Multiple Intestinal Anomalies in a Newborn with 22q11.2 Microdeletion Syndrome: A Case Report and Literature Review.

Although 40 years have passed since the first case of DiGeorge's syndrome was described, and the knowledge about this disorder has steadily increased since that time, 22q11.2 deletion syndrome (DS) remains a challenging diagnosis because its clinical presentation varies widely. We describe an infant with 22q11.2 DS who presented with annular pancreas, anorectal malformation, Morgagni-type congenital diaphragmatic hernia, and ventricular septal defect. This constellation of anomalies has never been described in DiGeorge's syndrome. Here, we provide a case presentation and a thorough review of the literature.

Reproducibility study of intravoxel incoherent motion and apparent diffusion coefficient parameters in normal pancreas.

BACKGROUND: The consistency of pancreatic apparent diffusion coefficient (ADC) values and intravoxel incoherent motion (IVIM) parameter values across different magnetic resonance imaging (MRI) devices significantly impacts the patient's diagnosis and treatment. AIM: To explore consistency in image quality, ADC values, and IVIM parameter values among different MRI devices in pancreatic examinations. METHODS: This retrospective study was approved by the local ethics committee, and informed consent was obtained from all participants. In total, 22 healthy volunteers (10 males and 12 females) aged 24-61 years (mean, 28.9 ± 2.3 years) underwent pancreatic diffusion-weighted imaging using 3.0T MRI equipment from three vendors. Two independent observers subjectively scored image quality and measured the pancreas's overall ADC values and signal-to-noise ratios (SNRs). Subsequently, regions of interest (ROIs) were delineated for the IVIM parameters (true diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction) using post-processing software. These ROIs were on the head, body, and tail of the pancrease. The subjective image ratings were assessed using the kappa consistency test. Intraclass correlation coefficients (ICCs) and mixed linear models were used to evaluate each device's quantitative parameter values. Finally, a pairwise analysis of IVIM parameter values across each device was performed using Bland-Altman plots. RESULTS: The Kappa value for the subjective ratings of the different observers was 0.776 (P < 0.05). The ICC values for inter-observer and intra-observer agreements for the quantitative parameters were 0.803 [95% confidence interval (CI): 0.684-0.880] and 0.883 (95%CI: 0.760-0.945), respectively (P < 0.05). The ICCs for the SNR between different devices was comparable (P > 0.05), and the ICCs for the ADC values from different devices were 0.870, 0.707, and 0.808, respectively (P < 0.05). Notably, only a few statistically significant inter-device agreements were observed for different IVIM parameters, and among those, the ICC values were generally low. The mixed linear model results indicated differences (P < 0.05) in the f-value for the pancreas head, D-value for the pancreas body, and D-value for the pancreas tail obtained using different MRI machines. The Bland-Altman plots showed significant variability at some data points. CONCLUSION: ADC values are consistent among different devices, but the IVIM parameters' repeatability is moderate. Therefore, the variability in the IVIM parameter values may be associated with using different MRI machines. Thus, caution should be exercised when using IVIM parameter values to assess the pancreas.

A Unique Presentation of Solid Pseudopapillary Neoplasm of the Pancreas Requiring Pancreaticoduodenectomy Without Pancreatojejunostomy: A Case Report and Literature Review.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors that predominantly affect young females and are typically located in the body and tail of the pancreas. Here, we present the case of a 59-year-old male with a large, heavily calcified SPN in the pancreatic head. His surgical history includes an aborted pancreaticoduodenectomy due to vascular involvement, followed by a gastrojejunostomy. Twenty years after the initial discovery, a pancreaticoduodenectomy was performed - the first of its kind - where the pancreas was completely atrophied, and no pancreaticojejunostomy was performed. Histological examination revealed typical features of SPN. This case demonstrates that even with relatively large lesions in a male patient over an extended duration, SPNs can still exhibit favorable features, highlighting the absence of specific preoperative markers for aggressive tumors. Therefore, unless there is an absolute contraindication, complete resection of all SPNs remains advisable.

Posttransplant Lymphoproliferative Disease Following Pancreas Transplantation: A 40 Year Single-Center Experience.

BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.

Predictive capacity of fetal pancreatic circumference for gestational diabetes mellitus.

OBJECTIVE: To assess the capacity of fetal pancreatic size, before standard blood testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. RESULTS: Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). CONCLUSIONS: Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Surgical management of pancreatic cancer in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a 5 years retrospective descriptive study.

INTRODUCTION: The incidence of Pancreatic cancer is different in different parts of the world. It is a cancer with the worst prognosis of all malignancies. Pancreatic cancer is predominantly a disease of an older population. There are different environmental (modifiable) and non-modifiable risk factors associated with the development of pancreatic cancer. At present, surgical resection is the only potential cure for pancreatic cancer. However, as only 10-20% of the patients have resectable disease at the time of diagnosis. The morbidities associated with surgeries for pancreatic cancers remain high though the post-operative mortality has shown significant reduction in the past few decades. So far, no study has been conducted to investigate pancreatic cancer in Ethiopia. OBJECTIVES: To assess the clinico-pathologic profile, associated factors, surgical management and short-term outcome of patients with pancreatic cancer in Tikur Anbessa Specialized hospital. METHODS: A 5 years retrospective hospital-based cross-sectional study was conducted on 52 patients operated with the diagnosis of pancreatic cancer with either curative or palliative intents. The study period was from April 2016 to July 2021. The data collected includes demographic profile, associated risk factors and comorbidities, clinical presentations, biochemical parameters, pathologic features of the tumors as well as type of treatment offered and short term treatment outcome. The data was analyzed using SPSS version 25. RESULT: The mean and median age of patients was 54.1 and 54.5% respectively. Males constitute about 52% the patients. 21% of the patients have potential risk factors; whereas only 10 (19.2%) of the patients had medical comorbidities. Median duration of symptoms at diagnosis was 12 weeks. Abdominal pain (88.5%) was the most common presenting symptom followed by anorexia (80.8%) and significant weight loss (78.8%), while 71.2% of the patients have jaundice. On clinical evaluation, 69.2% were jaundiced, while 34.6% had a palpable gallbladder. More than two third of patients presented with advanced disease. 76.9% of the tumors are located in the head of pancreas. More than three quarters (77%) of the surgeries performed were palliative. Postoperative morbidity and mortality were 19.2% and 3.8% respectively. CONCLUSION: Age at first diagnosis of pancreatic cancer is relatively earlier in our setup. Most patients present with advanced condition, only amenable for palliative measures. The post-operative morbidity and mortality are more or less comparable with similar studies. The need for adjuvant therapy in pancreatic cancer should be emphasized.

Heterotopic pancreas in the gallbladder: A case report.

BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.

Diffusion-weighted Echo Planar Imaging with Compressed SENSE (EPICS-DWI) for Pancreas Assessment: A Multicenter Study.

PURPOSE: This study aimed to evaluate the feasibility of single-shot echo planar diffusion-weighted imaging with compressed SENSE (EPICS-DWI) for pancreas assessment by comparing with single-shot echo planar DWI with parallel imaging (PI-DWI). METHODS: This multicenter prospective study included 27 consecutive participants with untreated pancreatic ductal adenocarcinoma (PDAC) (15 men; mean age, 67 ± 10 years) who underwent pancreatic protocol MRI including both PI-DWI and EPICS-DWI. Two radiologists independently and randomly reviewed the high b-value DWI images and qualitatively assigned confidence scores for overall image quality, image noise, pancreas conspicuity, and PDAC conspicuity using a 5-point scale. One radiologist measured the PDAC-to-pancreas contrast-to-noise-ratio (CNR) on high b-value DWI images and the apparent diffusion coefficient (ADC) value of PDAC. Qualitative and quantitative parameters were compared between PI-DWI and EPICS-DWI using the Wilcoxon signed-rank test. RESULTS: The confidence scores for overall image quality (P < 0.001 in both radiologists) and image noise (P < 0.001 in both radiologists) were higher in EPICS-DWI than in PI-DWI. The pancreas conspicuity was better in EPICS-DWI than in PI-DWI in one of the radiologists (P = 0.02 and 0.06). The PDAC conspicuity was comparable between PI-DWI and EPICS-DWI (P > 0.99 in both radiologists). The PDAC-to-pancreas CNR was higher in EPICS-DWI than in PI-DWI (P = 0.02), while the ADC value of PDAC in PI-DWI was not significantly different compared to that in EPICS-DWI (P = 0.48). CONCLUSION: The image quality and PDAC-to-pancreas CNR was improved in EPICS-DWI compared to PI-DWI. However, the conspicuity and ADC value of PDAC were comparable between PI-DWI and EPICS-DWI.

An imaging-based model to predict the malignant potential of intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVES: To develop and validate imaging-based models for predicting the malignancy risk of intraductal papillary mucinous neoplasm (IPMN). MATERIALS AND METHODS: We retrospectively analyzed data from 241 IPMN patients who underwent preoperative CT and MRI for model development. Cyst size, presence and size of the enhancing mural nodule (EMN), main pancreatic duct (MPD) diameter, thickened/enhancing cyst wall, abrupt MPD caliber change with distal atrophy, and lymphadenopathy were assessed. Multiple logistic regression models predicting malignancy risk were created using either continuous (Model C) or dichotomized variables (Model D) using these imaging features. Validation included internal (n = 55) and external (n = 43) datasets. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and compared with that of the international guideline-based model (Model F). RESULTS: Model C identified age, EMN size, MPD diameter, and lymphadenopathy as independent predictors on CT, and age and presence and size of EMN on MRI. Model D identified age ≥ 68, cyst size ≥ 31 mm, EMN ≥ 6 mm, MPD ≥ 7 mm, and lymphadenopathy as independent predictors on CT, and age ≥ 68, EMN ≥ 4.5 mm, and lymphadenopathy on MRI. Model C (AUC, 0.763-0.899) performed slightly better than Model D (AUC, 0.753-0.912) without statistical significance. No significant difference was observed between Models C and F (AUC, 0.729-0.952). Combining Model C with obstructive jaundice improved performance (AUC, 0.802-0.941) without statistical significance. CONCLUSION: Our imaging-based models effectively predicted the malignancy risk of IPMNs, comparable to international consensus guidelines. CLINICAL RELEVANCE STATEMENT: Imaging features are important for predicting the malignant potential of IPMNs. Our imaging-based model may help determine surgical candidacy for patients with IPMNs. KEY POINTS: Non-invasively determining the malignant potential of intraductal papillary mucinous neoplasms (IPMNs) allows for appropriate treatment decision-making We identified multiple imaging features that are associated with malignant transformation and developed models for this prediction. Our model performs comparably with international consensus guidelines in predicting the malignant potential of IPMNs.

Small molecular weight epigenetic inhibitors modulate the extracellular matrix during pancreatic acinar ductal metaplasia.

The pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment is distinguished by a high degree of fibrosis and inflammation, known as desmoplasia. Desmoplasia increases the stromal deposition and extracellular matrix (ECM) stiffness observed in the tumor microenvironment, contributing to the dampened penetration of pharmacological agents. The molecular and biophysical composition of the ECM during the earliest cellular changes in the development of PDAC, i.e. acinar ductal metaplasia (ADM), has not been extensively explored. We report that the mRNA expression of key protein components of the ECM increases during ADM in p48Cre/+;LSL-KrasG12D (KC) mouse acinar organoids cultured in Matrigel. Treatment of the organoids with small molecular weight epigenetic modulating compounds that inhibit or reverse ADM (largazole, FK228 and chaetocin) dramatically reduced the tissue mRNA expression of collagens, hyaluronan synthase, laminin and fibronectin. The storage moduli, determined by video tracking of fluorescent nanoparticles embedded into the Matrigel, increased during ADM and was reduced following treatment with the epigenetic modulating compounds. We report that the ECM of mouse organoids stiffens during ADM and is further enhanced by the presence of mutant Kras. Moreover, select HDAC and HMT inhibitors reduced the mRNA expression of ECM components and ECM stiffness during inhibition and reversal of ADM, suggesting that these compounds may be useful as adjuvants to enhance the tumor penetration of agents used to treat PDAC.

[Synchronous primary multiple cancer: distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail]. / Sinkhronnyi pervichno-mnozhestvennyi rak: distal'naya kholangiokartsinoma intrapankreaticheskoi chasti obshchego zhelchnogo protoka i vnutriprotokovaya papillyarnaya mutsinoznaya opukhol' v assotsiatsii s protokovoi adenokartsinomoi khvosta podzheludochnoi zhelezy.

We present a combination of distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail. This clinical case is unique. When analyzing the literature, we found no any case of similar primary multiple malignant tumor. Importantly, final diagnosis of simultaneous malignant pancreatobiliary neoplasia is possible only via intraoperative biopsy after adequate morphological dissection and research of resected organ complex including molecular genetic analysis due to identical histological and immunohistochemical picture of ductal neoplasia.

[Robotic enucleation of pancreatic insulinoma]. / Robot-assistirovannaya enukleatsiya insulinomy podzheludochnoi zhelezy.

We demonstrate robot-assisted treatment of a patient with benign pancreatic insulinoma. A 31-year-old patient suffered from attacks of weakness, numbness of the fingertips and «turbidity of consciousness¼ for 2 years. These symptoms occurred on an empty stomach and regressed after eating. We found pancreatic insulinoma. The patient underwent robotic enucleation of pancreatic tumor. Surgery time was 145 min. Postoperative period proceeded without complications. Hyperglycemia up to 10.5 mmol/l on the first postoperative day was followed by normalization after 4 days. The patient was discharged in 6 days after surgery. Minimally invasive robotic enucleation of insulinoma minimizes surgical trauma and provides precise resection of tumor. The key aspect of safe enucleation is localization of tumor at a distance of at least 2 mm from the pancreatic duct.

Celiac and superior mesenteric ganglia removal improves glucose tolerance and reduces pancreas islet size.

The sympathetic nervous system is crucial for the regulation of visceral organ function. For instance, the activation of the sympathetic nervous system promotes glycogenolysis in the liver and modulates glucagon and insulin release from the pancreas, thereby raising blood glucose levels. A decrease in sympathetic nerve activity has the opposite effect. Although such acute effects of sympathetic activity changes have been studied, their long-term outcomes have not been previously examined. In this study, we removed the celiac/superior mesenteric ganglia, where sympathetic postganglionic neurons innervating pancreas and liver locate, and examined its effects on glucose homeostasis and islet size several weeks after surgery. Consistent with the reduction in gluconeogenesis, glucose tolerance improved in gangliectomized mice. However, contrary to our expectation that the inhibition of pancreatic function by sympathetic nerves would be relieved with gangliectomy, insulin or C-peptide release did not increase. Examining the size distribution of pancreatic islets, we identified that the gangliectomy led to a size reduction in large islets and a decrease in the proportion of α and ß cells within each islet, as analyzed by immunostaining for insulin and glucagon, respectively. These results indicate that the absence of sympathetic nerve activity reduces the size of the pancreatic islets within a few weeks to reinstate the homeostatic mechanism of blood glucose levels.

Thermal effects and biological response of breast and pancreatic cancer cells undergoing gold nanorod-assisted photothermal therapy.

To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 µg/mL of GNRs and 4.5 W/cm2 laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies.

Optimizing terminology for pancreatectomy: Introducing a new notation system.

We introduce a novel notation system for pancreatectomy designed to provide a clear and concise representation of surgical procedures. As surgical techniques and the scope of pancreatic surgeries continue to diversify, existing communication methods among medical professionals regarding the specifics of the surgeries have proven inadequate. Our proposed notation system clearly indicates the approach (open, laparoscopic, or robot-assisted), type of surgery (e.g., pancreatoduodenectomy, distal pancreatectomy), and extent of resection and accompanying resected organs or vasculature. These elements are all recorded in this order by using abbreviations. For example, a pancreatoduodenectomy with pancreatic transection just above the SMA and combined resection of the SMV would be noted as "OPD(hb')-SMV". This new notation system allows for concise expression of the essential information on performed procedures of pancreatic resection, leading to smooth information sharing. This initiative is an essential step towards standardizing pancreatic surgery documentation on a global scale. Here, we present the development and application of this system, highlighting its potential to transform surgical communication and documentation.

Sudden rupture of a giant solid pseudopapillary tumour of the pancreas during caesarean delivery in a pregnant woman with severe preeclampsia: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Nonspecific presentations during pregnancy can mask early signs and symptoms of upper abdominal tumours, making the preoperative diagnosis of upper abdominal tumours difficult. Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare exocrine tumour of the pancreas, and SPN in combination with preeclampsia during pregnancy is even rarer. CASE PRESENTATION: In this paper, we report a case of SPN combined with preeclampsia during pregnancy and sudden rupture of a giant retroperitoneal SPN during a caesarean section, which resulted in life-threatening intra-abdominal haemorrhage. After exclusion of obstetric factors, a rapid response team was activated, multidisciplinary treatment (MDT) was carried out, and the patient was treated promptly and appropriately by resection of the giant retroperitoneal tumour, partial resection of the body and tail of the pancreas, and abdominal drainage. CLINICAL DISCUSSION: To our knowledge, this is the first reported case of SPN combined with preeclampsia during pregnancy, and a rapid and timely MDT could have ensured the patient's life. CONCLUSION: When dealing with a pregnant woman with an acute abdomen, the obstetrician should communicate fully with the woman to ensure that the most likely diagnosis is obtained. In the event of an unexpected accident during a caesarean section, it is important to remain calm, activate the Rapid Response Team and seek an MDT to ensure the life of the mother.

How to improve pre-operative diagnostics of pancreatobiliary lesions? From immunohistochemistry to Next Generation Sequencing.

Preoperative cytopathology of pancreatobiliary neoplastic lesions is a sensitive and specific method and is irreplaceable in the diagnosis and clinical management of these diseases. Pathologists should make every attempt to provide diagnosis as precise as possible and minimize the rate of "atypical" results, which create management dilemmas. The diagnostic accuracy of cytopathology can be significantly improved by judicious use of ancillary studies, including immunohistochemistry and molecular genetics. Next generation sequencing (NGS) is the latest addition to pancreatobiliary cytopathology diagnostic arsenal. NGS is not only a very robust diagnostic tool, but also carries significant prognostic and therapeutic information.

Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with ß-cell dysfunction in the golden (Syrian) hamster.

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed ß-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with ß-cell dysfunction, the most common type of T2D in East Asian countries, including Japan.

Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology.

Ras-related Rap1A GTPase is implicated in pancreas ß-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein ß (Ero1lß), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lß and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15-30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.

Future acceptance of automated insulin delivery systems in youths with type 1 diabetes: validation of the Italian artificial pancreas-acceptance measure.

AIM: The purpose of this study was to develop a questionnaire to examine the future acceptance of Automatic insulin delivery systems (AIDs), their perceived usefulness, ease of use, and trust in the device in subjects with type 1 diabetes (T1D). METHODS: A questionnaire in Italian, based on the Technology Acceptance Model, was developed to examine intention to use AIDs, considered as a measure of future acceptance, and its determinants to use the system. A total of 43 questions for children and 46 for parents were included, and a 5-point Likert scale was used. RESULTS: 239 subjects with T1D using multiple daily injections (MDI) or sensor-augmented pump (SAP) and their parents completed the questionnaire. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient for children and adolescents was 0.92 and 0.93 for parents, indicating excellent internal consistency in both groups. Parent-youth agreement was 0.699 (95% confidence interval: 0.689-0.709), indicating a good agreement between the two evaluations. Factor analysis identified measurement factors for the "artificial pancreas (AP)-acceptance labeled benefits and hassles of AIDs, and the internal consistency of the total scale was alpha = 0.94 for subjects with T1D and 0.95 for parents. The level of AP acceptance was more than neutral: 3.91 ± 0.47 and 3.99 ± 0.43 (p = 0.07) for youths and parents, respectively (possible score range 1 to 5, neutral score is 3.0). Parents reported higher scores in the benefit items than children-adolescents (p = 0.04). CONCLUSIONS: We developed a new questionnaire based on the items available in the literature, and we demonstrated that the "AP-acceptance" reveals a meaningful factor structure, good internal reliability, and agreement between parent-young people evaluations. This measure could be a valuable resource for clinicians and researchers to assess AP acceptance in pediatric patients with T1D and their parents. This patient profiling approach could help to enroll candidates for AIDs with proper expectations and who most likely will benefit from the system.