Capsule endoscopy interpretation: the role of physician extenders

Background and aims: capsule endoscopy (CE) allows for a new era in small-bowel examination. Nevertheless, physicians’ time for CE-interpretation remains longer than desirable. Alternative strategies to physicians have not been widely investigated. The aim of this study was to evaluate the accuracy of physician extenders in CE-interpretation. Material and methods: one CE-experienced gastroenterologist and two physician extenders reviewed independently 20 CEprocedures. Each reader was blinded to the findings of their colleagues. A consensus formed by the readers and a second CE-experienced gastroenterologist was used as gold standard. Number, type and location of images selected, character of CEexams and their relationship with indications were recorded. Gastric emptying time (GEt), small-bowel transit time (SBTt) and time spent by readers were also noted. Results: sensitivity and specificity for “overall” lesions was 79 and 99% for the gastroenterologist; 86 and 43% for the nurse; and 80 and 57% for the resident. All 34 “major” lesions considered by consensus were found by the readers. Agreement between consensus and readers for images classification and procedures interpretation was good to excellent (κ from 0.55 to 1). No significant differences were found in the GEt and SBTt obtained by consensus and readers. The gastroenterologist was faster than physician extenders (mean time spent was 51.9 ± 13.5 minutes versus 62.2 ± 19 and 60.9 ± 17.1 for nurse and resident, respectively; p < 0.05). Conclusions: physician extenders could be the perfect complement to gastroenterologists for CE-interpretation but gastroenterologists should supervise their findings. Future cost-efficacy analyses are required to assess the benefits of this alternative

Use of low-resolution CT scans for construction of detailed geometric models of mandibles with and without teeth

Detailed geometric models of a mandible can improve the accuracy of computer simulations. However, cost, time and qualified labor available for their construction may hinder or delay the task. The purpose of this article is to describe a technique for reconstructing a mandible with and without teeth from clinical CT scans of low resolution. The method allows modeling geometric details usually difficult to reconstruct with these scans, such as the periodontal ligament. The models of a toothless and toothed mandible resulting from the process are available online for non-commercial use. The models can be used in various fields such as orthodontics, implantology, orthopedics and traumatology as presented or as a basis for simulations

Efecto de la osteotomía medializante de calcáneo sobre tejidos blandos de soporte del arco plantar: un estudio computacional

Medializing calcaneal osteotomy forms part of the treatment options for adult acquired flat foot. The structural correction that is achieved is widely known. However, the effect of this procedure on the soft tissues that support the plantar arch has been little studied, since it is not possible to quantify experimentally the tension and deformation variations generated. Therefore, the objective of this study was to evaluate the effect of medializing calcaneal osteotomy on the soft tissue that supports the plantar arch, using a computational model of the human foot designed with a clinical approach. The proposed finite element model was reconstructed from computerized tomography images of a healthy patient. All the bones of the foot, the plantar fascia, cartilages, plantar ligaments and the calcaneus-navicular ligament were included, respecting their anatomical distribution and biomechanical properties. Simulations were performed emulating the monopodal support phase of the human walk of an adult. The effect on each tissue was evaluated according to clinical and biomechanical criteria. The results show that calcaneal osteotomy reduces the tension normally generated on the evaluated tissues, with the effect on the calcaneus-navicular ligament and the plantar fascia being the most notable. The deformation results obtained are consistent with experimental tests and clinical knowledge. The versatility of this model allows the objective assessment of different conditions and supports decision making for the treatment of adult acquired flat foot in middle and advanced stages

Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen

PURPOSE: The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported. Experimental Design: The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses. RESULTS: We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA(653-667)), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR 9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA(652-660), which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas. CONCLUSION: These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA(653-667) could be used for immunotherapy against tumors expressing CEA

Use of colonoscopy as a primary screening test for colorectal cancer in average risk people

The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. METHODS: The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. RESULTS: Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. CONCLUSIONS: Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscop

Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy

For colorectal cancer screening, the predictive value of distal findings in the ascertainment of proximal lesions is not fully established. The aims of this study were to assess distal findings as predictors of advanced proximal neoplasia and to compare the predictive value of endoscopy alone vs. combined endoscopic and histopathologic data. METHODS: Primary colonoscopy screening was performed in 2210 consecutive, average-risk adults. Age, gender, endoscopic (size, number of polyps), and histopathologic distal findings were used as potential predictors of advanced proximal neoplasms (i.e., any adenoma > or =1 cm in size, and/or with villous histology, and/or with severe dysplasia or invasive cancer). Polyps were defined as distal if located in the descending colon, the sigmoid colon, or the rectum. Those in other locations were designated proximal. RESULTS: Neoplastic lesions, including 11 invasive cancers, were found in 617 (27.9%) patients. Advanced proximal neoplasms without any distal adenoma were present in 1.3% of patients. Of the advanced proximal lesions, 39% were not associated with any distal polyp. Older age, male gender, and distal adenoma were independent predictors of advanced proximal neoplasms. The predictive ability of a model with endoscopic data alone did not improve after inclusion of histopathologic data. In multivariate logistic regression analysis, the predictive ability of models that use age, gender, and any combination of distal findings was relatively low. The proportion of advanced proximal neoplasms identified if any distal polyp was an indication for colonoscopy was only 62%. CONCLUSIONS: A strategy in which colonoscopy is performed solely in patients with distal colonic findings is not effective screening for the detection of advanced proximal neoplasms in an average-risk populatio

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy

Capsule endoscopy interpretation: the role of physician extenders

Background and aims: capsule endoscopy (CE) allows for a new era in small-bowel examination. Nevertheless, physicians’ time for CE-interpretation remains longer than desirable. Alternative strategies to physicians have not been widely investigated. The aim of this study was to evaluate the accuracy of physician extenders in CE-interpretation. Material and methods: one CE-experienced gastroenterologist and two physician extenders reviewed independently 20 CEprocedures. Each reader was blinded to the findings of their colleagues. A consensus formed by the readers and a second CE-experienced gastroenterologist was used as gold standard. Number, type and location of images selected, character of CEexams and their relationship with indications were recorded. Gastric emptying time (GEt), small-bowel transit time (SBTt) and time spent by readers were also noted. Results: sensitivity and specificity for “overall” lesions was 79 and 99% for the gastroenterologist; 86 and 43% for the nurse; and 80 and 57% for the resident. All 34 “major” lesions considered by consensus were found by the readers. Agreement between consensus and readers for images classification and procedures interpretation was good to excellent (κ from 0.55 to 1). No significant differences were found in the GEt and SBTt obtained by consensus and readers. The gastroenterologist was faster than physician extenders (mean time spent was 51.9 ± 13.5 minutes versus 62.2 ± 19 and 60.9 ± 17.1 for nurse and resident, respectively; p < 0.05). Conclusions: physician extenders could be the perfect complement to gastroenterologists for CE-interpretation but gastroenterologists should supervise their findings. Future cost-efficacy analyses are required to assess the benefits of this alternative