The gene that produces the precursor RNA transcript to the three largest structural rRNA molecules (rDNA) is present in multiple copies and organized into gene clusters. The 10 human rDNA clusters represent <0.5% of the diploid human genome but are critically important for cellular viability. Individual genes within rDNA clusters possess very high levels of sequence identity with respect to each other and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. We recently developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. To prove that this dysregulated recombination is a potential driving force of genomic instability in human cancer, we assayed the rDNA for structural rearrangements in prospectively recruited adult patients with either lung or colorectal cancer, and pediatric patients with leukemia. We find that over half of the adult solid tumors show detectable rDNA rearrangements relative to either surrounding nontumor tissue or normal peripheral blood. In contrast, we find a greatly reduced frequency of rDNA alterations in pediatric leukemia. This finding makes rDNA restructuring one of the most common chromosomal alterations in adult solid tumors, illustrates the dynamic plasticity of the human genome, and may prove to have either prognostic or predictive value in disease progression. [Cancer Res 2009;69(23):9096-104]
Objectives: On completion of this article, the reader should be able to review diagnostic testing confirming diagnosis of acute colonic pseudo-obstruction, identify initial conservative treatment measures, and discuss pharmacologic and endoscopic options for decompression.Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive distension of colon without mechanical obstruction. Ischemia and perforation remain the endpoint of progressive untreated distension and early recognition and timely intervention is of utmost importance. The diagnosis of ACPO depends on excluding mechanical bowel obstruction and its subsequent management has evolved with improved understanding of its pathophysiology and pharmacologic and endoscopic treatment options. Historical BackgroundACPO is also known by the eponym Ogilvie syndrome. Sir William Heneage Ogilvie described two patients diagnosed with colonic pseudo-obstruction in 1948.1 Both patients had Keywords► acute colonic pseudoobstruction ► ogilvie syndrome AbstractAlthough acute colonic pseudo-obstruction (ACPO), also known as Ogilvie syndrome, is a well-known clinical entity, in many respects it remains poorly understood and continues to challenge physicians and surgeons alike. Our understanding of ACPO continues to evolve and its epidemiology has changed as new conditions have been identified predisposing to ACPO with critical illness providing the common thread among them. A physician must keep ACPO high in the list of differential diagnoses when dealing with the patient experiencing abdominal distention, and one must be prepared to employ and interpret imaging studies to exclude mechanical obstruction. Rapid diagnosis is the key, and institution of conservative measures often will lead to resolution. Fortunately, when this fails pharmacologic intervention with neostigmine often proves effective. However, it is not a panacea: consensus on dosing does not exist, administration techniques vary and may impact efficacy, contraindications limit its use, and persistence and or recurrence of ACPO mandate continued search for additional medical therapies. When medical therapy fails or is contraindicated, endoscopy offers effective intervention with advanced techniques such as decompression tubes or percutaneous endoscopic cecostomy providing effective results. Operative intervention remains the treatment of last resort; surgical outcomes are associated with significant morbidity and mortality. Therefore, a surgeon should be aware of all options for decompression-conservative, pharmacologic, and endoscopic-and use them in best combination to the advantage of patients who often suffer from significant concurrent illnesses making them poor operative candidates.
Laparoscopic-assisted sigmoid colectomy for diverticulitis can be safely performed. Conversion appears to be associated with complicated diverticulitis (fistula or abscess), which may be better approached by laparotomy. Short-term follow-up indicates that recurrence is rare and suggests that laparoscopic-assisted sigmoid colectomy achieves adequate resection. Laparoscopic-assisted sigmoid colectomy offers benefits of decreased ileus and length of stay and may represent the procedure of choice for elective resection for uncomplicated sigmoid diverticulitis.
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