EXTRADIGESTIVE MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE: DEMOGRAPHIC, CLINICAL, BIOLOGICAL AND ENDOSCOPIC FEATURES.

UNLABELLED: Gastroesophageal reflux disease (GERD) with extradigestive manifestations is a disorder increasingly recognized both by gastroenterologists, pneumologists, otolaryngologists and cardiologists. AIM: To evaluate the demographical, clinical, biological and endoscopic features of the patients with gastroesophageal reflux disease and extradigestive manifestations (chronic laryngitis, asthma, pseudoangina). MATERIAL AND METHODS: Prospective case-control study, including 137 patients selected from patients referred to the Iasi Institute of Gastroenterology and Hepatology between July 2014-September 2015. In the presence of typical GERD symptoms (heartburn or regurgitation), the patients were assessed by upper digestive endoscopy for the detection or exclusion of esophagitis. Despite the absence of esophageal lesions, the patients were further assessed by impedance-pHmetry. RESULTS: Depending on the dominant extradigestive manifestation, the patients were assigned into 3 groups: 94 chronic laryngitis patients, 24 asthma patients and 19 pseudoangina patients. Females were more frequent among pseudoangina patients (68.4%). Mean age of the male patients with dysphonia or asthma was lower (p=0.002), the majority (78.1%) living in urban areas. Obesity was predominant in pseudoangina group (52.6%), as compared to dysphonia group (16%) the differences being statistically significant (p=0.002). A share of 57.9% of pseudoangina patients were dyslipidemic, in contrast to dysphonia (24.5%) or asthma group (37.5%) (p=0.013). Esophagitis was also more frequent at pseudoangina group (84.2%), but with no significant statistical difference between the study groups (79.8% and 75%, respectively) (p=0.115). It seems that Helicobacterpylori infection tends to be protective in patients with GERD and pseudoangina (RR=0.61), but it can not be extrapolated to the general population (p=0.459). CONCLUSION: GERD with extradigestive manifestations is a prevalent and heterogeneous disease. There are demographic, clinical, biological and endoscopic differences between patiens with extradigestive GERD.

IMPLICATIONS OF GHRELIN AXIS IN BREAST CANCER--REVIEW.

Breast cancer is, by far, the most frequent cancer among women and many factors influence the physiological and pathological growth and development of the mammary gland. There is developing evidence that the hormone ghrelin, known for the growth hormone releasing effect and food intake modulator, could also play a role in the pathogenesis of breast cancer and may represent a new diagnostic marker and a potential therapeutic target. We performed a PubMed Database search of relevant studies and ten papers were included in our systematic review. Ghrelin axis seems to be definitely involved in the pathogenesis of breast cancer, although a precise role has not been yet established. In order to verify the precise role of ghrelin axis in breast cancer further studies with larger populations are necessary that should include the analysis of metabolic, genetic and environmental factors which are expected to influence the results.

NONALCOHOLIC FATTY LIVER DISEASE AND ITS COMPLICATIONS--ASSESSING THE POPULATION AT RISK. A SMALL SERIES REPORT AND LITERATURE REVIEW.

UNLABELLED: The aim of the study was to highlight correlations between serum biochemical markers and different degrees of liver inflammation or fibrosis revealed by liver biopsy in morbidly obese patients. We also wanted to emphasize that the occurrence of hepatocellular carcinoma (HCC) is increasingly associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease. MATERIAL AND METHODS: A clinical retrospective study was carried out on a series of 13 patients operated for morbid obesity in our surgical unit. Included in this study were only the obese patients referred for bariatric surgery without other risk factors for liver disease and in whom a liver biopsy was taken during metabolic surgery. RESULTS: The pathology report revealed different stages of nonalcoholic fatty liver disease in all 13 patients: pathological features of steatohepatitis (7 patients), hepatic steatosis (5 patients) and lesions specific for evolving cirrhosis (1 patient). Regardless of the pathological changes of the liver, except the patient with evolving cirrhosis, none of these patients showed changes in classical liver function blood tests. DISCUSSIONS: Hepatic alteration in obese patients, ranging from simple steatosis to steatohepatitis or even cirrhosis, is not always correlated with the values of classical biological liver function tests. Literature data suggest the involvement of adipokines in the development and progression of steatosis as the hepatic expression of metabolic and chronic inflammation syndrome occurring in obese patients. Furthermore, these proteins secreted by adipose tissue seem to be related to the HCC occurrence. However, none of these studies show the exact pathway followed by the hepatic cell from simple fatty liver to hepatocellular carcinoma. CONCLUSIONS: finding and selecting the population at risk for fatty liver disease progression and for HCC development among obese patients is mandatory.

PSYCHOMETRIC HEPATIC ENCEPHALOPATHY SCORE FOR THE DIAGNOSIS OF MINIMAL HEPATIC ENCEPHALOPATHY IN ROMANIAN CIRRHOTIC PATIENTS--PARTIAL RESULTS.

UNLABELLED: In Romania, minimal hepatic encephalopathy (MHE) is underdiagnosed and undertreated in patients with liver cirrhosis. The psychometric hepatic encephalopathy score (PHES) is recommended as the first-line tool for the diagnosis of MHE. AIM: To use PHES in a group of Romanian cirrhotic patients and highlight the relationships between demographic and biological factors and tests results. MATERIALS AND METHODS: Of the 148 patients with liver cirrhosis admitted to the Iasi Institute of Gastroenterology and Hepatology between August 2014 and February 2015 only 80 who met the eligibility criteria were enrolled and completed the study. Blood samples for routine tests and serum ammonia were collected from all patients on the day of PHES evaluation. RESULTS: In the study group (n = 80) mean age was 57.7 ± 8.5 years, and the average number of years of education was 11.2 ± 2.7. The main causes of cirrhosis were alcohol consumption (31 patients--38.8%), hepatitis C virus infection (29 patients--36.3%) and hepatitis B virus infection (17 patients--21.3%). Age, number of years of education, severity of liver disease (measured by using Child-Pugh and MELD scores) and some biological constants (albumin, bilirubin, International Normalized Ratio-INR) were significantly correlated (p < 0.05) with most psychometric tests. CONCLUSIONS: PHES is a practical, objective and useful method for the diagnosis of MHE. Demographic and biological factors correlated with the results of the psychometric test. The PHES requires standardization before applying it in Romanian cirrhotic patients.

THE TRIBES AND TRIBULATIONS OF LARYNGOPHARYNGEAL REFLUX: A REVIEW OF RECENT STUDIES WITH IMPLICATIONS FOR INTERDISCIPLINARY COLLABORATIONS BETWEEN OTOLARYNGOLOGISTS AND GASTROENTEROLOGISTS.

Laryngopharyngeal reflux has been recognized since 2006 (Montreal Consensus) as an extradigestive manifestation of gastroesophageal reflux disease. However, despite numerous research studies, the relationship between these two pathologies is yet to be fully understood. The aim of this paper is to review the literature of the last five years available via the PubMed database, looking at the controversies about the prevalence, pathophysiology and diagnosis of laryngopharyngeal reflux.

Unmasking a young adult migratory deep venous thrombosis--case report.

Venous thromboembolism is a known complication of cancer which impacts on patient mortality and quality of life. The primary site of cancer is an important risk factor, with highest rates observed in patients with brain, pancreas, gastric, kidney, ovary and lung cancers. The extent of metastatic spread further adds to the risk. In this article, we present the case of a young patient who was diagnosed with an aggressive form of pancreatic neoplasm with secondary determinations, without any previous digestive symptoms, with the occasion of a recurrent and migratory deep venous thrombosis (DVT).

Overweight and gastrointestinal symptoms among adults of working age in Iasi City, Romania.

UNLABELLED: The objectives were to determine the presence of gastrointestinal symptoms and overweight in a sample of working age adults, from Iasi city (North-East Romania) and relationship with eating habits. MATERIAL AND METHODS: For this survey a sample was randomly chosen from family doctors records and 158 adults participated (65 males and 93 females, aged 19-64 years). Eating habits and food-frequency questionnaires were conducted, and Body Mass Index (BMI), waist and Body Fat Percent (FAT) were measured. For recent symptoms we used Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: 43.1% of male and 47.3% of female were overweight and 21.5% of male and 21.6% of female were obese. The total body fat exceeded its normal limits in 70.8% of men and in 32.3% of women. Waist was high (abdominal obesity) in 49.5% of women and in 26.2% of men. Present gastrointestinal symptoms were: reflux (23.4%), abdominal pain (8.9%), indigestion (32.9%), diarrhea (6.3%) and constipation (8.9%). Overweight or obese subjects accused reflux, indigestion (p < 0.01) and constipation (p < 0.05) more frequently than those with normal weight. Odd ratio value and 95% confidence interval for obese versus normal weighted subjects was 8.23 (2.15-37.58) for reflux and 11.65 (3.34-45.5) for indigestion. CONCLUSIONS: Our findings up-date epidemiological data and suggest the need to promote healthy eating habits in order to reduce the tendency of obesity and to improve digestive function in population.

Malignant tumors of digestive organs and liver metastases at the time of diagnosis.

AIM: Malignant tumors localized in the digestive tract have a tendency to local growth and invasion with lymph node metastasis. Distant metastases through blood with prevalent liver location are detected late in disease progression, in an advanced stage, when therapeutic possibilities are often limited to palliative therapy. MATERIAL AND METHODS: The study included a series of 139 patients with liver metastases admitted to the Center of Gastroenterology and Hepatology lasi between January 1 and October 10, 2011 for the identification of primitive tumor. The patients were investigated by endoscopy, imaging, laboratory tests including tumor markers. RESULTS: At 99 of the patients (71%) we identified primitive digestive tumors, in 19 patients (13.6%) we found tumors with extradigestive location and in 21 patients (15%) the primitive tumor could not be identified. Primitive.tumor was located in various segments of the digestive tract, liver, and pancreas was follows: esophagus 4 - (4%), eso-cardial-tuberositary 2 - (2%), eso-cardial-tuberositary with pancreatic invasion 1 -(1%), stomach 15 - (15%), ileocolon 1 - (1%), colon 19 - (19%), rectum 12 - (12%), liver, multicentric hepatolcellular carcinoma 23 - (23%) billiary tract - cholangiocarcinoma 2 (2%), pancreas 2 - (20%). In a series of 586 patients with malignant tumors of the digestive organs referred to the Iasi Oncology Outpatient Unit between January 1 and September 30, 2011, 132 patients (23%) had liver metastases at the time of diagnosis; the most common locations were the stomach 41% cases (42/119 patients), followed by the pancreas, 35%, and colon 31% patients (28/79 patients and 37/119 patients, respectively). Males were most affected, regardless of primitive tumor. CONCLUSIONS: Although diagnostic and therapeutic methods have made remarkable progress in recent years, these tumors, by their frequency and advanced stage at diagnosis, remain both an oncologic and public health problem mainly due to the limitations of curative treatment.

Laryngeal morphological changes due to gastroesophageal reflux disease.

UNLABELLED: Chronic laryngitis may have life impact on professional voice users. Besides smoking and excessive alcohol intake, GERD is a determiniing factor in the etiology of dysphonia. AIM: To evaluate the laryngeal alteration due to GERD in professional voice users. MATERIAL AND METHODS: The study included 96 vocal professionals (teachers, actors, singers and priests), 58 males and 38 females, with a mean age of 38.3 +/- 7.5 years, presented for chronic laryngeal symptoms. The patients filled out a standardized questionnaire and were examined laryngoscopically. RESULTS: Laryngeal changes were scaled 0 (absence) to 7 (maximum) - arytenoid edema (5.07 +/- 1.08), interarytenoid edema (6.18 +/- 1.12), vocal folds edema (5.67 +/- 1.04), ventricular bands edema (4.96 +/- 0.97), laryngeal edema 4.12 +/- 0.83). CONCLUSIONS: Laryngoscopic changes may suggest the concomitance of GERD in professional voice users with dysphonia.

[Liver cirrhosis--procoagulant stasis]. / Ciroza hepatica--stare procoagulanta?

Abnormal hemostasis tests and bleeding are often associated in liver cirrhosis. In these patients the balance between hypo- and hypercoagulation status is more fragile than in healthy people. In the hemostatic abnormalities associated with chronic liver disease are two main chategory factors: favoring hemorrage and favoring thrombosis. The main factors that favoring hemorrage are: low platelet count, impaired platelet function, decreased levels coagulation factors (II, V, VII, IX, X, XI), quantitative and qualitative abnormalities of fibrinogen, vitamin K defiency, low levels of trombin activable fibrinolisis inhibitor, activat plasminogenic tisular. The factors favoring thrombosis are elevated levels of factors VIII and von Willebrand, decreased levels of protein C, protein S, antithrombin, decreased levels of plasminogen. Traditionally it was thought that arterial and venous thrombosis is rare events in cirrhotic patients but recent studies have indicated that thrombotic complications can paradoxically occur even if clinically an increased risk of hemorrhage is considered. Treatment of venous thrombosis in patients with cirrhosis using routine anticoagulation with heparin and vitamin K antagonists has been described but with a high level of bleeding complications. So, based on the limited data available, AASLD guidelines stated no recommendations for or against the use of anticoagulation in cirrhotic patients with portal thrombosis. Although abnormal hemostasis tests and bleeding are often associated in patients with chronic liver disease it is a relatively poor correlation between hemorrhagic risk and routine diagnostic tests of hemostasis. Management of bleeding complications in liver cirrhosis varies and no general guidelines are available. The main therapeutic strategies are: red cell concentrate, plasma, platelet concentrate, recombinant factor VIIa, factor concentrates, desmopressin, antifibrynolitic agents, thrombopoietin receptor agonists, antibiotics. Clinical studies examining safety and efficacy of the various products for the different bleedeing or trombotic complications of liver cirrhosis need to be initiaded.

Spiral enteroscopy--a novel method for the management of small bowel diseases--case report and description of technique.

Small bowel diseases are associated with difficult management. Recently, new methods such as single or double balloon enteroscopy and capsule endoscopy have been implemented for the investigation of small bowel, but none is perfect. Spiral enteroscopy seems to be an alternative primising technique for the diagnosis and therapy of small bowel diseases. We report two cases in which spiral enetroscopy was useful both for diagnosis and therapy. One was the case of a man with repeated digestive bleeding of unknown cause and spiral enteroscopy helped for diagnosis and treatment with argon plasma coagulation of the vascular lesions. The later was a patient with Gartner Syndrome with multiple duodenal and intestinal polyps and spiral enteroscopy allowed small bowel evaluation. In conclusion, this novel method seems to allow a rapid and efficient diagnosis of small bowel diseases.

[Peptic ulcer disease in liver cirrhosis: role of Helicobacter pylori infection and therapeutic approach]. / Maladia peptica in ciroza hepatica: rolul infectiei cu Helicobacter pylori si conduita terapeutica.

Peptic ulcer has frequently been associated with liver cirrhosis. The death rate for peptic ulcer in cirrhotics has been reported to be five times higher than in general population. The underlying mechanisms are poorly understood. Different factors have been claimed to be involved, such as alterations in serum gastrin level, gastric acid secretions, mucosal blood flow and decreased prostaglandin production in gastric mucosa. Moreover, Helicobacter pylori infection, when accurately assessed, is detectable in most peptic ulcer cirrhotics. Since the H. pylori infection strongly correlates with peptic ulcer in general population, it is necessary to clarify the role of H. pylori in the pathogenesis of peptic ulcer in cirrhosis before eradication can be proposed as a preventive measure.

[Cardiomyopathy in liver cirrhosis--an undiagnosed entity?]. / Cardiomiopatia--complicatie subevaluata în ciroza hepatica?

Cirrhotic cardiomyopathy is a condition recently known in liver cirrhosis consisting of systolic dysfunction to stress factors, diastolic dysfunction and electrophysiological abnormalities in the absence of cardiac disease. The prevalence of cirrhotic cardiomyopathy remains unknown until now. It can be diagnosed by using a combination of electrocardiograph, 2-dimensional echocardiography, and various serum markers (brain natriuretic factor--BNP, proBNP, TnI). Pathogenic mechanisms underlying cirrhotic cardiomyopathy development include abnormal signaling betaadrenergic, cardiomyocites membrane fluidity changes, interstitial fibrosis, myocardial hypertrophy, altered transmembrane ion channels as intervention with negative inotropic effect of different substances whose concentration is increased in cirrhosis. Major stresses on the cardiovasculary system such as liver transplantations, infections, insertion of transjugular portosystemic stent-shunt (TIPSS) have been demonstrated to put in evidence the presence of cirrhotic cardiomyopathy. Heart failure is a significant cause of mortality after liver transplantation but the improvement of liver function determines cardiac abnormalities reversal. Current management recommendations include empirical, nonspecific and mainly supportive measures, no specific treatment can be recommended, and cardiac failure should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and oxygen therapy when necessary. The exact prognosis remains unclear. The extent of cirrhotic cardiomyopathy generally correlates to the degree of liver insufficiency. Reversibility is possible (either pharmacological or after liver transplantation), but further studies are needed.

[Hemostatic disorders in liver disease]. / Anomaliile hemostazei in suferintele hepatice.

Hemorrhagic complications are common in patients with liver diseases and contribute to the morbidity and mortality associated to this condition. The liver plays a central role in the hemostatic process as here all clotting factors and their inhibitors are synthetized. Liver damage is commonly associated with variable impairment of hemostasis due to multiple causes: decreased synthesis of clotting and inhibitor factors, decreased clearance of activated factors, hyperfibrinolysis, accelerated intravascular coagulation, quantitative and qualitative platelet defects. Their clinical implications remain to be elucidated, so further studies addressing this issue are needed.

[Postoperative upper gastrointestinal bleeding in patients with cardiovascular surgery]. / Hemoragia digestiva superioara postoperatorie la pacientii cu interventie chirurgicala cardio-vasculara studiu prospectiv.

UNLABELLED: Patients with cardio-vascular surgery are at risk for upper digestive bleeding due to several factors. AIM: To determine the utility of medication and endoscopy in preventing gastrointestinal bleeding (GB) after cardiovascular surgery. MATERIAL AND METHOD: 79 patients (60 males and 19 women, mean age 61 +/- 16.1 years) were prospectively included in the study from the 850 patients operated in the period 2004 - 2006. Inclusion criteria were: patients with digestive symptoms (dyspepsia) and with risk for GB (personal history of peptic ulcer, gastroduodenitis, esophagitis, hiatus hernia, gastric cancer, gastric surgery and GB). All patients with symptoms and partially patients with risk were evaluated by endoscopy. Patients received standard medication for prevention of GB. RESULTS: Prophylactic medication was partially efficient in GB prophylaxis vs. no prophylaxis (7% vs. 11% p < 0.05). Patients with endoscopy examination before surgery had significantly lower incidence of bleeding (6.6% vs. 10.9%, p < 0.05%). CONCLUSIONS: Gastrointestinal bleeding may occur despite prophylactic medication. Gastrointestinal endoscopy prior surgery may be useful in preventing the bleeding.

[Radiofrequency ablation in the multimodal treatment of liver metastases--preliminary report]. / Utilizarea termoablatiei prin radiofrecventa in tratamentul multimodal al metastazelor hepatice.

UNLABELLED: Although the "gold standard" in the multimodal treatment of liver primary and secondary tumors is the surgical ablation, the rate of resection, despite the last decades advances, remains still low (10 - 20%). In addition, the interest for non-surgical ablation therapies is increasing. Among them, regional or systemic chemotherapy, intra-arterial radiotherapy as well as locally targeted therapies--cryotherapy, alcohol instillation and radiofrequency (RF) are the most valuable options as alternative to the surgical approach. MATERIAL AND METHOD: Between February 2005 - January 2007, 9 patients with liver metastases underwent open RF ablation of their secondaries in the III-rd Surgical Unit, "St. Spiridon" Hospital. An Elektrotom 106 HiTT Berchtold device with a 60W power generator and a 15 mm monopolar active electrode was used. RESULTS: Destruction of the tumors was certified with intraoperative ultrasound examination. Pre- and postoperative CarcinoEmbryonic Antigen (CEA) together with imaging follow-up was carried out, in order to determine local or systemic recurrencies. Six patients died between 6 month - 4 years after the RF ablation. Median survival is 29.2 months. CONCLUSION: RF ablation is a challenge alternative in non-resectable liver tumors.

[Variceal upper digestive bleeding--an ever new complication in liver cirrhosis]. / Hemoragia digestiva superioara variceala-- complicatie mereu in actualitate in ciroza hepatica.

Variceal bleeding in liver cirrhosis is a medical emergency with a high mortality. The therapeutic options in patients with portal hypertension are: treatment of acute bleeding from varices, prevention of the first bleeding episode and prevention of rebleeding. Treatment of acute bleeding from varices includes: blood volume restitution, use of antibiotics for preventing bacterial infections, vasoactive drug therapy (terlipressin, somatostatin, vapreotide, octreotide), endoscopic band ligation for acute esophageal bleeding and endoscopic therapy with tissue adhesive (cyanoacrylate) for acute gastric variceal bleeding. Endoscopic treatments are best used in association with pharmacological therapy. In primary prophylaxis non-selective beta- blocker therapy and endoscopic band ligation are useful. Beta blockers, band ligation or both should be used for prevention of recurrent bleeding. In patients who fail endoscopic and pharmacological treatment for prevention of rebleeding TIPS and transplantation should be considered.

[Voice exploratory methods into professional vocal singers]. / Metode de explorare a vocii la solistii profesionisti.

The aims of this study was to evaluated methods of voice explored to professional vocal singers. The modern methods microlaryngoscopy, stroboscopy, electroglottography are presented and comparatively evaluated with classic explorations, as direct and indirect laryngoscopy.

[Eosinophilic esophagitis--from a rare pediatric disease to the forefront of adult gastroenterology]. / Esofagita eosinofilica--de la o afectiune sporadica la copil la o boala digestiva de prim rang a adultului.

Eosinophilic esophagitis (EE) is a disease whose presence has exploded in clinical practice. Because of its relative novelty, the epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment of EE are constantly evolving. EE was first recognized as a disease predominantly of children, but the publications in the last few years describe it like an adult disease, too. It is not known if its frequency is truly increasing in an antigen underexposed society or the disease was previously not recognized. The diagnosis requires the histologic finding of more than 20 eosinophils per high powered field in esophageal squamous mucosa. The specific antigens that initiate EE are unknown, but both food and aeroallergens are involved. The mechanisms by which EE induces esophageal dis-motility, chronic inflammation with fibrosis, and stricture formation are still unclear. The mucosa of the patients affected by EE contains increased numbers of CD8 lymphocytes, tumor necrosis factor alpha, I1-5 and eotaxin. The main symptoms in adult are: dysphagia and food impaction. Endoscopy commonly reveals strictures, mucosal rings, linear furrowing, corrugation, and white plaques. The common treatment regimens in children and adults involve the ingestion of topical corticosteroids.

Extragastric manifestations of Helicobacter pylori infection.

The role of Helicobacter pylori (HP) in some digestive diseases (gastritis, ulcer, gastric cancer, MALT lymphoma) is well known. It has been suggested relatively recently that infection with HP can be involved in various extra-digestive conditions: respiratory disorders (chronic obstructive pulmonary disease, bronchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma); vascular disorders (ischaemic heart disease, stroke, primary Raynaud phenomena, primary headache); autoimmune disorders (Sjogren syndrome, Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune thyroiditis, Parkinson's disease, idiopathic chronic urticaria, rosacea, alopecia areata); other disorders (iron deficiency anaemia, growth retardations, liver cirrhosis). Case studies, small patient series and non-randomized trials that have shown a beneficial effect of HP eradication in different conditions are not convincing. According to Mastricht III the only conditions where HP eradication is indicated are immune thrombocytopenic purpura and iron deficiency anaemia.