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Artificial Intelligence in Medicine Jun 2024Pancreatic cancer does not show specific symptoms, which makes the diagnosis of early stages difficult with established image-based screening methods and therefore has...
Pancreatic cancer does not show specific symptoms, which makes the diagnosis of early stages difficult with established image-based screening methods and therefore has the worst prognosis among all cancers. Although endoscopic ultrasonography (EUS) has a key role in diagnostic algorithms for pancreatic diseases, B-mode imaging of the pancreas can be affected by confounders such as chronic pancreatitis, which can make both pancreatic lesion segmentation and classification laborious and highly specialized. To address these challenges, this work proposes a semi-supervised multi-task network (SSM-Net) to leverage unlabeled and labeled EUS images for joint pancreatic lesion classification and segmentation. Specifically, we first devise a saliency-aware representation learning module (SRLM) on a large number of unlabeled images to train a feature extraction encoder network for labeled images by computing a contrastive loss with a semantic saliency map, which is obtained by our spectral residual module (SRM). Moreover, for labeled EUS images, we devise channel attention blocks (CABs) to refine the features extracted from the pre-trained encoder on unlabeled images for segmenting lesions, and then devise a merged global attention module (MGAM) and a feature similarity loss (FSL) for obtaining a lesion classification result. We collect a large-scale EUS-based pancreas image dataset (LS-EUSPI) consisting of 9,555 pathologically proven labeled EUS images (499 patients from four categories) and 15,500 unlabeled EUS images. Experimental results on the LS-EUSPI dataset and a public thyroid gland lesion dataset show that our SSM-Net clearly outperforms state-of-the-art methods.
PubMed: 38941908
DOI: 10.1016/j.artmed.2024.102919 -
Biochemistry Jun 2024Protein advanced glycation end products (AGEs) can be formed via nonenzymatic glycation and accumulated intracellularly to disrupt cellular homeostasis for protein...
Protein advanced glycation end products (AGEs) can be formed via nonenzymatic glycation and accumulated intracellularly to disrupt cellular homeostasis for protein clearance. Here, we investigated the formation particulars of intracellular protein AGEs and sought to elucidate the molecular events implicated in the impact of cellular clearance systems. The formation and accumulation of intracellular protein AGEs increased protein aggregation and protease resistance, potentially overwhelming the ubiquitin-proteasome system (UPS). At high levels of protein AGEs, the abundance of many E3 ligases decreased and the overall ubiquitination level was reduced, all of which indicated decreased UPS activity. On the other hand, autophagy activity was stimulated, as evidenced by the upregulation of autophagy marker LC3II and important proteins in autophagosome and autolysosome formation, as well as downregulation of mTOR. Understanding the functional impacts of intracellular protein AGEs on the UPS and autophagy could pave the way for the future development of pharmaceutical agents targeting AGE-related diseases.
PubMed: 38941592
DOI: 10.1021/acs.biochem.4c00250 -
Medicine Jun 2024Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor...
BACKGROUND
Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR's prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers.
METHODS
A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR's relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR's association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628).
RESULTS
Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility.
CONCLUSION
suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR's role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.
Topics: Humans; Pancreatitis; Receptors, Urokinase Plasminogen Activator; Prognosis; Biomarkers; Systematic Reviews as Topic; Severity of Illness Index; Length of Stay; Acute Disease
PubMed: 38941433
DOI: 10.1097/MD.0000000000037064 -
Magyar Sebeszet Jun 2024Bevezetés: A posztoperatív pancreasfistula mind proximalis, mind distalis pancreatectomia után a legjelentősebb sebészi szövődménynek számít. A...
Bevezetés: A posztoperatív pancreasfistula mind proximalis, mind distalis pancreatectomia után a legjelentősebb sebészi szövődménynek számít. A szakirodalomban nincs egyértelműen ajánlott, megbízható módszer ezen probléma kiküszöbölésére, emiatt történnek újítások szerte a világon. Jelen közleményünkben a technikai innovációinkról számolunk be. Anyag és módszerek: 2013. január 1-jétől 2023. november 30-ig terjedő időszakban 205 Whipple-műtétet végeztünk nyitottan, mely során a pancreatojejunalis anastomosist az általunk módosított dohányzacskó-öltéses módszerrel készítettük el. 2019. január 1. és 2023. november 30. között pedig 30 betegnél történt nyitott distalis pancreatectomia, amikor a pancreascsonkot az általunk kifejlesztett technikával, szabad rectus fascia-peritoneum grafttal fedtük, majd azt cirkuláris öltéssel rögzítettük. Közleményünkben ezen két módszerrel elért eredményeket ismertetjük. Eredmények: a demográfiai adatok megfeleltek a betegségnél szokásosnak. A posztoperatív ápolási idő és a transzfúzió igény terén észlelt különbségek tükrözték a kétféle beavatkozás eltérő invazivitását. A releváns pancreasfistula kialakulási rátája kedvező képet mutatott, Whipple-műtét után 7,3% volt, míg distalis pancreatectomát követően nem fejlődött ki. A reoperációs és a halálozási arányok megfeleltek az elvártaknak és korreláltak a műtétek kiterjedtségével. Következtetés: pancreas resectiók utáni komplikációk csökkentésére tett törekvéseink során a módosított dohányzacskó-öltéses pancreatojejunostomia és a pancreascsonk fedésére kidolgozott módszerünk egyaránt kedvező eredményekkel járt.
Topics: Humans; Pancreatic Fistula; Postoperative Complications; Female; Male; Pancreatectomy; Middle Aged; Pancreaticojejunostomy; Aged; Pancreaticoduodenectomy; Treatment Outcome; Adult
PubMed: 38941151
DOI: 10.1556/1046.2024.20002 -
JAMA Network Open Jun 2024While most patients with acute pancreatitis (AP) fulfill diagnostic criteria with characteristic abdominal pain and serum lipase levels of at least 3 times the upper...
IMPORTANCE
While most patients with acute pancreatitis (AP) fulfill diagnostic criteria with characteristic abdominal pain and serum lipase levels of at least 3 times the upper limit of normal (reference range) at presentation, early imaging is often used for confirmation. A prior prediction model and corresponding point-based score were developed using nonimaging parameters to diagnose AP in patients presenting to the emergency department (ED).
OBJECTIVE
To evaluate the performance of the prediction model to diagnose AP in a prospective patient cohort.
DESIGN, SETTING, AND PARTICIPANTS
This prospective diagnostic study included consecutive adult patients presenting to the ED between January 1, 2020, and March 9, 2021, at 2 large academic medical centers in the northeastern US with serum lipase levels at least 3 times the upper limit of normal. Patients transferred from outside institutions or with malignant disease and established intra-abdominal metastases, acute trauma, or altered mentation were excluded. Data were analyzed from October 15 to October 23, 2023.
EXPOSURES
Participants were assigned scores for initial serum lipase level, number of prior AP episodes, prior cholelithiasis, abdominal surgery within 2 months, presence of epigastric pain, pain of worsening severity, duration from pain onset to presentation, and pain level at ED presentation.
MAIN OUTCOME AND MEASURES
A final diagnosis of AP, established by expert review of hospitalization records.
RESULTS
Prospective scores in 349 participants (mean [SD] age, 53.0 [18.8] years; 184 women [52.7%]; 66 Black [18.9%]; 199 White [57.0%]) demonstrated an area under the receiver operating characteristics curve of 0.91. A score of at least 6 points achieved highest accuracy (F score, 82.0), corresponding to a sensitivity of 81.5%, specificity of 85.9%, positive predictive value of 82.6%, and negative predictive value of 85.1% for AP diagnosis. Early computed tomography or magnetic resonance imaging was performed more often in participants predicted to have AP (116 of 155 [74.8%] with a score ≥6 vs 111 of 194 [57.2%] with a score <6; P < .001). Early imaging revealed an alternative diagnosis in 8 of 116 participants (6.9%) with scores of at least 6 points, 1 of 93 (1.1%) with scores of at least 7 points, and 1 of 73 (1.4%) with scores of at least 8 points.
CONCLUSIONS AND RELEVANCE
In this multicenter diagnostic study, the prediction model demonstrated excellent AP diagnostic accuracy. Its application may be used to avoid unnecessary confirmatory imaging.
Topics: Humans; Pancreatitis; Female; Male; Prospective Studies; Middle Aged; Adult; Lipase; Emergency Service, Hospital; Aged; Predictive Value of Tests; Acute Disease; Abdominal Pain
PubMed: 38941094
DOI: 10.1001/jamanetworkopen.2024.19014 -
Annals of Surgery Jun 2024We aimed to establish global benchmark outcomes indicators for L-RPS/H67.
OBJECTIVE
We aimed to establish global benchmark outcomes indicators for L-RPS/H67.
BACKGROUND
Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted.
METHODS
This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff.
RESULTS
There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively.
CONCLUSIONS
The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.
PubMed: 38939972
DOI: 10.1097/SLA.0000000000006418 -
Annals of Surgery Jun 2024To propose to our community a common language about extreme liver surgery.
OBJECTIVE
To propose to our community a common language about extreme liver surgery.
BACKGROUND
The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers.
METHODS
We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages.
RESULTS
A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery.
CONCLUSION
Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.
PubMed: 38939929
DOI: 10.1097/SLA.0000000000006421 -
JACS Au Jun 2024This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as...
This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as molecularly targeted drugs and have been applied for cancer, autoimmune diseases, and infections. In many cases, enzyme inhibitors that are used for therapeutic applications interact directly with enzymes in a molecule-to-molecule manner. We found that the aggregates of a small compound, Mn007, inhibited bovine pancreatic DNase I. Once Mn007 molecules formed aggregates, they exhibited inhibitory effects specific to DNases that require divalent metal ions. A DNase secreted by causes streptococcal toxic shock syndrome (STSS). STSS is a severe infectious disease with a fatality rate exceeding 30% in patients, even in this century. disrupts the human barrier system against microbial infections through the secreted DNase. Until now, the discovery/development of a DNase inhibitor has been challenging. Mn007 aggregates were found to inhibit the DNase secreted by , which led to the successful suppression of growth in human whole blood. To date, molecular aggregation has been outside the scope of drug discovery. The present study suggests that molecular aggregation is a vast area to be explored for drug discovery and development because aggregates of small-molecule compounds can inhibit disease-related enzymes.
PubMed: 38938790
DOI: 10.1021/jacsau.4c00210 -
Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
Gut and Liver Jun 2024The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic...
BACKGROUND/AIMS
The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals.
METHODS
This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies.
RESULTS
The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC.
CONCLUSIONS
Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.
PubMed: 38938175
DOI: 10.5009/gnl240241