Liver exhibits thermal variations according to the stage of fibrosis progression: A novel use of modulated-differential scanning calorimetry for research in hepatology.

AIM: Liver fibrosis results in a disproportion of the hepatic composition and architecture, characterized by a progressive accumulation of fibrillar proteins at the liver parenchyma. Modulated-differential scanning calorimetry (mDSC) is an experimental methodology able to determine the specific thermal signature from any biological substance, based on the variation in heat flow and heat capacity. As these physicochemical properties are directly influenced by compositional and structural changes, we decided to study the thermal behavior of the liver during fibrosis using mDSC. METHODS: Liver fibrosis was induced in rats by bile duct ligation or carbon tetrachloride administration. Degree of liver fibrosis was determined by histological examination using the Masson-trichrome stain, accompanied by hepatic expression of α-smooth muscle actin. The thermal analysis was performed in a modulated-differential scanning calorimeter using 20 mg of fresh liver mass. RESULTS: The liver showed a characteristic thermal signature in control animals, which progressively differed among mild (F1), moderate (F2) and advanced (F3-F4) liver fibrosis. For heat flow, the hepatic thermal signature from F3-F4 rats exhibited significant differences when compared with F1, F2 and controls. In terms of heat capacity, liver specimens provided a specific thermal signature for each stage of disease, characterized by a transition temperature onset at 95°C for controls, whereas in F1, F2 and F3-F4 animals this temperature significantly decreased to 93°C, 84°C and 75°C, respectively. CONCLUSION: Because the liver shows a differential thermal signature according to the degree of fibrosis, mDSC could be a novel tool in the study of liver fibrosis progression.

Lower serum IL-10 is an independent predictor of IBS among volunteers in Mexico.

OBJECTIVES: Studies suggest that altered immune activation, manifested by an imbalance in anti- and pro-inflammatory cytokine levels, exists in a subgroup of irritable bowel syndrome (IBS) patients. However, similar studies have not been conducted in Latin populations. The objective of this study was to measure serum levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in subjects fulfilling symptom criteria for IBS and controls. METHODS: Volunteers (n=178) from a university population in Mexico City, participated in the study. Of the sample, 34.8% met Rome II criteria for IBS and 65.2% were designated as controls. Serum cytokines were measured by enzyme-linked immunoabsorbent assay. Analysis of covariance models were used to test main effects between gender, IBS symptoms, and bowel habit subtype to explain the cytokine serum levels. Statistical models were tested using body mass index as a covariate. RESULTS: IL-10 levels were significantly lower in IBS vs. controls (mean (95% confidence interval): 15.6 (14.8, 16.3) vs. 18.6 (17.9, 19.4) pg/ml, P<0.001), while TNF-α levels were higher in IBS (20.9 (19.1, 23.0) vs. 17.9 (16.7, 19.3) pg/ml, P=0.010). IBS and female gender were independent predictors for IL-10 (P<0.05). In contrast, female gender was an independent predictor for TNF-α. In addition, women with IBS-D had the lowest IL-10 (P<0.001) and highest TNF-α (P=0.021) vs. other subtypes. CONCLUSIONS: The lower serum IL-10 in our subjects fulfilling IBS Rome II symptom criteria suggests an altered immune regulation. Further studies are needed to elucidate if a lower serum IL-10 may be useful as a biomarker for IBS in the Mexican population, especially for women with IBS-D.

Early endocrine and molecular changes in metabolic syndrome models.

The twenty-first century arrived in the middle of a global epidemic of metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). It is generally accepted that an excess of nutrients linked to a low physical activity triggers the problem. However, the molecular features that interact to develop the MS are not clear. In an effort to understand and control them, they have been extensively studied, but this goal has not been achieved yet. Nonhuman animal models have been used to explore diet and genetic factors in which experimental conditions are controlled. For example, only one factor in the diet, such as fats or carbohydrates can be modified to better understand a single change that would be impossible in humans. Most of the studies have been done in rodents. However, it is difficult to directly compare them, because experiments are different in more than one variable; genetic strains, amount, and the type of fat used in the diet and sex. Thus, the only possible criteria of comparison are the relevance of the observed changes. We review different animal models and add some original observations on short-term changes in metabolism and beta cells in our own model of adult Wistar rats that are not especially prone to get fat or develop DM2, treated with 20% sucrose in drinking water. One early change observed in pancreatic beta cells is the increase in GLUT2 expression that is located to the membrane of the cells. This change could partially explain the presence of insulin hypersecretion and hyperinsulinemia in these rats. Understanding early changes that lead to MS and in time to pancreatic islet exhaustion is an important biomedical problem that may contribute to learn how to prevent or even reverse MS, before developing DM2.

Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state.

BACKGROUND AND AIM: Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential. METHODS: To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA. RESULTS: Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%). CONCLUSIONS: Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases.

Triggering receptor expressed on myeloid cells-1 expression on monocytes is associated with inflammation but not with infection in acute pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is usually a mild and self-limiting disease, but some patients develop a severe form that is associated with high mortality. In AP, local inflammation is followed first by the systemic inflammatory response syndrome and then by the compensatory anti-inflammatory response syndrome, which is defined by low human leukocyte antigen (HLA)-DR expression on monocytes, increased concentration of the anti-inflammatory cytokine IL-10, and decreased monocyte function. Our aim was to measure the expression of triggering receptor expressed on myeloid cells (TREM)-1 (a proposed marker of infection or inflammation) and HLA-DR on monocytes, and the serum concentrations of IL-6 (a proinflammatory cytokine) and IL-10 in patients with AP to determine whether these markers can identify patients at high risk of developing severe AP or infection. METHODS: Fifty healthy volunteers, 18 patients with mild AP, and 11 patients with severe AP were included in this study. Samples were taken at admission and one and three days later. TREM-1 and HLA-DR expression was evaluated by flow cytometry, and soluble TREM-1, IL-6 and IL-10 concentrations were measured by ELISA. RESULTS: TREM-1 expression was higher in patients with AP than in healthy volunteers, but there was no difference between patients with mild and severe AP. TREM-1 expression was not associated with mortality or with the presence of infection. Soluble TREM-1 concentration in serum was higher in non-survivors than in survivors. HLA-DR expression was lower and IL-6 concentration higher in patients with severe AP and in infected patients. CONCLUSIONS: Increased TREM-1 expression was associated with the presence of inflammation but not infection in AP. In patients with AP, low HLA-DR expression and high IL-6 concentration could predict severity and infection in samples taken shortly after admission.

Time frames for analysis of inflammatory mediators in acute pancreatitis: improving admission triage.

Improving the outcome of acute pancreatitis through prognostic markers has been a matter of ample research. We evaluate the clinical usefulness of four serum markers in comparison to Ranson's score. Serum measurements of C-reactive protein (CRP), interleukin-6, -10 (IL-6, IL-10), and pancreatitis-associated protein (PAP) were performed. The usefulness of each marker for predicting severity was compared with that of Ranson's score. Time of evolution was considered for improving their usefulness. Seventy-one patients were studied. Severe cases had higher levels of all markers, although only IL-10 had better accuracy than Ranson's. In patients admitted during the first 48 h, IL-6, IL-10, and PAP had improved accuracy over Ranson's; however, after this time frame, only CRP outperformed Ranson's score. Analysis of time frames improved the accuracy of all markers. Therefore, time of evolution should be considered when using these parameters for a better prognosis.

The association between obesity and outcomes in acute pancreatitis: an individual patient data meta-analysis.

OBJECTIVES: There are data to suggest that obesity is associated with local and systemic complications as well as mortality in acute pancreatitis (AP). Cohort studies to date, however, have shown conflicting results from mostly unadjusted analyses. Therefore, we performed an individual patient data meta-analysis with the primary aim to investigate the association between obesity and mortality in AP. Our secondary aim was to investigate the association between obesity and necrosis, organ failure, multiple organ failure, and invasive intervention. PATIENTS AND METHODS: We systematically searched four electronic databases for prospective studies on obesity and outcomes in AP. Researchers of eligible studies were invited to share individual patient data using a standardized data collection form. All end points were investigated with a one-stage mixed effects Poisson model with random intercepts and forced entry of relevant confounders. RESULTS: We included five databases with 1302 patients, of whom 418 (32%) were obese. In total, 466 (36%) patients had necrosis, 328 (25%) had organ failure, 188 (14%) had multiple organ failure, 210 (16%) had an intervention, and 84 (7%) patients died. We found no significant association between obesity and mortality [relative risk (RR) 1.40, 95% confidence interval (CI): 0.89-2.20], necrosis (RR: 1.08, 95% CI: 0.90-1.31) or invasive intervention (RR: 1.10, 95% CI: 0.83-1.47) after adjustment for confounders. However, obesity was independently associated with the development of organ failure (RR: 1.38, 95% CI: 1.11-1.73) and multiple organ failure (RR: 1.81, 95% CI: 1.35-2.42). CONCLUSION: Obesity is independently associated with the development of organ failure and multiple organ failure in AP. However, there is no association between obesity and mortality, necrosis, and an intervention.

Expression and localization of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in human pancreas and pancreatic adenocarcinoma.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) was recently identified as the first tissue-specific angiogenic molecule. EG-VEGF (the gene product of PROK-1) appears to be expressed exclusively in steroid-producing organs such as the ovary, testis, adrenals and placenta. Since the human pancreatic cells retain steroidogenic activity, in the present study we ascertained whether this angiogenic factor is expressed in normal pancreas and pancreatic adenocarcinoma. Tissue samples from normal males (n=5), normal females (n=5) and from surgically resected adenocarcinomas (n=2) were processed for RT-PCR and immunohistochemical studies. Results from semi-quantitative analysis by RT-PCR suggest a distinct expression level for EG-VEGF in the different tissue samples. The relative amount of EG-VEGF mRNA in pancreas was more abundant in female adenocarcinoma (0.89) followed by male adenocarcinoma (0.71), than normal female (0.64) and normal male (0.38). The expression of mRNA for EG-VEGF in normal tissue was significantly higher in females than in males. All samples examined showed specific immunostaining for EG-VEGF. In male preparations, the positive labeling was localized predominantly within the pancreatic islets while in female preparations the main staining was detected towards the exocrine portion. Specific immunolabeling was also observed in endothelial cells of pancreatic blood vessels. Our data provide evidence that the human pancreas expresses the EG-VEGF, a highly specific mitogen which regulates proliferation and differentiation of the vascular endothelium. The significance of this finding could be interpreted as either, EG-VEGF is not exclusive of endocrine organs, or the pancreas should be considered as a functional steroidogenic tissue. The extent of the expression of EG-VEGF appears to have a dimorphic pattern in normal and tumoral pancreatic tissue.

[Steroid hormones and pancreas: a new paradigm]. / Las hormonas esteroides y el páncreas: un nuevo paradigma.

The relation between steroid hormones and pancreatic function has been poorly discussed and not very well understood. In general, there is a lack of recognition among the scientific community about the importance of steroids in pancreatic function (current paradigm). In the present article we present basic, as well as clinic and epidemiologic data that demonstrate steroid synthesis and steroid biotransformation by pancreatic tissue, how exocrine and endocrine functions are modulated by steroids, the gender specific frequency and behavior of some tumors and the use of synthetic steroids and steroid action antagonists as therapeutic agents. With the available information it is possible to establish that: 1. Pancreatic tissue synthesize and transform steroid hormones. 2. Pancreatic tissue respond to steroid hormones and express steroid specific receptor molecules. 3. Some endocrine functions such as insulin synthesis and release are modulated by steroids. 4. Tumor growth is modulated by steroids and anti-steroid drugs. This set of data creates a new paradigm for the holistic study of pancreas and opens new research fields. The application of this new paradigm might result in an increase in the knowledge of pancreatic physiology, in the design of new and better diagnostic methods and eventually in the design of more effective medical treatments for the pancreatic cancers.

Expression of steroidogenic factors 1 and 2 in normal human pancreas.

Orphan nuclear receptor steroidogenic factor-1 (SF-1) is crucial for development and function of steroidogenic organs. The steroidogenic factor-2 (SF-2) is an essential factor involved in cholesterol transfer and activation of promoters of steroidogenic enzymes CYP11A1, CYP17 and Steroidogenic Acute Regulatory Protein (StAR). We have previously demonstrated steroidogenic activity in pancreatic tissue. The aim of this study was to investigate the presence of SF-1 and SF-2 in human pancreas. Total RNA was extracted from normal male (five) and female (five) samples, obtained from the organs donor program. RT-PCR approach was used to analyze the expression of SF-1 and SF-2. Immunohistochemical analysis was performed for SF-1. The bands of expression were present in both male and female samples, although differential expression was observed. For both factors, the signal detected was more evident in males than in females. A similar pattern was present in the immunohistochemical study. Normal human pancreas expresses SF-1 and SF-2 factors similarly to ovary and adrenals. A distinctive characteristic is the sexually dimorphic expression of these factors. Our data provide evidence suggesting that the pancreas achieves steroidogenic activity supporting the presence of gender- and location-related differences in the expression of these steroidogenic factors.

Is leptin related to systemic inflammatory response in acute pancreatitis?

AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis. METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-alpha, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria. RESULTS: Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058). CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

Association of alcohol-metabolizing genes with alcoholism in a Mexican Indian (Otomi) population.

Association studies provide a powerful approach to link DNA variants and genetic predisposition to complex diseases. In this study, we determined the genotype and allelic frequencies of genes encoding enzymes involved in alcohol metabolism in alcoholic and nonalcoholic subjects of related ethnicity. A total of 118 individuals of Otomi Mexican Indian ancestry were included. Fifty-nine were chronic alcoholics according to WHO criteria and alcohol dependents according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria. They were compared to 59 teetotalers or alcohol consumers of <10 g per day. The restriction fragment length polymorphisms analyzed were ADH1B/MaeIII, ALDH2/MboII, CYP2E1/DraI, CYP2E1/RsaI, and CYP2E1/TaqI. Of the studied polymorphisms, a significant difference between alcoholic and nonalcoholic Otomies was observed only in the CYP2E1/TaqI. The common genotype in alcoholics was A1/A2 (54%), and in nonalcoholics the homozygous A2/A2 (63%) (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.13-0.60; P=.002). The frequency of the mutant allele A1 was significantly higher in alcoholics than in nonalcoholics (41 vs. 21%; OR: 2.4; 95% CI: 1.3-4.3; P=.003). This documents the presence of a polymorphism of CYP2E1 that is overexpressed in alcoholic Otomies, in which the variant allele (A1 of CYP2E1/TaqI) is associated with increased susceptibility to alcoholism. The appreciation that this finding may be an additional factor contributing to the high frequency of liver cirrhosis in Otomies requires further investigation.

Hemoconcentration is a poor predictor of severity in acute pancreatitis.

AIM: To determine whether the hematocrit (Hct) at admission or at 24 h after admission was associated with severe acute pancreatitis (AP), organ failure (OF), and pancreatic necrosis. METHODS: A total of 336 consecutive patients with a first AP episode were studied. Etiology, Hct values at admission and at 24 h, development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF and mortality were recorded. Hemoconcentration was defined as Hct level >44% for males and >40% for females. The t-test and chi2 test were used to assess the association of hemoconcentration to the severity, necrosis and OF. Diagnostic accuracy was also determined. RESULTS: Biliary disease was the most frequent etiology (n = 148). Mean Hct levels at admission were 41+/-6% for females and 46+/-7% for males (P<0.01). Seventy-eight (23%) patients had severe AP, and OF developed in 45 (13%) patients. According to contrast-enhanced computed tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels were elevated in 58% (55/96) and 61% (33/54) patients with interstitial and necrotizing pancreatitis, respectively. Neither Hct levels at admission nor hemoconcentration at 24 h were associated with the severity, necrosis or OF. Sensitivity, specificity and positive predictive values for both determinations were very low; and negative predictive values were between 61% and 86%, being the highest value for OF. CONCLUSION: Hct is not a useful marker to predict a worse outcome in acute pancreatitis. In spite of the high negative predictive value of hemoconcentration, the prognosis gain is limited due to an already high incidence of mild disease.

Intestinal involvement is not sufficient to explain hypertransaminasemia in celiac disease?

Chronic unexplained hypertransaminasemia is an isolated clinical manifestation of celiac disease (CD) and lacks of a clear physiopathological explanation. Since CD and tropical sprue (TS) have similar intestinal functional and histological pattern of injury and that an increased inflammatory response has been reported to occur in patients with irritable bowel syndrome (IBS), liver involvement might be expected to occur either in TS or IBS. However, according to author's prior observations, the frequency of hypertransaminasemia is significantly higher in CD than in TS and IBS-diarrhea predominant patients (IBS-D). Thus, based on current knowledge, intestinal mucosal damage, increased intestinal permeability and/or an active intestinal inflammatory response do not completely explain liver damage in CD. We hypothesize that other factors, unique to CD not present in TS or IBS-D, like gluten toxicity and the presence of tissular transglutaminase (tTG) an auto-antigen with pro-inflammatory and remodeling properties, act in addition to intestinal mucosal injury and account to hypertransaminasemia in CD. Further research focusing on the mechanisms of gluten and tTG hepatic toxicity, and/or the characterization of the expression, secretion and enteral-hepatic transport of certain pro-inflammatory cytokines is needed, to understand the possible links between intestinal and liver disorders seen in CD.

[Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy]. / Efecto del drenaje biliar preoperatorio en la evolución posquirúrgica de la pancreatoduodenectomía.

BACKGROUND/AIM: There are theoretic arguments in favor and against biliary drainage before the pancreatoduodenectomy. Most of the studies failed to show any beneficial effect of this approach whereas others even reported an increased postoperative morbidity related with biliary drainage. Therefore, the role of preoperative biliary drainage remains controversial. So, we decided to analyze our own results in a series of patients undergoing pancreatoduodenectomy in order to determine the association between preoperative biliary drainage and postoperative outcome. PATIENTS AND METHODS: We analyzed 109 patients undergoing pancreatoduodenectomy between January 1990 and May 2003. Patients were classified in 3 groups: Group 1 (n = 64) patients without preoperative biliary drainage, Group 2 (n = 27) patients who underwent preoperative biliary drainage with sphincterotomy and stent placement, and Group 3 (n = 18) only sphincterotomy. Demographic characteristics, surgical risk, comorbility, type of surgery, pathology and biochemical parameters were analyzed. We also, stratified patients with and without cholestasis (total bilirubin > 3 mg/dL), and divided patients in two groups: with biliary drainage and without biliary drainage. Surgical and medical complications, the frequency of patients with at least one complication (global morbidity) and mortality were compared between groups. Kruskal-Wallis, Mann-Whitney U, chi2 and Fisher tests were used for the analysis of categorical and dimensional variables. RESULTS: The most frequent postoperative diagnoses were biliopancreatic tumors. Global postoperative morbidity and mortality were 40% (n = 44) and 10% (n = 11), respectively. The frequency of surgery and medical complications were no significantly different among the 3 groups. However, when only patients with cholestasis were analyzed (n = 65), there was a lower frequency of surgical complications and global postoperative morbidity in patients with preoperative biliary drainage (p = 0.02, OR 0.14, CI 95% 0.04-0.50 and p < 0.001, OR 0.18, CI 95% 0.05-0.65, respectively). There were not significant differences in the frequency of medical complications (p = 0.09) and mortality. CONCLUSIONS: Preoperative biliary drainage should not be considered as a routine procedure in candidates undergoing pancreatoduodenectomy; however, this maneuver decreased approximately seven times the risk of postoperative global morbidity in patients with cholestasis, mainly by reducing surgical complications reduction.

Emerging concepts in inflammation and fibrosis.

Hepatic and pancreatic response to several insults commonly includes similar pathways of inflammation, fibrogenesis/regeneration, which may occur simultaneously and without appropriate coordination, resulting in chronic inflammation, scarring, and organ dysfunction. This review highlights the opinion of experts gathered for the Mexican Digestive Disease Week (2001) to analyze these molecular events with emphasis on identifying possible therapeutic opportunities. Inflammatory response encompasses leukocyte infiltration, favored by adhesion molecules of the selectin family, chemokines, integrins, and activated stellate cells (SC). Quiescent SC undergo activation mediated by mechanical stress and expression of cytokines, oxidative stress products, and growth factors and play a significant role in fibrosis and in reparation toward synthesis of extracellular matrix components. Also, hepatocytes and acinar cells contribute to the inflammatory and fibrotic response. Molecules that down-regulate this response are overexpressed. Therapeutic strategies with targeting to such mechanisms underlying chronic hepatic and pancreatic injury are an emerging reality.

Single pancreatic metastasis from a previously resected carcinoma of the cecum: a case report.

OBJECTIVE: To report a case of an isolated pancreatic metastasis from a primary cecum carcinoma. BACKGROUND: Carcinoma of the colon and rectum commonly metastasizes to distant sites such as liver, lung, bone, brain, and ovaries. Only a few cases of pancreatic metastasis from a primary colonic carcinoma had been reported. Metastasic lesions to the pancreas are found only in 3% to 12% of autopsies from advanced malignancies. Primary tumors that commonly metastasize to the pancreas are lung and kidney. Most of the patients with metastatic lesions to pancreas also had extrapancreatic metastatic disease. CASE: We report a case of a 86-year-old woman with a single pancreatic metastasis from a primary cecum carcinoma resected 8 months before. CONCLUSIONS: The finding of an isolated metastasis to the pancreatic body from a primary cecum adenocarcinoma is extremely rare.

[Diabetes mellitus in acute pancreatitis]. / Diabetes mellitus en pancreatitis aguda.

Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.