Evaluation of monoenergetic imaging to reduce metallic instrumentation artifacts in computed tomography of the cervical spine.

OBJECT Monoenergetic imaging with dual-energy CT has been proposed to reduce metallic artifacts in comparison with conventional polychromatic CT. The purpose of this study is to systematically evaluate and define the optimal dual-energy CT imaging parameters for specific cervical spinal implant alloy compositions. METHODS Spinal fixation rods of cobalt-chromium or titanium alloy inserted into the cervical spine section of an Alderson Rando anthropomorphic phantom were imaged ex vivo with fast-kilovoltage switching CT at 80 and 140 peak kV. The collimation width and field of view were varied between 20 and 40 mm and medium to large, respectively. Extrapolated monoenergetic images were generated at 70, 90, 110, and 130 kiloelectron volts (keV). The standard deviation of voxel intensities along a circular line profile around the spine was used as an index of the magnitude of metallic artifact. RESULTS The metallic artifact was more conspicuous around the fixation rods made of cobalt-chromium than those of titanium alloy. The magnitude of metallic artifact seen with titanium fixation rods was minimized at monoenergies of 90 keV and higher, using a collimation width of 20 mm and large field of view. The magnitude of metallic artifact with cobalt-chromium fixation rods was minimized at monoenergies of 110 keV and higher; collimation width or field of view had no effect. CONCLUSIONS Optimization of acquisition settings used with monoenergetic CT studies might yield reduced metallic artifacts.

High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7% (75/145). HPV 16 was found in 30.6% (23/75) and HPV 58 in 24% (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8% (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9%. Regarding HPV 58 variants, 94.4% of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.

Cervical myelopathy in hereditary multiple exostoses.

Spinal cord compression due to cervical exostoses is a rare but recognized complication of hereditary multiple exostosis (HME), an autosomal dominant disorder. This disease, also called multiple osteochondromatosis, is characterised by osteocartilaginous exostoses, typically involving the juxtaepiphyseal regions of long bones. Complications such as transformation to sarcoma (1 to 5%) or neurological compression (of the spinal cord, 1 to 9%) can arise during the course of the disease. We report the case of a 64-year-old man with progressive difficulties in walking over many years, ascribed to congenital rachitism. A diagnosis of HME was not made until late in the disease course. Investigations revealed cervical myelopathy due to vertebral exostosis as well as multiple exostoses in other sites. His gait was not improved after surgical decompression. A better knowledge of this disease could have prevented this neurological complication.

Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma.

BACKGROUND Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. METHODOLOGY/PRINCIPAL FINDINGS RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). CONCLUSIONS/SIGNIFICANCE It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.

Evaluation of the GlideScope (R) for tracheal intubation in patients with cervical spine immobilization by a semi-rigid collar

Background: In patients with cervical spine injury, a cervical collar may prevent cervical spine movements but renders tracheal intubation with a standard laryngoscope difficult if not impossible. We hypothesized that despite the presence of a semi-rigid cervical collar and with the patient's head taped to the trolley, we would be able to intubate all patients with the GlideScopeR and its dedicated stylet. Methods: 50 adult patients (ASA 1 or 2, BMI ≤35 kg/m2) scheduled for elective surgical procedures requiring tracheal intubation were included. After standardized induction of general anesthesia and neuromuscular blockade, the neck was immobilized with an appropriately sized semi-rigid Philadelphia Patriot® cervical collar, the head was taped to the trolley. Laryngoscopy was attempted using a Macintosh laryngoscope blade 4 and the modified Cormack Lehane grade was noted. Subsequently, laryngoscopy with the GlideScopeR was graded and followed by oro-tracheal intubation. Results: All patients were successfully intubated with the GlideScopeR and its dedicated stylet. The median intubation time was 50 sec [43; 61]. The modified Cormack Lehane grade was 3 or 4 at direct laryngoscopy. It was significantly reduced with the GlideScopeR (p <0.0001), reaching 2a in most of patients. Maximal mouth opening was significantly reduced with the cervical collar applied, 4.5 cm [4.5; 5.0] vs. 2.0 cm [1.8; 2.0] (p <0.0001). Conclusions: The GlideScope® allows oro-tracheal intubation in patients having their cervical spine immobilized by a semi-rigid collar and their head taped to the trolley. It furthermore decreases significantly the modified Cormack Lehane grade.

Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies

The purpose of this study was to compare the histopathological analysis with polymerase chain reaction (PCR) methods to predict the presence of human papillomavirus (HPV) infection in oral squamous cell carcinoma biopsies. Eighty-three paraffin-embedded tissue specimens from patients with oropharynx and mouth floor squamous cell carcinoma were submitted to histopathological analysis under light microscopy, specifically for the determination of the presence of koilocytes. Subsequently, DNA was purified from the same paraffin-embedded specimens and submitted to PCR. Fisher's exact test showed no statistically significant correlation between the two methods. The results suggest that the presence of koilocytes is unreliable for the detection of HPV presence in oral and oropharynx squamous cell carcinoma.

Clinical performance of cervical restorations: a meta-analysis.

OBJECTIVES: To carry out a meta-analysis in order to assess the influencing factors on retention loss and marginal discoloration of cervical restorations made of composites and glass ionomer (derivates). METHODS: The literature was searched for prospective clinical studies on cervical restorations with an observation period of at least 18 months. RESULTS: Fifty clinical studies involving 40 adhesive systems matched the inclusion criteria. On average, 10% of the cervical fillings were lost and 24% exhibited marginal discoloration after 3 years. The variability ranged from 0% to 50% for retention loss and from 0% to 74% for marginal discoloration. Hardly any secondary caries was detected. When linear mixed models with a study and experiment effect were used, the analysis revealed that the adhesive/restorative class had the most significant influence, with 2-step self-etching adhesive systems performing best and 1-step self-etching adhesive systems performing worst; 3-step etch-and-rinse systems, glass ionomers/resin-modified glass ionomers, 2-step etch-and-rinse systems and polyacid-modified resin composites were ranked in between. Restorations placed in teeth whose dentin/enamel had been prepared/roughened showed a statistically significant higher retention rate than those placed in teeth with unprepared dentin (p<0.05). Beveling of the enamel and the type of isolation used (rubberdam/cotton rolls) had no significant influence. SIGNIFICANCE: The clinical performance of cervical restorations is significantly influenced by the type of adhesive system used and/or the adhesive class to which the system belonged and whether the dentin/enamel is prepared or not. 2-Step self-etching- and 3-step etch&rinse systems shall be chosen over 1-step self-etching systems and glass ionomer derivates. The dentin (and enamel) surface shall be roughened before placement of the restoration.

A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization

Background: Transcatheter arterial chemoembolization (TACE) has been shown to offer a survival benefit for patients with intermediate-stage hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes the administration of a doxorubicin-in-oil emulsion followed by gelatine sponge particles. Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. Purpose of this randomized trial was to compare conventional TACE with DEB-TACE for the treatment of intermediate-stage HCC in patients with cirrhosis. Methods: Two hundred and twelve patients (185 males and 27 females; mean age, 67 years) with Child-Pugh A or B liver cirrhosis and large and/or multinodular, unresectable HCC were randomized to receive DEB-TACE (DC Bead; Biocompatibles, UK) uploaded with doxorubicin or conventional TACE with doxorubicin, lipiodol, and gelatin sponge particles. Randomization was stratified according to Child Pugh status (A or B), performance status (ECOG 0 or 1), bilobar disease (yes or no) and prior curative treatment (yes or no). Tumor response at 6 months was the primary study endpoint. An independent, blinded review of magnetic resonance imaging studies was conducted to assess tumor response according to amended RECIST criteria. Results: DEB-TACE with doxorubicin showed a higher rate of complete response, objective response and disease control compared with conventional TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%, respectively; p>0.05). Patients with Child Pugh B, ECOG 1, bilobar disease and recurrence following curative treatment showed a significant increase in objective response (p=0.038) compared to the control. There was a marked reduction in serious liver toxicity in patients treated with DEB-TACE. The rate of doxorubicin related side effects was significantly lower (p=0.0001) in the DEB-TACE group compared with the conventional TACE group. Conclusions: DEB-TACE with doxorubicin is safe and effective in the treatment of intermediate-stage HCC and may offer benefit to patients with more advanced disease.

Metastasis of renal cell carcinoma to the buccal mucosa 19 years after radical nephrectomy

Renal cell carcinoma (RCC) has high metastatic potential, which requires early diagnosis to optimize the chance of cure. Metastasis of RCC to the head and neck region is less common and metastasis to the buccal mucosa is extremely rare. This phenomenon occurs mostly in patients with generalized dissemination, especially with lung metastases. In this article we report a case of buccal mucosa metastasis from RCC in a 65-year-old man who presented 19 years after undergoing a left radical nephrectomy for clear cell RCC. Surgical excision of the buccal lesion was performed without evidence of recurrence or new metastatic lesions after 6 years of followup. To our knowledge, this is the first case of metastasis to the buccal mucosa from a RCC reported in the literature.

Human Papillomavirus (HPV) Type Distribution in Females with Abnormal Cervical Cytology. A Correlation with Histological Study

The aim of this study was to determine human papillomavirus (HPV) types distribution in cervical preneoplasic lesions in a Southern Spanish population and their relationship between HPV type and grade of histopathological abnormality. Finally, 232 cervical samples from 135 women with previous cytological abnormalities were included in this study. Colposcopy studies and biopsies were performed. Haematoxylin-eosin stained slides were observed and detection of HPV DNA in cervical swabs was carried out with use of a polymerase chain reaction and microarrays technology. The relationship between the presence of HPV infection and diagnostic variables was evaluated. HPV 16 was the most common type followed by HPV 58, 51, 33 and 31. However, the two HPV types targeted in the prophylactic vaccines such as HPV type 16 and 18 were detected in only 37 (21.2%) and 2 (1.1%) cases respectively. Thirty-three (18.9%) of samples were infected with multiple types, the majority of them with two types. In addition, during the follow-up of patients many changes in type distribution were observed. Several studies will be necessary in order to evaluate the HPV type distribution for therapeutically and prophylactic purposes such as vaccine treatment. Also, because of the differences obtained depending of use of various DNA technologies, the performance of some comparative studies of the different methods from detection of HPV would be advisable in a high population of patients and with the most homogeneous conditions possible.

Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib.

Background: Targeted therapies for metastatic renal cell carcinoma (RCC), including mammalian target of rapamycin (mTOR) inhibitors and small-molecule multikinase inhibitors, have produced clinical effects. However, most patients acquire resistance over time. Thus, new therapeutic strategies need to be developed. Here, we evaluated the effect of the dual PI3K/mTOR inhibitor NVP-BEZ235, in combination with the multikinase inhibitor sorafenib on renal cancer cell proliferation and survival in vitro as well as on tumor growth in vivo.Methods: The renal carcinoma cell lines 786-0 and Caki-1 were treated with NVP-BEZ235 or sorafenib, either alone or in combination. Tumor cell proliferation and apoptosis were investigated in vitro. The anticancer efficacy of NVP-BEZ235 alone, or in combination with sorafenib, was also evaluated on RCC xenografts in nude mice.Results: Treatment of 786-0 and Caki-1 cells with NVP-BEZ235 or sorafenib resulted in reduced tumor cell proliferation and increased tumor cell apoptosis in vitro. The combination of NVP-BEZ235 and sorafenib was more effective than each compound alone. Similarly, in vivo, NVP-BEZ235 or sorafenib reduced the growth of xenografts generated from 786-0 or Caki-1 cells. The antitumor efficacy of NVP-BEZ235 in combination with sorafenib was superior to NVP-BEZ235 or sorafenib alone.Conclusions: Our findings indicate that the simultaneous use of NVP-BEZ235 and sorafenib has greater antitumor benefit compared to either drug alone and thus provides a treatment strategy in RCC.

Impact of Prophylactic Cranial Irradiation Timing on Brain Relapse Rates in Patients With Stage IIIB Non-Small-Cell Lung Carcinoma Treated With Two Different Chemoradiotherapy Regimens.

PURPOSE: To retrospectively assess the influence of prophylactic cranial irradiation (PCI) timing on brain relapse rates in patients treated with two different chemoradiotherapy (CRT) regimens for Stage IIIB non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A cohort of 134 patients, with Stage IIIB NSCLC in recursive partitioning analysis Group 1, was treated with PCI (30 Gy at 2 Gy/fr) following one of two CRT regimens. Regimen 1 (n = 58) consisted of three cycles of induction chemotherapy (ICT) followed by concurrent CRT (C-CRT). Regimen 2 (n = 76) consisted of immediate C-CRT during thoracic radiotherapy. RESULTS: At a median follow-up of 27.6 months (range, 7.2-40.4), 65 patients were alive. Median, progression-free, and brain metastasis-free survival (BMFS) times for the whole study cohort were 23.4, 15.4, and 23.0 months, respectively. Median survival time and the 3-year survival rate for regimens 1 and 2 were 19.3 vs. 26.1 months (p = 0.001) and 14.4% vs. 34.4% (p < .001), respectively. Median time from the initiation of primary treatment to PCI was 123.2 (range, 97-161) and 63.4 (range, 55-74) days for regimens 1 and 2, respectively (p < 0.001). Overall, 11 (8.2%) patients developed brain metastasis (BM) during the follow-up period: 8 (13.8%) in regimen 1 and 3 (3.9%) in regimen 2 (p = 0.03). Only 3 (2.2%) patients developed BM at the site of first failure, and for 2 of them, it was also the sole site of recurrence. Median BMFS for regimens 1 and 2 were 17.4 (13.5-21.3) vs. 26.0 (22.9-29.1 months), respectively (p < 0.001). CONCLUSION: These results suggest that in Stage IIIB NSCLC patients treated with PCI, lower BM incidence and longer survival rates result from immediate C-CRT rather than ITC-first regimens. This indicates the benefit of earlier PCI use without delay because of induction protocols.

Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: preliminary results.

BACKGROUND AND OBJECTIVE: In bladder cancer, conventional white light endoscopic examination of the bladder does not provide adequate information about the presence of "flat" urothelial lesions such as carcinoma in situ. In the present investigation, we examine a new technique for the photodetection of such lesions by the imaging of protoporphyrin IX (PpIX) fluorescence following topical application of 5-aminolevulinic acid (ALA). STUDY DESIGN/MATERIALS AND METHODS: Several hours after bladder instillation of an aqueous solution of ALA in 34 patients, a Krypton ion laser or a filtered Xenon arc-lamp was used to excite PpIX fluorescence. Tissue samples for histological analysis were taken while observing the bladder wall either by means of a video camera, or by direct endoscopic observation. RESULTS: A good correlation was found between the PpIX fluorescence and the histopathological diagnosis. On a total of 215 biopsies, 143 in fluorescent and 72 in nonfluorescent areas, all visible tumors on white light cytoscopy appeared in a bright red fluorescence with the photodetection technique. In addition, this method permitted to discover 47 unsuspected carcinomatous lesions on white light observation, among which 40% were carcinoma in situ. CONCLUSION: PpIX fluorescence induced by instillation into the bladder of 5-ALA is an efficient method of mapping the mucosa in bladder carcinoma.