Development of a novel remote-controlled and self-contained audiovisual-aided interactive system for immobilizing claustrophobic patients.

In radiotherapy, only a few immobilization systems, such as open-face mask and head mold with a bite plate, are available for claustrophobic patients with a certain degree of discomfort. The purpose of this study was to develop a remote-controlled and self-contained audiovisual (AV)-aided interactive system with the iPad mini with Retina display for intrafractional motion management in brain/H&N (head and neck) radiotherapy for claustrophobic patients. The self-contained, AV-aided interactive system utilized two tablet computers: one for AV-aided interactive guidance for the subject and the other for remote control by an operator. The tablet for audiovisual guidance traced the motion of a colored marker using the built-in front-facing camera, and the remote control tablet at the control room used infrastructure Wi-Fi networks for real-time communication with the other tablet. In the evaluation, a programmed QUASAR motion phantom was used to test the temporal and positional accuracy and resolution. Position data were also obtained from ten healthy volunteers with and without guidance to evaluate the reduction of intrafractional head motion in simulations of a claustrophobic brain or H&N case. In the phantom study, the temporal and positional resolution was 24 Hz and 0.2 mm. In the volunteer study, the average superior-inferior and right-left displacement was reduced from 1.9 mm to 0.3 mm and from 2.2 mm to 0.2 mm with AV-aided interactive guidance, respectively. The superior-inferior and right-left positional drift was reduced from 0.5 mm/min to 0.1 mm/min and from 0.4 mm/min to 0.04 mm/min with audiovisual-aided interactive guidance. This study demonstrated a reduction in intrafractional head motion using a remote-controlled and self-contained AV-aided interactive system of iPad minis with Retina display, easily obtainable and cost-effective tablet computers. This approach can potentially streamline clinical flow for claustrophobic patients without a head mask and also allows patients to practice self-motion management before radiation treatment delivery.

Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.

Drug-induced liver injury is the most common cause of market withdrawal of pharmaceuticals, and thus, there is considerable need for better prediction models for DILI early in drug discovery. We present a study involving 223 marketed drugs (51% associated with clinical hepatotoxicity; 49% non-hepatotoxic) to assess the concordance of in vitro bioactivation data with clinical hepatotoxicity and have used these data to develop a decision tree to help reduce late-stage candidate attrition. Data to assess P450 metabolism-dependent inhibition (MDI) for all common drug-metabolizing P450 enzymes were generated for 179 of these compounds, GSH adduct data generated for 190 compounds, covalent binding data obtained for 53 compounds, and clinical dose data obtained for all compounds. Individual data for all 223 compounds are presented here and interrogated to determine what level of an alert to consider termination of a compound. The analysis showed that 76% of drugs with a daily dose of <100 mg were non-hepatotoxic (p < 0.0001). Drugs with a daily dose of ≥100 mg or with GSH adduct formation, marked P450 MDI, or covalent binding ≥200 pmol eq/mg protein tended to be hepatotoxic (∼ 65% in each case). Combining dose with each bioactivation assay increased this association significantly (80-100%, p < 0.0001). These analyses were then used to develop the decision tree and the tree tested using 196 of the compounds with sufficient data (49% hepatotoxic; 51% non-hepatotoxic). The results of these outcome analyses demonstrated the utility of the tree in selectively terminating hepatotoxic compounds early; 45% of the hepatotoxic compounds evaluated using the tree were recommended for termination before candidate selection, whereas only 10% of the non-hepatotoxic compounds were recommended for termination. An independent set of 10 GSK compounds with known clinical hepatotoxicity status were also assessed using the tree, with similar results.

Comparative evaluation of adhesion formation, strength of ingrowth, and textile properties of prosthetic meshes after long-term intra-abdominal implantation in a rabbit.

BACKGROUND: Effective laparoscopic ventral herniorrhaphy usually mandates the use of an intraperitoneal prosthetic. Visceral adhesions and changes in textile characteristics of prosthetics may complicate repairs, especially long-term. The aim of this study was to compare the adhesion formation, tissue ingrowth, and textile characteristics one year after intra-abdominal placement of the commonly used prosthetic meshes. MATERIALS AND METHODS: Forty (4 x 4 cm) meshes were sutured using absorbable suture to an intact peritoneum in 20 New Zealand white rabbits. The study groups included: polypropylene (PP) [Marlex; C.R. Bard Inc, Cranston, NJ], expanded polytetrafluoroethylene (ePTFE) [DualMesh; WL Gore, Flagstaff, AZ], ePTFE and PP (ePTFE/PP) [Composix, C.R. Bard Inc], reduced weight PP and oxidized regenerated cellulose (rPP/C) [Proceed; Ethicon, Inc, Somerville, NJ]. The meshes were explanted after one year. Adhesions were scored as a percentage of explanted biomaterials' affected surface area. Prosthetic shrinkage was calculated. The strength of incorporation and mesh compliance were evaluated using differential variable reluctance transducers. Mesh ingrowth was measured as the load necessary to distract the mesh/tissue complex. Mesh compliance was calculated as the change in linear displacement of the sensors due to applied load. The groups were compared using Student's t-test and Fisher's exact test. RESULTS: ePTFE had significantly less adhesions (0%) than both ePTFE/PP (40%) and PP (80%) groups (P < 0.001). The mean area of adhesions for the rPP/C (10%) and the ePTFE/PP (14%) groups was less than that for the PP group (40%) (P = 0.02). Prosthetic shrinkage was greatest in the ePTFE (32%) group than in any other group (P = 0.001). There were no differences in mesh incorporation between the groups. At explantation, mesh compliance in the ePTFE group was superior to other meshes (P < 0.0001). The rPP/C mesh induced the smallest change in the compliance of the tissue adjacent to the mesh (P = 0.0001). CONCLUSIONS: Prosthetic materials demonstrate a wide variety of characteristics. Although exposed PP formed the most adhesions, up to 40% of the other PP-based meshes formed adhesions despite protective barriers. The ePTFE mesh did not induce adhesions and was the most compliant, however, this prosthetic's contraction was greatest. Reduced weight polypropylene (rPP/C) mesh induced the smallest change in the adjacent tissue pliability/compliance. Understanding of the long-term effects of various prosthetic materials is important to ensure an adequate hernia repair while minimizing postoperative morbidity and patient discomfort.

Meshes in hernia repair.

The search for safe and effective means of herniorrhaphies has been ongoing for more than a century. Evidence strongly supports tension-free hernia repairs in most patients, which result in a 50% reduction in a ten-year cumulative rate of hernia recurrence compared with tissue repairs. Polypropylene mesh revolutionized the field approximately 50 years ago; however, limitations of traditional polypropylene mesh have fueled the research and development of other prosthetic and biologic mesh products. Newer polyester and expanded polytetrafluoroethylene (ePTFE) products are designed to improve pliability and reduce adhesiogenic potential. Combination meshes capitalize on the ideal properties of biomaterials by strategically positioning particular mesh surfaces to selectively impede or promote tissue ingrowth. The most recent improvement in mesh products is the introduction of "lightweight" meshes. In response to mounting evidence that the traditional formulations of polypropylene meshes are over-engineered, lightweight meshes were designed with less polypropylene per surface area. Future research may prove that most meshes used currently are "mechanical overkill," which may lead to a widespread use of lightweight meshes to provide a durable repair, minimize chronic mesh-related discomfort, and improve the overall quality of life of hernia patients.

Prospective histologic evaluation of intra-abdominal prosthetics four months after implantation in a rabbit model.

BACKGROUND: Placement of an intraperitoneal prosthetic is required for laparoscopic ventral hernia repair. The biocompatibility of these prosthetics determines the host's inflammatory response, scar plate formation, tissue ingrowth, and subsequent mesh performance, including prosthetic compliance and prevention of hernia recurrence. We evaluated the host response to intraperitoneal placement of several prosthetics currently used in clinical practice. METHODS: A 4-cm x 4-cm piece of mesh was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included expanded polytetrafluoroethylene (ePTFE) (DualMesh), ePTFE and polypropylene (Composix, heavyweight polypropylene), polypropylene and oxidized regenerated cellulose (Proceed, midweight polypropylene), and polypropylene (Marlex, heavyweight polypropylene). At four months, standard hematoxylin and eosin and Milligan's trichrome stains of the mesh-tissue interaction were analyzed by three observers blinded to the mesh types. Each specimen was evaluated for scar plate formation, inflammatory response, and tissue ingrowth. Each of these three categories was graded on a standard scale of 1-4 (1 = normal tissue and 4 = severe inflammatory response). The scores were analyzed using Wilcoxon rank sum test with p < 0.05 as significant. RESULTS: Ten samples of each mesh type were evaluated. There was no difference in tissue incorporation between the groups. The mean scar plate formation was greater in the heavyweight polypropylene meshes than for DualMesh (p = 0.04). With Proceed, the reduction in scar plate formation compared with that for Composix and Marlex approached statistical significance (p = 0.07). The mean number of inflammatory cells was greater around the ePTFE when compared with the midweight polypropylene (p = 0.02) but equal to the other meshes. CONCLUSIONS: The four prosthetic materials evaluated in this study demonstrate comparable host biocompatibility as evidenced by the tissue ingrowth. Scar plate formation around DualMesh was significantly less than that around Composix and Marlex. Interestingly, more inflammatory cells were noted surrounding the DualMesh which was equal to that of the heavyweight meshes. Proceed, a midweight polypropylene mesh, has the potential for improved patient tolerance compared to heavyweight polypropylene meshes based on its favorable histologic findings.

Retained foreign bodies after surgery.

BACKGROUND: Medical errors during surgery are not well studied. To define risk factors associated with this type of error, we performed a case control analysis. METHODS: We retrospectively reviewed medical records involving the ICD-9 code (998.4) for unintentional foreign object remaining in the body during surgery and incident reports gathered by the Department of Risk Management over a 10 year period from 1996 to 2005. Thirty cases were matched with at least four randomly selected controls (131 control patients) that underwent the same type of operation during the same time period. RESULTS: Thirty patients had retained foreign objects (52% sponges and 43% instruments). The abdominal cavity was most commonly involved (46%) followed by the thoracic cavity (23%) although no body cavity remained uninvolved. Eight patients required readmission (30%), 25 patients required reoperation (83%), and there was no mortality. When compared with controls, patients with retained foreign objects were more likely to have had a greater number of major surgical procedures at the same time (2.7 versus 1.8, P=0.004), to have multiple surgical teams (13% versus 2%, P=0.02), and more likely to have had an incorrect instrument/sponge count recorded (13% versus 2%, P=0.01). In multivariate analysis, factors associated with a significantly higher risk of retained foreign objects were the total number of major procedures performed [odds ratio 1.6; 95% confidence interval (CI), 1.1-2.3; P=0.008] and an incorrect count (odds ratio 16.2; 95% CI, 1.3-197.8; P=0.02). CONCLUSION: Retained foreign objects after surgery are associated with multiple major surgical procedures being performed at the same time and an incorrect instrument or sponge count. Identification of these risk factors using case-control analysis should influence operating room policy and reduce these types of errors.

Outcomes of adrenal cortical carcinoma in the United States.

BACKGROUND: Improvements in the sensitivity of radiographic imaging have lead to an increase in the number of adrenal masses diagnosed. The purpose of this study is to determine if technologic advancements have resulted in the diagnosis of earlier-staged adrenal cortical cancer (ACC) and to determine if the survival of patients with ACC has improved over the past 15 years. METHODS: Patients with ACC were identified in the Surveillance, Epidemiology, and End Results database between 1988 and 2002. Changes in demographics, stage, size, and treatment were analyzed by standard statistical testing. RESULTS: We identified 602 patients with a mean age of 53 years and an average tumor size of 11.8 cm. Two hundred thirty-eight (39.5%) patients presented with localized disease (stages I and II), and 311 (52%) patients presented with advanced disease (stages III and IV). The comparison of smaller lesions and number of patients were 5 to 6 cm in 24 (4%) patients, 4 to 5 cm in 27 (4.5%) patients, and <4 cm in 19 (3.1%) patients. Patients with masses less than 5 cm were statistically more likely to have localized disease (P <. 001). Age (P = .10), tumor size (P = .85), tumor stage (P = .45), and 5-year survival (P = .5) did not change over the 15-year study. CONCLUSIONS: Over the 15-year study, patients with ACC were not diagnosed at an earlier stage or with tumors smaller, and survival did not improve.

Laparoscopic expertise increases hospital volume of adrenal surgery.

The laparoscopic approach is preferred for most adrenal tumors but technical challenges limit its use. We evaluated the effects of the availability of laparoscopic expertise on the volume of the adrenal surgery at a tertiary care hospital. Patients undergoing adrenalectomy 5 years before and 5 years after an advanced laparoscopic program was established were retrospectively reviewed. The average annual volume increased from 2 cases during the first period to 15 cases during the 5 years (1999-2003) after laparoscopic expertise became available. The average distance of travel to the hospital was significantly greater for the latter patients and significantly more patients were referred from outside of a 30-mile radius. Although the average statewide annual number of adrenalectomies has not significantly changed, the proportion of adrenalectomies performed at our institution rose. Offering a laparoscopic approach has altered physicians' referral patterns and has significantly increased the volume of adrenal surgery at the institution.

Prospective evaluation of adhesion formation and shrinkage of intra-abdominal prosthetics in a rabbit model.

Laparoscopic ventral hernia repair requires an intraperitoneal prosthetic; however, these materials are not without consequences. We evaluated host reaction to intraperitoneal placement of various prosthetics and the functional outcomes in an animal model. Mesh (n = 15 per mesh type) was implanted on intact peritoneum in New Zealand white rabbits. The mesh types included ePTFE (DualMesh), ePTFE and polypropylene (Composix), polypropylene and oxidized regenerated cellulose (Proceed), and polypropylene (Marlex). Adhesion formation was evaluated at 1, 4, 8, and 16 weeks using 2-mm mini-laparoscopy. Adhesion area, adhesion tenacity, prosthetic shrinkage, and compliance were evaluated after mesh explantation at 16 weeks. DualMesh had significantly less adhesions than Proceed, Composix, or Marlex at 1, 4, 8, and 16 weeks (P < 0.0001). Marlex had significantly more adhesions than other meshes at each time point (P < 0.0001). There were no statistically significant differences in adhesions between Proceed and Composix meshes. After mesh explantation, the mean area of adhesions for Proceed (4.6%) was less than for Marlex (21.7%; P = 0.001). The adhesions to Marlex were statistically more tenacious than the DualMesh and Composix groups. Overall prosthetic shrinkage was statistically greater for DualMesh (34.7%) than for the remaining mesh types (P < 0.01). Mesh compliance was similar between the groups. Prosthetic materials demonstrate a wide variety of characteristics when placed inside the abdomen. Marlex formed more adhesions with greater tenacity than the other mesh types. DualMesh resulted in minimal adhesions, but it shrank more than the other mesh types. Each prosthetic generates a varied host reaction. Better understanding of these reactions can allow a suitable prosthetic to be chosen for a given patient in clinical practice.

Advantages of laparoscopic appendectomy in the elderly.

Laparoscopic appendectomy (LA) has gained in popularity in recent years. The number of elderly patients undergoing appendectomy has increased as that segment of the population has increased in number; however, the utility and benefits of LA in the elderly population are not well established. We hypothesized that LA in the elderly has distinctive advantages in perioperative outcomes over open appendectomy (OA). We queried the 1997 to 2003 North Carolina Hospital Association Patient Data System for all patients with the primary ICD-9 procedure code for OA and LA. Patients > or = 65 years of age (elderly) were identified and reviewed. Outcomes including length of stay (LOS), charges, complications, discharge location, and mortality were compared between the groups. There were 29,244 appendectomies performed in adult patients (>18 years old) with 2,722 of these in the elderly. The annual percentage of LA performed in the elderly increased from 1997 to 2003 (11.9-26.9%, P < 0.0001). When compared with OA, elderly patients undergoing LA had a shorter LOS (4.6 vs 7.3 days, P = 0.0001), a higher rate of discharge to home (91.4 vs 78.9%, P = 0.0001) as opposed to a step-down facility, fewer complications (13.0 vs 22.4%, P = 0.0001), and a lower mortality rate (0.4 vs 2.1%, P = 0.007). When LA was compared with OA in elderly patients with perforated appendicitis, LA resulted in a shorter LOS (6.8 vs 9.0 days, P = 0.0001), a higher rate of discharge to home (86.6 vs 70.9%, P = 0.0001), but equivalent total charges (dollars 22,334 vs dollars 23,855, P = 0.93) and mortality (1.0 vs 2.98%, P = 0.10). When elderly patients that underwent LA were compared with adult patients (18-64 years old), they had higher total charges (dollars 16,670 vs dollars 11,160, P = 0.0001) but equivalent mortality (0.37 vs 0.15%, P = 0.20). The use of laparoscopy in the elderly has significantly increased in recent years. In general, the safety and efficacy of LA is demonstrated by a reduction in mortality, complications, and LOS when compared with OA. The laparoscopic approach to the perforated appendix in the elderly patient has advantages over OA in terms of decreased LOS and a higher rate of discharge to home as opposed to rehabilitation centers, nursing homes, or skilled nursing care. When compared with all younger adults, the laparoscopic approach in the elderly was associated with equal mortality rates even though hospitalization charges were higher. Laparoscopy may be the preferred approach in elderly patients who require appendectomy.

Evaluation of the efficacy of the electrosurgical bipolar vessel sealer (LigaSure) devices in sealing lymphatic vessels.

Various sources of ultrasonic and thermal energy have been developed to facilitate blood vessel ligation. However, their efficacy in sealing lymphatics has not been clearly established to date. We hypothesized that the electrosurgical bipolar vessel sealer (EBVS) produces reliable and durable sealing of large lymphatic vessels in a porcine model. Thoracic ducts from 4 adult pigs were explanted and sealed at multiple levels by using 3 different EBVS devices: LigaSure Atlas, XTD, and V. Fifteen seals (5 per group) were analyzed for sealing time and visual quality. Seal burst strength was measured by using a graduated pressure saline injection system. Twelve intact seals also underwent a histologic analysis. The mean overall burst strength of the seals was 271+/-78 mm Hg (127 to 360 mm Hg). The burst pressures in the 3 groups were not statistically different. The overall mean time to achieve a seal was 5.1+/-2.2 seconds (3 to 10 seconds). Seals were achieved significantly faster in the V group (4.1+/-0.6 seconds) compared with the Atlas (6.3+/-2.3 seconds) and XTD (6.4+/-2.6 seconds) groups. Qualitative seal assessment revealed minimal sticking and charring, a favorable degree of seal tissue clarity, and desiccation in the 3 groups. Histologic analysis demonstrated a fusion of lymphovascular channels with a complete obliteration of the lumens. We demonstrated that the use of EBVS results in a fast and effective sealing of large porcine lymphatic vessels. The seals created by all 3 devices burst at markedly supraphysiologic intraluminal pressures. Ongoing randomized human trials may prove the clinical benefits of the routine use of EBVS devices for various tissue dissections.

Minimally invasive abdominal surgery: lux et veritas past, present, and future.

BACKGROUND: Laparoscopic surgery has developed out of multiple technology innovations and the desire to see beyond the confines of the human body. As the instrumentation became more advanced, the application of this technique followed. By revisiting the historical developments that now define laparoscopic surgery, we can possibly foresee its future. DATA SOURCES: A Medline search was performed of all the English-language literature. Further references were obtained through cross-referencing the bibliography cited in each work and using books from the authors' collection. CONCLUSION: Minimally invasive surgery is becoming important in almost every facet of abdominal surgery. Optical improvements, miniaturization, and robotic technology continue to define the frontier of minimally invasive surgery. Endoluminal resection surgery, image-guided surgical navigation, and remotely controlled robotics are not far from becoming reality. These and advances yet to be described will change laparoscopic surgery just as the electric light bulb did over 100 years ago.

Energy sources in laparoscopy.

Traditional monopolar and bipolar electrosurgery remain very useful in laparoscopic surgery. The need for meticulous hemostasis and the tedium of vessel ligation in advanced cases has propelled the development of new energy source devices that have proved to be remarkably helpful in both laparoscopic and open surgery. Energy sources in the form of argon beam coagulation, ultrasonic coagulation, and bipolar vessel sealing systems have revolutionized laparoscopic surgery. Although each of these energy sources has improved the efficiency and safety of minimally invasive techniques, they can also be associated with distressing complications. This report describes the biophysics of these tools, their spectrum of effectiveness, and methods of application that may improve our ability to perform surgery in a safe and proficient manner.