Neurological manifestations of celiac disease. Importance of searching and understanding the spectrum. Potential novel markers for the diagnosis.

currently Celiac Disease corresponds to an entity mainly managed by expert gastroenterologists on the topic but which must be faced on many occasions by primary care physicians or general gastroenterologists. It is important for a good diagnosis to look closely at all the factors that lead to a correct diagnosis (manifestations, antibodies, biopsy). In the spectrum of manifestations we find the classic ones, where the patient suffers from gastrointestinal symptoms typical of a classic Celiac Disease. At the same time, it is important to know that some of these patients do not have these classic symptoms and sometimes their only expression is neurological.

Immune checkpoint inhibitor-mediated colitis in a patient with epidermoid metastatic lung cancer: new and emerging toxicities.

In recent years, the development of immunotherapy has been stablished with monoclonals antibodies against control immune molecules in T lymphocytes, tumor cells and other cells, which block lymphocyte activation and suppress immune response. These molecules are Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death-ligand 1 (PD-1). Despite clinical benefits, these therapies are not exempt from side effects known as immune-related adverse events (irAEs). We report the case of a 68-year-old female with stage IIIB epidermoid lung cancer diagnosed in 2017.

Uncommon etiology of Cullen´s sign and Grey Turner sign.

Cullen´s sign and Grey Turner sign are, respectively, the cutaneous ecchymoses located in periumbilical region and tissues flanks along the lower portion of the abdomen. Both have been observed in <1% of individuals with acute pancreatitis, suggesting poor prognosis in terms of gravity and mortality. However, these signs are not exclusive for acute pancreatitis, as they can appear in other identities such as: ruptured ectopic pregnancy, aortic aneurysm, rectus abdominis muscle hematoma, perforated duodenal ulcer, common bile duct rupture and biliary peritonitis, idiopathic perirenal hemorrhage, infectious mononucleosis with splenic rupture, metastatic esophageal and thyroid cancer, non-Hodgkin lymphoma, amoebic liver abscess, portal hypertension, and liver tumor disease. Based on the review of the literature, it is patent that Cullen´s sign and Grey Turner sign are neither sensitive nor specific for acute pancreatitis, therefore it may be best to relate these findings in the physical examination to conditions associated with abdominal pathology and retroperitoneal hemorrhage. We report the case of a 60-year-old Spanish female, with previous history of squamous small cell neuroendocrine lung carcinoma with hepatic extension in follow-up by palliative care services. Due to disease progression after two palliative chemotherapy sessions, the patient came to the emergency room with jaundice and abdominal pain in superior regions. On physical examination, notable findings included ecchymoses in the right flank and periumbilical region. Laboratory findings showed elevated bilirubin and transaminase levels, as well as a small increase in the serum amylase and lipase levels. Cholangioresonance was performed to discard acute biliary pancreatitis. The imaging revealed no enlargement of the pancreas, dilatation of the common bile duct without visible stone, and a liver full of new cancerous liver implants. These findings were consistent with diffuse distribution metastases lesions, concluding the progression of liver disease.

An uncommon cause of digestive neoplasm: duodenal melanoma.

We present and discuss the case of one patient that presented to the emergency room with abdominal pain in the right hypochondrium radiated to epigastrium and low-grade fever with blood test that shows dissociated colesthasis therefore admitted in the gastroenterology service with choledocholithiasis suspicion. cholangioresonance performed with a sudden stenosis of the bile duct in its intrapancreatic portion due a tumor in the pancreatic head. CT without lessions in other parts of the body. Upper endoscopy shows an ulcerated growth in the papillary area whose biopsies found neoplastic proliferation with S100, SOX10, MelanA and HMB45 positivity.

Blue rubber bleb nevus syndrome.

Gastrointestinal bleeding of obscure origin accounts for less than 5% of gastrointestinal hemorrhages. It is typically difficult to diagnose due to limited accessibility through standard endoscopic techniques and generally requires a significant number of procedures to reach a diagnosis. The "blue rubber bleb nevus syndrome" is a rare condition, of a probably hereditary origin, characterized by the presence of multiple hemangiomatous lesions, which can manifest as gastrointestinal bleeding of obscure origin. These lesions are generally nodular, rubbery to the touch, and have a submucosal appearance, primarily affecting the skin and gastrointestinal tract. We present the case of a 72-year-old male who was investigated for iron deficiency anemia with upper and lower gastrointestinal endoscopies conducted on two occasions, without revealing any findings that could explain the condition. Subsequently, a study with video-capsule endoscopy was performed, which revealed multiple submucosal and vascular lesions, measuring between 3-5 mm, located in the distal duodenum and jejunum, consistent with "Blue rubber bleb nevus syndrome".

Detection of Neuroendocrine Tumours by Enteroscopy: A Case Report.

We present the case of a 62-year-old patient who developed melenas and in whom conventional endoscopic tests could not detect any bleeding lesion. In our case, capsule endoscopy and enteroscopy were the pivotal elements in establishing the diagnosis of a neuroendocrine tumour with an atypical location. As a result, it was possible to surgically remove the lesions at an early stage of the malignancy without metastatic disease and without the need for adjuvant therapy. Our case demonstrates the need for these new techniques in tumours of atypical location and aggressive course. Otherwise, this malignancy may be underdiagnosed until an advanced stage.

[Gastric mucosa as a target of persistent proinflammatory aggression: pathogenic models of chronic gastritis]. / La mucosa gástrica como estructura diana de agresiones proinflamatorias persistentes: modelos patogénicos de gastritis crónica.

There are several causes of damage and regeneration of the gastric epithelium (erosive gastropathy) and/or histological inflammation of the gastric mucosa (acute or chronic gastritis). After outlining the usual morphology of chronic gastritis, the authors attempt to identify the biological profile of the main pathogenic models. The first, and by far the most frequent, is the model associated with Helicobacter pylori, which, without crossing the mucosal epithelium, provokes an immune reaction. Although incapable of eradicating this bacterium, this immune reaction contributes to the inflammatory lesion provoked by H. pylori in the mucosa. The second -and much less frequent- model is that causing progressive atrophic gastritis through a humoral and cellular autoimmune mechanism. In third place are a group of models defined by a peculiar cytohistologic pattern of inflammation (granulomatous, lymphocytic or eosinophilic gastritis), suggesting similar pathogenic mechanisms for each of these rare morphological forms of gastritis. Lastly, there is a model barely fitting within the scope of this review, which is that provoking chemical gastropathies (bile reflux, NSAIDs, etc.) with minimal cellular inflammation, i.e., minimal gastritis. To aid understanding of the article, the authors provide a brief outline of the functional histology of the gastric wall and the mechanisms defending its integrity in physiological conditions.

[Multifactorial etiology and pathogenic factors in inflammatory bowel disease]. / Etiología multifactorial y parcelas patogénicas de la enfermedad inflamatoria intestinal.

All the currently available evidence suggests that the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), involve a conflict between the immune system of the intestinal mucosa and intraluminal antigens, mainly the intestinal microflora, which are normally tolerated by the immune system. This conflict is modulated by numerous environmental factors and a clear polygenetic predisposition. The present article reviews the behavior of all the etiologic circumstances (microbial, genetic and environmental) and subsequently analyzes the possible pathogenic factors in which the etiologies can be found, namely: dysfunction of the intestinal epithelium, innate immune system alterations, and distortion of the cellular and humoral arms of the acquired immune system. The role of tissue ischemia in CD and expression of "extraintestinal inflammatory metastases", both in CD and UC, are briefly discussed. Finally, the view that IBD may be a spectrum of pathological processes provoked by distinct etiopathogenic factors and the possible biological significance of the growing incidence of this disease in the western world, coinciding with the decline in infectious diseases in this geographical area, are discussed.

Primitive neuroectodermal tumor of the esophagus with metastasis in the pineal gland.

Primitive neuroectodermal tumors (PNET) are very rare tumors that belong to a family of malignant neoplasms of tiny round cells which are derived from the neural crest. This report discusses a rare case of an adult woman with esophageal PNET, confirmed by immunohistochemistry, that presented with metastasis to the pineal gland. To our knowledge, this is the first case report of a PNET with these features. Despite surgery and chemotherapeutic treatment, our case has shown disease progression.

[Deposits of lanthanum in the gastric mucosa of a patient with chronic kidney disease]. / Depósito de lantano en la mucosa gástrica de paciente con enfermedad renal crónica.

Lanthanum carbonate is a non-calcium phosphorus chelator used in the treatment of hyperphosphatemia associated with chronic renal disease. Deposits of lanthanum in the gastrointestinal wall have been recently described but its clinical significance is uncertain. We present a case of a 62-year-old male with chronic renal disease treated with lanthanum carbonate for 3 years, with deposits in his gastric mucosa, found on biopsy for dyspepsia. The deposits were acellular and of irregular shape, surrounded by macrophages and foreign body giant cells. The presence of lanthanum in the deposits was confirmed by X-ray spectroscopy. Diagnosis is reached with knowledge of its microscopic appearance and a thorough clinical history.

[Genetic abnormalities of digestive tract adenocarcinomas and correlation with the histologic sequence of their development]. / Alteraciones genéticas de los adenocarcinomas del aparato digestivo y su correlación con la secuencia de su gestación.

Over 90% of digestive tract malignancies are adenocarcinomas (ADC) and almost 95% of them have gastric (G), colorectal (CR) or pancreatic (P) localizations. The objectives of this work are to review the genetic abnormalities of ADC in these locations and their potential coincidences, along with the histogenetic correlation of their emergence. Genetic abnormalities affecting over 50% of cases include: in G-ADC, inactivation of suppressor genes of p53, APC and DCC tumor in its intestinal variant, hypoexpression of of caderine E in the diffuse variant and hyperexpression of cyclooxygenase-2 and cyclyn D in the intestinal form; in in CR-ADC, inactivation of of genes p53, APC and DCC together with mutational activation of k-ras oncogen, and in P-ADC, the inactivation of suppressor genes p53, p16 and DPC4 along with mutational activation of k-ras oncogen. P-ADC is the one showing a more characteristic and exclusive genetic mark, followed by CR-ADC. Finally, the histogenetic correlation in the tumorigenic sequence is more evident in CR-ADC, followed by P-ADC. The complex biologic reality of G-ADC makes it more difficult to draw its genetic profile and its histogenetic correlation. In order to understand better the arguments of this work, the authors comment on the genetic-molecular basis governing the life and death of normal somatic cells and the biologic profile of the groups of genes mainly involved in tumorigenesis.

[Gastrointestinal carcinoid tumors: cellular biology, molecular expression and physiopathological consequences of an enigmatic neoplasia]. / Tumores carcinoides gastrointestinales. Biología celular, expresión molecular y consecuencias fisiopatológicas de una neoplasia enigmática.

Gastrointestinal carcinoid tumors arise from cells of the diffuse neuroendocrine system localized in the digestive trace and represent more than 70% of all carcinoid tumors in humans. The present article reviews the following topics: 1) The biological profile of these tumors (histopathology, cytokine markers, metabolic alterations, storage of neuroamines and hormonal proteins, cytodynamic behavior, and biological behavior according to embryological origin). 2) The etiological circumstances (exceptional hereditary factors, association of gastric carcinoid tumors with autoimmune gastritis, little-known exogenous factors). 3) Pathogenic aspects (persistent mitogenesis of endocrine cells associated with hypergastrinemia, inactivation of some putative tumor suppressor genes, the doubtful participation of oncogenes, autocrine action of some cellular growth-stimulating proteins). 4) The repercussions of certain physiopathological events (peritumoral desmoplastic reaction causing the "mass effect" on the digestive tube, the "kidnapping" of dietary tryptophan by tumoral cells toward an abnormal metabolic pathway; the easy metastatic dissemination coexisting with low tumoral aggressivity, and the release into the bloodstream of stored secretory products leading to "carcinoid syndrome" and some endocrine hyperfunction syndromes. Finally, it should be remembered that gastrointestinal carcinoid tumors represent only a proportion of the neoplasms classified as neuroendocrine tumors.

[Gastric adenocarcinoma: approach to a complex biological reality]. / Adenocarcinoma gástrico: intento de aproximación a una realidad biológica compleja.

The authors review the complex biological reality of gastric adenocarcinoma from several viewpoints. It is a neoplasm histologically expressed as a dual process (intestinal and diffuse types) with a broad cytological diversity. From an epidemiological point of view, it behaves as an entity with a deep geographical asymmetry and a changing incidence, currently decreasing. There is a multifactorial etiology with a combination of genetic, infectious (H. pylori), nutritional and environmental factors. It might have a multiphasic gestation from precancerous lesions, though not always following a lineal sequence. We only know fragmentary portions of its pathogenesis whose common denominator is a potentially mutagenic mitogenic activation of the epithelial cells implicated. A good knowledge of this complex biological reality will allow the identification of better markers for an early diagnosis as well as vulnerable etiopathogenetic points for a useful prevention and therapy.

[Genetic profile and molecular bases of pancreatic carcinogenesis]. / Perfil genético y bases moleculares de la carcinogénesis pancreática.

The possibility that carcinogenesis is a multiphasic process has been well demonstrated in colorectal cancer, at least in cancers arising from a benign adenomatous polyp. However, because of the difficulty of performing histopathological studies of the pancreas, the multiphasic nature of carcinogenesis is proving more difficult to demonstrate in pancreatic ductal adenocarcinoma (d-ADC), although a series of findings, reviewed in the present article, strongly support this characteristic. Firstly, d-ADC shows a fairly exclusive genetic-molecular profile, found in 70% of cases; this profile consists of the association of the K-ras oncogene and inactivation of the tumor suppressor genes p16, p53 and DPC4. Secondly, a series of lesions in the ductal epithelium, in healthy pancreatic tissue close to a d-ADC, have been identified, which seem to represent precancerous histopathological stages. Lastly, there is the suspicion that the mutations defining this genetic-molecular profile appear gradually, in a certain sequence, throughout the stages of progression. Most probably, rather than the order of appearance, the accumulation of these genetic-molecular events are what prompt quiescent ductal epithelium to progress to mitogenic cellular hyperplasia, leading to irreversible mutagenic cellular dysplasia.

[Inflammatory pancreatic disease due to enzyme autodigestion: an exceptional model of glandular crinophagy]. / Enfermedad inflamatoria del páncreas por autoagresión enzimática: un modelo excepcional de crinofagia glandular.

The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases a <> sequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of an <>.

[Eosinophilic granulocytes: from common residents in normal gastrointestinal mucosa to aggressive agents of eosinophilic gastroenteritis]. / Los granulocitos eosinófilos: de residentes habituales de la mucosa gastrointestinal normal a protagonistas agresivos de la gastroenteritis eosinofílica.

Because of their biological affinity for normal gastrointestinal (GI) mucosa, eosinophilic granulocytes are "normal residents" in the mucosa. This physiological GI eosinophilia translates into a state of "permanent normal inflammation", which means that the mucosa's local immune system is constantly confronted by dietary proteins and indigenous microorganisms. This eosinophilic infiltration of the GI mucosa is increased, reactively, in the course of local inflammatory processes, collagenosis, infections (especially helminthic infections), vasculitis, neoplasms and IgE-dependent allergic reactions to food. Lastly, GI eosinophilia that is clearly aggressive, both because of its intensity and its persistence, is what characterizes eosinophilic gastroenteritis. In the present article, we summarize the ethiopathogenic and clinico-epidemiological features of this process, as well as its position within the field of immunopathologic food intolerance.

Effect of C-reactive protein on Fcgamma receptor II in cultured bovine endothelial cells.

The major CRP (C-reactive protein) receptor on leucocytes has been identified as the low-affinity IgG receptor Fcgamma receptor II (CD32). Our aim was to assess whether inflammation may modify the presence of the CD32 receptor in BAEC (bovine aortic endothelial cells). Confocal microscopy experiments showed a weak expression of the CD32 receptor in control BAEC that was slightly increased by 10 microg/ml CRP. Incubation of BAEC with TNF-alpha (tumour necrosis factor-alpha) did not modify the fluorescence signal of CD32. Addition of CRP to TNF-alpha-incubated BAEC enhanced the fluorescence signal of the CD32 receptors. The CD32 receptors showed a perinuclear cytoplasmic localization in BAEC. An alteration of the NO (nitric oxide)-dependent vasorelaxation has been defined as endothelial dysfunction. Endothelial dysfunction has been associated with the presence of superoxide anion and with a reduction in the expression of the eNOS (endothelial NO synthase). A concentration of CRP similar to that detected in patients with cardiovascular risk (10 microg/ml) failed to modify the generation of superoxide anion stimulated by TNF-alpha. Western blot experiments showed that TNF-alpha decreased the expression of the eNOS protein, which was partially protected by treatment with 10 microg/ml CRP. The protective effect of 10 microg/ml CRP on eNOS expression in TNF-alpha-incubated BAEC was prevented by an antibody against CD32 receptors. In conclusion, the present results suggest that, although CRP has been associated with inflammation, CRP may protect the expression of eNOS protein against pro-inflammatory mediators such as TNF-alpha.

Aspirin inhibits endothelial nitric oxide synthase (eNOS) and Flk-1 (vascular endothelial growth factor receptor-2) prior to rat colon tumour development.

Formation of blood vessels is a fundamental element in the control of tumour growth in which vascular endothelial growth factor (VEGF) and nitric oxide (NO) have been demonstrated to be involved. Our aim was to analyse whether changes in the expression of endothelial NO synthase (eNOS) and VEGF in colonic tissue could be detected early and even before the identification of colon tumour-associated morphological modifications in azoxymethane-treated rats. We studied further whether aspirin treatment changed these parameters. An increased expression of both eNOS and VEGF in colonic tissue from azoxymethane-treated rats compared with that from control rats was found. Aspirin treatment (10 mg/kg of body weight per day) reduced eNOS expression, but failed to modify the expression of VEGF in the colonic tissue of azoxymethane-treated rats. No evidence of aberrant crypt formation or changes in the number of blood vessels were observed in the colon of any of the animals studied. Expression of the VEGF receptor Flk-1, but not Flt-1, was increased in colonic tissue of azoxymethane-treated rats compared with control rats. The expression of Flk-1 was mainly localized in the epithelial cells, particularly in the lower part of the crypt. Aspirin treatment reduced Flk-1 expression in both control and azoxymethane-treated rats. Caspase-3 activity, which has been considered as an apoptotic index, was almost undetectable in azoxymethane-treated rats. Aspirin treatment stimulated caspase-3 activity. Overexpression of eNOS, VEGF and its receptor Flk-1 occurred early after azoxymethane administration in rat colonic tissue, even before morphological changes associated with tumour generation were observed, and aspirin prevented the overexpression of both eNOS and VEGF receptor Flk-1.