A ventral brainstem neurenteric cyst - A case report and review of the pre-brainstem location.

Background: Neurenteric cysts are uncommon, benign endoderm-derived lesions that result from aberrant embryologic development of the notochord. They are typically located in the intradural extramedullary spinal cord and rarely located intracranially. Contrary to spinal-located cysts, intracranial cysts are rarer in the pediatric population. Clinically, they may present with symptoms of mass effect, or they can be incidentally discovered. Case Description: A 10-year-old healthy female child presented with recurrent headaches. The physical and neurological examination was unremarkable. Brain magnetic resonance imaging (MRI) showed a well-demarcated lesion anterior to the pontomedullary junction with striking T1 and T2/T2 fluid-attenuated inversion recovery high-signal intensity and a small rounded nodule within of low signal on T1, T2, and T2*. On initial conservative strategy with serial brain MRI, there was a progressive enlargement of the lesion with significant mass effect on the brainstem. The patient underwent a right retrosigmoid craniotomy, and the cyst wall was fenestrated and drained. Part of the cyst wall and the solid nodule were adherent to the brainstem and basilar artery and were not removed. The histologic findings were consistent with the diagnosis of a benign endodermal cyst. The postoperative period was uneventful. Conclusion: We report a successful surgical treatment of this rare congenital cyst located in the ventral brainstem. We present pre-and post-operative imaging findings, intraoperative microscopic images of the procedure, and a brief review of relevant clinical literature on the topic.

Posterior Cervical Glomus Tumor Mimicking Neurogenic Occipital Pain.

Glomus tumors, typically localized in digits, palms, and soles, rarely occur in the posterior cervical region. This case report describes a unique presentation of an epithelioid glomus tumor in a 49-year-old male with a history of progressive occipital headaches. A 49-year-old male, referred with a five-year history of worsening occipital headaches, presented a palpable lesion in the right suboccipital area. MRI identified a 2.3 cm subcutaneous lesion adjacent to the right occipital artery, raising initial suspicion of a schwannoma. Subsequent excisional biopsy unveiled an unexpected diagnosis - an epithelioid glomus tumor. The rarity of glomus tumors in the posterior cervical region, coupled with their potential to mimic neurogenic tumors like schwannomas, underscores the diagnostic complexity. This encounter of a glomus tumor in an uncommon posterior cervical location serves as a pertinent reminder for neurosurgeons to consider atypical differentials. This case underscores the need for heightened clinical vigilance when faced with unusual presentations in neurosurgical practice.

Calciphylaxis and skin ulcers: a diagnostic and therapeutic challenge.

INTRODUCTION: Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare and severe disorder that presents with skin ischemia and necrosis. Diagnosis is challenging, and even if the condition is diagnosed in the early stages, the mortality rate is exceptionally high, ranging from 45% to 80%. CASE REPORT: A 55-year-old male with chronic kidney disease secondary to diabetic nephropathy presented with painful, severe, necrotic ulcers in the lower legs and underwent treatment with sodium thiosulfate, debridement of necrotic tissue, and topical oxygen therapy. Complete healing of the ulcers was achieved within 3 months. CONCLUSION: This case report raises awareness of this rare condition and details successful treatment in 1 patient.

Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

A 68-Year-Old Woman Presenting with Recurrent Abdominal Pain and a Diagnosis of a Presacral Retroperitoneal Benign Schwannoma that Mimicked an Ovarian Tumor on Pelvic Magnetic Resonance Imagining.

BACKGROUND Schwannomas are benign tumors and their appearance in the pelvic region is rare and poses a major diagnostic problem. They can be sporadic or associated with genetical syndromes. They have a slow growth rate and may be asymptomatic for many years. Symptoms are usually nonspecific and due to compression of adjacent structures. Abdominal imaging modalities may not be able to differentiate a benign schwannoma from a malignant retroperitoneal tumor. This report is of a case of a 68-year-old woman presenting with recurrent abdominal pain and a diagnosis of a presacral retroperitoneal benign schwannoma that mimicked an ovarian tumor on pelvic magnetic resonance imaging. CASE REPORT The patient had a history of a femoral hernia repair and recurrent lower abdominal pain. Pelvic imaging raised the suspicion of a primary ovarian tumor. The mass appeared to have clear cleavage planes with the surrounding structures, so the patient was proposed for an exploratory laparotomy. Prior to the surgery, an additional pelvic computed tomography (CT) was performed (10 months after the first one), which did not show progression of the disease. The histological examination result was compatible with a benign retroperitoneal schwannoma and not an ovarian tumor. CONCLUSIONS This report highlights that the diagnosis of retroperitoneal and pelvic masses can be challenging. In women, a primary ovarian tumor should be excluded on imaging and the diagnosis of a benign tumor, such as schwannoma, must be confirmed by histopathology, either preoperatively or following tumor resection.

Primary Cilia in Pancreatic ß- and α-Cells: Time to Revisit the Role of Insulin-Degrading Enzyme.

The primary cilium is a narrow organelle located at the surface of the cell in contact with the extracellular environment. Once underappreciated, now is thought to efficiently sense external environmental cues and mediate cell-to-cell communication, because many receptors, ion channels, and signaling molecules are highly or differentially expressed in primary cilium. Rare genetic disorders that affect cilia integrity and function, such as Bardet-Biedl syndrome and Alström syndrome, have awoken interest in studying the biology of cilium. In this review, we discuss recent evidence suggesting emerging roles of primary cilium and cilia-mediated signaling pathways in the regulation of pancreatic ß- and α-cell functions, and its implications in regulating glucose homeostasis.

Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by hyperglucagonaemia and perturbed function of pancreatic glucagon-secreting alpha cells but the molecular mechanisms contributing to these phenotypes are poorly understood. Insulin-degrading enzyme (IDE) is present within all islet cells, mostly in alpha cells, in both mice and humans. Furthermore, IDE can degrade glucagon as well as insulin, suggesting that IDE may play an important role in alpha cell function in vivo. METHODS: We have generated and characterised a novel mouse model with alpha cell-specific deletion of Ide, the A-IDE-KO mouse line. Glucose metabolism and glucagon secretion in vivo was characterised; isolated islets were tested for glucagon and insulin secretion; alpha cell mass, alpha cell proliferation and α-synuclein levels were determined in pancreas sections by immunostaining. RESULTS: Targeted deletion of Ide exclusively in alpha cells triggers hyperglucagonaemia and alpha cell hyperplasia, resulting in elevated constitutive glucagon secretion. The hyperglucagonaemia is attributable in part to dysregulation of glucagon secretion, specifically an impaired ability of IDE-deficient alpha cells to suppress glucagon release in the presence of high glucose or insulin. IDE deficiency also leads to α-synuclein aggregation in alpha cells, which may contribute to impaired glucagon secretion via cytoskeletal dysfunction. We showed further that IDE deficiency triggers impairments in cilia formation, inducing alpha cell hyperplasia and possibly also contributing to dysregulated glucagon secretion and hyperglucagonaemia. CONCLUSIONS/INTERPRETATION: We propose that loss of IDE function in alpha cells contributes to hyperglucagonaemia in type 2 diabetes.

Diaphragmatic hernia as a rare cause of bowel obstruction.

Mechanical intestinal obstruction is a common cause of acute abdominal pain that brings patients to the emergency department. One of the main causes is adhesion in the abdomen after abdominal surgery, but rarer causes exist and are a diagnostic challenge due to the similarity of the presenting symptoms. Here, we present a case of intestinal obstruction caused by diaphragmatic hernia.

Effects of Fasting and Feeding on Transcriptional and Posttranscriptional Regulation of Insulin-Degrading Enzyme in Mice.

Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed Zn2+-metallopeptidase that regulates hepatic insulin sensitivity, albeit its regulation in response to the fasting-to-postprandial transition is poorly understood. In this work, we studied the regulation of IDE mRNA and protein levels as well as its proteolytic activity in the liver, skeletal muscle, and kidneys under fasting (18 h) and refeeding (30 min and 3 h) conditions, in mice fed a standard (SD) or high-fat (HFD) diets. In the liver of mice fed an HFD, fasting reduced IDE protein levels (~30%); whereas refeeding increased its activity (~45%) in both mice fed an SD and HFD. Likewise, IDE protein levels were reduced in the skeletal muscle (~30%) of mice fed an HFD during the fasting state. Circulating lactate concentrations directly correlated with hepatic IDE activity and protein levels. Of note, L-lactate in liver lysates augmented IDE activity in a dose-dependent manner. Additionally, IDE protein levels in liver and muscle tissues, but not its activity, inversely correlated (R2 = 0.3734 and 0.2951, respectively; p < 0.01) with a surrogate marker of insulin resistance (HOMA index). Finally, a multivariate analysis suggests that circulating insulin, glucose, non-esterified fatty acids, and lactate levels might be important in regulating IDE in liver and muscle tissues. Our results highlight that the nutritional regulation of IDE in liver and skeletal muscle is more complex than previously expected in mice, and that fasting/refeeding does not strongly influence the regulation of renal IDE.

Small Bowel Obstruction Due to Incarcerated Obturator Hernia: Successfull Surgical Management with Modified Mesh-Plug Hernioplasty.

BACKGROUND Obturator hernia is an uncommon (0.07-1% incidence rate) subtype of hernia of the abdominal wall, with its incarceration being a rare cause of bowel obstruction. Obturator hernia has a higher incidence in elderly women and in malnourished people. This type of hernia has the highest morbidity and mortality rates of all abdominal wall hernias. This article reports a case of an emaciated 93-year-old woman who presented with small bowel obstruction due to incarcerated obturator hernia, successfully managed surgically with a modified mesh-plug hernioplasty. CASE REPORT An emaciated 93-year-old woman presented with diffuse abdominal pain, more intense on the right iliac fossa, radiating to the right thigh, with 8-h evolution and associated with dark-colored vomiting but normal bowel transit. This patient had a surgical history of right Richter´s femoral hernia, strangulated, with previous intestinal resection and a right femoral hernioplasty. A computed tomography (CT) scan revealed an incarcerated obturator hernia on the right side containing a short segment of small intestine. The patient underwent an exploratory laparotomy and a mesh-plug hernioplasty. During follow-up, there was no evidence of recurrence or complications. CONCLUSIONS Obturator hernia diagnosis is challenging due to its rarity and its signs and symptoms being often unspecific. CT scan has the highest sensitivity and is the best diagnostic tool. Surgical management is the only possible treatment for obturator hernia. Awareness of this condition is essential to allow an earlier approach and attempt to mitigate the associated high morbidity and mortality rates.

Duodenal recurrence of endometrial carcinoma: report of a rare metastatic site.

Endometrial carcinoma is one of the most common gynaecologic malignancies in the western society. Treatment of recurrent disease became more refined, with the study of molecular and hormonal receptors playing a central role. A 76-year-old caucasian woman presented to the emergency department with growing tiredness, and melaena. Past medical history included an endometrioid adenocarcinoma. The patient had undergone a hysterectomy with bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy and was disease-free for 2 years. The endoscopy revealed an ulcerated lesion involving the second and third portions of the duodenum. Histopathologic examination confirmed a poorly differentiated adenocarcinoma of endometrial origin. She started palliative chemotherapy, remaining with adequate symptomatic control. Endometrial cancer recurrence typically occurs locally. The liver is the intra-abdominal organ most commonly involved. There are scarce reports of duodenal metastasis of malignancies originated in distant organs. The duodenum remains an uncommon metastization site and is rarely associated with endometrial cancer.

Adenocarcinoma of the jejunum: management of a rare small bowel neoplasm.

Small bowel adenocarcinomas are rare malignant tumors that account for less than 2% of gastrointestinal tumors. Despite a thorough history, physical examination and complete diagnostic workup, the correct diagnosis of small intestinal neoplasm has been established preoperatively in only 50% of cases. Due to the rarity of this disease, there are very few established guidelines for its management and it has been primarily treated the same way as colorectal cancer, even though patient's prognostic outcome is worse. With new guidelines in 2020, we review a clinical case of a 64-year-old male patient with adenocarcinoma of the jejunum treated in our institution.

Low-Grade Dysplastic Intracholecystic Papillary Neoplasia: A Case Report.

BACKGROUND The World Health Organization classification of premalignant gallbladder lesions includes adenomas, intraductal papillary neoplasms, biliary intraepithelial neoplasia, and intracystic papillary neoplasms. Noninvasive neoplastic lesions >1 cm that originate from the pancreatobiliary system are defined as intraductal papillary neoplasia when they occur in the biliary ducts. The clinical and pathological features of preinvasive lesions arising in the gallbladder are not yet well defined. However, the most widely accepted classification is that of intracholecystic papillary neoplasm (ICPN). CASE REPORT We present the case of a 71-year-old woman referred to a General Surgery outpatient clinic for suspicious findings on imaging of the gallbladder, namely irregular infundibular parietal thickening. The patient underwent a laparoscopic cholecystectomy and histological examination revealed a thickened gallbladder with mucosa partially surrounded by ICPN with an intestinal pattern and some foci of low-grade dysplasia but no foci of high-grade dysplasia or invasive neoplasia. At follow-up at 30 months, the patient remains clinically well, with no changes visible on computed tomography scan. CONCLUSIONS ICPN of the gallbladder appears to be part of a spectrum of alterations encompassing bile duct or pancreatic lesions. Although it is uncommon, more than half of the lesions are known to have foci of invasive neoplasia at the time of diagnosis. Despite that, the prognosis for these neoplasms is more favorable than for gallbladder neoplasia that originates from another type of lesion. Pathological study of ICPN is essential to define the main characteristics that impact prognosis and survival in these patients.

Targeting Insulin-Degrading Enzyme in Insulin Clearance.

Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50-80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn2+-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky's seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients.

Congenital peritoneal encapsulation-a rare entity presented with small bowel obstruction.

Congenital peritoneal encapsulation is a rare congenital malformation in which all or part of the small bowel is covered by a thin accessory peritoneal membrane. Despite being usually asymptomatic and an incidental finding during surgery or autopsy, there is a small number of reports in the literature whose diagnosis was established in the context of intestinal obstruction. The authors review the topic and describe a case report undergoing surgery for intestinal obstruction. Intraoperatively, there was a partial peritoneal encapsulation of the small bowel with signs of intestinal malrotation. Peritoneal membrane excision, terminal ileum release and complementary appendicectomy were performed. There was a favorable clinical evolution in the postoperative period. Although rare, it is important to remember this entity in the differential diagnosis of patients with intestinal obstruction, in the absence of other etiologic factors.

Non-Islet Cell Tumor Hypoglycemia Caused by Recurrent Pelvic Solitary Fibrous Tumor.

Non-islet cell tumor hypoglycemia is a rare paraneoplastic condition caused by an extra-pancreatic tumor. We report a rare case of hypoglycemia caused by a relapsing pelvic solitary fibrous tumor associated with Big-IGF-2 production. A 72-year-old woman was admitted to our hospital because of loss of consciousness and hypoglycemia. She had a history of ovarian solitary fibrous tumor, which has relapsed. From investigation, serum levels of insulin and C-peptide were suppressed; IGF-1 was slightly reduced and IGF-2 was within the normal range, but the IGF-2: IGF-1 ratio was elevated, indicating the presence of Big-IGF-2 secreting non-islet cell tumor. Contrast-enhanced computed tomography (CT) showed a large pelvic mass. She was then submitted to surgical resection of the mass, which histologically proved to be a solitary fibrous tumor. Three months later, she remains asymptomatic. Non-islet cell tumor hypoglycemia should be considered in the differential diagnosis of patients presenting with tumors and recurrent hypoglycemia.

Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme.

Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic ß-cells. Investigation of mice with tissue-specific genetic deletion of Ide in the liver and pancreatic ß-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE's function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.