IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6%noninferiority margin was chosen according to clinical relevance estimation. RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7%of laparoscopic resection cases (95%CI, 76.8%–86.6%) and 86.9%of open resection cases (95%CI, 82.5%–91.4%) and did not support noninferiority (difference, −5.3%; 1-sided 95%CI, −10.8%to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3%of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95%CI, 27.7–63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95%CI, −0.6 to 1.1), readmission within 30 days (3.3%vs 4.1%; difference, −0.7%; 95%CI, −4.2%to 2.7%), and severe complications (22.5%vs 22.1%; difference, 0.4%; 95%CI, −4.2%to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5%of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3%open resection; P = .11). Distal margin result was negative in more than 98%of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00726622

Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

BACKGROUND Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30 percent of inflammatory bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the overlap of clinical and histologic features. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) permits a histology-directed cellular protein analysis of tissues. As a pilot study, we evaluated the ability of histology-directed MALDI-MS to determine the proteomic patterns for potential differences between CC and UC specimens. METHODS Mucosal and submucosal layers of CC and UC colon resection samples were analyzed after histologic assessment. To determine whether MALDI-MS would distinguish inflammation, the uninflamed [n=21] vs. inflamed submucosa [n=22] were compared in UC and the uninflamed [n=17] vs. inflamed submucosa [n=20] in CC. To determine whether there were proteomic differences between the colitides, the uninflamed UC submucosa [n=21] was compared vs. the uninflamed CC submucosa [n=17], the inflamed UC submucosa [n=22] was compared vs. the inflamed CC submucosa [n=20], and inflamed UC mucosa vs. inflamed CC mucosa. Pair-wise statistics comparisons of the subsets were performed. RESULTS Pair-wise comparative analyses of the clinical groups allowed indentifying subsets of features important for classification. Comparison of inflamed vs. uninflamed CC submucosa showed two significant peaks: m/z 6445 (p=0.0003) and 12692 (p=0.003). In the case of inflamed vs. uninflamed UC submucosa, several significant differentiating peaks were found, but classification was worse. Comparisons of the proteomic spectra of inflamed submucosa between UC and CC identified two discrete significant peaks: m/z 8773 (p=0.006) and 9245 (p=0.0009). Comparisons of the proteomic spectra of uninflamed submucosa between UC and CC identified three discrete significant peaks: m/z 2778 (p=0.005), 9232 (p=0.005), and 9519 (p=0.005). No significantly different features were found between UC and CC inflamed mucosa. CONCLUSION MALDI-MS was able to distinguish CC and UC specimens while profiling the colonic submucosa. Further analyses and protein identification of the differential protein peaks may aid in accurately diagnosing IBD and developing appropriate personalized therapies.

Tumor protein phosphorylation analysis may provide insight into intracellular signaling networks underlying tumor behavior, revealing diagnostic, prognostic or therapeutic information. Human tumors collected by The Cancer Genome Atlas (TCGA) program potentially offer the opportunity to characterize activated networks driving tumor progression, in parallel with the genetic and transcriptional landscape already documented for these tumors. However, a critical question is whether cellular signaling networks can be reliably analyzed in surgical specimens, where freezing delays and spatial sampling disparities may potentially obscure physiological signaling. To quantify the extent of these effects, we analyzed the stability of phosphotyrosine (pTyr) sites in ovarian and colon tumors collected under conditions of controlled ischemia and in the context of defined intratumoral sampling. Cold-ischemia produced a rapid, unpredictable, and widespread impact on tumor pTyr networks within 5 minutes of resection, altering up to 50% of pTyr sites by more than 2-fold. Effects on adhesion and migration, inflammatory response, proliferation, and stress response pathways were recapitulated in both ovarian and colon tumors. Additionally, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intra-tumoral spatial heterogeneity and pTyr dynamic response to ischemia varied dramatically between tumors collected from different patients. Overall, these findings reveal unforeseen phosphorylation complexity, thereby increasing the difficulty of extracting physiologically relevant pTyr signaling networks from archived tissue specimens.In light of this data, prospective tumor pTyr analysis will require appropriate sampling and collection protocols to preserve in vivo signaling features.

Patients who underwent segmental colectomy and sustained a period of intraoperative hypothermia were no more likely to develop an SSI than those who were normothermic.