Hepatocellular carcinoma in patients with autoimmune hepatitis - a systematic review of the literature published between 1989-2016.

BACKGROUND AND AIMS: Liver cancer is one of the most common cause of deaths from cancer. Hepatocellular carcinoma (HCC) was reported at a frequency of 7% of patients with autoimmune hepatitis (AIH) - related cirrhosis in 1988. We aimed to provide a systematic literature review on the frequency of HCC in patients with AIH, after the discovery of hepatitis C virus (HCV), in order to avoid any possible confounding etiology. METHODS: A literature search of the PubMed database between 1989-2016 was performed, using the relevant keywords "hepatocellular carcinoma" and "autoimmune hepatitis". We followed the PRISMA statement guidelines during the preparation of this review. RESULTS: Eleven studies (n=8,460 patients with AIH) were retained for the final analysis. HCC was diagnosed in 0-12.3% of the AIH patients included in these studies. The overall occurrence of HCC in patients with AIH was estimated in two studies, at 5.1% and 6.2%, respectively. In patients with AIH and cirrhosis, the percentage of HCC varied between 0.2%-12.3%. The proportion of HCC in patients with AIH without cirrhosis was estimated at 1.03%. The percentage of cirrhosis in AIH patients varied from 18.7% to 83.3% in Japan, and from 12% to 50.2% in the other areas. The mean follow-up of the patients with AIH was of 10 years. CONCLUSIONS: The development of HCC in patients with AIH appeared to be similar before and after the discovery of HCV, and it was mainly associated to cirrhosis. The number of patients developing cirrhosis in relation with AIH was impressive. The long evolution of AIH to cirrhosis and, eventually, to HCC, has been be suggested.

Epidemiological trends in digestive cancers in Romania, 1955-2012, compared to alcohol consumption. Correlation or coincidence?

BACKGROUND AND AIMS: Cancer has emerged as the leading cause of death in human populations. The contribution of alcohol has been highly suspected. The purpose of this paper was to analyze the time trend of digestive cancers in Romania, in terms of mortality rates (1955-2012), and incidence rates (2008-2012), and the alcohol consumption data (1961-2010), aiming to find out if there is any association. METHODS: The data on six more common digestive cancers mortality rates (1955-2012) and incidence rates (2008-2012) were obtained from the historical and recent country statistics and publications of International Agency for Research on Cancer (IARC)/World Health Organisation (WHO), as age-standardized rate expressed per 100,000 population (ASRw). Data on alcohol consumption were obtained from the statistics and publications of WHO and United European Gastroenterology (UEG), as liters of pure alcohol/year. RESULTS: Between 1955-2012, the ASRw of mortality registered an increase of the cancers of the esophagus in M (from 2.03 to 3.90), and of colorectal cancer in both sexes (from 4.65 to 18.20 in M, and from 4.57 to 9.70 in F). Between 1980-2012, an increasing trend of mortality was registered, in both sexes, for the cancers of the pancreas (from 5.50 to 9.30 in M and from 2.92 to 5.10 in F) and liver (from 1.77 to 11.00, in M, and from 0.83 to 4.20 in F). In terms of incidence, between 2008-20012, an increasing trend of ASRw was registered for the cancers of the esophagus in M (from 3.90 to 4.30), gastric cancer in M (from 15.90 to 16.30), colorectal cancer in both sexes (from 27.60 to 34.50 in M and from 19.00 to 20.20 in F), pancreatic cancer in F (form 5.20 to 5.90), and liver cancer in M (from 8.10 to 9.20). Alcohol consumption per capita (liters pure alcohol/year) increased in the same period, from an average of 5 in 1961, to 12.8 in 2003-2005, and to 14.4 in 2008-2010. CONCLUSIONS: Given the parallel increase of some digestive cancers and alcohol consumption registered in our area, alcohol could represent more than a coincidence.

Gastrointestinal endoscopy in patients on direct oral anticoagulants. A consensus paper of the Romanian Society of Gastroenterology and Hepatology.

Management of patients undergoing endoscopy and under treatment with the newer direct oral anticoagulants (DOACs) is a common and a complex clinical issue that gastroenterologists have to face more and more often these days. The increasing use of DOACs in patients requiring both short- and long-term anticoagulation is mostly due to the advantages these agents offer, among which the lack of monitoring requirements and the reduced need of dose adjustments are perhaps the most important ones. Managing these patients in the peri-endoscopic period implies balancing the risk for thrombosis that a certain patient carries and the bleeding risk associated with the endoscopic procedure itself. The Romanian Society of Gastroenterology and Hepatology decided to create a consensus paper to serve to practitioners and teachers. After reviewing the available published data and existing recommendations, a Delphi consensus process was carried out involving the leaders of opinion in this field. After reaching expert consensus, we provide herein guidance for a practical approach of DOACs therapy management in patients with endoscopic interventions.

Ultrasound-guided biopsy of osteolytic metastasis - could be less than three cores enough?

AIMS: The purpose of this study was to analyze the diagnostic yield and accuracy of the ultrasound (US) guided core biopsy in a population of patients with osteolytic metastasis. MATERIALS AND METHODS: We performed a retrospective analysis of 16 consecutive cases of US-guided core biopsies of osteolytic lesions performed in our Ultrasound Unit, from January 2006 to May 2017. We used 18G or 16G Tru-cut needles coupled with automated biopsy guns. We procured a maximum number of two tissue specimens per patient. RESULTS: We obtained a diagnostic yield and accuracy of 93.75% (15 of 16 patients) for US-guided core biopsy of osteolytic metastasis. Most of our cases were metastasis of adenocarcinomas (8 patients), squamous cell carcinomas (3 patients) followed by multiple myelomas (2 patients). Other pathologic lesions recorded were undifferentiated carcinoma (1 patient) and mesenchimal undifferentiated tumor (1 patient). The pathologic result was inconclusive in one patient. CONCLUSIONS: Our study supports the important diagnostic role of US-guided core biopsy for osteolytic bone metastasis. Two US-guided passages may be sufficient to procure a diagnostic tissue samples from osteolytic bone metastasis, if theirlength is at least 10 mm.

Mediastinal masses-transthoracic ultrasonography aspects.

Mediastinal masses are usually assessed by computer tomography (CT) and magnetic resonance imaging (MRI). Transthoracic ultrasonography (TUS) can also provide useful information concerning prevascular and posterior mediastinal masses abutting the thoracic wall, but is underused for mediastinal pathology. Moreover, it provides a valuable and safe method for guiding interventional procedures in those areas, even in cases when other approaches are difficult or impossible. Considering TUS a very useful imagistic method for diagnosing mediastinal masses, we present a pictorial essay of various mediastinal diseases which can be assessed by this method.

Ultrasound-guided bone lesions biopsies - a systematic review.

AIMS: Ultrasound (US) is a highly valuable imagistic tool used to guide numerous interventional procedures. The US guided bone lesions biopsy has not yet received a consensus or a guideline. We aimed to evaluate the evidence to support the US role in guiding bone lesions biopsies. MATERIAL AND METHODS: A computer literature search of PubMed was conducted using the keywords "ultrasound" and "bone biopsy", in order to detect relevant studies regarding the aim of our analysis. Records were screened for eligible studies and data were extracted and analyzed. RESULTS: We included 23 studies (n=610 patients) in the final analysis. The specificity and diagnostic yield of US guided biopsy were very good (between 78-100%), depending on the type and dimensions of the bone lesions. The type of the biopsy - aspiration or cutting - influenced theresults. The studies which included larger groups showed a better  performance for cutting needles (83.3-100% vs 50-80.5% for aspiration). The size of the bone lesion influences the diagnostic yield of the US guided bone biopsy. Most of the studies reported nil post-procedural complications. CONCLUSION: Core needle biopsy provided better diagnostic yield compared to fine needle aspiration. The number of the passages of the cutting needle biopsies in order to achieve the best diagnostic yield wasthree. Further studies are needed in order to standardize US-guided bone lesions biopsy and increase its role in the diagnosis algorithm of the bone lesions.

Adrenal glands transabdominal ultrasonography - pictorial essay.

Adrenal gland ultrasonography is one of the corner stones of the abdominal ultrasonography examination for many medical specialties. The adrenal areas can be easily overlooked though adrenal gland pathology is diverse. We present the normal aspects and various transabdominal ultrasonography findings of the adrenal glands, both common and rare. Even though ultrasound examination is operator and patient dependent, we consider the examination of the adrenal glands very important, due to relatively frequent incidental detection of an adrenal mass.

Unusual Discovery after an Examination for Abdominal Pain: Abernethy 1b Malformation and Liver Adenomatosis. A Case Report.

Congenital extrahepatic portosystemic shunt (Abernethy malformation) is a rare condition characterized by developmental abnormalities of the portal venous system resulting in the diversion of the portal blood from the liver to the systemic venous system through a complete or partial shunt of the portomesenteric blood. We report the case of an 18 year-old female examined for abdominal pain, presenting cholestasis syndrome and an elevated serum aspartate aminotransferase level. Liver ultrasound examination revealed the absence of the portal vein with a complete extrahepatic shunt of the portal blood, multiple focal liver lesions, and multiple associated vascular anomalies. A surgical portosystemic shunt and a secondary portosystemic shunt due to portal vein thrombosis were excluded, enabling the diagnosis of a congenital portosystemic shunt. A complex investigation also discovered bone anomalies, and the liver biopsy of the dominant focal lesion revealed adenoma. On a short-term follow-up under hepatoprotective medication, the biochemical parameters improved mildly; however, the size of the main focal lesion increased. Congenital absence of the portal vein often remains an incidental diagnosis. In experienced hands, ultrasonography can diagnose it, but a comprehensive thoraco-abdominal evaluation is compulsory, considering the many potential associated anomalies. In these patients, development of adenomatous liver lesions secondary to Abernethy type Ib malformation represents an indication for liver transplantation.

Mortality in Digestive Cancers, 2012: International Data and Data from Romania.

We aimed to compare the difference in case fatality rate between more developed and very high Human Development Index (HDI) regions, less developed and low HDI regions, and Romania. The incidence and mortality rates for digestive cancers were obtained from the IARC/WHO 2012 database. World mean mortality-to-incidence ratios registered the highest values in pancreatic cancer (0.97/0.94), and liver cancer (0.93/0.96) in males/females, respectively. The lowest values were recorded in colorectal cancer (0.48 in both sexes). Mortality-to-incidence ratios were generally higher in less developed areas, low HDI populations, and in Romania. The difference in case fatality rate between different areas showed higher variations for colorectal, gastric and gallbladder cancers, and smaller variations for esophageal, liver, and pancreatic cancers. In summary, mortality-to-incidence ratios of digestive cancers were high in 2012; higher values were registered in less developed and low HDI regions, and in Romania. Mortality-to-incidence ratios were similar in both sexes, even though the incidence was generally higher in men. Digestive cancer mortality variation suggests the necessity of finding better strategies for prevention, early diagnosis and treatment of digestive cancers.

Is there a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer?

PURPOSE: The aim of this study was to evaluate whether there is a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer (CRC). METHODS: Eighty six blood samples collected from patients with CRC (N=42), adenomas and/or hyperplastic polyps(AP, N=30) and individuals without colon pathology (control group/CTR, N=14) were used for this study. Twelve transcription factors and receptors were assessed by qRT-PCR in a case-control study. The molecules with a minimum of 30% differences in gene expression for CRC and AP compared to CTR were then analyzed separately for each sample. Gene expression was evaluated relatively to the CTR after normalization to the large ribosomal protein PO (RPLPO) housekeeping gene, and the differential expression between studied groups was assessed by ANOVA. RESULTS: Seven out of 12 genes presented differences in expression between 10-29% in CRC and/or AP compared to CTR. Considering the selection criteria, we further individually evaluated the levels of expression of 5 genes that had a minimum of 30% expression in the case-control study. Our data showed a significant up-regulation of platelet derived growth factor (PDGF) C in the blood of the patients with CRC compared to CTR (p=0.007). Likewise, clusterin (CLU) was significantly up-regulated both in CRC and AP groups compared to healthy subjects (p=0.01). For VEGFR1, PDGFRA and TGFB1 we didn't find significantly differential expression between any of the studied groups, even if increased levels were observed in both CRC and AP vs CTR. CONCLUSIONS: The results of our study indicated that increased blood level of PDGFC mRNA was associated with the presence of CRC (p=0.007). Additionally, high levels of circulating CLU mRNA were observed in both malignant and benign colorectal pathologies.

Value of hepatic elastography and Doppler indexes for predictions of esophageal varices in liver cirrhosis.

AIMS: Non-invasive methods are required to diagnose presence and grading of esophageal varices in patients with hepatic cirrhosis and in this respect we have evaluated the role of transient elastography and abdominal ultrasound parameters. MATERIAL AND METHODS: Cirrhotic patients were prospectively evaluated by transient elastography and Doppler ultrasound for diagnosis of presence and grading of esophageal varices, the results being compared with the findings of the esophagogastroduodenoscopy. RESULTS: Sixty patients with hepatic cirrhosis were analysed. The parameters that reached statistical significance for diagnosis of esophageal varices were: liver stiffness (LSM) > 15 kPa, hemodynamic liver index (PVr1) >/= 0.66, portal vascular resistance (PVR) > 17.66 and splenoportal index (SPI) > 4.77. The only parameter that reached statistical power for the diagnosis of large esophageal varices was LSM at a cut-off value of 28.8 kPa. CONCLUSIONS: Assessment of LSM in patients with liver cirrhosis can predict both the presence of esophageal varices and of large esophageal varices. The PVr1, PVR and SPI Doppler indexes can be used to diagnose the presence of esophageal varices but have no role in the prediction of large esophageal varices. Further studies are required to confirm these results and offer a stronger clinical significance.

Posttraumatic gastric wall hematoma in a patient under anticoagulant therapy. Case report and literature review.

We report the clinical observation of a 58-year old patient who presented with upper abdominal pain and a small ecchymosis located in the umbilical area. Personal history of the patient revealed ischemic heart disease and chronic atrial fibrillation. He was under treatment with oral anticoagulants (coumarins). The clinical data and especially the imaging investigations led to a diagnosis of gastric wall hematoma, possibly occurring post-traumatically in a patient under anticoagulant treatment. A conservative therapeutic approach was adopted and ultrasound surveillance. After 6 months the gastric parietal collection manifested complete resorption, spontaneously. In relation to the case presentation, we also discuss some issues on the frequency, diagnosis and therapeutic attitude in this rare complication of anticoagulant therapy.

The long-term evolution of chronic hepatitis B acquired in childhood.

UNLABELLED: The AIM of this study was to assess the long-term evolution of chronic hepatitis B acquired in childhood. METHODS: The study was carried out in 2007 - 2008 on a group of 77 adult patients who were diagnosed with chronic hepatitis B in childhood. The actual assessment included epidemiological, clinical, biological and virological data, ultrasound examination in all patients and liver histology in 3 patients. RESULTS: From the 77 patients, 69 were HBeAg positive and the other 8 patients were anti-HBe positive when the diagnosis was made in their childhood. Thirty-seven patients from the HBeAg positive group and 2 patients from the anti-HBe group had been treated in childhood with IFN-alpha and the other 38 patients remained untreated (32 patients with HBeAg positive and 6 patients anti-HBe positive). Overall, 78.26% seroconverted to anti-HBe (87.50% untreated and 70.27% of patients treated with IFN). After a median follow-up period of 13 years, 36 patients from the HBeAg positive group (48.65% of treated patients and 56.25% of untreated ones) became inactive carriers. Seroconversion to anti-HBs, in the HBeAg positive group, occurred in 10.14% of cases (8.1% in treated patients) without statistical significance. Three patients from the whole group developed cirrhosis but none developed hepatocellular carcinoma. CONCLUSION: The long-term outcome in our patients with CHB acquired in childhood did not differ between treated and untreated patients.

Cancer mortality in Romania, 1955-2004. Digestive sites: esophagus, stomach, colon and rectum, pancreas, liver, gallbladder and biliary tree.

AIM: Until recently, gastric cancer was the most frequent digestive neoplasia in our country. Our study presents the first synthesis of data regarding mortality rates from digestive cancers, for a period covering 50 years, in Romania. METHODS: Age-standardized mortality rates /100,000 population, general and/or per gender, concerning six digestive cancers, were identified from the statistics of IARC/OMS (Lyon, France) (years 1955-2002) and of the Ministry of Public Health (Bucharest, Romania) (year 2004). For 2002, incidence and mortality rates per sex from digestive cancers were available and case fatality ratios could be calculated as an approximation of survival rates, as well as sex ratio. RESULTS: Age standardized mortality rates per sex and cancer site registered the following changes: esophageal cancer increased from 2.03/0.62 (M/F) to 2.8/0.5; gastric cancer registered a decrease, from 33.14/18.77 to 17.0/6.6; colorectal cancer increased from 4.65/4.57 to 13.6/9.0; pancreatic cancer increased from 5.50/2.92 to 8.1/4.2 and liver cancer (including peripheric cholangiocarcinoma) increased from 1.77/0.83 to 8.8/3.9. In our population, the case fatality ratio appeared to be better only in colorectal cancer, 0.61 in males and 0.62 in females, respectively. Sex ratio was highest for esophageal cancer (males/females 5.8/1) and lowest for colorectal cancer (1.5/1). CONCLUSIONS: Our study found opposite trends in the mortality rates from digestive cancers, with gastric cancer rates decreasing and the other five digestive cancers increasing. A new hierarchy of digestive cancers has been drawn up, with colorectal cancer as the main cause of death, and gastric cancer in second position, followed by pancreatic, liver, esophageal, and gallbladder and biliary tree cancers.

Trends of mortality rates from gastric cancer and colorectal cancer in Romania, 1955-2003.

BACKGROUND: Steady and persisting falls in gastric cancer (GC) mortality rates have been observed worldwide in the last 50 years, and in Romania too. Colorectal cancer (CRC) is presently the most frequent digestive neoplasia in the Western countries. An increase of CRC incidence and mortality rates has been reported recently in Eastern European countries, including Romania. METHODS: Mortality data from GC and CRC, derived from population based mortality statistics, have been available on a national scale for 1955-2003. The data were identified from the statistics of the Ministry of Health (Bucharest, Romania) and of IARC/OMS (Lyon, France). GC and CRC mortality rates global and/or per gender were registered by time intervals. After 1995, only data on general mortality rates were available. RESULTS: Between 1955-59 and 1990-92, GC mortality rates/100,000 decreased from 33.14 to 17.70 in males and from 18.77 to 7.00 in females. Between 1995 and 2003, general mortality rates/100,000 from GC remained stable (17.54 and 17.74, respectively). Between 1955-59 and 1990-92, CRC mortality rates/100,000/gender increased from 4.65 to 10.10 in males and from 4.57 to 7.40 in females. Between 1995 and 2003, CRC general mortality rates/100 000 increased from 14.90 to 19.20. CONCLUSIONS: Our study reports opposite trends in GC and CRC mortality rates in the period under study, with GC declining and CRC increasing. A male predominance was registered in both neoplasms under study, more obvious in GC (male/female ratio: 2-3/1) than in CRC (male/female ratio: 1.5/1).

Pill esophagitis.

Pill esophagitis is a rare clinical diagnosis. We report a series of two patients who experienced ulcerative esophagitis while taking doxycycline (patient 1) and alendronate (patient 2). Both patients presented with retrosternal pain, odynophagia and dysphagia. Symptoms developed after 3 days of treatment with doxycycline in patient 1 and after 3 months of treatment with alendronate in patient 2. Endoscopy revealed ulcerative lesions in the mid-esophagus, sparing the distal esophagus. Biopsies showed inflammatory infiltrate (patient 1) and ulceration and hyperplastic cells (patient 2). Patient 1 recovered completely endoscopically after discontinuation of the antibiotic and a one month course of sucralfate treatment. Patient 2 did not accept the discontinuation of alendronate therapy. She also had a course of one month treatment with sucralfate. At one, two and even at seven months after the first diagnosis, endoscopy still showed the persistence of millimetric defects of epithelisation. She is still under endoscopical survey. In conclusion, doxycycline and alendronate can cause chemical esophagitis when taken improperly. In adults and elderly patients exclusion of esophageal carcinoma by histology is necessary. Continuation of treatment with the offending drug can delay healing. Pill esophagitis is a preventable cause of morbidity that consists of giving simple advice of how and when to take medication.