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A rare cause of recurrent melena was identified by capsule endoscopy: arteriovenous malformation
(2013)
Small bowel endoscopy is indicated for patients with an unidentified bleeding site in esophagogastroduodenoscopy and ileocolonoscopy and symptoms of intestinal blood loss or unexplained anemia. In approximately two-thirds of these cases, capsule endoscopy (CE) detects a lesion within the small bowel that explains the patient's symptoms.
The case of an 80-year-old female patient with recurrent melena and anemia is presented here by the authors. Endoscopy of the upper gastrointestinal tract as well as ileocolonoscopy did not show any pathological findings. CE revealed an area with abnormal mucosa in the middle third of the small bowel, which was strongly suspected of having malignant origin. Surgical exploration led to resection of a small jejunal segment with a palpable mass and increased blood flow. Surprisingly, the final diagnosis determined by the pathologist was arteriovenous malformation (AVM). This article is part of an expert video encyclopedia.
Small-bowel tumors are rare and account for approximately 5% of all gastrointestinal tumors. Approximately 65% of small-bowel tumors are malignant, and approximately 40% of these tumors are adenocarcinomas. Similar to colorectal adenocarcinoma, premalignant adenomas of the small bowel may progress to carcinoma. This occurs both sporadically and in the context of hereditary tumor syndromes such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer (Lynch syndrome). Herein cases with small-bowel adenocarcinomas visualized with both capsule endoscopy and double-balloon enteroscopy are presented. This article is part of an expert video encyclopedia.
The proportion of elderly women in the population is rising, and in tandem, the incidence of breast cancer rises with age. Because of health and tolerability concerns, as well as life expectancy, physicians may be reluctant to advise a standard treatment regimen for elderly patients with metastatic breast cancer. To elucidate this issue, we performed a literature review of clinical studies that included women with metastatic breast cancer who were over the age of 65. Our results show that although little clinical evidence exists, what is available suggests that standard treatment is tolerated and beneficial for patients meeting certain criteria. A geriatric assessment may identify specific patient groups (independent, dependent, or frail) and thereby guide treatment. Treatment recommendations for elderly patients with metastatic breast cancer are sparse, although first-line endocrine treatment, usually aromatase inhibitors or tamoxifen, is recommended for hormone-sensitive disease. In general, the evidence from clinical studies suggests that aromatase inhibitors are more effective than either tamoxifen or megestrol acetate as first- or second-line treatment in postmenopausal women with metastatic breast cancer. Ultimately, quality of life, treatment effects, and comorbidities are important aspects in this population and may guide treatment choice. To provide evidence-based treatment guidance, future clinical trials should include more patients over the age of 65 years.
Cellular cytotoxicity is the hallmark of NK cells mediating both elimination of virus-infected or malignant cells, and modulation of immune responses. NK cytotoxicity is triggered upon ligation of various activating NK cell receptors. Among these is the C-type lectin-like receptor NKp80 which is encoded in the human Natural Killer Gene Complex (NKC) adjacent to its ligand, activation-induced C-type lectin (AICL). NKp80-AICL interaction promotes cytolysis of malignant myeloid cells, but also stimulates the mutual crosstalk between NK cells and monocytes.
While many activating NK cell receptors pair with ITAM-bearing adaptors, we recently reported that NKp80 signals via a hemITAM-like sequence in its cytoplasmic domain. Here we molecularly dissect the NKp80 hemITAM and demonstrate that two non-consensus amino acids, in particular arginine 6, critically impair both hemITAM phosphorylation and Syk recruitment. Impaired Syk recruitment results in a substantial attenuation of cytotoxic responses upon NKp80 ligation. Reconstituting the hemITAM consensus or Syk overexpression resulted in robust NKp80-mediated responsiveness. Collectively, our data provide a molecular rationale for the restrained activation potential of NKp80 and illustrate how subtle alterations in signaling motifs determine subsequent cellular responses. They also suggest that non-consensus alterations in the NKp80 hemITAM, as commonly present among mammalian NKp80 sequences, may have evolved to dampen NKp80-mediated cytotoxic responses toward AICL-expressing cells.
Background: The activating NK receptor NKp80 triggers cytotoxicity by human NK cells via a cytoplasmic hemITAM sequence.
Results: A non-consensus hemITAM residue impairs the capacity of NKp80 to recruit Syk kinase and to trigger cytotoxicity.
Conclusion: Unlike typical hemITAM receptors, NKp80 does not efficiently recruit Syk kinase resulting in attenuated effector responses.
Significance: An attenuated cytotoxic responsiveness critically impacts on the immunomodulatory function of NKp80.
Dieulafoy's lesion (DL) is a rare source of gastrointestinal tract bleeding that may occur at any site in the gastrointestinal tract and may be difficult to detect by endoscopy. DL is characterized by a large, tortuous arteriole in the submucosa. This is a case of duodenal DL that is detected and treated by endoscopy. This article is part of an expert video encyclopedia.
The author presents the case of a patient with severe bleeding from a duodenal ulcer that could not be controlled by endoscopic application of metal clips and injection of fibrin glue. Angiographic embolization with placement of coils into the feeding vessel stopped the bleeding. However, 3 days later, a fistula emerged from coil material penetrating into the dorsal duodenum and a peritoneal leakage developed. The fistula was completely closed by placing an over-the-scope clip on the enteral opening of the fistula. This article is part of an expert video encyclopedia.
In the stomach, neoplastic lesions often arise in the setting of precursor conditions such as gastritis, intestinal metaplasia, or adenomatous lesions. Biopsies may, therefore, underestimate disease severity or even miss the diagnosis (sampling error). Endomicroscopy is able to visualize typical features of such pathologies. It enables in vivo microscopy of gastritis with definition of enhanced vascularity and vascular leakage, but the typical cobblestone appearance of the gastric mucosa is preserved. The presence of intestinal metaplasia is confirmed by columnar absorptive cells with brush border and goblet cells within villiform foveolar epithelium. Gastric neoplasia is characterized by crowded glands with intraluminal folding and glandular budding and branching accompanied by increased density of dilated and distorted capillaries. Finally, in gastric cancer, gland and overall mucosal architecture is progressively lost. These features are shown side by side with white-light endoscopic findings. Endomicroscopy is used in such a setting to rapidly screen larger areas (optical biopsies) and subsequently target tissue sampling to areas with highly suspicious microscopic patterns. In experienced hands, it therefore constitutes an important part especially in the presence of neoplastic lesions within noncircumscript gastric premalignant conditions. This article is part of an expert video encyclopedia.
For the pathologist, the diagnosis of drug induced liver injury (DILI) is challenging, because histopathological features mimic all primary hepatic and biliary diseases, lacking changes that are specific for DILI. Therefore, in any patient of suspected DILI who underwent liver biopsy, the pathologist will assure the clinician that the observed hepatic changes are compatible with DILI, but this information is less helpful due to lack of specificity. Rather, the pathologist should assess liver biopsies blindly, without knowledge of prior treatment by drugs. This will result in a detailed description of the histological findings, associated with suggestions for potential causes of these hepatic changes. Then, it is up to the physician to reassess carefully the differential diagnoses, if not done before. At present, liver histology is of little impact establishing the diagnosis of DILI with the required degree of certainty, and this shortcoming also applies to herb induced liver injury (HILI). To reach at the correct diagnoses of DILI and HILI, clinical and structured causality assessments are therefore better approaches than liver histology results obtained through liver biopsy, an invasive procedure with a low complication rate.
The antineoplastic alkaloid ellipticine is a prodrug, the pharmacological efficiency of which is dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming DNA adducts in target tissues. Here, we found that this compound is cytotoxic to human BHT-101, B-CPAP and 8505-C thyroid cancer cells and blocks one or more phases of cell cycle in these cancer cells. Ellipticine toxicity to the thyroid cancer cells corresponded to levels of DNA adducts generated by the CYP- and/or peroxidase-mediated ellipticine metabolites, 12-hydroxy- and 13-hydroxyellipticine, in these cells. Cultivation of all tested cells under hypoxic conditions (1 % oxygen) led to a decrease in ellipticine toxicity. Such a lower sensitivity of cells to ellipticine correlates with a decrease in the formation of ellipticine-derived DNA adducts in these cells. Using Western blotting, the expression of CYP1A1, 1B1, 3A4, thyroid peroxidase (TPO), cyclooxygenase-1 (COX-1) and cytochrome b5, the enzymes that catalyze, and/or influence ellipticine metabolism, was investigated in the cancer cells. Furthermore, the effects of ellipticine treatment on the expression levels of these proteins in thyroid cancer cells were also examined. The results indicate that the highest expression levels of cytochrome b5 together with CYP1A1 and 3A4 determine the highest DNA adduct formation and cytotoxicity of ellipticine in B-CPAP cells. They also demonstrate that formation of covalent DNA adducts by ellipticine is the predominant mechanism responsible for its cytotoxicity in studied cells.
Operatively altered anatomy such as Billroth II gastroenterostomy represents a challenge in endoscopic retrograde cholangiopancreatography and might require dedicated instruments. In this article, the authors demonstrate the technique of endoscopic retrograde cholangiography and sphincterotomy in a patient with Billroth's operation-II. Sphincterotomy is performed with a specially designed Billroth papillotome to enable papillotomy in the direction of the papillary roof. This article is part of an expert video encyclopedia.