Retrospective Analysis of HBV Pre-Existing Mutations and Drug-induced Resistance Mutations in Patients with Hepatitis B Virus-Related Cirrhosis

Background: The reported prevalence and necessity of detection of HBV reverse transcriptase (RT) mutation prior to treatment is varied and remains controversial. This study aimed to identify the prevalence of HBV pre-existing gene resistance mutations and compare the difference between pre-existing mutations and drug-induced resistance mutations in patients with hepatitis B virus-related cirrhosis.Methods: 180 patients with hepatitis B virus-related cirrhosis which included 68 patients with virological breakthrough and 112 treatment-naive cirrhosis patients were retrospectively enrolled. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. One-way ANOVA analysis was performed in the comparison among different groups. Ratios difference was compared with the chi-square test.Results: There were 48 patients (48/112, 42.86%) with drug resistance mutations in nucleoside/nucleotide analogues (NAs) treatment-naive group, 59 patients (59/68, 86.76%) showed drug-resistant mutations in the NAs treatment group. The gene resistance mutation patterns in treatment-naive group were mainly rtS213T, rtV214A, 191V/I and rtN/H238T/D, and the types of resistance mutations in the treated group were different. The adefovir (ADV) group: mainly rtA181T/V and rtS213T; lamivudine/ telbivudine (LAM/LDT) group: rtL180M+ rtM204I/V/S and rtM204I/V/S or a complex mutation pattern containing 204 site; entecavir (ETV) group: The drug resistance pattern is the simultaneous presence of multiple site mutations. LAM/LDT sequential ADV group: The variant type was multi-site and resistant to both ADV and LAM.Conclusion: There was a prevalence of pre-existing mutations in RT region of HBV polymerase in patients with hepatitis B virus-related cirrhosis, The mutation pattern is mainly related to LAM and ADV-related compensatory mutations, while the drug-induced mutation pattern is more complicated, mainly related to the antiviral drugs used and there are mainly primary mutations. Patients with cirrhosis should be tested genetic resistance mutation before using antiviral drugs.

Giant Cystic Pancreatic Lymphangioma with Mediastinal Extension: A Case Report and Review of the Literature

Lymphangioma is an infrequent benign tumour that is formed usually from a congenital malformation of the lymphatic ducts causing lymphangiectasis. The abdominal location represents 1-5%, with dominance in the mesentery and retroperitoneum, however, the pancreatic location is very rare having described less than 100 cases published worldwide. The clinical symptoms of the lymphangiomas are non-specific and depend of the tumour’s size and location. Here we present a clinical case of a pancreatic lymphangioma with mediastinal extension who was treated with a complete resection and this case shows that the diagnosis of cystic pancreatic lymphangioma must be taken as a differential diagnosis of pancreatic cystic lesions.

Miliary Tuberculosis with Mediastinal and Cervical Lymph Node Involvement Complicated by an Eso- Mediastinal Fistula

Esophageal involvement in tuberculosis is rare even in highly endemic areas for tuberculosis and is most often secondary to concomitant mediastinal lymph node infection. Endoscopy and imaging are essential for diagnosis. Conservative treatment is possible but the major risk is mediastinitis secondary to an eso-mediastinal fistula.

Abdominal Pain-An Unusual Case of Anti-Phospholipid Syndrome

Antiphospholipid Syndrome (APS), an autoimmune disease associated with hypercoagulability, commonly presents as arterial and/or venous thrombosis, recurrent spontaneous abortions, and moderate thrombocytopenia. It can manifest as a standalone syndrome or a manifestation of a primary systemic disease. The incidence and prevalence of APS without an acquired cause is not well known, although some estimates show around 5 new cases per 100,000 persons per year. Antiphospholipid antibodies (APLA) include anti-cardiolipin, Lupus anticoagulant (LA), and antibeta-2 glycoproteins which are responsible for the underlying pathophysiology. APS is known to be associated with SLE, connective tissue disorders, various autoimmune diseases, malignancies, HIV, and drugs. Anti-cardiolipin antibody causing thrombosis represents a spectrum of APS which is usually associated with an acquired condition and rarely presents as a primary syndrome. We present the case of an African American female, aged 30, with an atypical presentation of a thrombotic episode and the presence of anti-cardiolipin antibodies without any associated secondary cause. Our case stands out because of the primary nature of APS and the atypical presentation with abdominal signs, both of which are rare and constitute only 1.5% of cases of APS. Sharp clinical suspicion with prompt diagnosis can potentially prevent progression to a catastrophic event.

Gastric Myoelectrical Activity and Autonomic Nervous System Abnormalities in Patients with Chronic Unexplained Nausea and Vomiting and in Patients with Gastroparesis

Background: Patients with chronic unexplained nausea and vomiting (CUNV) and Gastroparesis (GP) have similar symptoms, suggesting they share pathophysiological abnormalities along a continuum of disease.Objectives: To determine the incidence of gastric myoelectrical, accommodation dysfunction and autonomic abnormalities in patients with CUNV and GP.Methods: Outpatients with CUNV and GP who underwent standard 4-hr solid phase gastric emptying, upright tilt table test and electrogastrogram (EGG) recordings with water load satiety test (WLST) were identified from chart review. Subjects with normal emptying were in the CUNV group; those with delayed emptying were in the GP group. EGGs were recorded before and 30 minutes after the WLST and symptoms were recorded on a 100mm visual analog scale.Results: 44 patients (35 women and 9 men, ages 17-76 years) were identified: 24 had normal gastric emptying and CUNV and 20 had GP. Gastric dysrhythmias were found in 70% of CUNV and 69% of GP patients. Twenty percent of CUNV patients and 44% of GP patients ingested abnormally low volumes (< 300mL) during the WLST. Nausea increased similarly after the WLST in the subjects with CUNV and GP (Ps > 0.05). Postural orthostatic tachycardia syndrome (POTS) was diagnosed in 17% of CUNV patients and 20% of GP patients.Conclusions: Gastric myoelectrical and accommodation abnormalities and autonomic nervous system (ANS) dysfunctions frequently occur in subjects with CUNV and GP. These pathophysiological abnormalities support the idea that CUNV and GP occur along the same continuum of gastric neuromuscular dysfunction and may be targets for therapeutic approaches.

The 9-bp Deletion at Position 8272 in Region V of Mitochondrial DNA is Associated with Outcome of Colorectal Cancer

The 9-bp deletion of CCCCCTCTA at position 8272 in region V of mitochondrial DNA is one of the mitochondrial DNA microsatellite instability (mtMSI) sites that associated with cancers. In the present study, we investigated the association of 8272 deletion with the cancer risk and outcome for colorectal cancer (CRC). By the log-rank analysis, the 8272 CCCCCTCTA/del was identified as a prognostic marker for outcome of colorectal cancer patients with the deleted ones associated with shorter postoperative survival. After adjusted with Cox Hazard model, this MSI was associated independently with CRC outcome (relative risk, 2.038; 95%CI, 1.20-3.707; p = 0.020). The analysis of mtMSI can help to identify patient subgroups that are at high risk for poor disease outcomes.

Expression of Angiogenin is inversely correlated to Progression of Gastric Tumors

Objective: Angiogenin (ANG) is upregulated in a variety of cancers including those of prostate, cervix, pancreas, liver, oral cavity, skin, and etc., however, the role of ANG in gastric cancer has not been fully elucidated yet. We use tissue microarray (TMA) to examine ANG expression to investigate the role of ANG in the progression of gastric cancer. Method: Immunohistochemistry was used to evaluate ANG expression in TMA with 208 spots from 104 patients diagnosed with gastric cancer and the corresponding adjacent tissue. Results: In normal adjacent tissue, ANG was expressed mainly in cytoplasm at basal gland of the gastric mucus where gastric stem cells are reserved, and also sparsely expressed in the nucleus of gastric mucosal gland cells at isthmus where gastric stem cells are gathered. In cancer tissues, ANG was very sparsely expressed in the nucleus of gastric glandular cells. ANG expression in the cytoplasm was found to be significantly associated with pathological types (p<0.001) and malignancy (p<0.001). ANG expression in the nucleus was inversely correlated with malignancy (p=0.019), differentiation status (p< 0.001), and tumor stage (p= 0.048).Conclusion: ANG might play an important role in gastric cancer development.

A typical Presentation of Acute Infectious Mononucleosis (AIM) with Isolated Hyperbilirubinemia

Epstein - Barr virus (EBV) induced hepatitis and subsequent hyperbilirubinemia is a strikingly rare cause of jaundice. Lack of other common infectious mononucleosis symptoms makes the diagnosis difficult with history and physical exam alone. With differential diagnoses more commonly including HAV, HCV, and HBV hepatitis infections; alcoholic hepatitis; autoimmune hepatitis; and hepatocellular carcinoma, suspicion for EBV induced hepatitis is often low. We present a noteworthy case of isolated hyperbilirubinemia due to EBV virus confirmed with biopsy, without other infectious mononucleosis symptoms such as fever, sore throat, or splenomegaly. Furthermore, we review the pathophysiology, diagnosis, treatment, and prognosis of EBV-induced hepatitis.

Case Report: Epstein-Barr virus Positive Gastric Carcinoma

In 2014, The Cancer Genome Atlas provided a molecular classification defining Epstein-Barr virus (EBV)-positive gastric cancer as a separate subtype. While its prognostic role is still debatable, emerging potential biomarker role for personalized treatment strategies is already recognized by international guidelines. We report a case with successful combined therapy of a 64-year-old EBV-positive gastric cancer male patient. Patient initially presented with locally advanced gastric cancer, which was treated surgically; three years later patient developed recurrence within the remnant stomach and was treated surgically. Two years after operation patient developed distant metastases and was enrolled in a clinical trials’ (NCT01630083) arm 2: receiving chemotherapy and monoclonal antibody claudiximab. This treatment induced durable disease stabilisation for 34 months. After progression, second line chemotherapy with docetaxel and cisplatin provided additional disease stabilisation and symptom control for 8 months. Patient’s overall survival reached 9.1 years. Presented report shows EBV- ositive gastric cancer case with better overall survival compared to reported average, which contributes to the meaningfulness of its distinction as a separate subtype, evidence that targeted therapy is more effective in selected patient groups, and EBV as an emerging biomarker.

Current Advancement of the miR-17-92 Cluster in Gastrointestinal Cancers

Gastrointestinal (GI) cancers, especially including esophageal, gastric and colorectal cancer, are common types of cancer with high morbidity and mortality worldwide. Despite great advances having been made for these cancers, current treatments including surgery, Radiotherapy (RT) and Chemotherapy (CT) are still far from satisfactory as these cancers are usually discovered in advanced stages that are associated with short longevity and poor outcomes. MicroRNAs (miRNAs) are short noncoding strands of RNA that regulate gene expression, affecting proliferation, development, differentiation, apoptosis, metabolism and Epithelial-mesenchymal Transition (EMT). The miR-17-92 cluster was detected as “oncomir-1”, which is involved in the onset and progression of numerous human cancers. This review presents the recent developments in knowledge about miR-17-92 clusters for diagnosing and treating GI cancers based on genetic functions, biological phenotypes, related mechanisms, biomarkers and therapeutic perspectives, which could provide a wider horizon for future use.