Postoperative Bowel Perforation due to Heterotopic Ossification (Myositis Ossificans Traumatica): A Case Report and Review of the Literature

Heterotopic ossification (HO) is the ectopic development of normal bone within soft tissue that can occur after traumatic injury. It is uncommon and may be missed or misdiagnosed, which can lead to complications. We report the case of an 84-year-old male with a previous history of a laparotomy who underwent resection of an intra-abdominal tumor through a midline incision. On postoperative day six, the patient was taken to the operating room, as succus was draining from the incision. Upon re-exploration, sharp bone-like material was found in the wound directly adjacent to an enterotomy. Pathology confirmed mature lamellar bone and the diagnosis of HO. This is the first report of postoperative intestinal perforation secondary to HO in a midline wound. We report this case to encourage accurate reporting of HO and its morbidity and complications for the benefit of appropriate surgical planning and epidemiologic tracking of outcomes

Mechanisms of base selection by the E.coli mispaired uracil glycosylase

The repair of the multitude of single-base lesions formed daily in the cells of all living organisms is accomplished primarily by the base-excision repair (BER) pathway that initiates repair through a series of lesion-selective glycosylases. In this paper, single-turnover kinetics have been measured on a series of oligonucleotide substrates containing both uracil and purine analogs for the E. coli mispaired uracil glycosylase, MUG. The relative rates of glycosylase cleavage have been correlated with the free energy of helix formation, and with the size and electronic inductive properties of a series of uracil 5-substituents. Data is presented that MUG can exploit the reduced thermodynamic stability of mispairs to distinguish U:A from U:G pairs. Discrimination against the removal of thymine results primarily from the electron-donating property of the thymine 5-methyl substituent, while the size of the methyl group relative to a hydrogen atom is a secondary factor. A series of parameters have been obtained that allow prediction of relative MUG cleavage rates that correlate well with observed relative rates that vary over five orders of magnitude for the series of base analogs examined. We propose that these parameters may be common among DNA glycosylases, however, specific glycosylases may focus more or less on each of the parameters identified. The presence of a series of glycosylases which focus on different lesion properties, all coexisting within the same cell, would provide a robust and partially redundant repair system necessary for the maintenance of the genome

Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers

AbstractDeregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents

Cecal dermoid cyst

AbstractDermoid cysts of the cecum are very rare; including this report only three cases have been described in pediatric patients. We describe a case of a girl found to have a cecal dermoid cyst with no previous history of abdominal trauma or intraabdominal operations. Unlike acquired dermoid cysts that likely result from epithelial implantation following a surgical procedure or trauma, congenital dermoid cysts of the abdominal viscera are thought to result from ectodermal implantation during embryogenesis. We discuss the distinction between acquired and congenital dermoid cysts, their presentation as well as differential diagnoses

MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

<div><p>Purpose</p><p>Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, <i>MRE11</i>, as a consequence of contraction of a T₁₁ mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.</p><p>Patients and Methods</p><p>Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T₁₁ tract in the <i>MRE11</i> gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.</p><p>Results</p><p>Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T₁₁ tract in one or both <i>MRE11</i> alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T₁₁ tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.</p><p>Conclusions</p><p>Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/results?term=NCT00003835" target="_blank">NCT00003835</a></p></div

Assessment of tumor MRE11 status as predictive of benefit from FU/LV and IFL.

<p>(A) Top: Disease free survival for dMRE11 vs. pMRE11 treated with FU/LV [n = 320; dMRE11 n = 31; events = 11; 5-yr rate: 67% (95% CI: 52–86%); pMRE11 n = 289; events = 122; 5-yr rate: 61% (95% CI: 56–67%)] or with IFL [n = 305; dMRE11 n = 39; events = 13; 5-yr rate: 67% (95% CI: 53–83%); pMRE11 n = 266; events = 118; 5-yr rate: 57% (95% CI: 51–63%)]. Bottom: Overall survival for dMRE11 vs. pMRE11, treated with FU/LV [n = 320; dMRE11 n = 31; events = 10; 5-yr rate: 70% (95% CI: 55–89%); pMRE11 n = 289; events = 98); 5-yr rate: 73% (95% CI: 68–79%)] or with IFL [n = 305; dMRE11 n = 39; events = 13; 5-yr rate: 67% (95% CI: 53–83%); pMRE11 n = 266; events = 96; 5-yr rate: 69% (95% CI: 63–75%)]. (B) Top: Disease-free survival for IFL vs. FU/LV treated dMRE11 [n = 70; IFL N = 39; events = 13; 5-yr rate: 67% (95% CI: 53–83%); FU/LV n = 31; events = 11; 5-yr rate: 67% (95% CI: 52–86%)] or pMRE11 (n = 555; IFL n = 266; events = 118; 5-yr rate: 57% (95% CI: 51–63%; FU/LV n = 289; events = 122; 5-yr rate: 61% (95% CI: 56–67%)]. Bottom: Overall survival for IFL vs. FU/LV-treated dMRE11 [n = 70; IFL n = 39; events = 13; 5-yr rate: 67% (95% CI: 53–83%); FU/LV n = 31; events = 10; 5-yr rate: 70% (95% CI: 55–89%) or pMRE11 [(n = 555; IFL n = 266; events = 96; 5-yr rate: 69% (95% CI: 63–75%); FU/LV n = 289; events = 98; 5-yr rate: 73% (95% CI: 68–79%)].</p

Genomic PCR assay of <i>MRE11</i> intron 4 T₁₁ tract.

<p>(A) Diagram of the <i>MRE11</i> intron 4/exon 5 junction, showing the T₁₁ tract in intron 4, flanking sequence and primers. Contraction of the T₁₁ tract impairs the lariat formation step in mRNA splicing and leads to skipping of exon 5. The resulting mutant mRNA encodes a truncated MRE11 polypeptide with potentially dominant negative effect on protein function <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0108483#pone.0108483-Wen1" target="_blank">[12]</a>. MRE11 is essential for cell viability, and the <i>MRE11</i> mutations that occur in MMR-D CRC are not null alleles but reduce expression and activity of the MRE11 protein. (B) Sequence traces of the region of <i>MRE11</i> intron 4 that carries the T₁₁ tract in four tumor samples. Lengths of tracts in nt shown at left.</p