Tumor deposits in rectal adenocarcinoma after neoadjuvant chemoradiation are associated with poor prognosis.

Although tumor deposits have been associated with poor prognosis in colorectal carcinoma, the prevalence and clinical significance of tumor deposits in rectal adenocarcinoma following neoadjuvant chemoradiation are relatively unexplored. The aims of this study are to assess the clinical significance of tumor deposits in rectal adenocarcinoma patients, including those receiving neoadjuvant therapy. Pathology slides and medical records from 205 consecutive patients who underwent resection for rectal adenocarcinoma between 1990 and 2010 at a single tertiary care center were reviewed. Patients with tumor deposits had higher tumor grade (P=0.006) and worse tumor stage (P<0.001) at presentation than patients without tumor deposits. Among 110 patients who underwent neoadjuvant chemoradiation, tumor deposits were associated with higher rates of lymph node involvement (P=0.035) and distant metastases (P=0.006), and decreased survival (P=0.027). These patients had a trend toward lower treatment response scores (P=0.285) and higher local recurrence (P=0.092). Of 52 patients with tumor deposits, those who underwent neoadjuvant chemoradiation had significantly worse pretreatment stage by endoscopic ultrasound (P<0.001) but interestingly had significantly lower rates of lymphovascular invasion on resection (P<0.001) compared with those who had not received neoadjuvant chemoradiation. Despite treatment with neoadjuvant chemoradiation, tumor deposits were present in over one-fifth of rectal adenocarcinoma patients. Overall, the outcome of patients with tumor deposits in treated and untreated patients were similar, however the association of tumor deposits with deeply invasive tumors and less tumor regression when comparing with treated patients without tumor deposits raises the possibility that these tumors could have a more aggressive biology, possibly explaining the association of tumor deposits with higher rates of recurrence and lower survival after neoadjuvant chemoradiation. Overall, tumor deposits appear to be a poor prognostic marker among rectal adenocarcinoma patients following neoadjuvant chemoradiation and may identify a subset of patients who require aggressive adjuvant therapy to prevent recurrence.

Increasing Lynch syndrome identification through establishment of a hereditary colorectal cancer registry.

BACKGROUND: Lynch syndrome contributes to 5% of all colorectal cancers. Patients seen in most surgical clinics have limited or no family histories documented and are rarely assessed for hereditary syndromes. In 2007 a clinic-based hereditary colorectal cancer registry was established to screen for Lynch syndrome and facilitate genetic counseling/testing. OBJECTIVE: To evaluate the effectiveness of the hereditary colorectal cancer registry to identify high-risk colorectal cancer patients and have them referred for genetic counseling/testing for Lynch syndrome. DESIGN: A retrospective review and cohort comparison of both prospectively collected and retrospective data. SETTING: The colorectal surgical clinic at Vanderbilt University Medical Center. PATIENTS: All newly diagnosed colorectal cancer patients seen between January 2006 and October 2010. MAIN OUTCOME MEASURES: To assess the identification of colorectal cancer patients at high risk for Lynch syndrome and for the occurrence of genetic counseling/testing before and after the establishment of a hereditary registry by comparing the results from the colorectal cancer patients seen the year prior to the establishment of the registry (January - December 2006, "control period") with those patients seen after initiation of the registry (January 2007 - October 2010, "registry period"). RESULTS: During the "registry period," 495 colorectal cancer patients were seen in the clinic and 257 (51.9%) were high risk for Lynch syndrome. Forty-nine patients (9.8%) underwent genetic testing, with 27 (5.4%) positive for a gene mutation, of which half were >50 years old. By comparison, in 2006, 115 colorectal cancer patients were seen in the clinic but only 4 patients (3.5%) went on for further assessment, and only 1 had genetic testing. Retrospective assessment showed that at least 22 patients (19.1%) had warranted further investigation in 2006. LIMITATIONS: This was a single-institution, retrospective review. CONCLUSION: Establishment of a hereditary colorectal cancer registry with a clinic-based protocol improves identification of Lynch syndrome.

Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review.

PURPOSE: Iron and/or vitamin B12 deficiency anemias, which have adverse effects on patients' quality of life, are commonly observed and often overlooked complications after restorative proctocolectomy. We performed a systematic review of publications on the prevalence of anemia as well as on the impact of anemia on a range of clinical, functional, quality of life, and economic outcomes in restorative proctocolectomy patients. This information is important to help healthcare providers through a comprehensive overview to increase awareness about a condition that could require therapy to improve patient healthcare and quality of life. METHODS: We reviewed the English language publications on the incidence of anemia and its adverse effect after restorative proctocolectomy The United States National Library of Medicine database (MEDLINE), the Excerpta Medica database (EMBASE), the Cochran Library, and the Google search engine were searched for published articles on the prevalence and impact of anemia in post-restorative proctocolectomy surgical patients. RESULTS: The long-term complication most frequently described after RPC is pouchitis. Pouchitis is significantly associated with iron deficiency anemia caused by pouch mucosal bleeding. Other causes are insufficient and/or impaired iron absorption. It has also been observed, however, that restorative proctocolectomy patients with underlying familial adenomatous polyposis rarely develop pouchitis yet show higher rates of iron deficiency anemia compared to those patients with underlying ulcerative colitis. Other causes shown as independent risk factors for iron deficiency anemia in restorative proctocolectomy patients are malignancy, desmoid tumors, and J-pouch configuration. Vitamin B12 deficiency anemia is also common after restorative proctocolectomy. About one-third of restorative proctocolectomy patients show abnormal Schilling test and 5 percent have low referenced serum cobalamin. It has been observed that the degree resection of the terminal-ileum, malabsorption, bacterial overgrowth, and dietary factors are among the known causes of cobalamin deficiency. Folate deficiency has not been reported in restorative proctocolectomy patients. Describing restorative proctocolectomy surgery and its outcomes, in patients without anemia, the quality of life is reported excellent regardless of operative technique. CONCLUSIONS: Anemia is not uncommon following restorative proctocolectomy and has been shown to have negative effects on the patient's quality of life and the economy and may substantially increase healthcare costs. The treatment of anemia and its underlying causes is important to improving clinical and economic outcomes.

A randomized prospective trial of endoscopic ultrasound to guide combination medical and surgical treatment for Crohn's perianal fistulas.

AIMS: To prospectively determine if rectal endoscopic ultrasound (EUS) can guide combination medical and surgical therapy and improve outcomes for patients with perianal fistulizing Crohn's disease. METHODS: Ten patients with perianal Crohn's disease were prospectively enrolled in a randomized prospective pilot study. The patients were randomized to either the EUS cohort or the control group. All patients underwent a rectal EUS to delineate fistula anatomy followed by an examination under anesthesia by a colorectal surgeon with seton placement and/or incision and drainage, as indicated. The surgeon was blinded to the initial EUS results of patients in the control group. Medical treatment was maximized with 6-mercaptopurine (1.0-1.5 mg/kg) or azathioprine (2.0-2.5 mg/kg), ciprofloxacin (1,000 mg a day) or metronidazole (1,500 mg a day), and infliximab (5 mg/kg at 0, 2, and 6 wk and then every 8 wk). For patients in the control group, additional interventions (seton removal and repeat surgery) were at the discretion of the surgeon (without EUS guidance). Patients in the EUS cohort had EUS performed at weeks 22 and 38, with additional surgical interventions based on EUS findings. The primary end point was complete cessation of drainage at week 54. All patients had a repeat EUS performed at week 54 to determine the fistula status on EUS (secondary end point). The need for additional surgery was defined as a treatment failure. RESULTS: Ten patients were enrolled in the study. One of 5 (20%) in the control group and 4 of 5 (80%) in the EUS group had complete cessation of drainage. From the control group, 3 patients failed due to repeat surgery (2 for persistent/recurrent fistula and 1 for abscess), and 1 had a persistent drainage at week 54. In the EUS cohort, 1 patient had a recurrent abscess after his seton fell out prematurely. In the EUS cohort, the median time to cessation of drainage was 99 days, and the time to EUS evidence of fistula inactivity was 229 days. CONCLUSION: This pilot study suggests that using EUS to guide combination medical and surgical therapy for perianal fistulizing Crohn's disease improves the outcomes.

Laparoscopic surface scanning and subsurface targeting: implications for image-guided laparoscopic liver surgery.

Segmental liver resection and locoregional ablative therapies are dependent upon accurate tumor localization to ensure safety as well as acceptable oncologic results. Because of the liver's limited external landmarks and complex internal anatomy, such tumor localization poses a technical challenge. Image guided therapies (IGT) address this problem by mapping the real-time, intraoperative position of surgical instruments onto preoperative tomographic imaging through a process called registration. Accuracy is critical to IGT and is a function of: 1) the registration technique, 2) the tissue characteristics, and 3) imaging techniques. The purpose of this study is to validate a novel method of registration using an endoscopic Laser Range Scanner (eLRS) and demonstrate its applicability to laparoscopic liver surgery. Six radiopaque targets were inserted into an ex-vivo bovine liver and a computed tomography (CT) scan was obtained. Using the eLRS, the liver surface was scanned and a surface-based registration was constructed to predict the position of the intraparenchymal targets. The target registration error (TRE) achieved using our surface-based registration was 2.4 +/- 1.0 mm. A comparable TRE using traditional fiducial-based registration was 2.6 +/- 1.7 mm. Compared to traditional fiducial-based registration, laparoscopic surface scanning is able to predict the location of intraparenchymal liver targets with similar accuracy and rate of data acquisition.

Small bowel adenocarcinoma complicating Crohn's disease: case series and review of the literature.

Colonic adenocarcinoma frequently complicates inflammatory bowel disease of the colon, but small bowel adenocarcinoma (SBA) is a rare complication of Crohn's disease (CD). We present two patients with SBA in CD and review the literature with regards to CD-related SBA. A 45-year-old male with a 17-year history of ileal CD presented with obstructive symptoms but no radiographic evidence of a mass. After laparoscopic ileocolectomy and repair of incidental ileosigmoid fistula, pathology showed a T3N0 adenocarcinoma within the ileal CD. Two years after his resection he was without evidence of disease. A 59-year-old male with a 15-year history of CD presented with an acute exacerbation. Small bowel follow through demonstrated a long ileal stricture for which he underwent an ileocolic resection. Postoperative pathology confirmed a T3N1 CD-related SBA. He died from metastatic cancer 3 months later. Review of the literature identified 154 cases of SBA complicating CD with several distinguishing features from de novo SBA. Patients with SBA and CD are, as a group, younger and more likely to be male. SBA is rarely diagnosed preoperatively in these patients, and has a poor prognosis due to its advanced stage at diagnosis.

Clinical characterization of in vivo inflammatory bowel disease with Raman spectroscopy.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), affects over 1 million Americans and 2 million Europeans, and the incidence is increasing worldwide. While these diseases require unique medical care, the differentiation between UC and CD lacks a gold standard, and therefore relies on long term follow up, success or failure of existing treatment, and recurrence of the disease. Here, we present colonoscopy-coupled fiber optic probe-based Raman spectroscopy as a minimally-invasive diagnostic tool for IBD of the colon (UC and Crohn's colitis). This pilot in vivo study of subjects with existing IBD diagnoses of UC (n = 8), CD (n = 15), and normal control (n = 8) aimed to characterize spectral signatures of UC and CD. Samples were correlated with tissue pathology markers and endoscopic evaluation. The collected spectra were processed and analyzed using multivariate statistical techniques to identify spectral markers and discriminate IBD and disease classes. Confounding factors including the presence of active inflammation and the particular colon segment measured were investigated and integrated into the devised prediction algorithm, reaching 90% sensitivity and 75% specificity to CD from this in vivo data set. These results represent significant progress towards improved real-time classification for accurate and automated in vivo detection and discrimination of IBD during colonoscopy procedures.

Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease.

Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.

Correction: Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease.

[This corrects the article DOI: 10.1371/journal.pone.0179710.].

Use of endoscopic ultrasound to guide combination medical and surgical therapy for patients with Crohn's perianal fistulas.

BACKGROUND: This study was performed to assess if using endoscopic ultrasound (EUS) to assess and guide combination medical and surgical therapy during fistula healing will lead to a high rate of durable fistula closure and a low or absent incidence of perianal abscess formation in patients with Crohn's perianal fistulas. METHODS: This is a retrospective analysis of 21 patients who presented with a symptomatic Crohn's perianal fistula. Patients were enrolled in a clinical practice protocol of serial EUS exams. All patients underwent a baseline rectal EUS and were placed on maximal medical treatment with 6-mercaptopurine (6-MP) or azathioprine, Cipro, and infliximab (5 mg/kg at 0, 2, and 6 wk and then every 8 wk). Patients were also assessed at baseline by a colorectal surgeon who was aware of the EUS findings. Seton placement and incision and drainage were performed when appropriate. Serial EUS examinations were performed, and the findings were used to guide therapy (i.e., the presence of fistula healing on EUS was used to guide seton removal, discontinuation of infliximab, and Cipro). RESULTS: In the 21 patients enrolled, the median duration of active perianal symptoms was 9 wks (1-36). 10 patients (48%) had previous perianal surgery and 5 (24%) had received infliximab previously. The fistulas treated included 8 trans-sphincteric, 2 superficial, 3 recto-vaginal, and 7 with multiple and horseshoe fistulas. 13 patients (62%) had associated abscesses at presentation. Eighteen of 21 patients (86%) had complete cessation of drainage initially. Median time to cessation of drainage was 10.6 weeks (range, 4-32 wk). Sixteen of 21 patients (76%) maintained long-term cessation of drainage. The median length of follow-up was 68 weeks (range, 35-101 wk). No abscess developed during treatment in any patient. EUS evidence of persistent fistula activity was seen in 10 patients (48%). Of the 11 patients (52%) in whom EUS showed no persistent fistula activity, 7 (64%) have maintained fistula closure off of infliximab and Cipro. Median duration from last infliximab infusion was 47 weeks (range, 20-80 wk). The remaining 4 patients continued infliximab to maintain remission of their luminal disease. Only 1 patient with a horseshoe fistula showed complete healing on EUS. CONCLUSION: In conclusion, using EUS to guide therapy for Crohn's perianal fistulas with infliximab, an immunosuppressive, and an antibiotic is associated with a high short and long-term fistula response rate. EUS may identify a subset of patients who can discontinue infliximab without recurrence of fistula drainage.

Calcaneal ultrasound bone densitometry is not a useful tool to screen patients with inflammatory bowel disease at high risk for metabolic bone disease.

BACKGROUND: Up to 42% of patients with inflammatory bowel disease (IBD) have significant metabolic bone disease. The current method of screening for osteopenia or osteoporosis involves dual-energy x-ray absorptiometry (DXA). This is relatively costly and involves radiation exposure. What is needed is a safe, inexpensive, and quick screening tool to identify patients who would benefit from DXA testing. This would reduce the number of patients undergoing DXA testing unnecessarily. We tried to determine if calcaneal ultrasound bone densitometry is a useful tool in screening high-risk patients with IBD for metabolic bone disease. METHODS: Patients with IBD who presented to the clinic between August 29, 2003 and December 22, 2003 were enrolled in this prospective study. All patients underwent calcaneal ultrasound bone densitometry screening using a GE Lunar Achilles Insight quantitative ultrasound densitometry machine (QUS). Patients who were at high risk for significant metabolic bone disease (i.e., significant previous prednisone use or a long history of severe IBD) or who had a T-score on QUS less than or equal to -0.7 had DXA testing performed. The DXA results and QUS results were compared. The radiologist was blinded to the results of QUS. RESULTS: One hundred twenty-four patients with IBD were enrolled. Fifty (40%) were considered high risk for metabolic bone disease. This cohort was comprised of 29 men (58%), of which 21 (73%) had Crohn's disease (CD). Eighty percent of this high-risk group had CD, and in both groups, the majority had used corticosteroids. The overall risk of significant metabolic bone disease in this high-risk group was 62% (DXA < or = -1.0). Heel density (T-score) correlated poorly with DXA (T-score) at either hip or spine at 0.40 even when 2 outlier patients (QUS = -2.9, DXA spine = 0.7, DXA hip = 0.8 and QUS = -3.6, DXA spine = -3, DXA hip = -4) were excluded. Likewise, no association in osteopenia or osteoporosis was seen between multiple variables. These included sex, disease type (ulcerative colitis or CD), smoking, and prior intestinal resection. The sensitivity of QUS to identify patients with significant metabolic bone disease was 74%, and specificity was 63%. A positive predictive value of 81% and negative predictive value of 53% were also less than ideal. The Altman-Bland analysis showed that the agreement between QUS and DXA was poor (-2.0, 2.1). Based on this analysis, QUS cannot replace DXA in the individual patient with IBD. CONCLUSIONS: Calcaneal ultrasound bone densitometry is not a useful tool to screen high-risk patients with IBD for metabolic bone disease.

Development of a three-dimensional freehand endorectal ultrasound system for use in rectal cancer imaging.

The initial study reporting the accuracy of an optically tracked endorectal ultrasound (TERUS) probe for the purpose of improving the staging of rectal cancer is presented here. In this work we describe the need for a more accurate ERUS system and why the incorporation of image guidance makes this goal feasible. A rectal phantom was constructed with five targets placed in positions where tumors normally occur. The locations of these targets were found using two different imaging modalities, CT and ultrasound, and the target registration error (TRE) between these two image sets was calculated. The average TRE of 33 image captures of the five targets using TERUS was 2.1 mm. This is a promising outcome because the desired tumor margins for rectal cancer are on the order of centimeters. These preliminary results support the proof of concept for a TERUS system that should improve ultrasound imaging in rectal cancer.

Resection of mesenteric inflammatory veno-occlusive disease causing ischemic colitis.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of mesenteric ischemia that is diagnosed by histologic examination of the operative specimen. Recurrence of symptoms occurs, but further resection of ischemic intestine is seldom required. We describe the case of MIVOD in a young patient with clinical findings of ischemic colitis. The patient experienced complete resolution of the process, thus confirming the relatively benign course of this disease following resection. This report substantiates resolution of the inflammatory process after resection, colostomy, and reanastomosis. We review the literature and make conclusions regarding the clinical management of this disease.

Association of Perioperative Hypothermia During Colectomy With Surgical Site Infection.

IMPORTANCE: Maintaining perioperative normothermia has been shown to decrease the rate of surgical site infection (SSI) after segmental colectomy and is part of the World Health Organization's Guidelines for Safe Surgery. However, strong evidence supporting this association is lacking, and an exact definition of normothermia has not been described. OBJECTIVE: To determine whether intraoperative hypothermia in patients who undergo segmental colectomy is associated with postoperative SSI. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective cohort study at a single tertiary-referral hospital, 296 adult patients who underwent elective segmental colectomy from January 1, 2005, through December 31, 2009, were included. Exclusion criteria included postoperative stoma, emergent or urgent operation, and diagnosis of inflammatory bowel disease. EXPOSURES: Perioperative temperature was measured continuously, and 4 possible definitions of hypothermia were explored, including temperature nadir, mean intraoperative temperature, percentage of time at the temperature nadir, and percentage of time with a temperature of less than 36.0°C. MAIN OUTCOMES AND MEASURES: The primary outcome measure was 30-day SSI. Secondary outcome measures included clinical leak, return to the operating room, and nasogastric tube placement (a surrogate for ileus). RESULTS: The mean (SD) findings were as follows: intraoperative temperature, 35.9°C (0.6°C); temperature nadir, 34.3°C (2.8°C); percentage of time at the nadir, 4.7% (10.8%); and percentage of time with a temperature of less than 36.0°C, 49.9% (42.0%). The rate of SSI was 12.2% (n = 36). There was no statistically significant difference in temperature measurements between the patients who developed an SSI and those who did not. Logistic regression models evaluated each exposure measure and its effect on SSI, adjusting for body mass index, smoking status, and sex. The adjusted analyses revealed no association between intraoperative hypothermia and 30-day SSI (odds ratio, 1.17; 95% CI, 0.76-1.81; P = .48). Increased body mass index (odds ratio, 1.39; 95% CI, 1.10-1.76; P = .007) was significantly associated with SSI in all 4 logistic regression models. CONCLUSIONS AND RELEVANCE: 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.

Smoking as dominant risk factor for anastomotic leak after left colon resection.

BACKGROUND: Some risk factors for anastomotic leak have been identified, but the effect of smoking is unknown. METHODS: This study aimed to evaluate the effect of smoking on clinical leak after left-sided anastomoses. Adult patients who underwent elective left colectomy between January 1, 2008 and December 31, 2012 were included. Those with stomas and inflammatory bowel diseases were excluded. Primary outcome was anastomotic leak requiring percutaneous drainage or operative intervention within 30 days. RESULTS: There were 246 patients included; 56% were female. Most had a diagnosis of diverticular disease (53%) or cancer (37%). Anastomotic leak rate was 6.5% (n = 16). The rate in smokers was 17% versus 5% in nonsmokers (P = .01). Smokers had over 4 times greater chance of leak (odds ratio 4.2, 95% confidence interval 1.3 to 13.5, P = .02). CONCLUSION: Smoking is a risk factor for leak after left colectomy. Consideration should be given to delaying elective left colectomy until smoking cessation is achieved.

Phosphotyrosine signaling analysis in human tumors is confounded by systemic ischemia-driven artifacts and intra-specimen heterogeneity.

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 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 physiologic 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. In addition, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intratumoral 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.

Design and implementation of a PC-based image-guided surgical system.

In interactive, image-guided surgery, current physical space position in the operating room is displayed on various sets of medical images used for surgical navigation. We have developed a PC-based surgical guidance system (ORION) which synchronously displays surgical position on up to four image sets and updates them in real time. There are three essential components which must be developed for this system: (1) accurately tracked instruments; (2) accurate registration techniques to map physical space to image space; and (3) methods to display and update the image sets on a computer monitor. For each of these components, we have developed a set of dynamic link libraries in MS Visual C++ 6.0 supporting various hardware tools and software techniques. Surgical instruments are tracked in physical space using an active optical tracking system. Several of the different registration algorithms were developed with a library of robust math kernel functions, and the accuracy of all registration techniques was thoroughly investigated. Our display was developed using the Win32 API for windows management and tomographic visualization, a frame grabber for live video capture, and OpenGL for visualization of surface renderings. We have begun to use this current implementation of our system for several surgical procedures, including open and minimally invasive liver surgery.

Adenocarcinomas After Prophylactic Surgery For Familial Adenomatous Polyposis.

The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch; however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers; 15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.

Perioperative core body temperatures effect on outcome after colorectal resections.

The World Health Organization has set a standard of maintaining a core body temperature above 36°C in the perioperative period. The purpose of this study was to examine the relationship between both intraoperative temperature (IOT) and immediate postop core body temperature as it relates to postop complications. A retrospective analysis of a prospective database of patients who underwent an elective segmental colectomy without a stoma, for 3 diagnoses was performed. Six postoperative outcomes were examined: length of stay (LOS), placement of a nasogastric tube, return to the operating room, placement of an interventional drain, diagnosed leak, and surgical site infection (SSI). Statistics were calculated using a two-sample Wilcoxon rank-sum (Mann-Whitney) test. Seventy-nine patients met the inclusion criteria and there were no preoperative differences between the groups (those with a postop complication vs without). LOS > 9 days (36.64°C vs 35.98°C; P = 0.011) and clinical leak (37.06°C vs 35.99°C; P = 0.005) both had a statistically higher average IOT than those who did not. Patients with SSI trended to a higher IOT (36.44°C vs 35.99°C; P = 0.062). When the last IOT recorded was compared with the six outcomes, again length of stay and leak both were statistically significant (P = 0.018, P = 0.012) showing a higher temperature related to a higher complication rate. No other complications were related to IOT, nor did postop temperature relate to complication. In our data, relatively lower IOTs were protective for LOS and clinical leaks, with a trend of lower SSI rates. Further research is needed to fully endorse or refute the absolute recommendations for core body temperature.

Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides.

BACKGROUND: Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can be difficult and may lead to inaccurate diagnoses in up to 30% 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) versus inflamed submucosa (n = 22) were compared in UC and the uninflamed (n = 17) versus inflamed submucosa (n = 20) in CC. To determine whether there were proteomic differences between the colitides, the uninflamed UC submucosa (n = 21) was compared versus the uninflamed CC submucosa (n = 17), the inflamed UC submucosa (n = 22) was compared versus the inflamed CC submucosa (n = 20), and inflamed UC mucosa versus inflamed CC mucosa. Pairwise statistics comparisons of the subsets were performed. RESULTS: Pairwise comparative analyses of the clinical groups allowed identifying subsets of features important for classification. Comparison of inflamed versus uninflamed CC submucosa showed two significant peaks: m/z 6445 (P = 0.0003) and 12692 (P = 0.003). In the case of inflamed versus 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. CONCLUSIONS: 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.