Prevalence and correlates of Benign Pancreatic Hyperenzymemia in a large general population sample: The Damocles sword perception.

BACKGROUND: Benign Pancreatic Hyperenzymemia (BPH) is characterized by a long-term increase of serum pancreatic enzymes (PE) in otherwise healthy subjects. The study investigates the prevalence and correlates of the condition using data from Electronic Health Records (EHR) in a large sample of general population, to identify subjects potentially affected by BPH. METHODS: Cross-sectional retrospective observational study integrated by a follow-up visit. RESULTS: The database of a reference laboratory identified, out of 577.251 admittances from 2011 to 2015, 4964 patients tested at least for one PE assay and 1688 subjects who had at least 3 PE tests (normal or increased) over two years. Forty-two individuals showed an increase of PE at least three times throughout 2 years without any evidence of pancreatic disease, even after matching with the ICD 9-CM code in the GPs database. Data retrieved at follow-up visit showed that for 34 the diagnosis of BPH could be made. CONCLUSIONS: Our data indicate that BPH prevalence among subjects underwent blood testing for multiple PE testing is 2%. This condition, even if not a disease, is perceived by nearly all the BPH patients as a serious threat to their life. Further studies are needed to manage its heavy psychological impact.

Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis.

BACKGROUND & AIMS: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. METHODS: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. RESULTS: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). CONCLUSIONS: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.

Network analysis of drug prescriptions.

PURPOSE: Networks exist in many different aspects of the world, at social, economical, biological, and molecular levels. Network science studies their parameters, or quantitative indicators; its instruments make it possible to draw and analyze networks from a mathematical perspective. The present study is an attempt to apply network science techniques to the drug prescription process, a typical subject of Epidemiology for Public Health studies. METHODS: A drug prescription network was created using the set of drug prescriptions written during a 6-month period by a group of 99 general practitioners (GPs) operating in Italy. In this network, named co-prescription network, each drug represented a node, and different drugs prescribed to the same patient at the same moment were considered linked together. Drug prescription data for a total of 42 965 patients and 631 232 drug packages were studied. A number of co-prescription networks were obtained and analyzed on the basis of different subsets of patients by age and gender. The network parameters were measured and compared for the various subsets. RESULTS: All the drug prescription networks studied showed scale invariance behavior. The age- and gender-related co-prescription networks showed different patterns, with different levels of complexity. CONCLUSIONS: The present study shows that the drug prescription process has specific network aspects and dynamics and, more generally, that it is possible to apply instruments of network science to study public health phenomena from a new, different perspective. Further studies should be encouraged and performed.

Role of chemoembolization as a rescue treatment for recurrence of resected hepatoblastoma in adult patients.

INTRODUCTION: Hepatoblastoma is the most common malignant liver tumor in children, but it is extremely rare in adults. MATERIALS AND METHODS: A 33-year-old man was admitted with nausea, vomiting, weight loss, and right upper quadrant pain. A preoperative magnetic resonance imaging showed a nodular hepatic lesion infiltrating the lesser curvature of the stomach. A left hepatectomy and a subtotal gastrectomy were performed. The histological diagnosis was hepatoblastoma. A recurrence in the right lobe was seen. RESULTS: Three cycles of transcatheter arterial chemoembolization (TACE) were performed 40, 70, and 130 days after surgery. No sign of recurrence was present at the time of the second chemoembolization. CONCLUSION: The TACE was well tolerated by the patient and controlled the recurrence. The patient survived 11 months after recurrence of disease and died 1 year after the liver resection. The use of TACE to treat the hepatic recurrence was never described.

Prescribing Behavior of General Practitioners for Generic Drugs.

The factors influencing General Practitioners' (GPs) prescribing behavior are diverse in terms of health care policies and regulations, GPs' education and experience, demographic trends and disease profiles. Thus, it can be useful to analyze the specific local patterns, as they affect the quality of healthcare and the stability of the healthcare market. The aim of the present longitudinal retrospective study is to investigate the prescription of generic drugs in a database of about 4.6 million prescriptions from a sample of 38 GPs practicing in Salerno, Italy, within a timeframe of 15 years, from 2001 to 2015. The GPs in our study show a general tendency to increase prescriptions of generic drugs during the studied time span, to fulfill regulatory obligations and with some differences in prescription behavior according to age, gender and experience. The generics prescription depends also on the different diagnoses, with some diagnostic areas showing a greater generic drug prescription rate. Expanding this research to larger datasets would allow deepening the knowledge of the patterns of GPs' prescribing decisions, to provide evidence to be used in comparison between different national settings.

Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: a new variant of "Bouveret's syndrome".

Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

General Practitioners Records Are Epidemiological Predictors of Comorbidities: An Analytical Cross-Sectional 10-Year Retrospective Study.

BACKGROUND: Comorbidity represents the co-occurrence of pathological conditions in the same individual, and presents with very complex patterns. In most cases, reference data for the study of various types of comorbidities linked to complex diseases are those of hospitalized patients. Such patients may likely require cure due to acute conditions. We consider the emerging role of EHR (Electronic Healthcare Records), and study comorbidity patterns in a general population, focusing on diabetic and non-diabetic patients. METHODS: We propose a cross-sectional 10-year retrospective study of 14,958 patients and 1,728,736 prescriptions obtained from family doctors, and thus refer to these data as General Practitioner Records (GPR). We then choose networks as the tools to analyze the diabetes comorbidity patterns, distinguished by both prescription type and main patient characteristics (age, gender). RESULTS: As expected, comorbidity increases with patients' age, and the network representations allow the assessment of associations between morbidity groups. The specific morbidities present in the diabetic population justify the higher comorbidity patterns observed in the target group compared to the non-diabetic population. CONCLUSIONS: GPR are usually combined with other data types in EHR studies, but we have shown that prescription data have value as standalone predictive tools, useful to anticipate trends observed at epidemiological level on large populations. This study is thus relevant to policy makers seeking inference tools for an efficient use of massive administrative database resources, and suggests a strategy for detecting comorbidities and investigating their evolution.

The Risk of Hepatocellular Carcinoma After Directly Acting Antivirals for Hepatitis C Virus Treatment in Liver Transplanted Patients: Is It Real?

INTRODUCTION: Since directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) were introduced, conflicting data emerged about the risk of hepatocellular carcinoma (HCC) after interferon (IFN)-free treatments. We present a case of recurrent, extra-hepatic HCC in a liver-transplanted patient soon after successful treatment with DAAs, along with a short review of literature. CASE PRESENTATION: In 2010, a 53-year old man, affected by chronic HCV (genotype 1) infection and decompensated cirrhosis, underwent liver resection for HCC and subsequently received orthotopic liver transplantation. Then, HCV relapsed and, in 2013, he was treated with pegylated-IFN plus ribavirin; but response was null. In 2014, he was treated with daclatasvir plus simeprevir to reach sustained virological response. At baseline and at the end of HCV treatment, computed tomography (CT) scan of abdomen excluded any lesions suspected for HCC. However, alpha-fetoprotein was 2.9 ng/mL before DAAs, increasing up to 183.1 ng/mL at week-24 of follow-up after the completion of therapy. Therefore, CT scan of abdomen was performed again, showing two splenic HCC lesions. CONCLUSIONS: Overall, nine studies have been published about the risk of HCC after DAAs. Patients with previous HCC should be carefully investigated to confirm complete HCC remission before starting, and proactive follow-up should be performed after DAA treatment.

Impact of dose and volume on subcutaneous fibrosis.

The multifactorial genesis of radiation-induced fibrosis makes a general outline of the occurence of this late toxicity fairly unpredictable. Scientific knowledge about dose fractionation, irradiated volume, total time, conformation procedures including IMRT can help provide better treatments. Chemical and physical therapies aimed at the removal of fibrosis are still limited or under study. The system of monitoring late toxicity used by the authors is presented.

A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report.

INTRODUCTION: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. CASE PRESENTATION: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000 mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. CONCLUSIONS: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team.

Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree.

AIM: To evaluate the relationship between hepatocellular carcinoma (HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence. METHODS: This retrospective study included 165 patients (143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing (< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based on location. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ(2) test. RESULTS: Of the 163 patients with imaging evidence of viable tumor, 156 (95.7%) had hypervascular and 7 (4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19 (15.2%) had grade 1, 56 (44.8%) grade 2, 40 (32%) grade 3 and 4 (3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients (4.8%). A significant association was found between imaging vascularity and pathological grade (P = 0.035). Post-transplantation recurrence rate was 14.55% (24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients (12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients (58.3%), intrahepatic in 7 patients (29.2%) and both intrahepatic and extrahepatic in 3 patients (12.5%). Two patients had a variation in imaging characteristics between the primary HCC (hypervascular) and the intrahepatic recurrent HCC (hypovascular), while 1 patient had a variation of histopathological characteristics (from moderate to poor differentiation), however no association was found between imaging and histopathological variations. CONCLUSION: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.

Biological factors and therapeutic modulation in brain tumor radiotherapy.

Diagnosticotherapeutic approaches aimed at the improvement of prognosis of the most aggressive brain tumors tend to include new tools of investigation. Functional imaging, biologic markers, radiosensitizers, the combination of different modalities of radiation therapy and chemotherapy are being experimented. These new approaches to the neoplastic metabolism require increased resources and a close follow-up during treatment to better define the biological target volume. More sophisticated and aggressive techniques as intensity modulated radiation therapy or brachycurietherapy can be suitably included in combined modality therapy.

Biological optimization of the dose in stereotactic radiotherapy of brain tumors.

The techniques of radiotherapy with a high dose gradient require several demanding choices but represent a major innovation in the radiation therapy of brain tumors. To optimize the expected outcomes in terms of effectiveness and efficacy some recent acquisitions of biological parameters of integration of the linear-quadratic model are illustrated, aimed at the progressive understanding of the role of histology, dose fractionation, timing, toxicity and combined modality therapy.

[Locoregional treatment of hepatocellular carcinoma: comparison between percutaneous alcohol administration and intraarterial chemoembolization]. / Trattamento locoregionale del carcinoma epatocellulare: confronto tra alcolizzazione percutanea e chemioembolizzazione intrarteriosa.

Between 1991 and 1998, 45 cirrhotic patients with hepatocellular carcinoma (1 or 2 lesions smaller than 5 cm) were treated either with percutaneous ethanol injection (26 patients) or with trans arterial chemoembolization (19 patients) in our Department. Percutaneous ethanol injection was performed on 37 nodules: mean diameter of 3.1 +/- 0.8 cm. Transarterial chemoembolization was performed on 27 nodules: mean diameter of 2.8 +/- 0.7 cm. Therapeutic success at first treatment was obtained in 81.5% of percutaneous ethanol injection treated lesions and in 60.0% of trans arterial chemoembolization treated lesions. Local recurrence after first treatment occurred in 7 of 22 percutaneous ethanol injection patients (31.8%) and 8 of 15 transarterial chemoembolization patients (53.3%). Distant hepatic recurrence after first treatment occurred in 16 of 26 (61.5%) alcolization treated patients and in 14 of 25 (56.0%) chemoembolization treated. Multivariate analysis selected therapeutic success and modality of treatment as the best predictor of better survival probability in all treated patients. Survival probability at 12/24/36/48 months was 96.1/80.8/61.6/42.3% in percutaneous ethanol injection group and 89.5/68.4/36.8/15.8% in transarterial chemoembolization group (p < 0.05 Log rank). Few data are available comparing the efficacy of percutaneous ethanol injection and transarterial chemoembolization in patients with hepatocellular carcinoma. Our data confirm that percutaneous ethanol injection is better than trans arterial chemoembolization in the treatment of patients with one or two lesions of hepatocellular carcinoma.

Absence of viable HCC in the native liver is an independent protective factor of tumor recurrence after liver transplantation.

BACKGROUND: Prognostic factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) are still a matter of debate. The absence of viable tumor in the native liver, due to effectiveness of pre-LT locoregional treatment or liver resection, is an intriguing prognostic factor that had never been evaluated. METHODS: Between November 2000 and December 2011, 210 LTs were performed in patients with evidence of HCC and cirrhosis. RESULTS: Fifty-three (25.2%) patients did not show any evidence of active residual HCC in the native liver (Group NVH), whereas 157 (74.8%) patients showed viable HCC (Group VH). All patients in Group NVH were treated before LT with a multimodal approach combining transarterial chemoembolization, liver resection, radiofrequency ablation, percutaneous ethanol injection, or sorafenib, whereas, in Group VH, 110 of the 157 (70.1%) patients received bridging therapy (P<0.001). HCC recurrence occurred in none of the patients in Group NVH (0%) and in 25 (15.9%) patients in Group VH (P=0.003). Liver resection was the most effective treatment in obtaining absence of HCC on liver explantation. The results of multivariate analysis showed that existence of pathologic HCC findings outside of the University of California-San Francisco criteria (P=0.001; odds ratio, 4; confidence interval, 1.7-9.2) and the presence of viable HCC (P=0.003; odds ratio, 5.9; confidence interval, 1.5-17.6) were independently associated with HCC recurrence. CONCLUSIONS: The histologic absence of viable HCC in the native liver after LT and morphologic criteria, due to the high effectiveness of pre-LT bridging treatments, is a highly positive prognostic factor against HCC recurrence after LT.