Statin use and survival in resectable pancreatic cancer: confounders and mechanisms.

A first point regards the possible activity of drugs other than statins, such as aspirin or metformin, against pancreatic cancer. As many patients use a combination of these drugs, one might speculate that the association between simvastatin and overall survival in resected pancreatic cancer patients might also be explained by the concomitant use of aspirin or metformin, or that these drugs might result synergistic, as hypothesized for colorectal cancer (3). We wonder whether the authors had access to data on aspirin or metformin use for their population. A second point regards the very high 45% rate of simvastatin or lovastatin users reported by the authors. This figure is different from that of many European countries, thus possibly limiting the attributable fraction of cases for whom the observed findings can be replicated

Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic 'mucosal healing' and implication for management

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/ histological repor ts performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mildmoderate disease

The use of complementary and alternative medicine is frequent in patients with pancreatic disorder

BACKGROUND: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. AIM OF THE STUDY: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. MATERIALS AND METHODS: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. RESULTS: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. DISCUSSION: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a "healthier lifestyle." Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physician

Epidemiology, clinical features and treatment of chronic pancreatitis. current knowledge and future perspectives [Epidemiologia, clinica e terapia medica della pancreatite cronica: evidenze attuali e sviluppi per il futuro]

La pancreatite cronica è una patologia dal complesso inquadramento sia dal punto di vista epidemiologico, con dati incerti sull’esatta prevalenza, sia dell’eziologia, a volte non individuabile e per la quale si sta delineando sempre più la rilevanza delle forme post-pancreatite acuta, con il fumo come fattore di rischio spesso sottovalutato rispetto all’alcol. La pancreatite cronica si associa ad aumento della mortalità e morbilità, legate soprattutto a patologie extrapancreatiche. L’eventuale presenza di insufficienza esocrina o endocrina pancreatica può essere, inoltre, alla base di complicanze anche gravi e spesso non prevenute per tempo. I deficit vitaminici e di micro- e macronutrienti vanno attentamente ricercati e corretti; questo sarà inoltre fondamentale per evitare complicanze quali l’osteoporosi. Il dolore è il sintomo più rilevante, ha una patogenesi complessa, legata non solo a fattori ostruttivi e meccanici o alla flogosi, ma anche un’alterazione cronica del processo di adattamento al dolore a livello del sistema nervoso centrale. Anche per questo la terapia del dolore è spesso inefficace. La chirurgia derivativa è indicata nelle forme con ostruzione duttale con risultati che sembrano superiori a quelli dell’endoscopia, e quella resettiva in quelle associate a massa infiammatoria. Una nuova frontiera è rappresentata poi dalla pancreasectomia totale con trapianto di insule, che offre ottimi risultati in termini di controllo del dolore con possibilità di evitare il diabete in una buona percentuale di pazienti. Questa rassegna discute tali “hot topics” racchiudendo sia le evidenze più recenti sull’argomento sia una riflessione su come evolveranno le nostre conoscenze su tale patologia.Chronic pancreatitis is a complex disease both for the epidemiology, with uncertain data on the exact prevalence, but also for the etiology, often not identified and for whom, compared to the past, post acute pancreatitis forms are showing a high impact; also smoking is an etiological factor often underestimated compared to alcohol. Chronic pancreatitis is associated with high mortality and morbidity, mostly due to extrapancreatic diseases. The eventual occurrence of exocrine or endocrine pancreatic insufficiency can lead to complications, often serious and not prevented in time. It is, in fact, well known how this can cause micro or macronutrient and vitamin deficit which, if not screened and corrected, can cause complications such as osteoporosis. Abdominal pain is the most relevant symptom, with a complex pathogenesis, due not only to obstructive or mechanical factors or inflammation, but also to a chronic alteration of the adaptation process of pain in the central nervous system. Also for this reason, therapies are often not effective. Derivative surgery is indicated in obstructive forms, with results superior to those of endoscopy, while resective surgery is indicated when an inflammatory mass is present. A new opportunity is total pancreatectomy with islet autotransplantation, which offers excellent results in terms of pain relief and possibility to avoid diabetes in a high percentage of patients. This review will discuss these hot topics comprehending both most recent evidence and a view on how our knowledge on this disease will change in the upcoming years

Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing (AS) of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence-free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favor the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, upregulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to upregulation of PTBP1 and modulation of PKM AS in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.Oncogene advance online publication, 3 August 2015; doi:10.1038/onc.2015.270

Hypergastrinemia and enterochromaffin-like cell hyperplasia.

The enterochromaffin-like (ECL) cells, the most frequent endocrine cells of the oxyntic mucosa of the stomach, are under the trophic stimulus of gastrin. These cells undergo a hyperplastic increase in variety of hypergastrinemic diseases. The most widely accepted nomenclature for the description of hyperplastic proliferation has been retrospectively arranged in a sequence presumed to reflect a temporal evolution of the proliferative process. A comparative, prospective study aimed to verify, in human hypergastrinemic diseases such as atrophic body gastritis (ABG), Zollinger-Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH), the effect of exposure of ECL cells to different pattern of gastrin hypersecretion, is lacking. To this purpose, we studied a series of consecutive patients with ABG, ZES and AGCH at the time of first diagnosis. Material and Methods: The patients included in this study (124 ABG, 18 ZES and 10 AGCH) were selected on the basis of two previously performed screening studies aimed to diagnose these diseases. All patients at the time of diagnosis underwent gastroscopy, with multiple biopsies of the gastric body mucosa for the evaluation of qualitative pattern of ECL cells hyperplasia, and basal fasting gastrin determination. A sample of hypergastrinemic patients from each group was further investigated by meal-stimulation of gastrin secretion and quantitative morphometry for CgA positive gastric body endocrine cells. Results: AGCH patients showed only the normal or simple hyperplasia pattern. In the ZES group, simple and linear grades accounted for 38.4 percent and 46.1 percent, respectively. MEN-I patients showed only these two patterns. The majority of ABG patients showed the presence of micronodular pattern (59.7 percent). A correlation analysis between fasting gastrin levels and grade of hyperplasia (r = 0.5580, p < 0.0001), indicates that the greater the gastrin levels, the higher is the degree of severity of ECL hyperplasia pattern. In conclusion, our data support the role of gastrin as the selective contributor to the progression of ECL cell hyperplasia in humans

Iron deficiency anemia caused by nonspecific (idiopathic) small bowel ulceration: an uncommon presentation of an uncommon disease.

Ulcers of the small bowel are rare, and in most cases are due to infections, inflammatory bowel diseases, malignancies or drugs. When none of these causes is recognized, they are classified as 'nonspecific' or idiopathic. Such lesions are uncommon, and in most cases present with occlusion. A case of a middle-aged woman with iron deficiency anemia due to occult bleeding, with negative gastroscopy and colonoscopy is presented. The diagnosis of a small bowel pathology resembling Crohn's disease was made by small bowel follow through and small intestine contrast ultrasonography. An ileal ulcer was identified at surgery, and after resection the patient experienced a stable recovery from the anemia without ulcer recurrence. Neither histology nor clinical or biochemical features suggested the diagnosis of an inflammatory bowel disease. Other possible causes were unlikely and the lesion was therefore diagnosed as idiopathic. This report also focuses on the need and the modality to investigate the small bowel in iron deficiency anemia patients

The prevalence of pancreatic cystic lesions in patients with liver cirrhosis is double that in controls

Background and aims: Pancreatic cystic lesions (PCLs) are commonly diagnosed incidentally and are often preneoplastic. Their presence may influence the management of patients with chronic diseases such as liver cirrhosis (LC). This study evaluated the prevalence and nature of PCLs in LC patients. Methods: The images of 192 LC patients and 192 controls who underwent either computed tomography scan or nuclear magnetic resonance were reviewed for the presence and nature of PCLs. The prevalence of PCLs in both groups and differences between LC patients with and without PCLs were analysed. Multiple logistic regression analysis was used to investigate factors associated with PCLs. Results: Thirty-five of 192 LC patients (18%) and 19/192 controls (10%) had PCLs (p =.027). The prevalence of presumptive intraductal pancreatic mucinous neoplasm (IPMN) was double in LC patients compared with controls (14% vs 7%; p =.065). In multivariate analysis, age, LC and having undergone a magnetic resonance cholangiopancreatography were factors associated with PCLs and IPMNs. LC patients with PCLs were older at the time of imaging and had a longer history of liver disease (67 vs. 43 months; p = 0.039) compared with LC patients without PCLs. Conclusions: PCLs are more common in LC patients than in controls, and most are IPMNs. The occurrence of PCLs in LC patients seems to be related to age and disease duration

The Adult Carer Quality of Life Questionnaire (AC-QoL) : comparison with measures of burden and well-being, and Italian validation

Purpose: Family caregivers are essential assets in the rehabilitation process, and their psychophysical health should represent a concern for healthcare services. This study aims to investigate the psychometric properties of the Adult Carer Quality of Life Questionnaire (AC-QoL), Italian version, and its convergent-discriminant validity with measures of caring burden, resilience, health and well-being. Materials and Method: Participants were 591 parents (89.2% females; aged 25-69) of children treated as outpatients in 14 centers of \u201cIstituto Medea - La Nostra Famiglia\u201d, an Italian rehabilitation institution. They completed: AC-QoL, a 40-item scale assessing care-related challenges, resources and benefits; Caregiver Burden Inventory; Resilience Scale for Adults; Satisfaction With Life Scale; Health Survey SF-36. The psychometric properties of the Adult Carer Quality of Life Questionnaire were investigated through exploratory and confirmatory factor analyses and reliability evaluation; correlation coefficients assessed convergent and discriminant validity with burden and well-being measures. Results: The original eight-factor structure of the Adult Carer Quality of Life Questionnaire showed good adequacy and internal consistency; convergent and discriminant validity with measures of burden, resilience, satisfaction, physical and mental health were satisfactory. Conclusions: The Italian version of the Adult Carer Quality of Life Questionnaire is a reliable and valid instrument to assess caregivers\u2019 perceived challenges and resources. As a parsimonious and easily administrable tool, it can be used to evaluate caregivers\u2019 quality of life and related interventions

Diagnosis and treatment of acute pancreatitis: The position statement of the Italian Association for the study of the pancreas

BACKGROUND AND AIM: Till now, no Italian studies providing information on acute pancreatitis have been published. The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospectively collected epidemiological, anamnestic, laboratory, radiological, therapeutic (pharmacological, endoscopic and surgical) data, relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000. RESULTS: One thousand two hundred and six case report forms were collected, but 201 patients (16.6%) were subsequently eliminated from the final analysis. We therefore studied 1005 patients, 533 (53%) males and 472 (47%) females, mean age 59.6 +/- 20 years. On the basis of the Atlanta classification of acute pancreatitis, 753 patients of the 1005 cases analysed (75%) were mild and 252 patients (25%) severe. The aetiology was biliary in 60% of the patients, related to alcohol abuse in 8.5%, while in 21% of the cases it could not be identified. Over 80% of the patients (83%) were admitted to hospital within 24 h from the onset of clinical symptoms, while only 6% were admitted after 48 h. In particular, 65% of the patients were admitted to hospital within the first 12 h. Antibiotics were used in 85% of the severe and 75% of mild forms. Endoscopic therapy was carried out in 65% of the severe cases, but only in 40% it was carried out prior to 72 h. Eighty-five patients (8.5% of the total, 34% of the severe forms) underwent surgical intervention: 20% on the first day, 38.5% within the fourth day, and the remaining (41.5% of the cases) later on for infected necrosis. The mean duration of hospitalisation for patients with mild pancreatitis was 13 +/- 8 days, while for the severe disease it was of 30 +/- 14 days. The overall mortality rate was 5%, 17% in severe and 1.5% in mild pancreatitis. CONCLUSIONS: Acute pancreatitis in Italy is more commonly a mild disease with a biliary aetiology. The treatment of the disease is not optimal and, on the basis of these data, needs to be standardised. Despite this, the overall mortality rate is low (5%BACKGROUND AND AIM: Till now, no Italian studies providing information on acute pancreatitis have been published. The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospectively collected epidemiological, anamnestic, laboratory, radiological, therapeutic (pharmacological, endoscopic and surgical) data, relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000. RESULTS: One thousand two hundred and six case report forms were collected, but 201 patients (16.6%) were subsequently eliminated from the final analysis. We therefore studied 1005 patients, 533 (53%) males and 472 (47%) females, mean age 59.6 +/- 20 years. On the basis of the Atlanta classification of acute pancreatitis, 753 patients of the 10