Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report.

BACKGROUND: Highly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management. CASE PRESENTATION: A 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus. Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome. CONCLUSION: The reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed. Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Epigenetic inactivation of FAT4 contributes to gastric field cancerization.

BACKGROUND: Gastric cancer (GC) is highly influenced by aberrant methylation, and accumulation of aberrant methylation in gastric mucosae produces an epigenetic field for cancerization. Nevertheless, the individual driver genes involved in such field cancerization are still unclear. Here, we aimed to demonstrate that FAT4, a novel tumor suppressor identified by exome sequencing of GC, is methylation-silenced and that such methylation is involved in epigenetic field cancerization for GC. METHODS: A transcription start site was determined by the 5' rapid amplification of complementary DNA ends method. DNA methylation was analyzed by bisulfite sequencing with use of a next-generation sequencer or quantitative methylation-specific PCR. Gene expression was analyzed by quantitative reverse transcription PCR. RESULTS: A single transcription start site was identified for FAT4 in gastric epithelial cells, and a CpG island was located in the FAT4 promoter region. FAT4 was highly methylated in two of 13 GC cell lines and was not expressed in them. Removal of FAT4 methylation by a DNA demethylating agent (5-aza-2'-deoxycytidine) restored its expression in the two cell lines. In primary GC samples, FAT4 was methylated in 12 of 82 GCs (14.6 %). FAT4 methylation was associated with the presence of the CpG island methylator phenotype but not with prognosis, tumor invasion, lymph node metastasis, or histological types. In noncancerous gastric mucosae, high FAT4 methylation levels were associated with the presence of GC and Helicobacter pylori infection. CONCLUSIONS: FAT4 was methylation-silenced in GCs. Its methylation in gastric mucosae was associated with H. pylori infection and likely contributed to epigenetic field cancerization.

Hepatitis B viral reactivation secondary to imatinib treatment in a patient with gastrointestinal stromal tumor.

Hepatitis B virus (HBV) reactivation is a known risk in cancer patients receiving cytotoxic or immunosuppressive therapy; however, the risk associated with newer molecularly-targeted agents has not been well-quantified. Imatinib, a small molecule inhibitor directed against BCR-ABL, CKIT, and other tyrosine kinases, has been associated with HBV reactivation primarily in patients treated for chronic myelogenous leukemia. Herein we present the first reported case of a patient who developed HBV reactivation while receiving imatinib therapy for a gastrointestinal stromal tumor (GIST) in the adjuvant setting. This eventually resulted in fulminant liver failure and was effectively treated with living-related donor liver transplant and anti-viral medication. Currently, no guidelines exist for HBV screening prior to imatinib therapy. This report emphasizes the need for such guidelines and supports the idea that viral reactivation is a risk in all imatinib-treated patients, regardless of the underlying disease.

Increased risk of tuberculosis after gastrectomy and chemotherapy in gastric cancer: a 7-year cohort study.

BACKGROUND: Gastrectomy for peptic ulcers and chemotherapy for malignancy are known risk factors for tuberculosis (TB). However, this relationship has rarely been investigated in patients with gastric cancer. METHODS: In a retrospective cohort study from 2000 to 2006, data for 2215 patients diagnosed with gastric cancer at our hospital were compared with data from the Centers for Disease Control (CDC), Taiwan, to identify confirmed cases of TB. RESULTS: In patients with gastric cancer without a history of gastrectomy and without previous anti-TB treatment, the overall crude incidence of new-onset TB was 788 per 100,000 person-years. Compared with the general population, the overall age-sex standardized incidence (SI) in gastric cancer patients was 134.3 (SI ratio [SIR]: 2.11, p < 0.05), and the recurrence rate among patients with previous anti-TB treatment was 18% (4/22) after gastric cancer diagnosis. Gastrectomy was a significant risk factor for active TB incidence [SI 159 (95% confidence interval [CI], 80-237, SIR: 2.5, p < 0.05), and chemotherapy alone seemed to be a risk factor, but was without statistical significance (SIR: 12.5, p > 0.05). Multivariate analysis showed old age, male gender, previous anti-TB treatment, and gastrectomy as significant risk factors for TB. In stratified analysis, an interaction between old TB patterns on chest films and chemotherapy was observed. CONCLUSIONS: Old age, male gender, previous anti-TB treatment, and gastrectomy were significant risk factors for TB. An increased risk of TB incidence after chemotherapy was observed in patients with old TB pattern chest films initially, suggesting an interaction between chest film patterns and chemotherapy.

Immunohistochemical and molecular assessment of human herpesvirus type 8 in gastrointestinal tumours.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, histologically identified as highly cellular spindle or epithelioid cell tumours, and often positive for CD34 (60-70%). Kaposi's sarcomas (KSs) are similar to GISTs: they are most often found in the gastrointestinal tract (although cutaneous lesions do occur), they are also composed of spindle or epithelioid cells (although erythrocytes are also seen), and the tumour cells are nearly all positive for CD34. Human herpesvirus type 8 (HHV-8) DNA has been found consistently in all types of KS, in particular in CD34 positive KS tumour cells. However, the association between HHV-8 and GIST has not been investigated. AIMS: To assess the presence of HHV-8 in GISTs. METHODS: Paraffin wax embedded tissues of 86 primary GISTs and their recurrent or metastatic tumours were analysed immunohistochemically for the CD34 antigen and HHV-8 latent nuclear antigen 1 (LNA-1) and by means of the nested polymerase chain reaction (PCR) and real time PCR for HHV-8 DNA. RESULTS: None of the 86 GISTs contained HHV-8 DNA sequences or LNA-1 positive cells. CONCLUSIONS: These results demonstrate the lack of HHV-8 infection in GIST tumour cells. HHV-8 does not appear to play a role in the pathogenesis of GIST, irrespective of the status of the tumour.