Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections.

PURPOSE: In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. METHODS: The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. RESULTS: All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4 cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10 mm (2-15 mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. CONCLUSION: The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

Outcomes of a single-center experience with classification and treatment of endothermal heat-induced thrombosis after endovenous ablation.

OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a known complication of endothermal venous ablation procedures. EHIT can lead to deep vein thrombosis/pulmonary embolism, which cause significant disability and, rarely, death. Other studies have evaluated risk factors for EHIT. There is an accepted grading system for EHIT, but there is no consensus on treatment type, duration, or follow-up. We retrospectively evaluated all cases of EHIT after radiofrequency ablation or endovenous laser ablation at our institution during a 7-year period, focusing on classification, treatment, and outcomes of EHIT. METHODS: The analysis included all patients aged >18 years who underwent radiofrequency ablation or endovenous laser ablation at our institution, Spectrum Health Hospital Vein Solutions (Grand Rapids, Mich), between January 1, 2008, and December 31, 2014. Electronic medical records were queried retrospectively to identify patients with EHIT during the study interval by International Classification of Diseases-Ninth Revision code. Demographic data, including age, gender, comorbidities (eg, history of deep venous thrombosis, hypercoagulable state, family history of blood clots, etc), body mass index, Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, and use of preoperative anticoagulation were collected for each patient in the registry. Each patient had a required postoperative duplex ultrasound (US) examination within 1 to 2 weeks of the procedure. Preoperative and postoperative US imaging data and procedure-specific data were also recorded for each patient. EHIT was graded from 1 to 4 by review of the US studies. Each patient's treatment course was reviewed for type of anticoagulation, duration of treatment, follow-up imaging, and outcome. RESULTS: From 2008 to 2014, 4799 ablations were performed at Spectrum Health Hospital Vein Center, and EHIT was identified in 70 patients. At presentation, 87% of patients were asymptomatic, 10% reported pain, and 2.9% reported swelling. Patients with EHIT grades 1 or 2 were treated with daily aspirin, and most of those with grades 3 or 4 were treated with systemic anticoagulation. Repeat US imaging was performed at 1 to 2 weeks to evaluate progression. Progression was not seen in any patients treated with systemic anticoagulation (grades 3-4). Thrombus progression occurred in two patients with grades 1 or 2 EHIT treated with aspirin. A bleeding complication occurred in one patient. CONCLUSIONS: EHIT after endovenous ablation occurred in ∼1.5% of patients, which is similar to that reported in the literature. Our review shows that systemic anticoagulation is effective in the prevention of progression with a low risk of bleeding complications. Patients with EHIT grades 1 or 2 can be treated with aspirin alone with a low risk of progression (3%).

Cosmetic sclerotherapy.

Telangiectasias and spider veins are considered a common cosmetic concern for both women and men. Sclerotherapy is a frequently used, low-risk, and highly successful method to treat these venous problems. This article reviews the pathophysiology and diagnosis of telangiectasias and reticular veins as well as the currently available agents and techniques of sclerotherapy. The possible complications and adverse outcomes of sclerotherapy are described. Standard care and follow-up for patients after the procedure are outlined. Also included are tips and tricks found to be valuable in a busy vein practice.

Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium.

BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50 = 5-11 µM) of rhinovirus-induced type I IFNß, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need.

Outcomes for forearm and upper arm arteriovenous fistula creation with the transposition technique.

OBJECTIVE: To study the outcomes of three different types of arteriovenous fistula (AVF) transpositions (forearm cephalic vein transposition [FACVT], upper arm cephalic vein transposition [UACVT], and upper arm basilic vein transposition [UABVT]) for dialysis patients in a single center. METHODS: A 6-year retrospective review, from 2006 to 2012, was conducted at a single institution in which the surgical outcomes for three different types of AVF transposition were reviewed. Preoperative duplex vein mapping was obtained in all patients to choose the best vein for access. RESULTS: There were 165 patients identified with 77 FACVTs, 52 UACVTs, and 36 UABVTs. Primary access maturation rates for the FACVT, UACVT, and UABVT groups were 86%, 90%, and 97%, respectively (P = .19). All transposed, matured primary AVFs were used after a mean of 9.9 weeks, without additional intervention. Primary 1-year patency for the FACVT, UACVT, and UABVT groups were 63%, 61%, and 70%, respectively (P = .71). Primary assisted 1-year patency for the FACVT, UACVT, and UABVT groups were 93%, 93%, and 100%, respectively (P > .999). Mean operating room times and time to intervention were not significantly different between the groups. The postoperative hematoma rate was 2% and wound infection rate was 2%. Multivariate analysis indicated no significant predictors of time to failure (P > .05). CONCLUSIONS: With low primary failure rates, reduced need for secondary interventions before maturation, and 1-year primary assisted patency rates in excess of 93%, our study showed that the transposition technique, in our experience, is superior to previously published literature in hemodialysis access creation.

Combined Coronary Artery Bypass Grafting and Abdominal Aortic Aneurysm Repair: Presentation of 3 Cases and a Review of the Literature.

BACKGROUND: Coronary artery disease and abdominal aortic aneurysmal disease can occur in a single patient, and a therapeutic conundrum presents when open surgical repair is indicated for both conditions. The traditional standard of care is to conduct coronary artery bypass grafting (CABG) followed by abdominal aortic aneurysm (AAA) repair 2-6 months later, but there is significant risk with staging these 2 major surgeries. An alternative method is to surgically repair both diseases in 1 combined operation. The aim of our study is to review our own experience with the combined procedure and to review the published literature to assess morbidity and mortality of combined CABG and AAA repair. METHODS: A systematic search for relevant studies was performed in the PubMed/Medline database. Short-term mortality (<30 days) and postoperative complications were assessed from relevant case series from 1993 to 2013. We also conducted a retrospective chart review of all patients undergoing the combined procedure at our institution. RESULTS: Thirty case series with a total of 369 patients averaged a 30-day mortality of 3.0%. Fourteen percent and 6% of patients experienced a cardiovascular or respiratory complication, respectively. Other postoperative events included acute renal failure (7%) and superficial wound complications (5%). In our own experience, 3 patients underwent combined CABG and AAA repair. The mean age was 71 years, the average AAA size was 8.9 cm, and average operative time was 328 min. None experienced any postoperative complications. Two are still alive at 9 and 10 years after surgery, and 1 died of unrelated causes 8 years postoperatively. CONCLUSIONS: The results of this systematic review suggest that combined CABG and AAA repair is a viable procedure with low operative mortality. Patients with preserved ejection fractions, large AAA, and limited comorbidities appear to receive the most benefit from a combined approach based on reported data from the literature. We have experienced promising results in our highly selected patient population. More research is warranted to devise criteria to determine which patients would be good surgical candidates for this combined procedure.

Ubiquitin-specific protease 14 regulates c-Jun N-terminal kinase signaling at the neuromuscular junction.

BACKGROUND: Ubiquitin-specific protease 14 (USP14) is one of three proteasome-associated deubiquitinating enzymes that remove ubiquitin from proteasomal substrates prior to their degradation. In vitro evidence suggests that inhibiting USP14's catalytic activity alters the turnover of ubiquitinated proteins by the proteasome, although whether protein degradation is accelerated or delayed seems to be cell-type and substrate specific. For example, combined inhibition of USP14 and the proteasomal deubiquitinating enzyme UCH37 halts protein degradation and promotes apoptosis in multiple myeloma cells, whereas USP14 inhibition alone accelerates the degradation of aggregate-prone proteins in immortalized cell lines. These findings have prompted interest in USP14 as a therapeutic target both inside and outside of the nervous system. However, loss of USP14 in the spontaneously occurring ataxia mouse mutant leads to a dramatic neuromuscular phenotype and early perinatal lethality, suggesting that USP14 inhibition may have adverse consequences in the nervous system. We therefore expressed a catalytically inactive USP14 mutant in the mouse nervous system to determine whether USP14's catalytic activity is required for neuromuscular junction (NMJ) structure and function. RESULTS: Mice expressing catalytically inactive USP14 in the nervous system exhibited motor deficits, altered NMJ structure, and synaptic transmission deficits that were similar to what is observed in the USP14-deficient ataxia mice. Acute pharmacological inhibition of USP14 in wild type mice also reduced NMJ synaptic transmission. However, there was no evidence of altered proteasome activity when USP14 was inhibited either genetically or pharmacologically. Instead, these manipulations increased the levels of non-proteasome targeting ubiquitin conjugates. Specifically, we observed enhanced proteasome-independent ubiquitination of mixed lineage kinase 3 (MLK3). Consistent with the direct activation of MLK3 by ubiquitination, we also observed increased activation of its downstrea targets MAP kinase kinase 4 (MKK4) and c-Jun N-terminal kinase (JNK). In vivo inhibition of JNK improved motor function and synapse structure in the USP14 catalytic mutant mice. CONCLUSIONS: USP14's catalytic activity is required for nervous system structure and function and has an ongoing role in NMJ synaptic transmission. By regulating the ubiquitination status of protein kinases, USP14 can coordinate the activity of intracellular signaling pathways that control the development and activity of the NMJ.

Preliminary results of Zenith Fenestrated abdominal aortic aneurysm endovascular grafts.

BACKGROUND: Patients with juxtarenal aortic aneurysms who are unfit for open repair may be considered for fenestrated endovascular repair (fenEVAR). We report our initial experience with fenEVAR. METHODS: We reviewed the data on all our patients receiving fenEVAR for juxtarenal aortic aneurysms. RESULTS: Eight patients, average age 75 years, underwent fenEVAR. Endografts were designed from details obtained from preoperative computed tomography angiography. There were 6 grafts with superior mesenteric scallops and bilateral renal fenestrations, 1 with bilateral renal scallops, and 1 with a single renal fenestration. All patients survived 30 days. There was no renal failure requiring dialysis. At 10 weeks, 1 patient died from acute intestinal ischemia and multisystem organ failure, and another died from respiratory failure. CONCLUSIONS: It is feasible to offer fenEVAR to patients who are poor candidates for open repair. However, these procedures are technically challenging. Early outcomes are less favorable than other aortic endovascular procedures.

Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging.

Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis.

In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis.

Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SHG]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a long-term survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SHG. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer.

Diagnostic potential of multimodal imaging of ovarian tissue using optical coherence tomography and second-harmonic generation microscopy.

Ovarian cancer is particularly deadly because it is usually diagnosed after it has metastasized. We have previously identified features of ovarian cancer using optical coherence tomography (OCT) and second-harmonic generation (SHG) microscopy (targeting collagen). OCT provides an image of the ovarian microstructure while SHG provides a high-resolution map of collagen fiber bundle arrangement. Here we investigated the diagnostic potential of dual-modality OCT and SHG imaging. We conducted a fully crossed, multi-reader, multi-case study using seven human observers. Each observer classified 44 ex vivo mouse ovaries (16 normal and 28 abnormal) as normal or abnormal from OCT, SHG, and simultaneously viewed, co-registered OCT and SHG images and provided a confidence rating on a six-point scale. We determined the average receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and other quantitative figures of merit. The results show that OCT has diagnostic potential with an average AUC of 0.91 ± 0.06. The average AUC for SHG was less promising at 0.71 ± 0.13. The average AUC for simultaneous OCT and SHG was not significantly different from OCT alone, possibly due to the limited SHG field of view. The high performance of OCT and co-registered OCT and SHG warrants further investigation.

A 14-year experience with blunt thoracic aortic injury.

OBJECTIVE: This study reviewed the natural history of blunt thoracic aortic trauma (BTAT) over a 14-year period at our level 1 trauma center and compared open vs endovascular treatment. METHODS: All patients with BTAT presenting to a level 1 trauma center from 1998 to 2011 were included in a retrospective analysis. Multiple data points and short-term and midterm outcomes were ascertained through a retrospective record review. RESULTS: We identified 129 patients with BTAT. Of these, 32 (25%) were dead on arrival, 38 (29%) underwent a resuscitative thoracotomy and died, 33 (26%) underwent open repair, 14 (11%) underwent endovascular repair, 9 (7%) underwent simultaneous procedures, and 3 (2%) were managed nonoperatively. Mean Injury Severity Scores and Revised Trauma Scores were similar (P = .484, P = .551) between the open repair group (n = 36) and the endovascular repair group (n = 14). In the open repair group, there were 14 deaths (42%) ≤ 30 days of injury, 3 strokes (9%), 2 patients (6%) with paralysis, 2 myocardial infarctions (MIs; 6%), and 3 patients (9%) who required hemodialysis. In the endovascular group, there was 1 death (7%) ≤ 30 days of injury, 1 (7%) stroke, and 1 (7%) stent collapse. No paralysis, MI, or renal failure requiring hemodialysis was noted in the endovascular group. The average length of stay was 15 days for patients treated with endovascular repair vs 24 days for those treated with open repair (P = .003). CONCLUSIONS: The incidence of BTAT is low but the mortality associated with it is significant. During the 14-year period studied, there was a clear change in management preference from open repair to endovascular repair at our level 1 trauma center. Outcomes, including stroke, MI, renal failure, paralysis, length of stay, and death, appear to be reduced in the endovascular group.

7,12-dimethylbenz[a]anthracene-induced malignancies in a mouse model of menopause.

Ovarian cancer has a high mortality rate because there are few symptoms in early disease development. The incidence of ovarian cancer increases in women after menopause. Understanding early events in this disease can best be achieved by using animal models. Therefore, the objective of this study was to develop and track the onset of ovarian tumorigenesis in mice mimicking characteristics of postmenopausal epithelial cancer in women. Female B6C3F1 mice (age, 28 d) received 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg IV daily for 20 d) to cause ovarian failure. Four months after VCD treatment, via surgical intervention, each mouse received a single injection of 7,12-dimethylbenz[a]anthracene (DMBA) or vehicle control (sesame oil) under the bursa of the right ovary to cause ovarian neoplasms. The experimental groups were untreated controls (Con-Con), DMBA-treatment only (Con-DMBA), VCD treatment only (VCD-Con), and VCD+DMBA-treated (VCD+DMBA) mice. At 3, 5, 7, and 9 mo after DMBA injection, ovaries were collected for histologic and immunohistochemical evaluation. No tumors developed in Con-Con mice. All VCD-treated mice (with or without DMBA) exhibited ovarian failure. Mice that received both VCD and DMBA exhibited tumors at 3 mo (50%), 5 mo (14%), 7 mo (90%), and 9 mo (57%) after DMBA treatment; 31% of the tumors were epithelial in origin. Our findings confirm that inducing ovarian tumors in mice by chemical means is an effective method for studying early stages of tumor development that may be relevant to epithelial ovarian cancers that arise in postmenopausal women.

Sequential compression devices in postoperative urologic patients: an observational trial and survey study on the influence of patient and hospital factors on compliance.

BACKGROUND: Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. METHODS: 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. RESULTS: Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1-3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. CONCLUSIONS: Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety.

Two-photon excited fluorescence imaging of endogenous contrast in a mouse model of ovarian cancer.

BACKGROUND AND OBJECTIVE: Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease. STUDY DESIGN/MATERIALS AND METHODS: A mouse model of ovarian cancer was created by dosing with 4-vinylcyclohexene diepoxide, which induces follicular apoptosis (simulating menopause), and 7,12-dimethylbenz[a]anthracene, a known carcinogen. Imaging of ovarian tissue was completed ex vivo with a multiphoton microscope using excitation wavelength of 780 nm and emission collection from 405 to 505 nm. Two-photon excited fluorescence images and corresponding histologic sections with selective stains were used to identify endogenous fluorophores. RESULTS: The majority of collected fluorescence emission was attributed to NADH and lipofuscin, with additional contributions from collagen and elastin. Dim cellular fluorescence from NADH did not show observable changes with age. Changes in ovarian morphology with disease development frequently caused increased fluorescence contributions from collagen and adipose tissue-associated NADH. Lipofuscin fluorescence was much brighter than NADH fluorescence and increased as a function of both age and disease. CONCLUSIONS: Our finding of NADH fluorescence patterns similar to that seen previously in human ovary, combined with the observation of lipofuscin accumulation with age and disease also seen in human organs, suggests that the findings from this model may be relevant to human ovarian disease. Increased lipofuscin fluorescence might be used as an indicator of disease in the ovary and this finding warrants further study.

Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits.

Regulated protein degradation by the proteasome plays an essential role in the enhancement and suppression of signaling pathways in the nervous system. Proteasome-associated factors are pivotal in ensuring appropriate protein degradation, and we have previously demonstrated that alterations in one of these factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 (Usp14), can lead to proteasome dysfunction and neurological disease. Recent studies in cell culture have shown that Usp14 can also stabilize the expression of over-expressed, disease-associated proteins such as tau and ataxin-3. Using Usp14-deficient ax(J) mice, we investigated if loss of Usp14 results in decreased levels of endogenous tau and ataxin-3 in the nervous system of mice. Although loss of Usp14 did not alter the overall neuronal levels of tau and ataxin-3, we found increased levels of phosphorylated tau that correlated with the onset of axonal varicosities in the Usp14-deficient mice. These changes in tau phosphorylation were accompanied by increased levels of activated phospho-Akt, phosphorylated MAPKs, and inactivated phospho-GSK3ß. However, genetic ablation of tau did not alter any of the neurological deficits in the Usp14-deficient mice, demonstrating that increased levels of phosphorylated tau do not necessarily lead to neurological disease. Due to the widespread activation of intracellular signaling pathways induced by the loss of Usp14, a better understanding of the cellular pathways regulated by the proteasome is required before effective proteasomal-based therapies can be used to treat chronic neurological diseases.

Analysis of second-harmonic-generation microscopy in a mouse model of ovarian carcinoma.

Second-harmonic-generation (SHG) imaging of mouse ovaries ex vivo was used to detect collagen structure changes accompanying ovarian cancer development. Dosing with 4-vinylcyclohexene diepoxide and 7,12-dimethylbenz[a]anthracene resulted in histologically confirmed cases of normal, benign abnormality, dysplasia, and carcinoma. Parameters for each SHG image were calculated using the Fourier transform matrix and gray-level co-occurrence matrix (GLCM). Cancer versus normal and cancer versus all other diagnoses showed the greatest separation using the parameters derived from power in the highest-frequency region and GLCM energy. Mixed effects models showed that these parameters were significantly different between cancer and normal (P<0.008). Images were classified with a support vector machine, using 25% of the data for training and 75% for testing. Utilizing all images with signal greater than the noise level, cancer versus not-cancer specimens were classified with 81.2% sensitivity and 80.0% specificity, and cancer versus normal specimens were classified with 77.8% sensitivity and 79.3% specificity. Utilizing only images with greater than of 75% of the field of view containing signal improved sensitivity and specificity for cancer versus normal to 81.5% and 81.1%. These results suggest that using SHG to visualize collagen structure in ovaries could help with early cancer detection.

In vivo, dual-modality OCT/LIF imaging using a novel VEGF receptor-targeted NIR fluorescent probe in the AOM-treated mouse model.

PURPOSE: Increased vascular endothelial growth factor (VEGF) receptor expression has been found at the sites of angiogenesis, particularly in tumor growth areas, as compared with quiescent vasculature. An increase in VEGF receptor-2 is associated with colon cancer progression. The in vivo detection of VEGF receptor is of interest for the purposes of studying basic mechanisms of carcinogenesis, making clinical diagnoses, and monitoring the efficacy of chemopreventive and therapeutic agents. In this study, a novel single chain (sc)VEGF-based molecular probe is utilized in the azoxymethane (AOM)-treated mouse model of colorectal cancer to study delivery route and specificity for disease. PROCEDURES: The probe was constructed by site-specific conjugation of a near-infrared fluorescent dye, Cy5.5, to scVEGF and detected in vivo with a dual-modality optical coherence tomography/laser-induced fluorescence (OCT/LIF) endoscopic system. A probe inactivated via excessive biotinylation was utilized as a control for nonreceptor-mediated binding. The LIF excitation source was a 633-nm He:Ne laser, and red/near-infrared fluorescence was detected with a spectrometer. OCT was used to obtain two-dimensional longitudinal tomograms at eight rotations in the distal colon. Fluorescence emission levels were correlated with OCT-detected disease in vivo. OCT-detected disease was verified with hematoxylin and eosin stained histology slides ex vivo. RESULTS: High fluorescence emission intensity from the targeted probe was correlated with tumor presence as detected using OCT in vivo and VEGFR-2 immunostaining on histological sections ex vivo. The inactivated probe accumulated preferentially on the surface of tumor lesions and in lymphoid aggregate tissue and was less selective for VEGFR-2. CONCLUSION: The scVEGF/Cy probe delivered via colonic lavage reaches tumor vasculature and selectively accumulates in VEGFR-2-positive areas, resulting in high sensitivity and specificity for tumor detection. The combination of OCT and LIF imaging modalities may allow the simultaneous study of tumor morphology and protein expression for the development of diagnostic and therapeutic methods for colorectal cancer.

Effectiveness of a social marketing media campaign to reduce oral cancer racial disparities.

OBJECTIVES: The purpose of this study was to provide a systematic evaluation of a theory-driven oral cancer awareness media campaign. METHODS: We surveyed a cohort of residents in an intervention city (250) and a control city (250) immediately prior to and after the media campaign. Participants (125 black/African American and 125 white) in each city completed surveys at baseline and follow-up. Oral cancer campaign awareness was assessed in both cities, along with 4 hypothetical health campaigns. Oral cancer awareness, oral cancer exam awareness, intent to receive an oral cancer exam, interest in exam, and receipt of exam were also assessed in both cities, both at baseline and follow-up. RESULTS: Intervention city residents showed a significant increase in recognition of the campaign, awareness of the oral cancer exam, and interest in getting an exam, while no significant changes in those topics were found for the control city. Blacks/African Americans in the intervention city were significantly more likely than whites to demonstrate increases in awareness of the campaign, oral cancer awareness, and interest in receiving an oral cancer exam. CONCLUSIONS: A theory-driven media campaign was successful in increasing awareness of the oral cancer exam and interest in the exam among blacks/African Americans.

Factors associated with early-stage diagnosis of oral and pharyngeal cancer.

OBJECTIVES: The objective of this study was to examine the characteristics and treatment-seeking behaviors of patients diagnosed with oral and pharyngeal cancer (OPC) and to determine whether seeing an oral healthcare provider in the preceding year was associated with an earlier stage of diagnosis. METHODS: Trained interviewers administered a pretested survey instrument to a sample of 131 patients newly diagnosed with OPC at two cancer centers in Florida. Analyses were conducted to compare characteristics of patients by cancer summary stage (early or advanced) on receipt of OPC examination, patterns of dental care, and number of initial signs and symptoms. In addition, analyses were also conducted for characteristics of patients' dental care utilization (regular primary care dentist, time of most recent dental visit, and regular dental care) by receipt of OPC examination. RESULTS: Overall, 25.3% of participants reported receiving an OPC examination at their last dental visit and participants who received an OPC examination were significantly more likely (79%) to be diagnosed at early stages than those who did not receive an oral cancer examination (48%). Patients with a regular primary care dentist were more likely to be diagnosed at early stages (65%) than those without a regular primary care dentist (41%). Factors significantly associated with receiving an OPC examination included having a regular primary care dentist (P < 0.001), having a dental visit in the preceding 12 months (P < 0.001), and receiving regular care (P < 0.001). The number of signs or symptoms reported by the patient was significantly associated with the stage at diagnosis (P = 0.002) and the most common initial symptom reported by patients was soreness in the mouth. CONCLUSIONS: These results emphasize the importance of periodic and thorough OPC examinations.