Targeting in silico GPCR conformations with ultra-large library screening for hit discovery.

The use of deep machine learning (ML) in protein structure prediction has made it possible to easily access a large number of annotated conformations that can potentially compensate for missing experimental structures in structure-based drug discovery (SBDD). However, it is still unclear whether the accuracy of these predicted conformations is sufficient for screening chemical compounds that will effectively interact with a protein target for pharmacological purposes. In this opinion article, we examine the potential benefits and limitations of using state-annotated conformations for ultra-large library screening (ULLS) in light of the growing size of ultra-large libraries (ULLs). We believe that targeting different conformational states of common drug targets like G-protein-coupled receptors (GPCRs), which can regulate human physiology by switching between different conformations, can offer multiple advantages.

Regurgitation on pressure over the lacrimal sac versus lacrimal irrigation in determining lacrimal obstruction prior to intraocular surgeries.

Purpose: : To determine the diagnostic accuracy of manual regurgitation on pressure over the lacrimal sac (ROPLAS) versus lacrimal irrigation for screening nasolacrimal duct obstruction (NLDO) in adults prior to intraocular surgeries. Methods: This cross-sectional study took place in a tertiary eye care hospital in South Tamil Nadu, India. From January to December 2017 and included consecutive patients who presented for routine cataract surgery. Prospective data collection occurred in 8369 eyes of patients who underwent cataract surgery. All patients underwent ROPLAS testing by an ophthalmologist followed by lacrimal irrigation by trained ophthalmic assistants, rechecked or confirmed in equivocal cases by ophthalmologists who were masked to the ROPLAS status. The primary outcome, the sensitivity, specificity, positive, and negative predictive values to detect lacrimal occlusion by ROPLAS compared with lacrimal irrigation with 95% confidence intervals was estimated. Results: : A total of 8369 eyes underwent cataract surgery during the time periods of the study. ROPLAS and lacrimal irrigation were performed in all eyes. The sensitivity of ROPLAS to diagnose NLDO correctly was 54.5% (95% CI, 44.8%-63.9%) and its specificity was 100% (95% CI, 100%-100%). The positive and negative predictive values were 75.3% (95% CI, 65.6%-83.0%) and 99.4% (95% CI, 99.2%-99.5%), respectively. Conclusion: : We found that ROPLAS when used alone had very low sensitivity and low positive predictive value in detecting NLDO prior to cataract surgery as compared with lacrimal irrigation. Hence, we recommend performing ROPLAS and lacrimal irrigation in every patient as part of the routine preoperative workup prior to cataract surgery.

Missing lateral relationships in top-level concepts of an ontology.

BACKGROUND: Ontologies house various kinds of domain knowledge in formal structures, primarily in the form of concepts and the associative relationships between them. Ontologies have become integral components of many health information processing environments. Hence, quality assurance of the conceptual content of any ontology is critical. Relationships are foundational to the definition of concepts. Missing relationship errors (i.e., unintended omissions of important definitional relationships) can have a deleterious effect on the quality of an ontology. An abstraction network is a structure that overlays an ontology and provides an alternate, summarization view of its contents. One kind of abstraction network is called an area taxonomy, and a variation of it is called a subtaxonomy. A methodology based on these taxonomies for more readily finding missing relationship errors is explored. METHODS: The area taxonomy and the subtaxonomy are deployed to help reveal concepts that have a high likelihood of exhibiting missing relationship errors. A specific top-level grouping unit found within the area taxonomy and subtaxonomy, when deemed to be anomalous, is used as an indicator that missing relationship errors are likely to be found among certain concepts. Two hypotheses pertaining to the effectiveness of our Quality Assurance approach are studied. RESULTS: Our Quality Assurance methodology was applied to the Biological Process hierarchy of the National Cancer Institute thesaurus (NCIt) and SNOMED CT's Eye/vision finding subhierarchy within its Clinical finding hierarchy. Many missing relationship errors were discovered and confirmed in our analysis. For both test-bed hierarchies, our Quality Assurance methodology yielded a statistically significantly higher number of concepts with missing relationship errors in comparison to a control sample of concepts. Two hypotheses are confirmed by these findings. CONCLUSIONS: Quality assurance is a critical part of an ontology's lifecycle, and automated or semi-automated tools for supporting this process are invaluable. We introduced a Quality Assurance methodology targeted at missing relationship errors. Its successful application to the NCIt's Biological Process hierarchy and SNOMED CT's Eye/vision finding subhierarchy indicates that it can be a useful addition to the arsenal of tools available to ontology maintenance personnel.

Effects of serotonin depletion and dopamine depletion on bimodal divided attention.

Objectives: This study aimed to explore the effects of acute phenylalanine tyrosine depletion (APTD) and acute tryptophan depletion (ATD) on bimodal divided attention. A balanced amino acid mixture (BAL) served as control condition.Methods: Fifty-three healthy adults (final analyzed sample was N = 49, age: M = 23.8 years) were randomly assigned to APTD, ATD or BAL in a double-blind, between-subject approach. Divided attention was assessed after 4 h. Blood samples were taken before and 6 h after challenge intake.Results: Amino acid concentrations following challenge intake significantly decreased (all P ≤ 0.01). There was a significant difference in the mean reaction time (RT) towards auditory stimuli, but not towards visual stimuli between the groups. Post-hoc comparison of mean RTs (auditory stimuli) showed a significant difference between ATD (RT = 604.0 ms, SD = 56.9 ms) and APTD (RT = 556.4 ms, SD = 54.2 ms; P = 0.037), but no RT difference between ATD and BAL or APTD and BAL (RT = 573.6 ms, SD = 45.7 ms).Conclusions: The results indicate a possible dissociation between the effects of a diminished brain 5-HT and DA synthesis on the performance in a bimodal divided attention task. The difference was exclusively observed within the RT towards auditory signals.

Timely implementation of a retinopathy of prematurity telemedicine system.

PURPOSE: To examine the feasibility of a retinopathy of prematurity (ROP) telemedicine evaluation system of providing timely feedback to a neonatal intensive care unit (NICU) with at-risk premature infants. METHODS: This was a prospective observational study of premature infants with birth weights of <1251 g in five NICUs in the United States. Infants scheduled for clinically indicated ROP evaluations underwent indirect ophthalmoscopic examinations and digital imaging on the same day. Imaging was performed by nonphysician retinal imagers. Times required were determined from obtaining digital images of both eyes to submission via web-based system to a secure server for grading by trained readers at a central reading center to sending back grading results to the clinical center. RESULTS: A total of 1,642 image sets of eyes of 292 infants were obtained, from 823 imaging sessions. The mean turnaround time from submission of image sets of both eyes to return of the grading results to the clinical center was 10.1 ± 11.3 hours (standard deviation), with a median of 12.0 hours (1st quartile, 0.9 hours; 3rd quartile, 16 hours). Overall, 95.5% of gradings (95% CI, 93.9%-96.7%) were returned within 24 hours. Subgroup analyses found, for image sets submitted to the reading center before 2 p.m. Eastern Standard Time, median time to report was 1.7 hours (1st quartile, 0.7 hours; 3rd quartile, 15.5 hours) compared with those submitted after 2pm (median, 14.1 hours; 1st quartile, 11.2, hours; 3rd quartile, 16.3 hours). CONCLUSIONS: An ROP telemedicine approach can provide timely feedback to the NICU regarding the detection of potentially serious ROP and thus referral to an ophthalmologist for examination and consideration of treatment.

Analysis of Discrepancy Between Diagnostic Clinical Examination Findings and Corresponding Evaluation of Digital Images in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study.

IMPORTANCE: As effective treatments for potentially blinding retinopathy of prematurity (ROP) have been introduced, the importance of consistency in findings has increased, especially with the shift toward retinal imaging in infants at risk of ROP. OBJECTIVE: To characterize discrepancies in findings of ROP between digital retinal image grading and examination results from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity study, conducted from May 2011 to October 2013. DESIGN, SETTING, AND PARTICIPANTS: A poststudy consensus review of images was conducted by 4 experts, who examined discrepancies in findings between image grades by trained nonphysician readers and physician examination results in infants with referral-warranted ROP (RW-ROP). Images were obtained from 13 North American neonatal intensive care units from eyes of infants with birth weights less than 1251 g. For discrepancy categories with more than 100 cases, 40 were randomly selected; in total, 188 image sets were reviewed. MAIN OUTCOMES AND MEASURES: Consensus evaluation of discrepant image and examination findings for RW-ROP components. RESULTS: Among 5350 image set pairs, there were 161 instances in which image grading did not detect RW-ROP noted on clinical examination (G-/E+) and 854 instances in which grading noted RW-ROP when the examination did not (G+/E-). Among the sample of G-/E+ cases, 18 of 32 reviews (56.3%) agreed with clinical examination findings that ROP was present in zone I and 18 of 40 (45.0%) agreed stage 3 ROP was present, but only 1 of 20 (5.0%) agreed plus disease was present. Among the sample of G+/E- cases, 36 of 40 reviews (90.0%) agreed with readers that zone I ROP was present, 23 of 40 (57.5%) agreed with readers that stage 3 ROP was present, and 4 of 16 (25.0%) agreed that plus disease was present. Based on the consensus review results of the sampled cases, we estimated that review would agree with clinical examination findings in 46.5% of the 161 G-/E+ cases (95% CI, 41.6-51.6) and agree with trained reader grading in 70.0% of the 854 G+/E- cases (95% CI, 67.3-72.8) for the presence of RW-ROP. CONCLUSIONS AND RELEVANCE: This report highlights limitations and strengths of both the remote evaluation of fundus images and bedside clinical examination of infants at risk for ROP. These findings highlight the need for standardized approaches as ROP telemedicine becomes more widespread.

Validated System for Centralized Grading of Retinopathy of Prematurity: Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

IMPORTANCE: Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described. OBJECTIVE: To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study. DESIGN, SETTING, AND PARTICIPANTS: Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director. EXPOSURE: Digital retinal images. MAIN OUTCOMES AND MEASURES: Intragrader and intergrader variability and monitoring for temporal drift. RESULTS: Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5% requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9% for plus disease, 12.4% for zone I ROP, and 16.9% for stage 3 or worse ROP. The weighted κ for intergrader agreement (n = 80 image sets) was 0.72 (95% CI, 0.52-0.93) for RW-ROP, 0.57 (95% CI, 0.37-0.77) for plus disease, 0.43 (95% CI, 0.24-0.63) for zone I ROP, and 0.67 (95% CI, 0.47-0.88) for stage 3 or worse ROP. The weighted κ for grade-regrade agreement was 0.77 (95% CI, 0.57-0.97) for RW-ROP, 0.87 (95% CI, 0.67-1.00) for plus disease, 0.70 (95% CI, 0.51-0.90) for zone I ROP, and 0.77 (95% CI, 0.57-0.97) for stage 3 or worse ROP. CONCLUSIONS AND RELEVANCE: These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.

Validity of a telemedicine system for the evaluation of acute-phase retinopathy of prematurity.

IMPORTANCE: The present strategy to identify infants needing treatment for retinopathy of prematurity (ROP) requires repeated examinations of at-risk infants by physicians. However, less than 10% ultimately require treatment. Retinal imaging by nonphysicians with remote image interpretation by nonphysicians may provide a more efficient strategy. OBJECTIVE: To evaluate the validity of a telemedicine system to identify infants who have sufficiently severe ROP to require evaluation by an ophthalmologist. DESIGN, SETTING, AND PARTICIPANTS: An observational study of premature infants starting at 32 weeks' postmenstrual age was conducted. This study involved 1257 infants with birth weight less than 1251 g in neonatal intensive care units in 13 North American centers enrolled from May 25, 2011, through October 31, 2013. INTERVENTIONS: Infants underwent regularly scheduled diagnostic examinations by an ophthalmologist and digital imaging by nonphysician staff using a wide-field digital camera. Ophthalmologists documented findings consistent with referral-warranted (RW) ROP (ie, zone I ROP, stage 3 ROP or worse, or plus disease). A standard 6-image set per eye was sent to a central server and graded by 2 trained, masked, nonphysician readers. A reading supervisor adjudicated disagreements. MAIN OUTCOMES AND MEASURES: The validity of grading retinal image sets was based on the sensitivity and specificity for detecting RW-ROP compared with the criterion standard diagnostic examination. RESULTS: A total of 1257 infants (mean birth weight, 864 g; mean gestational age, 27 weeks) underwent a median of 3 sessions of examinations and imaging. Diagnostic examination identified characteristics of RW-ROP in 18.2% of eyes (19.4% of infants). Remote grading of images of an eye at a single session had sensitivity of 81.9% (95% CI, 77.4-85.6) and specificity of 90.1% (95% CI, 87.9-91.8). When both eyes were considered for the presence of RW-ROP, as would routinely be done in a screening, the sensitivity was 90.0% (95% CI, 85.4-93.5), with specificity of 87.0% (95% CI, 84.0-89.5), negative predictive value of 97.3%, and positive predictive value of 62.5% at the observed RW-ROP rate of 19.4%. CONCLUSIONS AND RELEVANCE: When compared with the criterion standard diagnostic examination, these results provide strong support for the validity of remote evaluation by trained nonphysician readers of digital retinal images taken by trained nonphysician imagers from infants at risk for RW-ROP. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01264276.

Blurry vision after orbital decompression surgery.

Pathologic myopia may be associated with abnormal vitreomacular adhesions that can portend a higher risk of retinal detachment. The authors report a case of rhegmatogenous retinal detachment with a complex macular tear after orbital decompression surgery in a patient with pathologic myopia. This case highlights the importance of retinal detachment in the setting of orbital decompression.

Changed trends of major causes of visual impairment in Sichuan, China from 1987 to 2006.

AIM: To study the trends of major causes of visual impairment (VI) in adults in Sichuan, China and evaluate the effect of aging on the trends. METHODS: We used data from the National Sample Survey on Disabilities (NSSD) in Sichuan province conducted in 1987 and 2006. The age-adjusted prevalence of major causes of VI and the prevalence stratified by age in each cause were calculated and compared. The association between age and each cause of VI was also analyzed. RESULTS: Retinal disease increased and became the second leading cause of VI in 2006 while blinding trachoma decreased markedly. Cataract and non-trachomatous corneal diseases were among the leading causes of VI in both years. We found associations between age and causes of VI, with age showing the strongest association with cataract and relatively lower associations with other causes. CONCLUSION: In the last two decades, dramatic changes occurred in the major causes of VI with significantly increased retinal disease and decreased blinding trachoma. Aging of the population might be an important factor accounting for the changed trends of VI. Understanding the prevalence of VI, its major causes and trends over time can assist in prioritizing and developing effective interventional strategies and monitoring their impact.

Posterior to the ridge laser treatment for severe stage 3 retinopathy of prematurity.

BACKGROUND: Current methods of treating the avascular retina with laser photocoagulation for severe retinopathy of prematurity (ROP) are not completely effective in the reduction of visual morbidity. We report a case series in which additional laser treatment, called 'posterior laser', was delivered posterior to the neovascular ridge, for eyes with severe stage 3 ROP in zone II with avascular retina posterior to the ridge. DESIGN: Retrospective chart review. PARTICIPANTS: Infants who underwent laser treatment, posterior to the neovascular ridge for severe ROP at the Alberta Children's Hospital, between January 2005 and October 2008. METHODS: Charts were reviewed for 18 eyes of 11 patients and collected information included demographic data, clinical examination results, and digital retinal images. MAIN OUTCOME MEASURES: Structural and functional outcomes of treatment. RESULTS: Four (22%) of 18 eyes received 'posterior laser' as primary treatment and the remainder of eyes (78%) received 'posterior laser' following previous laser photocoagulation anterior to the neovascular ridge. Mean birthweight was 688 g (552-930) and mean gestational age was 24 weeks (23-28). There were no complications because of the posterior laser treatment. In all, 16 of 18 eyes experienced rapid regression of the ridge and subsequent decrease in vascular dilation and tortuosity within 1 week. Two eyes required vitrectomy for 4A retinal detachment; however, no eyes developed stage 4B ROP. CONCLUSION: Posterior to the ridge laser in the setting of the morphological criteria described had no increased safety concerns and resulted in rapid regression of ROP with good outcomes.

Obstructive defecation syndrome: 19 years of experience with laparoscopic resection rectopexy.

BACKGROUND: In obstructive defecation syndrome (ODS) combinations of morphologic alterations of the pelvic floor and the colorectum are nearly always evident. Laparoscopic resection rectopexy (LRR) aims at restoring physiological function. We present the results of 19 years of experience with this procedure in patients with ODS. METHODS: Between 1993 and 2012, 264 patients underwent LRR for ODS at our department. Perioperative and follow-up data were analyzed. RESULTS: The female/male ratio was 25.4:1, mean age was 61.3 years (±14.3 years), and mean body mass index (BMI) was 25.2 kg/m(2) (±4.2 kg/m(2)). The pathological conditions most frequently found in combination were a sigmoidocele plus a rectocele (n = 79) and a sigmoidocele plus a rectal prolapse or intussusception (n = 69). The conversion rate was 2.3 % (n = 6). The mortality rate was 0.75 % (n = 2), the rate of complications requiring surgical re-intervention was 4.3 % (n = 11), and the rate of minor complications was 19.8 % (n = 51). Follow-up data were available for 161 patients with a mean follow-up of 58.2 months (±47.1 months). Long-term results showed that 79.5 % of patients (n = 128) reported at least an improvement of symptoms. In cases of a sigmoidocele (n = 63 available for follow-up) or a rectal prolapse II°/III° (n = 72 available for follow-up), the improvement rates were 79.4 % (n = 50) and 81.9 % (n = 59), respectively. CONCLUSIONS: LRR is a safe and effective procedure. Our perioperative results and long-term functional outcome strengthen the evidence regarding benefits of LRR in patients with an outlet obstruction. However, careful patient selection is essential.

[Open surgical versus laparoscopic treatment of iatrogenic colon perforation - results of a 13-year experience]. / Offen chirurgische versus laparoskopische Versorgung der iatrogenen Kolonperforation - Ergebnisse nach 13 Jahren Erfahrungen.

BACKGROUND: Iatrogenic colon perforation is a rare but life-threatening complication of colonscopy. As in other diseases, laparoscopic treatment has increasingly been propagated for the treatment of colonic disorders in the last years. The aim of this comparative study was to answer the question of whether laparoscopic surgical treatment may serve as a suitable treatment for the acute colon perforation comparable to open surgery. PATIENTS AND METHODS: The data of all patients who underwent surgery for iatrogenic colon perforation within a 13-year time period (1997-2009) were recorded prospectively and analysed retrospectively with regard to different perioperative parameters. In the following analysis the laparoscopically and open surgically treated patients were compared. RESULTS: In the observation period 24 patients with iatrogenic colon perforation were treated laparoscopically and 12 patients with open surgery. There were no significant differences concerning age in both groups. In both groups resection of the affected region was preferred [open surgically: 58 % (n = 7), laparoscopically: 80 % (n = 19)]. The median operation time was 105 min (range: 35 - 180) for the open surgically treated patients and 165 min (90 - 420) for laparoscopic procedures (p = 0.006). In 4 cases of the laparoscopic group a conversion via laparotomy was -necessary. There was no significant difference concerning the hospital stay between both groups with 14.5 days (7-40) for the open surgical and 11 days (7-25) for the laparoscopic group. Concerning the postoperative morbidity a significantly higher incidence could be seen in the open surgical group (p < 0.0001). CONCLUSION: An iatrogenic colon perforation mostly leeds to the immediate indication for a surgical treatment. The morbidity and mortality is -primarily determined through the appearance of postoperative complications due to delays in diagnostics and treatment. In this study the feasibility of a laparoscopic treatment could be shown. The laparoscopy with its minimal access trauma offers an enlargement of the diagnostics as well as a safe treatment of the perforation in most patients. However, the laparoscopic treatment especially in emergancy situations requires -advanced experience of the surgeon and always needs a critical benefit-risk consideration in the individual situation.

[Laparoscopic resection rectopexy as treatment for obstructive defecation syndrome]. / Die laparoskopische Resektionsrektopexie zur Therapie des obstruktiven Defäkationssyndroms.

Anorectal outlet obstruction constitutes one form of chronic constipation. Combinations of morphological alterations of the pelvis, the pelvic floor and the colorectum are nearly always evident. The goal of the diagnostic work-up is to identify those patients who will profit from a surgical intervention. Resection rectopexy aims at restoring the physiological anatomy thereby ameliorating the functional interaction of structures effected with the laparoscopic approach entailing all advantages of minimally invasive surgery. Besides a detailed description of the surgical technique used and an algorithm for indications to operate we present our results after 19 years of experience. Throughout this period, 264 laparoscopic resection rectopexies for outlet obstruction were performed. With a mean follow-up of 58.2 months the rate of improvement of obstructive symptoms was 79.5 % (n = 128 of 161 available for follow-up). Present studies suggest that (laparoscopic) resection rectopexy entails better results in comparison to non-resecting procedures and procedures with the implantation of allogenic material. Certainly, in order to achieve these results a correct patient selection and an expertise in laparoscopic surgery are essential. Both the perioperative and the functional results of our own collective fortify the advantages of laparoscopic resection rectopexy in patients with an outlet obstruction.

[Surgical treatment and prognosis of rectovaginal fistulae according to their origin]. / Chirurgische Versorgung und Prognose rektovaginaler Fisteln in Abhängigkeit ihrer Genese.

INTRODUCTION: The rectovaginal fistula is a rare entity with heterogenic causality. Its genesis seems to predict the extent of operative treatment and the prognostic outcome. The aim of this study was to present different surgical techniques in the treatment of rectovaginal fistulas and their results in correspondence to the genesis. MATERIAL AND METHODS: Between 1 / 2000 and 1 / 2010, the data of patients with rectovaginal fistulas were collected. The retrospective analysis included biographic and anamnestic data as well as clinical parameters, general and specific complications and postoperative data. RESULTS: In a timespan of ten years 36 patients with rectovaginal fistulas were treated. The most common causes were inflammatory diseases (n = 21) and earlier surgical measures (n = 6). Moreover tumour-associated fistulas (n = 5) and fistulas with unknown genesis (n = 4) were seen. As surgical techniques anterior resection (n = 21), transrectal flap plasty (n = 7), subtotal colectomy (n = 3), pelvine exenteration (n = 2) and rectal exstirpation (n = 1) were used. The closure of the vaginal lesion was performed by single suture (n = 25), flap plasty (n = 6), transvaginal omental plasty (n = 2) and posterior vaginal plasty (n = 1). All patients were provided with an omental plasty to perform a safe division of the concerned regions. Patients with a low fistula ( < 6 cm) were treated with transperineal omental plasty. The median follow-up was 12 months (6 - 36). Within this timespan 6 patients suffered from major complications [ARDS, anastomosis insufficiency, postoperative bleeding, recurrence of fistula (n = 3)]. Three patients died in the postoperative period (cerebellar infarct, septic complication associated with Crohn's disease, multiorgan failure in tumour recurrence). CONCLUSION: The genesis of rectovaginal fistulae is an important predictor for the size of resection which can range from simple excision to exenteration. For optimal therapy the surgical intervention needs to be integrated into an interdisciplinary therapy concept.

Transperineal omentum flap for the anatomic reconstruction of the rectovaginal space in the therapy of rectovaginal fistulas.

AIM: Deep rectovaginal fistulas are a rare entity and pose a delicate challenge for the surgeon. The present study introduces different operative interventions involved in transperineal omental flap surgery. METHOD: A retrospective analysis of all patients treated with a low or mid rectovaginal or enterovaginal fistula at the Department of Surgery of the University Hospital of Schleswig-Holstein, Campus Luebeck, was performed. Treatment results were discussed with respect to aetiology, localization, morbidity and outcome. RESULTS: Between the years 2000 and 2010, a total of nine patients with a low or mid rectovaginal fistula were treated at our clinic. After local fistulectomy, all patients were additionally treated by a laparoscopically assisted omental flap reconstruction of the rectovaginal and perineal space. Eight of the nine patients received a protective ileostomy or colostomy. Only the patient with a history of Crohn's disease had no ileostomy raised. At a median follow-up of 22 months, no patient experienced recurrence of a rectovaginal fistula. Perioperative mortality was zero and minor complications were observed in 22%. Major complications were an anastomotic insufficiency after low anterior resection that was treated without further interventions. Another complication was a persistent fistula within the sphincter that needed re-operation and bovine plug repair combined with a mucosa flap. CONCLUSIONS: Complete omental reconstruction of the rectovaginal space appears decisive in the operative therapy of deep rectovaginal or enterovaginal fistulas. Comparative studies on standard therapies are necessary although direct comparison of case series is difficult.

Simultaneous laparoscopic pyloroplasty and ileocecal resection in Crohn's disease.

BACKGROUND: The initial manifestation of Crohn's disease is often located within the terminal ileum. Other portions of the G.I. tract may be affected, however, as the disease involves the entire organ system. The disease often progresses chronically in flares and remissions and involves all layers of the intestinal wall, leading to strictures, stenosis and fistulas. These complications should only be treated surgically when clinically relevant in order to prevent acute exacerbations. METHODS: Laparoscopic surgery offers one the possibility to minimize surgical trauma with its very small incisions and proper dissection through the correct anatomical layers with 10-fold optic magnification. RESULTS: Multifocal procedures can be carried out in the same operation. We present the case of a 26-year-old female with terminal ileum stenosis and gastric outlet obstruction, who underwent simultaneous laparoscopic pyloroplasty and ileocecal resection. DISCUSSION: Providing the surgeon possesses the necessary expertise, complex laparoscopic simultaneous procedures.

[A comparison of the use of electrochemical treatment and radio frequency ablation in porcine liver]. / Intrahepatische Ablation: Radiofrequenzablation versus Elektrochemische Lyse.

BACKGROUND: Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are competing methods of intrahepatic ablation. We compared RFA and ECT in a perfusion model and in vivo in pigs. MATERIAL AND METHODS: Twenty-seven fresh porcine livers were obtained from a slaughterhouse and placed ex vivo into a perfusion model. RFA or ECT electrodes were inserted under ultrasound guidance in perivascular locations at a distance of 10 mm from a portal vessel. A total of 83 areas of ablation were created. In vivo ablations were performed at perivascular sites in 10 laparotomised pigs. Four areas of ablation were created per liver using RFA or ECL. Inflammatory parameters, liver values and cytokine levels were determined before and after surgery and on days 1, 3 and 7 after surgery. On day 7, the livers were harvested and specimens were analysed histo-logically by independent experts. RESULTS: In 29% of 59 ex vivo RFA ablations, the target temperature was not reached and the procedure was discontinued. Intact hepatocytes were detected in close proximity to 70 % of the vessels within necrotic areas. In 24 ECT applications, treatment time depended on the charge delivered and ranged between 50 min at 150 coulombs (C) and 200 min at 600 C. The pH level was 0.9 at the anode and 12.2 at the cathode. ECT always led to complete perivascular necrosis and vessel wall destruction. The animals had an in vivo -median weight of 39.5 kg. Neither RFA nor ECT caused major complications such as bleeding, bile leaks or abscesses. Treatment time was 67 min (200 C) for ECT and 12.4 min for RFA. In 73% of the cases, RFA led to incomplete perivascular areas of necrosis. ECT induced complete perivascular necrosis and vessel wall destruction. On day 1 after surgery, both ECT and RFA were associated with a significant increase in monocyte, C-reactive protein and aspartate aminotransferase levels. Leukocyte counts were elevated only after ECT, bilirubin levels only after RFA. There were no significant differences in interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and IL-1ß. CONCLUSION: Both RFA and ECL are safe methods of intrahepatic ablation. As a result of a heat sink effect of blood flow in nearby vessels, RFA leads to incomplete necrosis in perivascular sites both ex vivo and in vivo. ECT has the disadvantage of long treatment times but the advantage of lower costs since the platinum electrodes are reusable. Without a reduction in liver perfusion, the central application of RFA in close proximity to vessels should be considered problematic.