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Doege–Potter syndrome (DPS) is a very rare paraneoplastic condition that is marked by hypoglycemia brought on by a solitary fibrous tumor rather than an islet cell tumor. Soft tissue neoplasms termed as solitary fibrous tumors (SFTs) are rare and these tumors vary in the site of origin, from the pleural cavity, mediastinum, pericardium, retroperitoneal spaces, liver, thyroid, orbit, bladder, intestines, and soft tissues, while pelvic‐derived fibrous tumors are incredibly unusual. There are currently extremely few documented cases and literature reviews both domestically and internationally. In this case study, we present an 82‐year‐old woman who developed DPS as a result of malignant pelvic SFTs. Her hypoglycemia was clinically healed after she underwent laparoscopic retroperitoneal tumor resection in our institution, and thereafter, her quality of life improved. [ABSTRACT FROM AUTHOR]

Hypoglycemia in critical care is a well-documented phenomenon, linking both physiological and clinical evidence to harmful outcomes and an increased risk of mortality. Its implications span medical and non-medical consequences, such as cardiovascular and cerebrovascular complications, and escalated health care expenses and hospitalization duration. Mitigation measures for modifiable risk factors and education for both patients and health care providers on hypoglycemia can effectively prevent the onset of inpatient hypoglycemia. This concise clinical review offers a brief overview of hypoglycemia in critically ill patients, encompassing its pathophysiology, etiology, diagnosis, management, and prevention. [ABSTRACT FROM AUTHOR]

Background The lack of preoperative prognostic factors to accurately predict tumour aggressiveness in non-functioning pancreatic neuroendocrine tumours may result in inappropriate management decisions. This study aimed to critically evaluate the adequacy of surgical treatment in patients with resectable non-functioning pancreatic neuroendocrine tumours and investigate preoperative features of surgical appropriateness. Methods A retrospective study was conducted on patients who underwent curative surgery for non-functioning pancreatic neuroendocrine tumours at San Raffaele Hospital (2002–2022). The appropriateness of surgical treatment was categorized as appropriate, potential overtreatment and potential undertreatment based on histologic features of aggressiveness and disease relapse within 1 year from surgery (early relapse). Results A total of 384 patients were included. Among them, 230 (60%) received appropriate surgical treatment, whereas the remaining 154 (40%) underwent potentially inadequate treatment: 129 (34%) experienced potential overtreatment and 25 (6%) received potential undertreatment. The appropriateness of surgical treatment was significantly associated with radiological tumour size (P < 0.001), tumour site (P = 0.012), surgical technique (P < 0.001) and year of surgical resection (P < 0.001). Surgery performed before 2015 (OR 2.580, 95% c.i. 1.570 to 4.242; P < 0.001), radiological tumour diameter < 25.5 mm (OR 6.566, 95% c.i. 4.010 to 10.751; P < 0.001) and pancreatic body/tail localization (OR 1.908, 95% c.i. 1.119 to 3.253; P = 0.018) were identified as independent predictors of potential overtreatment. Radiological tumour size was the only independent determinant of potential undertreatment (OR 0.291, 95% c.i. 0.107 to 0.791; P = 0.016). Patients subjected to potential undertreatment exhibited significantly poorer disease-free survival (P < 0.001), overall survival (P < 0.001) and disease-specific survival (P < 0.001). Conclusions Potential overtreatment occurs in nearly one-third of patients undergoing surgery for non-functioning pancreatic neuroendocrine tumours. Tumour diameter emerges as the sole variable capable of predicting the risk of both potential surgical overtreatment and undertreatment. [ABSTRACT FROM AUTHOR]

Hypoglycaemic syndromes are rare in apparently healthy individuals and their diagnosis can be a difficult challenge for clinicians as there are no shared guidelines that suggest how to approach patients with a suspect hypoglycaemic disorder. Since hypoglycaemia symptoms are common and nonspecific, it's necessary to document the Whipple Triad (signs and/or symptoms compatible with hypoglycaemia; relief of symptoms following glucose administration; low plasma glucose levels) before starting any procedure. Once the triad is documented, a meticulous anamnesis and laboratory tests (blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate and anti-insulin antibodies) should be performed. Results can guide the physician towards further specific tests, concerning the suspected disease. In this review, we consider all current causes of hypoglycaemia, including rare diseases such as nesidioblastosis and Hirata's syndrome, describe appropriate tests for diagnosis and suggest strategies to differentiate hypoglycaemia aetiology. [ABSTRACT FROM AUTHOR]

A 12-year-old 4.3 kg intact female Terrier presented with a history of lethargy, anorexia, and melena for one month. The animal was dull and depressed. Dermatologic examination revealed some focal erythematous, crusty, and papulopustular lesions over the ventral abdomen. Ultrasonographic evaluation displayed an abnormal parenchymal pattern of the liver, which was noticed in the cranial part of the abdomen with diff use hepatic involvement with irregular, hypoechoic, and heterogeneous ill-defined areas [a honeycomb-like echotexture]. Lateral thoracocervical radiograph showed numerous well-defined, small lytic lesions [polyostotic punched-out lesions] in the dorsal spinous process of axis bone in C2-C5 and pelvis that were likely metastatic lesions. Despite hospitalization and treatment, the dog died after 2 weeks and a necropsy was performed. At postmortem examination, a 5-cm mass was observed in the pancreas adjacent to duodenal loops which was finally diagnosed as a pancreatic tumor. Abnormal laboratory findings included elevated blood urea nitrogen, creatinine, cholesterol, total bilirubin, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, and calcium. Histopathological examination of the affected pancreas revealed neoplastic cells which were arranged mainly as solid nests or clusters and the amounts of the tumor stroma among the cellular clusters or individual neoplastic cells were scant. According to an immunohistochemical study which was positive for chromogranine A, the condition was diagnosed as a pancreatic islet cell tumor. Although rare, pancreatic islet tumors should be included in the differential diagnosis of abdominal discomforts, pancreatic inflammation, and hepatopathies. The final diagnosis of the tumor is achieved by combining imaging techniques and advanced histopathologic evaluations. [ABSTRACT FROM AUTHOR]

Insulinoma is one of the pancreatic neuroendocrine tumors (PanNET) and is exceptionally rare in children. The tumor leads to severe hypoglycemia caused by excessive insulin release. We report a pediatric patient with malignant insulinoma who underwent liver transplantation (LT) due to liver metastases of the insulinoma. A 13-year-old girl presented with symptoms of hypoglycemia due to hyperinsulinism. On computed tomography (CT), a polycystic lesion in the head of the pancreas and enlarged lymph nodes were revealed. A modified Whipple's operation was performed, and histological examination confirmed PanNET. CT also showed an enlarged liver with numerous metastases. Allogeneic LT was carried out successfully. Positron emission tomography-CT using 68Ga-DOTA-labeled somatostatin analogs (SSAs) at the age of 22 years confirmed complete metabolic remission. The patient currently remains under immunosuppressive and anti-proliferative treatment. Multiple surgical interventions, LT combined with SSAs, and immunosuppressive medication proved effective in this case of metastatic malignant insulinoma. [ABSTRACT FROM AUTHOR]

PURPOSE: Biallelic germline pathogenic variants of the base excision repair (BER) pathway gene MUTYH predispose to colorectal cancer (CRC) and other cancers. The possible association of heterozygous variants with broader cancer susceptibility remains uncertain. This study investigated the prevalence and consequences of pathogenic MUTYH variants and MUTYH loss of heterozygosity (LOH) in a large pan-cancer analysis. MATERIALS AND METHODS: Data from 354,366 solid tumor biopsies that were sequenced as part of routine clinical care were analyzed using a validated algorithm to distinguish germline from somatic MUTYH variants. RESULTS: Biallelic germline pathogenic MUTYH variants were identified in 119 tissue biopsies. Most were CRCs and showed increased tumor mutational burden (TMB) and a mutational signature consistent with defective BER (COSMIC Signature SBS18). Germline heterozygous pathogenic variants were identified in 5,991 biopsies and their prevalence was modestly elevated in some cancer types. About 12% of these cancers (738 samples: including adrenal gland cancers, pancreatic islet cell tumors, nonglioma CNS tumors, GI stromal tumors, and thyroid cancers) showed somatic LOH for MUTYH , higher rates of chromosome 1p loss (where MUTYH is located), elevated genomic LOH, and higher COSMIC SBS18 signature scores, consistent with BER deficiency. CONCLUSION: This analysis of MUTYH alterations in a large set of solid cancers suggests that in addition to the established role of biallelic pathogenic MUTYH variants in cancer predisposition, a broader range of cancers may possibly arise in MUTYH heterozygotes via a mechanism involving somatic LOH at the MUTYH locus and defective BER. However, the effect is modest and requires confirmation in additional studies before being clinically actionable. Pan-Cancer Interrogation of MUTYH Variants Reveals Rare Biallelic Inactivation and Defective Base Excision Repair. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival and disease recurrence for pancreatic neuroendocrine tumors differs greatly. The aim of our retrospective study was to investigate prognostic factors influencing recurrence and survival of 413 patients. For outcome evaluation the cohort was split in three groups: those under surveillance, those who had surgery with the intention to cure, and those with unresectable disease. For small tumors (<2 cm) under surveillance only 1 of 59 required surgery. For those who had surgery 20% had recurrence within 5-years with tumor size, high Ki-67 index, and location in the pancreatic head as risk factors. Half of the patients with unresectable tumors survived longer than approximately 2 years with high age, high chromogranin A levels, and increased markers of tumor proliferation being linked to survival. In conclusion, the current results add valuable knowledge in terms of predicting outcomes for individuals with pancreatic neuroendocrine neoplasms. Introduction: The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial. Aim: To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3). Method: A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors. Results: 413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21–34) months, and tumor size was 1.0 (0.8–1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31–102) months, median tumor size 2 (1.2–3.4) cm, median Ki-67 index 5 (3–10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6–46) months, median tumor size 4.2 (2.6–7.0) cm, Ki-67 index 17 (9–64)%, the median disease-specific survival was 22 (6–75) months—99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors. Conclusion: Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection. [ABSTRACT FROM AUTHOR]

Simple Summary: We described post-operative complications, pancreatic sequelae, and post-surgical progression/relapse of pancreatic neuroendocrine neoplasms (PNENs) in 43 patients with multiple endocrine neoplasia type 1 (MEN1), who underwent major or minimal pancreatic surgeries. The performance of a more conservative intervention, compared to both pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), was associated with the absence of post-surgical complications, but required further pancreas surgeries for tumor relapse in 40.0% of the operated cases. Our data showed that major pancreatic resections (PD and DP) were effective in both preventing tumoral progression and guaranteeing a long-term PNEN relapse-free survival time in most of N+ and/or M+ patients. Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries. No post-operative mortality was observed. Metastatic cancers were found in 12 cases, prevalently from duodenal gastrinoma. Long-term cure of endocrine syndromes, by the 38 major pancreatic resections, was obtained in 78.9% of gastrinomas and 92.9% of insulinomas. In only one patient, hepatic metastases, due to gastrinoma, progressed to death. Out of the 38 major surgeries, only one patient was reoperated for the growth of a new PNEN in the remnant pancreas. No functioning PNEN persistence was reported in the five minimal pancreatic surgeries, PNEN relapse occurred in 60% of patients, and 40% of cases needed further pancreatic resection for tumor recurrence. No significant difference in PNEN relapse-free survival time after surgery was found between major and minimal pancreatic surgeries. [ABSTRACT FROM AUTHOR]

Background: Insulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis. Case presentation: Our patient experienced hypoglycemic coma in the 3rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified. Conclusions: Although pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia. [ABSTRACT FROM AUTHOR]

This study aims to analyze the effect of mangosteen peel on increasing the number of pancreatic islets in Langerhans endocrine cells and decreasing TNF-α in male white rats induced by streptozotocin. The research conducted was laboratory experimental in nature. The research design used is a Randomized Post Test Only Control Group Design. The samples were 24 male white rats of the Wistar strain. Rats were grouped into six groups: negative control group (KN), positive control STZ (K1), positive control metformin synthetic drug therapy (K2), mangosteen rind extract therapy dose of 200 mg/kgbb (K3), a dose of 400 mg/kgbb (K4), a dose of 600 mg/kgbb (K5). Administration of therapy for 14 days orally. Pancreatic organs were examined by HE and IHC staining. Pancreatic histopathological observation and TNF-α expression were carried out microscopically. Statistical analysis using the Kolmogorov-Smirnov, ANOVA test, and Pearson's correlation. The results of the effect of mangosteen peel extract can increase the proliferation of endocrine cells in the islets of Langerhans, at a dose of 600 mg/kg BW/day. While the decrease in TNF-α expression was shown by all doses of mangosteen peel extract and appeared to be significantly different when compared to the K1 group, namely the STZ-induced group without any therapy. Pearson's correlation results show that there is an inverse relationship between the number of endocrine cells and TNF-α expression. The conclusion is that administration of mangosteen peel extract can increase the number of pancreatic islets of Langerhans endocrine cells and decrease Tumor Necrosis Factor Alpha in streptozotocin-induced male white rats. Suggestions need to do research on anti-inflammatory cytokines that occur in endocrine cells of the islets of Langerhans due to streptozotocin-induced mangosteen peel extract in rats so that there is a balance with pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Simple Summary: In endocrinology, endoscopic ultrasound is a useful and reliable diagnostic technique in the assessment of multiple endocrine neoplasia type 1, localizing insulinomas, and identifying aldosterone-producing adenomas. In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information. [ABSTRACT FROM AUTHOR]

A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 μIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule. Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulininduced hypoglycemia in dogs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the protective effect of α-lipoic acid on sodium arsenite (NaAsO2) induced INS-1 cells injury and its mechanism. Methods: The cell viability was measured by CCK-8 assay. The autophagosomes was observed under transmission electron microscopy. The autophagosomes in cells transfected with green fluorescent protein microtubule-associated protein light chain 3 (GFP-LC3) plasmids were observed under a laser scanning con-focal microscope. The expression of LC3-II, P62, PI3K, and mTOR proteins in INS-1 cells treated with a combination of chloroquine (CQ, autophagy inhibitor) and NaAsO2 were detected by Western blot assay. The expression of LC3-II, P62, PI3K, and mTOR proteins were detected in INS-1 cells treated with a combination of rapamycin (autophagy inducer, mTOR inhibitor) and α-LA. Results: The cytotoxicity induced by NaAsO2 was reversed by α-LA, and the viability of NaAsO2-treated INS-1 cells increased. α-LA pretreatment decreased the autophagosome accumulation induced by NaAsO2. α-LA also reduced the fluorescence spot aggregation of GFP-LC3 in INS-1 cells exposed to NaAsO2 as observed under a laser scanning con-focal microscope. α-LA inhibited NaAsO2 induced autophagy by up-regulating PI3K and mTOR and down-regulating LC3-II and P62. CQ inhibited NaAsO2 induced autophagy by up-regulating PI3K, mTOR, P62 and down-regulating LC3-II. α-LA inhibited rapamycin-induced autophagy by up-regulating PI3K, mTOR and P62 and down-regulating LC3-II. The results showed that NaAsO2 could induce autophagy activation in INS-1 cells. The α-LA may inhibit autophagy activation by regulating the PI3K/mTOR pathway. Conclusion: The data indicated that α-LA might inhibit the NaAsO2-induced autophagic death of INS-1 cells by regulating the PI3K/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Insulinoma is an uncommon insulin-secreting neuroendocrine tumor that presents with severe recurrent hypoglycemia. Although cases of extrapancreatic insulinomas have been reported, the majority of insulinomas occur in the pancreas. The number of reported cases of ectopic insulinomas with follow-up assessments is limited and they do not report disease recurrence. The current report presents the first documented case of recurrent extrapancreatic insulinoma with 8 years of follow-up, provides relevant literature review, and proposes surveillance and treatment strategies. Case presentation: We describe an insulinoma localized in the duodenal wall of a 36-year-old female who presented in 2013 with weight gain and Whipple's triad and was successfully managed with duodenotomy and enucleation. She presented again in 2017 with recurrent Whipple's triad and was found to have metastatic disease localized exclusively to peripancreatic lymph nodes. Primary pancreatic insulinoma was not evident and her hypoglycemia resolved following lymph node dissection. Eight years after initial presentation continuous glucose monitoring (CGM) showed a trend for euglycemia, and PET-CT Gallium 68 DOTATATE scan evaluation indicated absence of recurrent disease. Conclusion: Insulinomas are rare clinical entities and extrapancreatic insulinomas are particularly uncommon. Follow-up evaluation and treatment strategies for ectopic insulinoma recurrence presents a significant clinical challenge as the condition has hitherto remained undescribed in the literature. Available evidence in the literature indicates that lymph node metastases of intrapancreatic insulinomas likely do not change prognosis. Given the absence of long-term data informing the management and monitoring of patients with extrapancreatic insulinoma, we suggest patient education for hypoglycemic symptoms, monitoring for hypoglycemia with CGM, annual imaging, and a discussion with patients regarding treatment with octreotide or alternative somatostatin receptor analog therapies. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine neoplasms (PanNENs) are rare and clinically challenging entities. At the molecular level, PanNENs' genetic profile is well characterized, but there is limited knowledge regarding the contribution of the newly identified genes to tumor initiation and progression. Genetically engineered mouse models (GEMMs) are the most versatile tool for studying the plethora of genetic variations influencing PanNENs' etiopathogenesis and behavior over time. In this review, we present the state of the art of the most relevant PanNEN GEMMs available and correlate their findings with the human neoplasms' counterparts. We discuss the historic GEMMs as the most used and with higher translational utility models. GEMMs with Men1 and glucagon receptor gene germline alterations stand out as the most faithful models in recapitulating human disease; RIP-Tag models are unique models of early-onset, highly vascularized, invasive carcinomas. We also include a section of the most recent GEMMs that evaluate pathways related to cell cycle and apoptosis, Pi3k/Akt/mTOR, and Atrx/Daxx. For the latter, their tumorigenic effect is heterogeneous. In particular, for Atrx/Daxx, we will require more in-depth studies to evaluate their contribution; even though they are prevalent genetic events in PanNENs, they have low/inexistent tumorigenic capacity per se in GEMMs. Researchers planning to use GEMMs can find a road map of the main clinical features in this review, presented as a guide that summarizes the chief milestones achieved. We identify pitfalls to overcome, concerning the novel designs and standardization of results, so that future models can replicate human disease more closely. [ABSTRACT FROM AUTHOR]

Jiedu Tongluo Tiaogan Formula (JTTF), a traditional Chinese herbal decoction, exhibits the potential to treat type 2 diabetes mellitus (T2DM) by inhibiting endoplasmic reticulum stress (ERS) and excessive autophagy, which are the risk factors for the abnormal development and progression of β cells. We aimed to assess the effect of JTTF on pancreatic glucotoxicity by inhibiting ERS and excessive autophagy, for which db/db mice and INS-1 insulinoma cells were used. The chemical composition of the JTTF was analyzed by UPLC-Q/TOF-MS. Diabetic (db/db) mice were treated with distilled water or JTTF (2.4 and 7.2 g/kg/day) for 8 weeks. Furthermore, INS-1 cells induced by high glucose (HG) levels were treated with or without JTTF (50, 100, and 200 μg/mL) for 48 h to elucidate the protective mechanism of JTTF on glucose toxicity. The experimental methods included an oral glucose tolerance test, hematoxylin–eosin staining, immunohistochemistry, western blotting, RT-qPCR, and acridine orange staining. 28 chemical components of JTTF were identified. Additionally, treatment with JTTF significantly decreased the severity of glycemic symptoms in the db/db mice. Moreover, the treatment partially restored glucose homeostasis in the db/db mice and protected the pancreatic β-cell function. JTTF protected INS-1 cells from HG injury by upregulating GSIS and PDX1, MafA mRNA expression. Further, treatment with JTTF downregulated GRP78 and ATF6 expression, whereas it inhibited Beclin-1 and LC3 activation. The treatment protected the cells from HG-induced ERS and excessive autophagy by downregulating the CaMKKβ/AMPK pathway. The present study findings show that JTTF may protects β-cells by inhibiting the CaMKKβ/AMPK pathway, which deepens our understanding of the effectiveness of JTTF as a treatment strategy against T2DM. [Display omitted] • JTTF is a traditional Chinese medicine formula with significant anti-hyperglycemic effects. • JTTF may protect pancreatic β-cells by inhibiting ERS and excessive autophagy. • In vivo and in vitro experiments evidence that JTTF can reduce pancreatic β-cells damage by regulating the CaMKKβ/AMPK pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: The differences between sporadic and multiple endocrine neoplasia type 1 (MEN-1)–associated insulinoma are not well described. Herein, we compared demographics, neoplasm characteristics, presentation, and survival in patients with sporadic vs MEN-1 insulinomas including benign and malignant disease. STUDY DESIGN: A retrospective study identified insulinoma patients. MEN-1 was defined based on genetic testing or clinically in patients with 2 or more primary MEN-1 tumor types. RESULTS: A total of 311 patients were identified: 84% benign and 16% malignant. The incidence of malignancy was similar (18% vs 16%, MEN-1 vs sporadic, p = 0.76). Within malignant patients, the median (interquartile range) age was 33 (25,44) years in MEN-1 vs 54 (41, 70) years in sporadic insulinoma (p = 0.04). There was no difference in sex or tumor size between MEN-1 and sporadic malignant insulinoma (p > 0.05). Of the 260 patients with benign insulinoma, 7% had MEN-1 syndrome. MEN-1 patients presented with insulinoma at a younger age: median (interquartile range) age was 38 (24, 49) years vs 52 (43, 65) years (p < 0.01). Resection of benign insulinoma was performed in 78% of the MEN-1 and 94% of the sporadic group (p = 0.03). Resected benign tumors were larger in the MEN-1 group: 2.0 (1.65, 2.45) cm vs 1.5 (1.2, 2.0) cm, respectively (p = 0.03). Concurrent insulinomas were more common in MEN-1 (17% vs 2%; p < 0.01). CONCLUSIONS: MEN-1 patients present with insulinoma at younger age and have larger benign pancreatic lesions at the time of resection compared with sporadic neoplasms. Younger patients and those with multifocal pancreatic neuroendocrine tumor in the setting of endogenous hyperinsulinism should be evaluated for MEN-1. [ABSTRACT FROM AUTHOR]

Virtual memory CD8+ T cells (TVM) have been described as cells with a memory-like phenotype but without previous antigen (Ag) exposure. TVM cells have the ability to respond better to innate stimuli rather than by TCR engagement, producing large amounts of interferon gamma (IFNγ) after stimulation with interleukin (IL)-12 plus IL-18. As a result of the phenotypic similarity, TVM cells have been erroneously included in the central memory T cell subset for many years. However, they can now be discriminated via the CD49d receptor, which is up-regulated only on conventional memory T cells (TMEM) and effector T cells (TEFF) after specific cognate Ag recognition by a TCR. In this work we show that systemic expression of IL-12 plus IL-18 induced an alteration in the normal TVM vs TMEM/TEFF distribution in secondary lymphoid organs and a preferential enrichment of TVM cells in the melanoma (B16) and the pancreatic ductal adenocarcinoma (KPC) tumor models. Using our KPC bearing OT-I mouse model, we observed a significant increase in CD8+ T cell infiltrating the tumor islets after IL-12+IL-18 stimulation with a lower average speed when compared to those from control mice. This finding indicates a stronger interaction of T cells with tumor cells after cytokine stimulation. These results correlate with a significant reduction in tumor size in both tumor models in IL-12+IL-18-treated OT-I mice compared to control OT-I mice. Interestingly, the absence of IFNγ completely abolished the high antitumor capacity induced by IL-12+IL-18 expression, indicating an important role for these cytokines in early tumor growth control. Thus, our studies provide significant new information that indicates an important role of TVM cells in the immune response against cancer. [ABSTRACT FROM AUTHOR]

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Pancreatic neuroendocrine tumors (PNETs) or islet cell tumors are neuroendocrine neoplasms that arise from cells of the endocrine and nervous system within the pancreas. Patients with PNET sometimes do not show any symptoms, known as nonfunctioning (NF) sporadic PNET. It is still debatable regarding the best approach in the NF for small PNET. Currently, the surgical approach is considered the best; however, it is a highly invasive procedure, and it has a potentially high risk of complications as it requires a skilled and experienced operator. Herewith, we reported a 48-year-old female with incidentaloma of nonfunctioning PNET (NF-PNET) whose tumor has been successfully treated with endoscopic ultrasound guided radiofrequency ablation (EUSRA). There was no adverse event observed during and after the EUS procedure, and even 1 week after the procedure. One year later, abdominal magnetic resonance imaging (MRI) examination was carried out and size of the tumor was significantly getting smaller where it could hardly be seen anymore. After 2 years of follow-up, the latest abdominal MRI study showed no solid part of the tumor could be seen anymore. In conclusion, EUSRA can be an alternative option for incidentaloma of NF-PNET management. [ABSTRACT FROM AUTHOR]

The article focuses on insulinoma, a rare neuroendocrine tumor in the pancreas that causes excessive insulin production, leading to severe hypoglycemia. Topics discussed include diagnostic techniques to identify the tumor, surgical and medical treatment options, and the importance of early detection for improved patient outcomes.

Background: Pancreatic neuroendocrine tumors (pNET) are rare diseases and surgical treatment is promising. In this study, we retrospectively analyzed the patients who underwent surgical treatment for pancreatic neuroendocrine tumor in our hospital in the last 11 years; We aimed to present our findings to the literature. Materials and Methods: The files of the patients who applied for pNET between January 2011 and March 2022 were retrospectively analyzed. Patients with multiple data deficiencies, who did not undergo surgery, and who were younger than 18 years of age were excluded from the study. The patients were evaluated in terms of age, gender, type of operation, tumor size, type and histological features, hospital stay, recurrent disease and survival. Results: Of the 33 patients included in the study, 13 were female and 20 were male, and the median age was 56 (18-86). There were 8 patients with functional tumors, one was somatostatinoma and the others were insulinomas. Enucleation in 7 of the patients; Pancreatectomy was performed in 26 of them. There were three patients whose main lesion was adenocarcinoma and serous cystadenoma, who underwent resection and whose specimen pathology had incidental pNET. We had 23, 7 and 3 patients with grade 1,2 and 3 tumors, respectively. The median value of tumor diameter was 24 (3-80) mm. The median value for hospital stay was 7 (2-50) days. The median value of follow-up was 24 (1-71) months; disease-free survival was 14 (1-71) months. Conclusions: pNETs are a rare disease that can be detected incidentally and should be carefully managed. Studies with larger series are needed to reach a consensus on the surgical and conservative treatment of pNET. [ABSTRACT FROM AUTHOR]

Background: ACTH-independent macronodular hyperplasia (AIMAH) is an uncommon disorder characterized by massive enlargement of both adrenal glands and hypersecretion of cortisol. Concomitant AIMAH and multiple endocrine neoplasia type1 (MEN1) is rare to our knowledge. Case presentation: Herein, we describe a 32 year old woman with long history of prolactinoma and secondary ammonhrea presented with not-severe manifestation of hypoglycemia due to concomitant presence of insulinoma with AIMAH leading to 12 years delay of MEN1 diagnosis. Laboratory tests showed severe hypoglycemia associated with hyper insulinemia (non-fasting blood sugar = 43 mg/dl, insulin = 80.6 μIU /ml, C-peptide = 9.3 ng/ml) hyperparathyroidism (calcium = 10.3 mg/dl, phosphor = 3.1 mg/dl, PTH = 280 pg/ml) and chemical evidence of an ACTH-independent hypercortisolism (serum cortisol value of 3.5, after 1 mg dexamethasone suppression test serum ACTH value of 17 pg/ml, and high urinary cortisol level). Abdominal CT scan demonstrated two enhancing well-defined masses 27*20 mm and 37*30 mm in the tail and body of the pancreas, respectively, and a 36*15 mm mass in left adrenal gland (seven Hounsfield units). Dynamic pituitary MRI revealed a partial empty sella. The physical examination of the patient was unremarkable. Distal pancreatectomy and a left adrenalectomy were performed. After the surgery, we observed clinical and biochemical remission of hyper insulinemia and gradual decrease in urinary cortisol. The histological features of the removed left adrenal gland were consistent with AIMAH. Histological examination of the pancreatic lesions revealed well differentiated neuroendocrine tumors. Genetic abnormalities in the MEN1, heterozygote for pathogenic variant chr11; 645,773,330-64577333AGAC, c.249-252delGTCT, p. (11e85Serfs Ter33) in exon 2 were found. It was recommended the patient undergoes parathyroidectomy as soon as possible. Conclusion: Given the history and presentation of our case, we recommend that the clinicians consider the possibility of autonomous cortisol production in MEN1 patients who do not show severe symptoms of hypoglycemia in the presence of insulinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Adult-onset familial insulinomatosis is a rare disorder with recurrent, severe hypoglycemia caused by multiple insulin-secreting pancreatic tumors. The etiology was unclear until the genetic variant p.Ser64Phe in the MAFA protein, a key coordinator of insulin secretion in pancreatic cells, was defined as the cause in two families. Based on the cases of two sisters with insulinomatosis, we aimed to identify further disease causes. The sequencing of the complete coding regions of the patients' genomes revealed a second genetic MAFA variant, p.Thr57Arg, as the cause of familial insulinomatosis, linking genetic, clinical, and biochemical analyses from the patients' family to the pre-described cell culture data. Thus, we confirm a defect in a crucial regulatory region of the MAFA protein as an important cause of a specific hereditary syndrome, which is characterized by insulinomatosis and/or mild hyperglycemia. This study extends the pathophysiological and diagnostic disease concept and verifies the inheritance pattern of familial insulinomatosis. Adult-onset familial insulinomatosis is a rare disorder with recurrent, severe hypoglycemia caused by multiple insulin-secreting pancreatic tumors. The etiology was unclear until the variant p.Ser64Phe in the transcription factor MAFA, a key coordinator of β-cell insulin secretion, was defined as the cause in two families. We here describe detailed genetic, clinical, and family analyses of two sisters with insulinomatosis, aiming to identify further disease causes. Using exome sequencing, we detected a novel, heterozygous missense variant, p.Thr57Arg, in MAFA's highly conserved transactivation domain. The impact of the affected region is so crucial that in vitro expression studies replacing Thr57 have already been performed, demonstrating a phosphorylation defect with the impairment of transactivation activity and degradation. However, prior to our study, the link to human disease was missing. Furthermore, mild hyperglycemia was observed in six additional, heterozygote family members, indicating that not only insulinomatosis but also MODY-like symptoms co-segregate with p.Thr57Arg. The pre-described MAFA variant, p.Ser64Phe, is located in the same domain, impairs the same phosphorylation cascade, and results in the same symptoms. We confirm MAFA phosphorylation defects are important causes of a characteristic syndrome, thus complementing the pathophysiological and diagnostic disease concept. Additionally, we verify the high penetrance and autosomal dominant inheritance pattern. [ABSTRACT FROM AUTHOR]

Background: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation. Case presentation: A 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m2.She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3rd decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms. Conclusions: Renal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype. [ABSTRACT FROM AUTHOR]

Background: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. Case presentation: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family. Conclusions: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype–phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families. [ABSTRACT FROM AUTHOR]

Objective Insulinomas are rare in the post-bariatric surgery setting. The differential diagnosis for hypoglycemia is broad, requiring laboratory testing to verify endogenous hyperinsulinemic hypoglycemia. Selective arterial calcium stimulation testing (SACST) can help localize abnormal insulin production. We describe a patient with histologically confirmed insulinoma after bariatric surgery diagnosed with the aid of SACST. Methods We present a 67 year old woman with a history of Roux-en-Y bypass surgery who presented with endogenous hyperinsulinemic hypoglycemia. Initially, no pancreatic lesion was identified radiologically. We pursued SACST to localize the source of insulin production. Results The SACST successfully localized the source of hyperfunctioning islet cells to the pancreatic tail with absolute insulin values in a range consistent with insulinoma. Additional radiologic studies showed a small tumor in the pancreatic tail. Pathology showed a well-differentiated neuroendocrine tumor, compatible with insulinoma. Conclusion This case study illustrates the usefulness of SACST for the diagnosis and localization of insulinoma. [ABSTRACT FROM AUTHOR]

Context: Insulinoma is the most common pancreatic functional neuroendocrine neoplasm, yet little information on recent clinical practice in patients with insulinoma, especially malignant insulinoma, is available.Objective: This work aims to clarify the characteristics and practice patterns in patients with insulinoma using a national inpatient database.Methods: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with insulinoma admitted between 2010 and 2018. We compared background characteristics and therapeutic interventions between patients with benign and malignant insulinoma. We also estimated the incidence of insulinoma using the number of patients with newly diagnosed insulinoma in 2012.Results: We identified 844 patients with benign insulinoma and 102 patients with malignant insulinoma. Patients with malignant insulinoma were younger (median, 55.5 vs 66.0 years, P < .001) and less likely to be female (55.9% vs 65.3%, P = .061) than patients with benign insulinoma. Analysis of therapeutic interventions revealed that patients with malignant insulinoma more frequently received medications (71.6% vs 49.6%, P < .001) but less frequently underwent pancreatic surgery (57.8% vs 72.0%, P = .003). Older patients were a smaller proportion of those undergoing surgery and a larger proportion of those managed with medications without surgery (P < .001). The incidence of insulinoma was estimated to be 3.27 (95% CI, 2.93-3.61) individuals per million Japanese adult population per year.Conclusion: The present study using a nationwide database had a larger sample size than previous studies and revealed definitive differences in patient characteristics and therapeutic patterns between benign and malignant insulinoma. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end. [ABSTRACT FROM AUTHOR]

Background: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon‐like peptide‐1 receptors enabling positron emission tomography–computed tomography imaging with its radiolabelled analogue; 68Ga‐DOTA‐Exendin‐4 (Exendin). Aim: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non‐insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post‐gastric bypass hypoglycaemia (PGBH). Methods: This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report. Results: Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH. Conclusion: In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is an autoimmune and inflammatory disease with excessive loss of pancreatic islet β -cells. Accumulating evidence indicated that endoplasmic reticulum (ER) stress played a critical role in β -cells loss, leading to T1D. Therefore, promoting the survival of pancreatic β cells would be beneficial for patients with T1D. Puerarin is a natural isoflavone that has been demonstrated to be able to decrease blood glucose in patients with T1D. However, it remains unknown whether puerarin improves ER stress to prevent β -cells from apoptosis. Here, we sought to investigate the role of puerarin in ER stress-associated apoptosis and explore its underlying mechanism in the mouse insulinoma cell line (MIN6). Flow cytometry and cell counting kit-8 (CCK8) experiments showed that puerarin caused a significant increase in the viability of MIN6 cells injured by H2O2. Furthermore, the protein kinase R-like ER kinase (PERK) signal pathway, a critical branch of ER stress response, was found to be involved in this process. Puerarin inhibited the phosphorylation of PERK, subsequently suppressed the phosphorylation of eukaryotic initiation factor 2 α (eIF2 α) , then decreased the activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, ultimately attenuating ER stress to prevent MIN6 cells from apoptosis. In addition, puerarin inhibited the activation of Janus kinase 2 (JAK2)/signal transducer and activators of transcription 3 (STAT3), which suppressed the PERK signal cascade with decreased ATF4 and CHOP levels. Taken together, our results firstly demonstrated that puerarin could prevent MIN6 cells from apoptosis at least in part by inhibiting the PERK-eIF2 α -ATF4-CHOP axis under ER stress conditions, which might be mediated by inactivation of the JAK2/STAT3 signal pathway. Therefore, investigating the mechanism underlying the effects of puerarin might highlight the potential roles of puerarin developing into an antidiabetic drug. [ABSTRACT FROM AUTHOR]

Insulinoma is a rare neuroendocrine tumor originating from hypersecreting beta-cells of islets of Langerhans in the pancreas. We report a case of 72-year-old male, with chronic alcohol abuse, presenting with atypical features like refractory recurrent secondary generalized seizures and behavioral disturbances with increased irritability, initially mistreated as alcohol withdrawal. Detailed history, particularly the relationship of the symptoms with food intake, made us think of other causes of seizures. Fasting biochemical investigations and localizing studies helped clinch the diagnosis. The tumor was localized with the help of endoscopic ultrasonography and whole-body Ga68-DOTANOC PET-CT. The patient was treated conservatively with diazoxide and is doing well on follow-up. The present case report emphasizes the importance of detailed clinical history, more so in atypically presenting cases of refractory seizures. Insulinoma can be medically managed despite surgery being the gold standard curative treatment. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic islet-cell tumors (PICT) often present with atypical signal-characteristics and are often missed on preoperative imaging. The aim of this study is to provide a multiparametric PICT characterization and investigate factors impeding PICT detection. Material and methods: This is a detailed MRI analysis of a prospective, monocenter study, including 49 consecutive patients (37 female, 12 male; median age 50) with symptoms due to endogenous hyperinsulinemic hypoglycemia (EHH) and mostly negative prior-imaging. All patients received a 3-T MRI and a 68Ga-DOTA-exendin-4-PET/CT. Pooled accuracy, sensitivity, specificity and inter-reader agreement were calculated. Reference-standard was histopathology and 68Ga-DOTA-Exendin-4-PET/CT in one patient who refused surgery. For PICT analyses, 34 patients with 49 PICTs (48 histologically proven; one 68Ga-DOTA-exendin-4-PET/CT positive) were assessed. Dynamic contrast-enhanced (DCE) Magnetic Resonance Images (MRI) with Golden-Angle-Radial-Sparse-Parallel (GRASP) reconstruction, enabling imaging at high spatial and temporal resolution, was used to assess enhancement-patterns of PICTs. Tumor-to-background (T2B) ratio for each sequence and the employed quantitative threshold for conspicuity of PICTs were analyzed in regard to prediction of true-positive PICTs. Results: Evaluation of 49 patients revealed a pooled lesion-based accuracy, sensitivity and specificity of 70.3%, 72.9% and 62.5%, respectively. Mean PICT size was 12.9±5.3mm for detected, 9.0±2.9mm for undetected PICTs (p-value 0.0112). In-phase T1w detected the most PICT (67.3%). Depending on the sequence, PICTs were isointense and poorly visible in 29–68%. Only 2/41(4.9%) PICTs showed typical signal-characteristics across T1w, T2w, DWI and ceT1w combined. 66.6% of PICTs enhanced simultaneously to the parenchyma, 17.8% early and 15.6% late. Predictor screening analysis showed number of sequences detecting a PICT, lesion size and in-phase T1w T2B ratio had the highest contribution for detecting a true-positive PICT. Conclusion: The majority of PICTs enhance simultaneously to surrounding parenchyma, present with atypical signal-characteristics and thus are poorly visible. In non-enhancing PICTs, radiologists should search for small lesions most likely conspicuous on unenhanced T1w or DWI. [ABSTRACT FROM AUTHOR]

A case study is presented of a 55-year-old male who was brought to the emergency department via EMS due to confusion, non- sensical speech, diaphoresis, and a serum glucose level. In order to confirm a hyperfunctioning pancre- atic tumor, a fasting blood glucose measurement was taken, after the dextrose infusion was turned off, his blood glucose decreased, and the findings were consistent with an insulinoma.

• Tyrosine kinase inhibitors Recent interest in the use of tyrosine kinase inhibitors such as toceranib phosphate (Palladia TM) has emerged, based on the efficacy of sutanib, another tyrosine kinase inhibitor, in clinical trials of humans with pancreatic neuroendocrine tumours. 20 Tumour size and Ki67 index (a proliferation marker depicting the mitotic rate of the tumour on histopathology) have also been identified as prognostic markers in canine insulinoma. Veterinary Ireland Journal I Volume 11 Number 3 172 Approach to canine insulinoma Myles McKenna MVB MVetSci MVetMed DACVIM (SAIM) DECVIM-CA MRCVS, assistant professor in small animal internal medicine at University College Dublin, presents an overview of canine insulinoma Insulinoma is defined as an insulin-secreting tumour of pancreatic beta-cells, and is the most common endocrine tumour of the pancreas in dogs. Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999). [Extracted from the article]

We present the case of a 70-year-old female patient with persistent hypoglycemia after total gastrectomy due to gastrointestinal stromal tumors. She was thought to have late dumping syndrome but was diagnosed with insulinoma after further examination. Dumping syndrome is mainly seen after stomach or esophageal surgery. It is divided into early dumping and late dumping syndrome. Late dumping syndrome is initially manifested by an exaggerated insulin response and reactive hypoglycemia after glucagon-like peptide-1 release. Diagnosis is based on clinical findings. Treatment mainly consists of reducing carbohydrate intake and not ingesting solid and liquid foods together. In cases where diet alone is not sufficient, acarbose, an a-glucosidase inhibitor that slows the digestion of carbohydrates, may be beneficial for late dumping. Octreotide can be used in resistant cases. However, the diagnosis of insulinoma, which leads to a similar clinical presentation in resistant dumping cases, should be kept in mind. Our patient who showed clinical signs of dumping syndrome after gastrectomy, and treatment-resistant hypoglycemia was diagnosed with insulinoma on the basis of further investigations. The patient's symptoms resolved after surgery for insulinoma. [ABSTRACT FROM AUTHOR]

We present the case of an 83-year-old woman with recurrent episodes of delirium occurring overnight, associated with hypoglycaemia. Other causes for delirium were excluded. Laboratory findings were in keeping with endogenous insulin production. Computerised tomography imaging revealed a small mass in the pancreas supporting a presumed diagnosis of an insulinoma. Given the patient's frailty and cognitive impairment, a conservative management approach was taken. Diazoxide was commenced with resolution of episodes of delirium. This case highlights hypoglycaemia, and insulinoma, as a rare, but treatable cause of delirium. It demonstrates the importance of blood sugar screening in delirium. It emphasises the holistic modifications to management, which must be taken to ensure patient-centred care when caring for an older adult living with frailty, who may have cognitive impairment. [ABSTRACT FROM AUTHOR]

We also reviewed the published literatures and summarized the clinical characteristics, diagnostic methods, treatment strategies and patient prognosis of multiple myeloma with involvement of the pancreas. A plain abdominal computed tomography (CT) scan showed dilatation of the upper segment of the common bile duct (CBD) and the intrahepatic bile duct. Surgical procedures other than distal pancreatectomy for isolated pancreatic tail involvement are not commonly performed due to the common systemic nature of the disease.5 ERCP can be used to treat obstructive jaundice via a biliary stent placement and has been increasingly used in patients with secondary pancreatic plasmacytoma in recent years. [Extracted from the article]

Aims: To evaluate the diagnostic relevance of autoantibodies against zinc transporter 8 (ZnT8) in schoolchildren from the general population as well as in people with autoimmune diabetes. Methods: A total of 137 schoolchildren positive for at least one of the three major diabetes‐associated autoantibodies, without diabetes heredity or preselection on HLA typing, from the Karlsburg Type 1 Diabetes Risk Study, as well as 102 people at type 1 diabetes onset, 88 people with latent autoimmune diabetes in adults and 119 people with type 2 diabetes, were analysed for different ZnT8 autoantibody variants. Results: Zinc transporter 8 autoantibody positivity was found in 18% of autoantibody‐positive schoolchildren, with a noticeable association with other autoantibodies associated with type 1 diabetes and disease progression. Furthermore, ZnT8 autoantibody positivity was associated with diabetes progression in schoolchildren positive for autoantibodies against insulinoma‐associated antigen‐2 (IA‐2) and, importantly, in seven IA‐2 autoantibody‐negative schoolchildren. Additionally, ZnT8 autoantibodies were found in 56% of people with type 1 diabetes, predominantly directed against all three ZnT8 variants and comparable to schoolchildren with multiple autoantibodies. In contrast, ZnT8 autoantibodies were detected in 10% of people with latent autoimmune diabetes in adults, none of them with reactivity to all three isoforms. Conclusion: Zinc transporter 8 autoantibodies are useful markers for prediction of type 1 diabetes in a general population, further stratifying the risk of progression in autoantibody‐positive children. ZnT8 autoantibodies are also important markers in adult‐onset diabetes, with a completely different reaction pattern in type 1 diabetes in comparison to latent autoimmune diabetes in adults, and may therefore help to differentiate between the two forms. [ABSTRACT FROM AUTHOR]

The article focuses on neuroendocrine tumors (NET) are a rare and heterogeneous group of neoplasms with variable biological behavior. Topics include the frequently metastasize to the liver, requiring active, multimodality treatment, the liver transplantation (LT) has emerged as a potential curative treatment due to relatively slow growth and indolent behavior of the metastases, and the selected patients with metastatic NET disease as an indication for LT treated in our center.

Background: Neuroendocrine tumors (NETs) are rare tumors harboring overexpression of somatostatin receptors (SSTRs) on their cell membrane. Because some organs, such as the spleen, adrenal glands and liver, physiologically express SSTR, it might be challenging to distinguish some pancreatic NETs located in the pancreatic tail from the accessory spleen next to the splenic hilum. In this manuscript, we report a case with hypoglycemia attack and 2 different masses displayed by Gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT). Case presentation: A 63-year-old woman presented to the hospital with confusion and profuse sweating. Biochemical diagnosis of insulinoma was established. 68Ga-DOTATATE PET/CT revealed two masses with increased tracer uptake located adjacent to the splenic hilum and inferior pole of the spleen which were initially reported as two separate accessory spleens. Then, 99mTc-labelled heat-denaturated red blood cell (99mTc-HDRBC) scintigraphy-single-photon emission computed tomography (SPECT)/CT was performed to distinguish a NET in the pancreatic tail from accessory spleen at the splenic hilum. Enhanced tracer uptake remained in the inferior pole of spleen, but not in the splenic hilum. The lesions were suggestive of insulinoma in the pancreatic tail and an accessory spleen adjacent to the inferior pole of the spleen. Conclusion: Approximately 10% of the population have an accessory spleen which can show similar imaging characteristics with pancreatic NETs, especially if located in the pancreatic tail. In our presented case, 99mTc-HDRBC scintigraphy-SPECT/CT is a useful nuclear medicine method to differentiate a NET in the pancreatic tail from accessory spleen at the splenic hilum which may avoid unnecessary surgeries in the presence of enhanced tracer uptake or vice versa. [ABSTRACT FROM AUTHOR]

These findings provide valuable insights on the mechanisms of ESCC progression mediated by cell-cell interactions among cancer cells, TAMs and CAFs in the tumor microenvironment. I have studied "the significance of cell-cell interactions between tumor cells and stromal cells" in the tumor microenvironment. Subsequent investingations on NKX2.2-negative non-Ewing round cell sarcomas evolved into detailed characterization of CIC-rearranged sarcoma and "SMARCA4-deficient thoracic sarcoma", which helped in establishing these tumor concepts. [Extracted from the article]

Solid Pseudopapillary Neoplasms of the pancreas are rare pancreatic tumors with low-grade malignant potential, typically affecting young females. In this review, we discuss the surgical anatomy; the imaging characteristics, and image reporting essentials for proper surgical planning along with the atypical features which should caution the physician regarding the risk of malignancy. We also discuss the common surgical procedures and organ preservation surgeries along with a comprehensive review of the literature. • Solid Pseudopapillary Neoplasms of the pancreas are rare pancreatic tumors with low grade malignant potential, typically affecting young females. • Small SPNs (< 3cm in diameter) usually appear as completely solid tumors with sharp margins and gradually enhancing, well encapsulated masses in the pancreas and may demonstrate varying amounts of hemorrhage. • Large lesions have mixed solid – cystic components showing early weak enhancement with gradual increase in enhancement in the hepatic venous phase. • Atypical features including extracapsular, as well as parenchymal invasion, simulation of islet cell tumors, calcifications, ductal obstruction, and metastasis are suspicious for malignant degradation. • The tumor is considered unresectable in the event that it invades or encases the aorta, encases >180 degree of the SMA regardless of tumor location in the pancreas, abuts the celiac artery (when the tumor is located in the pancreatic head) or encases >180 degree of the celiac artery (when the tumor is located in the body/tail of the pancreas). [ABSTRACT FROM AUTHOR]

A 37-year-old active duty male Air Force instructor pilot, with no prior medical history, was found unresponsive at his home after awakening with symptoms of altered mental status when the Emergency Medical Service (EMS) was called. The patient was found to be hypoglycemic with a glucose of 37 mg/dL. The patient recovered after administration of a dextrose bolus. Further investigation revealed that over the last several years, the patient exhibited symptoms of lightheadedness and tremors if fasted greater than 3 hours. Further clinical workup strongly suggested the presence of a neuroendocrine tumor. Initial imaging studies to include a multiphasic dedicated pancreatic computed tomography (CT) scan did not demonstrate a pancreatic lesion. However, the utilization of an innovative new nuclear medicine imaging modality, a 68Ga-Dotatate PET/CT, clearly demonstrated a 19 × 16 mm lesion of the distal pancreatic tail, which guided surgical resection. He underwent a robotic-assisted laparoscopic distal pancreatectomy, pathologically characterized as an insulinoma. The patient's symptoms immediately resolved with no recurrence over the next 6 months. The pilot was granted a waiver, returning him to his flying duties. The 68Ga-Dotatate PET/CT enabled the identification of an otherwise occult pancreatic neuroendocrine tumor ultimately leading to this patient's definitive cure and the salvage of this military asset's aviation career. [ABSTRACT FROM AUTHOR]