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1.
J Surg Case Rep ; 2024(7): rjae205, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39015115

ABSTRACT

Paragangliomas (PGLs) located around the pancreas are rare and challenging to diagnose preoperatively. Tumor resection with pancreatectomy is often performed for peripancreatic PGL. However, pancreas-sparing tumor resection can be indicated with an accurate preoperative diagnosis. Six patients with pathologically diagnosed peripancreatic PGL were included. The clinical data were retrospectively collected from medical records. Five of them were suspected of peripancreatic PGL on imaging studies due to the fat plane identified between the tumor and pancreas, and subsequently diagnosed with PGL preoperatively based on elevated urinary catecholamine levels and/or metaiodobenzylguanidine scintigraphy without biopsy. All patients underwent pancreas-sparing tumor resection with negative surgical margins, and they did not develop postoperative complications related to potential damage to the pancreas. A fat plane between the tumor and pancreas on imaging studies and hormone levels are key findings for obtaining an accurate preoperative diagnosis of peripancreatic PGL, which can be managed with pancreas-sparing tumor resection.

2.
Mol Ther Oncol ; 32(3): 200825, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39006944

ABSTRACT

Pancreaticobiliary cancer, encompassing malignancies of both the pancreatic and biliary tract, presents a formidable clinical challenge marked by a uniformly bleak prognosis. The asymptomatic nature of its early stages often leads to delayed detection, contributing to an unfavorable 5-year overall survival rate. Conventional treatment modalities have shown limited efficacy, underscoring the urgent need for alternative therapeutic approaches. In recent years, immunotherapy has emerged as a promising avenue in the fight against pancreaticobiliary cancer. Strategies such as therapeutic vaccines and the use of tumor-infiltrating lymphocytes have garnered attention for their potential to elicit more robust and durable responses. This review seeks to illuminate the landscape of emerging immunotherapeutic interventions, offering insights from both clinical and research perspectives. By deepening our understanding of pancreaticobiliary cancer and exploring innovative treatment modalities, we aim to catalyze improvements in patient outcomes and quality of life.

3.
Cureus ; 16(7): e64228, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39007019

ABSTRACT

Heterotopic pancreas (HP) is the presence of pancreatic tissue outside of its normal anatomical position without vascular continuity from the main pancreas. HP is most commonly found within the gastrointestinal tract, particularly the stomach through the jejunum. This report shares the case of a 57-year-old man who presented with persistent vomiting despite medical therapy. Given the nonspecific and broad differential diagnosis, a histopathological examination was warranted for a definitive diagnosis that showed a uniquely large and well-differentiated type I HP in the lesser curvature of the stomach. Resection was completed which was followed with resolution of symptoms.

4.
Cureus ; 16(5): e61467, 2024 May.
Article in English | MEDLINE | ID: mdl-38953073

ABSTRACT

We present a case report of a giant solitary fibrous tumor (SFT) with a review of the literature and discuss its biological features and diagnosis. A 43-year-old man presented to our emergency department with abdominal pain and distension with an evolution of two days. Contrast-enhanced computed tomography (CT) showed a large, well-circumscribed semisolid mass (12 cm x 10 cm x 12 cm) localized in the pancreatic head. The histological diagnosis obtained by endoscopic ultrasound-guided trans-duodenal tumor biopsy with fine-needle aspiration showed proliferating short spindle-shaped cells, suggesting a mesenchymal neoplasia of low grade. We proceeded to a Whipple surgical technique. The histopathological study of the resected tumor confirmed proliferating spindle-shaped cells in the tissue, and one mitotic figure was observed in 10 high-power fields (HPFs). Immunostaining was positive for CD34 and STAT-6. The histological diagnosis was a malignant pancreatic SFT. In the six months posterior to the surgical procedure, the patient has been free of recurrent disease. Preoperative diagnosis is difficult and requires comprehensive evidence including clinical, immunohistochemistry, and histological features. Since there are currently no recognized best practices, we advise total surgical excision and careful clinical monitoring.

5.
Pancreatology ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38960779

ABSTRACT

BACKGROUND/OBJECTIVES: Ambulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. METHODS: Patients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. RESULTS: The cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). CONCLUSION: VTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

6.
Artif Organs ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963003

ABSTRACT

BACKGROUND: A closed-loop bedside-type artificial pancreas for perioperative glucose control has previously been introduced. However, artificial pancreas therapy was often interrupted due to continuous blood sampling failure. We developed an interprofessional work manual to reduce the interruption time of artificial pancreatic therapy for perioperative blood glucose control due to continuous blood sampling failure. This study aimed to investigate the usefulness of this manual. METHODS: The manual consisted of the following sections: (1) the roles of the professionals in the preparation and management of the artificial pancreas, (2) how to address continuous blood sampling failure, and (3) checkpoints for interprofessional transfer of the artificial pancreas. We compared the results before the introduction of the manual and 2 years after the introduction of the manual. RESULTS: There were 35 and 37 patients in the Before and After groups, respectively. There were no significant differences in patient backgrounds between the two groups, although there was significantly less blood loss in the After group (1164 vs. 366 mL; p < 0.001). The mean artificial pancreas therapy and artificial pancreas therapy interruption times were 847 min and 20 min, respectively. Artificial pancreas therapy interruption time (34 vs. 8 min; p = 0.078) and time per interruption (24 vs. 4 min; p < 0.001) were significantly shorter in the After group than in the Before group. CONCLUSIONS: The interprofessional working manual was useful in reducing the artificial pancreatic therapy interruption time for perioperative glucose control.

7.
J Anesth Analg Crit Care ; 4(1): 39, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956707

ABSTRACT

BACKGROUND: Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery. METHODS: This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018-December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes. RESULTS: AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8-35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4-16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality. CONCLUSION: In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.

8.
Ann Gastroenterol Surg ; 8(4): 681-690, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957555

ABSTRACT

Background: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. Patients and method: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. Results: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. Conclusions: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

9.
Intern Emerg Med ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981984

ABSTRACT

The prevalence of pancreatic steatosis has increased and it has been linked to the rising prevalence of metabolic syndrome. Metabolic syndrome is known to have a strong connection with changes in intestinal microbiota. The aim of this study was to explore the relationship between pancreatic steatosis and the levels of trimethylamine N-oxide (TMAO) and butyrate. In this study, 136 individuals were randomly selected from outpatient clinics at Firat University Hospital. The study evaluated their demographic characteristics, anthropometric measurements, and biochemical parameters. The presence of pancreatic steatosis was assessed using abdominal ultrasonography. Additionally, the levels of TMAO and butyrate were measured. The mean age of individuals in the study was 44.5 ± 14.6. 84 of the subjects were females. Using the waist circumference, 61 were considered obese and 34 overweight. The detection rate of pancreatic steatosis was found to be 70.6%. The study found that individuals with steatosis had higher average age, presence of hepatic steatosis, BMI, waist circumference measurements, and presence of metabolic syndrome than those without steatosis. A significantly higher butyrate level was detected in those without steatosis (p = 0.001). TMAO levels were slightly higher in patients without steatosis than in those with steatosis; however, this was insignificant. Pancreatic steatosis is highly associated with alterations in levels of microbiota metabolites, indicating a potential role of these metabolites in the pathogenesis of the disease and subsequent therapeutic targets. Several other factors, such as age, hepatic steatosis, diabetes, and waist circumference, have also been identified as potential predictors of pancreatic steatosis.

10.
11.
Methods Mol Biol ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38997537

ABSTRACT

Regenerative medicine investigates the conversion of pancreatic ductal cells into functional islet cells, offering innovative treatments for conditions such as diabetes. Ductal cells, primarily supporting the pancreas' exocrine functions, can differentiate into various cell types, including islet cells, under specific conditions, opening new avenues in research and therapy. The outlined protocol elaborates on the conversion process, covering ductal cell differentiation induction, and insulin-producing capacity assessment. The primary objective is to address the shortage of insulin-secreting cells for transplantation, thereby advancing diabetes treatment methodologies.

12.
Endosc Int Open ; 12(7): E861-E867, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38989255

ABSTRACT

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

13.
Rozhl Chir ; 103(6): 208-218, 2024.
Article in English | MEDLINE | ID: mdl-38991784

ABSTRACT

Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , World Health Organization , Humans , Pancreatic Neoplasms/classification , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Carcinoma, Pancreatic Ductal/classification , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/surgery , Precancerous Conditions/pathology , Precancerous Conditions/classification , Prognosis
14.
Front Transplant ; 3: 1370945, 2024.
Article in English | MEDLINE | ID: mdl-38993783

ABSTRACT

Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients (n = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R- patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R- SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis (P = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21-41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis.

15.
World J Gastrointest Oncol ; 16(6): 2300-2303, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994133

ABSTRACT

Recent decades have seen a concerning surge in carcinogenic diseases, with cancer cases and deaths on the rise globally. Conventional diagnostic methods are often invasive and time-consuming, highlighting the need for fast, accurate, and painless alternatives. Non-invasive exhaled breath analysis emerges as a promising solution, with over 200 volatile organic compounds (VOCs) detected in exhaled air, showing potential as biomarkers for various diseases, including cancer. Despite the lack of standardized methodologies, advancements in analytical instruments have expanded detection capabilities, reaching 3500 VOCs. Studies have identified specific VOC patterns associated with different cancers, offering hope for non-invasive diagnosis. Techniques such as gas chromatography-mass spectrometry and electronic noses show promise in distinguishing between healthy individuals and cancer patients. However, further research and standardization are needed to realize the full clinical potential of breath-based diagnostics, particularly in the early detection of challenging cancers like pancreatic cancer.

16.
Int J Mol Sci ; 25(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39000422

ABSTRACT

Maternal obesity, caused by diets rich in fats and sugars during pregnancy, can predispose offspring to metabolic diseases such as diabetes. We hypothesized that obesity during pregnancy leads to increased DNA methylation and reduced protein expression in factors regulating ß-cell function and apoptosis. Female C57BL/6J mice were fed a high-fat diet (HFD; 42% fat content; n = 3) or a control diet (CON; 16% fat content; n = 3) for fourteen weeks before and during pregnancy. Offspring were euthanized at 8 weeks and pancreatic tissue was collected. Isolated DNA was analyzed using whole-genome bisulfite sequencing. Protein expression was quantified using LC-MS. No significant differences in body weight were observed between HFD and control pups (p = 0.10). Whole-genome bisulfite sequencing identified 91,703 and 88,415 differentially methylated regions (DMRs) in CON vs. HFD male and female offspring. A total of 34 and 4 proteins were determined to have changes in expression that correlated with changes in DNA methylation in CON vs. HFD males and females, respectively. The majority of these factors were grouped into the metabolic function category via pathway analyses. This study illustrates the complex relationship between epigenetics, diet, and sex-specific responses, therefore offering insights into potential therapeutic targets and areas for further research.


Subject(s)
DNA Methylation , Diet, High-Fat , Mice, Inbred C57BL , Pancreas , Animals , Female , Diet, High-Fat/adverse effects , Pregnancy , Mice , Male , Pancreas/metabolism , Prenatal Exposure Delayed Effects/genetics , Prenatal Exposure Delayed Effects/metabolism , Obesity/metabolism , Obesity/genetics , Obesity/etiology , Epigenesis, Genetic , Multiomics
17.
Int J Mol Sci ; 25(13)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39000526

ABSTRACT

In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis.


Subject(s)
Endocrine Disruptors , Liver , Mitochondria , Oxidative Stress , Pancreas , Humans , Oxidative Stress/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Endocrine Disruptors/toxicity , Animals , Pancreas/drug effects , Pancreas/metabolism , Pancreas/pathology
18.
Cancers (Basel) ; 16(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39001434

ABSTRACT

INTRODUCTION AND AIM: Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. METHODS: From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with 18F-6-fluoro-L-dihydroxyphenylalanine (18FDOPA, n = 30), 18F-fluoro-2-deoxy-D-glucose (18FDG, n = 21), or 68Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (68Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6-12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. RESULTS: The mean age was 61 [extremes, 31-92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7-381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. CONCLUSION: Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure.

19.
Molecules ; 29(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999054

ABSTRACT

Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C-terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C-terminal hydroxamate-derived [68Ga]Ga-LW02075 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [68Ga]Ga-LW02050 ([68Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [68Ga]Ga-SB3 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (Ki) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [68Ga]Ga-SB3 and [68Ga]Ga-LW02050 in PET images, but not by [68Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [68Ga]Ga-LW02050 was comparable to that of [68Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [68Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [68Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [68Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [68Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [68Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.


Subject(s)
Gallium Radioisotopes , Hydroxamic Acids , Positron-Emission Tomography , Radiopharmaceuticals , Receptors, Bombesin , Receptors, Bombesin/metabolism , Receptors, Bombesin/antagonists & inhibitors , Gallium Radioisotopes/chemistry , Animals , Humans , Positron-Emission Tomography/methods , Mice , Hydroxamic Acids/chemistry , Hydroxamic Acids/pharmacokinetics , Hydroxamic Acids/chemical synthesis , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Cell Line, Tumor , Tissue Distribution , Male , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/metabolism
20.
J Clin Med ; 13(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38999254

ABSTRACT

Background: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function. Methods: simultaneous pancreas-kidney transplants (SPKTs) conducted at the University Hospital of Leipzig from 1998 to 2018 were reviewed retrospectively. The transplants were categorized based on whether they began during daytime hours (8 a.m. to 6 p.m.) or nighttime hours (6 p.m. to 8 a.m.). We analyzed the demographics of both donors and recipients, as well as primary outcomes, which included surgical complications, patient survival, and graft longevity. Results: In this research involving 105 patients, 43 SPKTs, accounting for 41%, took place in the daytime, while 62 transplants (59%) occurred at night. The characteristics of both donors and recipients were similar across the two groups. Further, the rate of (surgical) pancreas graft-related complications and reoperations (daytime 39.5% versus nighttime 33.9%; p = 0.552) were also not statistically significant between both groups. In this study, the five-year survival rate for patients was comparable for both daytime and nighttime surgeries, with 85.2% for daytime and 86% for nighttime procedures (p = 0.816). Similarly, the survival rates for pancreas grafts were 75% for daytime and 77% for nighttime operations (p = 0.912), and for kidney grafts, 76% during the day compared to 80% at night (p = 0.740), indicating no significant statistical difference between the two time periods. In a multivariable model, recipient BMI > 30 kg/m2, donor age, donor BMI, and cold ischemia time > 15 h were independent predictors for increased risk of (surgical) pancreas graft-related complications, whereas the timepoint of SPKT (daytime versus nighttime) did not have an impact. Conclusions: The findings from our retrospective analysis at a big single German transplant center indicate that SPKT is a reliable procedure, regardless of the start time. Additionally, our data revealed that patients undergoing nighttime transplants have no greater risk of surgical complications or inferior results concerning long-term survival of the patient and graft. However, due to the small number of cases evaluated, further studies are required to confirm these results.

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