancreas are a different and also rare entity. In images, they have early arterial enhancement. In MRI, they are hyperintense on T2 and hypointense on T1, with avid contrast enhancement. A case of a patient with two focal lesions in the pancreas is presented and the importance of integrating clinical findings, semiology in diagnostic images and, if applicable, the histopathological result for the optimal management of pancreatic tumors is illustrated, highlighting the crucial role of a radiologist in this process.
PubMed: 38933621
DOI: 10.7759/cureus.61159 -
Frontiers in Bioengineering and... 2024Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for...
Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for modeling diabetes and conducting screening for treatment options. Prior to SC-islets becoming the established standard for disease modeling and drug development, it is essential to understand their response to various nutrient sources . This study demonstrates an enhanced efficiency of pancreatic endocrine cell differentiation through the incorporation of WNT signaling inhibition following the definitive endoderm stage. We have identified a tri-hormonal cell population within SC-islets, which undergoes reduction concurrent with the emergence of elevated numbers of glucagon-positive cells during extended culture. Over a 6-week period of culture, the SC-islets consistently demonstrated robust insulin secretion in response to glucose stimulation. Moreover, they manifested diverse reactivity patterns when exposed to distinct nutrient sources and exhibited deviant glycolytic metabolic characteristics in comparison to human primary islets. Although the SC-islets demonstrated an aberrant glucose metabolism trafficking, the evaluation of a potential antidiabetic drug, pyruvate kinase agonist known as TEPP46, significantly improved insulin secretion of SC-islets. Overall, this study provided cell identity dynamics investigation of SC-islets during prolonged culturing , and insights into insulin secretagogues. Associated advantages and limitations were discussed when employing SC-islets for disease modeling.
PubMed: 38933536
DOI: 10.3389/fbioe.2024.1392575 -
OncoTargets and Therapy 2024To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide...
OBJECTIVE
To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients.
METHODS
A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model's feasibility, accuracy, and reliability.
RESULTS
Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping.
CONCLUSION
Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.
PubMed: 38933411
DOI: 10.2147/OTT.S466213 -
Frontiers in Immunology 2024Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising...
INTRODUCTION
Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3 T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3 T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3 T-lymphocytes.
METHODS
A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3 T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included.
RESULTS
Total lymphocyte counts below 0.3 x 10/L had a high sensitivity (86%) as a surrogate marker of CD3 T-lymphocytes below 0.05 x 10/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 10/L as a surrogate marker for CD3 T-lymphocytes above 0.05 x 10/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3 T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3 T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment.
DISCUSSION
Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 10/L whereas the CD3 T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.
Topics: Humans; Antilymphocyte Serum; Lymphocyte Count; Retrospective Studies; Male; Female; Middle Aged; Adult; Graft Rejection; Immunosuppressive Agents; T-Lymphocytes; Kidney Transplantation; Aged; Pancreas Transplantation; CD3 Complex; Organ Transplantation
PubMed: 38933271
DOI: 10.3389/fimmu.2024.1419726 -
Frontiers in Immunology 2024Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune...
BACKGROUND
Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.
METHODS
The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.
RESULTS
Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, OR=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (OR=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (OR=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.
CONCLUSION
This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.
Topics: Humans; Pancreatic Neoplasms; Mendelian Randomization Analysis; Genome-Wide Association Study; Monocytes; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38933268
DOI: 10.3389/fimmu.2024.1402113 -
Acta Endocrinologica (Bucharest,... 2023Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk...
OBJECTIVE
Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk factors for T2DM. The aim of the present study was to demonstrate the relationship between PFC, LFC and T2DM.
METHODS
A total of 70 T2DM subjects and 30 non-diabetic volunteers who underwent Dixon-based magnetic resonance imaging (MRI) method at Yixing People's Hospital between December 2018 to December 2020 were included in the study. The three-point Dixon (3p-Dixon) method was used to measure the fat content in the pancreas and liver. Clinical indices including gender, age, body mass index (BMI), total cholesterol, triglyceride, glucose and C peptide levels were collected. The association between PFC, LFC, and OGTT-derived parameters was examined by Pearson and Spearman correlation analyses.
RESULTS
T2DM subjects had higher PFC and LFC than those measured in the non-diabetic subjects (p <0.05). PFC and LFC were associated positively with OGTT-derived parameters such as insulin secretion, insulin resistance, and early- and late-phase insulin secretion in the male T2DM subjects(p <0.05), but not in the non-diabetic and female T2DM subjects. The relationship between PFC and OGTT-derived parameters was also more obvious than that for LFC in overweight and obese male patients with T2DM whose BMI was >24 kg/m.
CONCLUSION
PFC and LFC were both associated with β-cell dysfunction and insulin resistance in males with T2DM. The relationship between PFC and β-cell dysfunction and insulin resistance was more obvious than that observed for LFC in overweight and obese male T2DM patients. More attention should therefore be paid to PFC in clinical settings.
PubMed: 38933258
DOI: 10.4183/aeb.2023.421 -
Acta Endocrinologica (Bucharest,... 2023This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided...
BACKGROUND
This study aimed to determine predictive clinical and endoscopic ultrasound (EUS) features for pancreatic neuroendocrine tumor (PNET) diagnosis, utilizing EUS-guided tissue acquisition.
METHODS
A prospective study from 2018-2022 included patients with pancreatic masses undergoing EUS with elastography. Univariate binomial logistic regression followed by multiple logistic regression with significant predictors was employed. A forward selection algorithm identified optimal models based on predictor numbers. Variables encompassed EUS tumor characteristics (e.g., location, size, margins, echogenicity, vascularity on Doppler, main pancreatic duct dilation, elastography appearance, vascular invasion, and hypoechoic rim), alongside demographic and risk factors (smoking, alcohol, diabetes).
RESULTS
We evaluated 165 patients (24 PNETs). EUS features significantly linked with PNET diagnosis were well-defined margins (79% . 26%, p < 0.001), blue elastography appearance (46% . 9.9%, p < 0.001), vascularization (67% . 25%, p < 0.001), hypoechoic rim (46% . 10%, p < 0.001). The top-performing model, with 89.1% accuracy, included two predictors: a homogeneous lesion (OR, 95% CI) and a hypoechoic rim (OR, 95% CI).
CONCLUSIONS
EUS appearance can differentiate PNETs from non-PNETs, with the hypoechoic rim being an independent predictor of PNET diagnosis. The most effective predictive model for PNETs combined the homogeneous lesion and presence of the hypoechoic rim.
PubMed: 38933251
DOI: 10.4183/aeb.2023.407