Placement of Covered Self-Expandable Metal Biliary Stent for the Treatment of Severe Postsphincterotomy Bleeding: Outcomes of Two Cases

We report two cases of severe postsphincterotomy bleeding in an adult and a pediatric patient treated, as first options, with available techniques to induce hemostasis without success. Because of persisting bleeding, an expandable, partially covered, metallic stent was placed into the choledocho to mechanically compress the bleeding site. The bleeding was stopped. In the following days, both patients remained hemodynamically stable with no further episodes of bleeding. We believe that the application of a covered metallic stent in a severe postendoscopic-sphincterotomy bleeding, refractory to injection therapy, should be considered to avoid additional interventions, which carry a higher risk of complications, even in pediatric patients

A new tissue acquisition technique in pancreatic cystic neoplasm: endoscopic ultrasound-guided through-the-needle forceps biopsy

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ClearPath-assisted underwater endoscopic mucosal resection of a laterally spreading tumor of the colon

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Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes

Several histopathological variants of colorectal carcinoma can be distinguished, some associated with specific molecular profiles. However, in routine practice, ninety/ninety-five percent of all large bowel tumors are diagnosed as conventional adenocarcinoma, even though they are a heterogeneous group including rare histotypes, which are often under-recognized. Indeed, colorectal cancer exhibits differences in incidence, location of tumor, pathogenesis, molecular pathways and outcome depending on histotype. The aim is therefore to review the morphological and molecular features of these rare variants of intestinal carcinomas which may hold the key to differences in prognosis and treatment

Poorly differentiated clusters (PDC) in colorectal cancer: Does their localization in tumor matter?

Poorly differentiated clusters (PDC) are aggregates of at least five neoplastic cells lacking evidence of glandular differentiation. By definition, they can be present at the invasive front (peripheral PDC or pPDC) and within the tumor stroma (central PDC or cPDC). In colorectal cancer (CRC), PDC are considered adverse prognosticators and seem to reflect epithelial mesenchymal transition (EMT). In this study, we have investigated the immuno-expression of two EMT-related proteins, E-cadherin and \u3b2-catenin, in PDC of primary CRCs and matched liver metastases. pPDC always showed nuclear \u3b2-catenin staining and diffusely reduced/absence of E-cadherin expression as opposed cPDC which showed nuclear \u3b2-catenin immunoreactivity and E-cadherin expression in about 50% of cases. In addition, the pattern of \u3b2-catenin and E-cadherin expression differed between PDC and the main tumor, and between primary CRC and liver metastasis (LM), in a percentage of cases. A discordant pattern of \u3b2-catenin and E-cadherin expression between pPDC and cPDC, between main tumor and cPDC, and between primary CRC and LM, confirms that EMT is a dynamic and reversible process in CRC. On the overall, this suggests that pPDC and cPDC are biologically different. We may advocate that PDC develop at the tumor center (cPDC) and then some of them migrate towards the tumor periphery while progressively completing EMT process (pPDC). Based on these results, PDC presence and counting may have different prognostic relevance if the assessment is done at the invasive front of the tumor or in the intratumor stroma

Anti-proliferative effects of Cetuximab and Trastuzumab in colorectal cancer cell lines

Colon cancer is one of the most common human malignancies and a leading cause of death worldwide. In Europe around 250.000 new colon cases are diagnosed each year, accounting for around 9% of all the malignancies (Labianca R et al., 2010; Berrino F et al., 2007). Dysregulation of the signalling pathways induced through EGF receptors (ErbB/ HER receptors) by their over-expression or constitutive activation can promote tumor processes (Lurje G et al., 2009), including colorectal cancer. Therefore, the ErbB/HER receptor family with their most prominent members EGFR and HER-2 represents validated targets for anti-cancer therapy. Cetuximab and trastuzumab are two monoclonal antibodies approved for treating, respectively, metastatic colorectal and breast cancer. Because the monotherapy with cetuximab in metastatic colorectal is often insufficient (Cunningham D et al., 2004), it is useful to develop complementary therapeutic strategies to enhance antibody efficacy. A possible approach is co-administration of inhibitors, targeting multiple members of the EGF receptor family. In this study we examined the effect of cetuximab and trastuzumab in combination using two human colon cancer cell lines as a model. We observed that the two drugs had a cytostatic effect and inhibited the proliferation of both the cell lines in a time- and concentration-dependent manner. However, the combination had lower efficacy on one cell line than the other, with growth inhibition of 31% in the former and 49% in the latter. This result was associated to specific changes in cell cycle distribution, while no apoptosis was observed. Chromosome copy number heterogeneity and aneuploidy in tumoral cell lines have been reported (Pellestor F et al., 1999). Our data deriving from the cell cycle analysis confirmed the aneuploidy and polyploidy in our cellular models and are useful to explain cellular response to the combination. We used fluorescent in situ hybridisation analysis to evaluate EGFR and HER-2 gene amplification status. Both the tumour cell lines resulted in an abnormal copy number for the two genes resulting from aneuploidy (polisomy of chromosome 7 and 17) which is not responsible for the difference in sensitivity to cetuximab and trastuzumab between the two cell lines. In order to understand and to improve the pharmacological efficacy of cetuximab and trastuzumab combination, it will be useful to elucidate the molecular mechanisms involved in their activity. This will allow to develop novel and interesting approaches to cancer therapy

Recent advances in molecular diagnostics of colorectal cancer by genomic arrays: proposal for a procedural shift in biological sampling and pathological report

Two forms of genetic instability have been described in colorectal cancer: chromosomal instability, characterized by structural and numerical chromosomal abnormalities and associated to aneuploidy; and microsatellite instability, characterized by a deficiency in the mismatch repair system that leads to slippage in microsatellites and is associated to euploidy. Thirteen colorectal cancer sample DNAs were analyzed after colectomy. High-resolution genome-wide DNA copy number and Single Nucleotide Polimorphism genotyping analysis was performed by Affymetrix SNP 6.0 arrays that interrogates 906,600 single nucleotide polymorphisms and 945,826 copy number probes. We implemented this analysis as part of a routine procedure that includes the sampling of fresh tissue from the tumor mass without affecting the subsequent standard histopathological procedure. The novel molecular technology allows the determination of a genome-wide molecular karyotype using only 500 ng of high-quality tumor DNA; it distinguishes the two main types of genomic instability, discriminating between chromosomal instability positive and negative tumors. It also detects loss of heterozygosity (LOH) regions, called copy neutral-LOH. Tumor-associated copy neutral-LOH regions may play a pivotal role in oncogenesis when they determine duplications of either activating or loss of function gene mutation. We observed recurrent gains of chromosomes 2, 7, 8q, 9, 12, 13, 20 and losses of chromosomes 4, 5, 8p, 15, 17p, 18, 22, and Y, in agreement with previous cytogenetic studies. The use of such sampling procedure could stimulate the routine detection of point mutations in specific genes, thus avoiding subsequent sectioning of formalin-fixed and paraffin-embedded samples

Adhesions due to peritoneal carcinomatosis caused by a renal carcinoma leading to mechanical gastric outlet obstruction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric outlet obstruction is a clinical syndrome caused by a variety of mechanical obstructions. Peptic ulcer disease used to be responsible for most gastric outlet obstruction, but in the last 40 years the prevalence of malignant tumors has risen significantly. Adhesive disease is an infrequent and insidious cause of mechanical gastric outlet obstruction.</p> <p>Case presentation</p> <p>We report the case of a 78-year-old Caucasian man who had a clinical history of a right nephrectomy for malignancy three years earlier and who was admitted for a severe gastric outlet obstruction (score of 1) confirmed both by an upper endoscopy and by a fluoroscopic view after contrast injection. A computed tomography scan and a laparotomy, with omental biopsies, showed a peritoneal carcinomatosis with the development of abdominal adhesions that prompted an abnormal gastric rotation around the perpendicular axis of his antrum with a dislocation in the empty space of his right kidney. Symptoms disappeared after surgical bypass through a gastrojejunostomy.</p> <p>Conclusions</p> <p>Our patient experienced a very rare complication characterized by the development of adhesions due to peritoneal carcinomatosis caused by a renal carcinoma treated with nephrectomy. These adhesions prompted an abnormal dislocation of his antrum, as an internal hernia, in the empty space of his right kidney.</p