Antonio Maria Morselli-Labate

Serum α-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease : influence of HBsAg and anti-HCV status

BACKGROUND It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection ☆

Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

Mucosal Immune Activation in Irritable Bowel Syndrome: Gender-Dependence and Association With Digestive Symptoms

OBJECTIVES:Immune activation may be involved in the pathogenesis of irritable bowel syndrome (IBS). However, the relative magnitude of this immune component and its correlation with gender and gastrointestinal complaints in IBS patients remains poorly elucidated.METHODS:We enrolled 48 IBS patients, with either diarrhea or constipation, 12 patients with microscopic colitis, 20 patients with ulcerative colitis, and 24 healthy controls. Colonic immunocytes were identified with quantitative immunohistochemistry on mucosal biopsies. Gastrointestinal symptoms were assessed using a validated questionnaire.RESULTS:IBS patients showed a significant 72% increase in mucosal immune cells compared to controls (P<0.001). Further analyses showed that increased immune cells were present in 50% of the IBS patients. The magnitude of the immune infiltrate in IBS was significantly lower than that of microscopic colitis or ulcerative colitis (42% and 124% increases vs. IBS, respectively; P<0.001). Compared with controls, IBS patients had increased numbers of CD3+, CD4+, and CD8+ T cells and mast cells (P<0.001). Compared to male IBS patients, female IBS patients had greater numbers of mast cells (P=0.066), but lower numbers of CD3+ and CD8+ T cells (P=0.002 and <0.001, respectively). Mucosal mast cell infiltration of IBS patients was significantly associated with abdominal bloating frequency (P=0.022) and with symptoms of dysmotility-like dyspepsia (P=0.001), but not ulcer-like dyspepsia.CONCLUSIONS:A large subset of IBS patients shows gender-dependent mucosal infiltration of immunocytes that correlates with abdominal bloating and dysmotility-like dyspepsia. These results provide the rationale for considering immune mechanisms as a pathophysiological component in a subset of IBS patients.

Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein.

The aim of this study was to compare the sensitivity, specificity, and diagnostic accuracy of serum interleukin-6, interleukin-8,β2-microglobulin, and C-reactive protein in the assessment of the severity of acute pancreatitis using commercial kits for their respective assays. Thirty-eight patients with acute pancreatitis (25 men, 13 women, mean age 59 years, range 16–97) were studied; the diagnosis was based on prolonged upper abdominal pain associated with a twofold increase of serum lipase, and it was confirmed by imaging techniques. According to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The four serum markers were determined in all patients on admission, as well as daily for the following five days. On the first day of the disease, the sensitivity (calculated on patients with severe pancreatitis), specificity (calculated on patients with mild pancreatitis), and the diagnostic accuracy of these serum markers for establishing the severity of acute pancreatitis were 100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81%, and 88% for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% forβ2-microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive protein (cutoff level 11 mg/dl). The results of our study indicate that, when assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8 are better markers thanβ2-microglobulin or C-reactive protein for evaluating the severity of acute pancreatitis.

Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

PURPOSE We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs). PATIENTS AND METHODS Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination. RESULTS CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%). CONCLUSION Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.

The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long‐term oestrogen–progestagen treatment

Little is known about the natural history of polycystic ovary syndrome (PCOS), although preliminary data indicate that affected women are more susceptible than the general population to diabetes and cardiovascular diseases at post‐menopausal ages. The aim of this study was to follow‐up all main features of the metabolic syndrome in a group of young women with PCOS and to investigate the long‐term effects on metabolism and body composition of oestrogen–progestagen (OP) compounds, which are frequently used in these women to treat hyperandrogenism and related clinical features.

Natural History of Chronic Idiopathic Intestinal Pseudo-Obstruction in Adults: A Single Center Study

BACKGROUND & AIMS Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a rare disease characterized by episodes resembling mechanical obstruction in the absence of organic, systemic, or metabolic disorders. Intestinal motor abnormalities have long been identified in CIIP patients. Little is known of the natural history of the disease in adults. This study evaluated the clinical course of CIIP over time. METHODS Fifty-nine consecutive CIIP patients without underlying collagen, vascular diseases, or mitochondrial cytopathies were evaluated between 1985 and 2001. Family history, onset of digestive symptoms, previous surgeries, episodes suggestive of subacute intestinal obstruction, digestive symptoms, body mass index, and feeding habits were recorded. Small bowel manometry was performed by a perfusion technique, and abnormal motor patterns were visually identified. Full-thickness biopsies were available in 11 cases and were processed for immunohistochemical analysis of myogenic and neurogenic components of the gut wall. RESULTS Patients were prospectively followed up for a median of 4.6 years (range, 1-13 years). Diagnosis was often made several years after symptom onset (median, 8 years). Thus, the majority of patients (88%) underwent useless and potentially dangerous surgeries (mean, 2.96 per patient). Manometry invariably showed abnormal motor patterns. Pathologic findings included neuropathies in all investigated cases and abnormalities of interstitial cells of Cajal in 5 of 11 cases. Long-term outcome was generally poor despite surgical and medical therapies; 4 patients died of disease-related complications, 4 underwent small bowel transplantation, almost one third required long-term home parenteral nutrition, and two thirds had some sort of nutritional limitations. CONCLUSIONS CIIP is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time.

Usefulness of serum IgG4 in the diagnosis and follow-up of autoimmune pancreatitis: a systematic literature review and meta-analysis

High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver–operating characteristic curve analysis was carried out by means of Meta‐DiSc open‐access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve [± SE]: 0.920 ± 0.073, 0.914 ± 0.191, and 0.949 ± 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.

Factors associated with neurological outcome and lesion progression in traumatic subarachnoid hemorrhage patients.

OBJECTIVE:Traumatic subarachnoid hemorrhage (tSAH) is a frequent finding after closed-head injuries, and its presence is a powerful factor associated with poor outcome. The exact mechanism linking tSAH and an adverse outcome is poorly understood. The aim of this study was to identify the factors that may predict outcomes and changes in the computed tomographic (CT) scans of lesions in a selected population of tSAH patients. METHODS:We evaluated 141 patients admitted consecutively from January 1, 1997, to January 31, 1999, with a CT diagnosis of tSAH. The admission and “worst” CT scans were recorded. CT scan changes were reported as “significant CT progression” (changes in the Marshall classification) or “any CT progression.” The amount of subarachnoid blood was recorded using a modified Fisher classification. Outcome was assessed at 6 months after injury with the Glasgow Outcome Scale. RESULTS:Twenty-eight patients (19.9%) had an unfavorable Glasgow Outcome Scale outcome. In the univariate analysis, prognosis was significantly related to age, admission Glasgow Coma Scale score, Marshall CT classification score at admission and on the worst CT scan, amount of tSAH, and volume of the associated brain contusions. From multivariate analysis, the only factors independently related to outcome were the Glasgow Coma Scale score (P < 0.01) and size of the tSAH at admission (P < 0.001). Thirty-four patients (24.1%) had significant CT lesion progression, and 66 patients (46.8%) had some lesion progression. Patients having significant progression of the lesion had a higher risk of an unfavorable outcome (32 versus 10%; P = 0.004). Unadjusted factors predicting CT progression were the Glasgow Coma Scale score at admission, the Marshall classification at admission, the amount of subarachnoid blood, and the presence or volume of associated brain contusions at admission. Independent factors associated with significant CT progression were the amount of tSAH (P < 0.001) and the presence or volume of brain contusions at admission (P < 0.001). CONCLUSION:The outcome of patients with tSAH at admission is related in a logistic regression analysis to the admission Glasgow Coma Scale score and to the amount of subarachnoid blood. These patients also have a significant risk of CT progression. The amount of subarachnoid blood and the presence of associated parenchymal damage are powerful independent factors associated with CT progression, thus linking poor outcomes and CT changes.

Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study

BACKGROUND Subclinical Cushings syndrome (SCS) is defined as alterations in hypothalamic-pituitary-adrenal axis without classic signs/symptoms of glucocorticoid excess. Whether SCS leads to metabolic and cardiovascular diseases is still controversial. AIM To evaluate the prevalence of hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and fractures, and their relationship to increasing patterns of subclinical hypercortisolism, in patients with nonsecreting adrenal adenomas (NSA) and SCS. METHODS Using the 1 mg dexamethasone suppression test (DST), 348 patients were classified as follows: 203 were defined as NSA and 19 SCS, using the most stringent cutoff values (<50 and >138 nmol/l respectively). Patients with cortisol post-DST (50-138 nmol/l) were considered as intermediate phenotypes and classified as minor (n=71) and major (n=55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools. RESULTS SCS patients showed higher prevalence of T2D, CHD, osteoporosis, and fractures with respect to NSA. Intermediate phenotypes also showed higher prevalence of CHD and T2D with respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis: both IP and SCS-secreting patterns showed a significant association with CHD (odds ratio (OR), 4.09; 95% confidence interval (CI), 1.47-11.38 and OR, 6.10; 95% CI, 1.41-26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR, 5.94; 95% CI, 1.79-19.68). CONCLUSIONS Patterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.