Use of a new vertical traction device for early traction-assisted staged closure of congenital abdominal wall defects: a prospective series of 16 patients.

PURPOSE: Abdominal wall closure in patients with giant omphalocele (GOC) and complicated gastroschisis (GS) remains to be a surgical challenge. To facilitate an early complete abdominal wall closure, we investigated the combination of a staged closure technique with continuous traction to the abdominal wall using a newly designed vertical traction device for newborns. METHODS: Four tertiary pediatric surgery departments participated in the study between 04/2022 and 11/2023. In case primary organ reduction and abdominal wall closure were not amenable, patients underwent a traction-assisted abdominal wall closure applying fasciotens®Pediatric. Outcome parameters were time to closure, surgical complications, infections, and hernia formation. RESULTS: Ten patients with GOC and 6 patients with GS were included. Complete fascial closure was achieved after a median time of 7 days (range 4-22) in GOC and 5 days (range 4-11) in GS. There were two cases of tear-outs of traction sutures and one skin suture line dehiscence after fascial closure. No surgical site infection or signs of abdominal compartment syndrome were seen. No ventral or umbilical hernia occurred after a median follow-up of 12 months (range 4-22). CONCLUSION: Traction-assisted staged closure using fasciotens®Pediatric enabled an early tension-less fascial closure in GOC and GS in the newborn period.

Muscle hypertrophy and neuroplasticity in the small bowel in short bowel syndrome.

Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in muscle layers and especially in the myenteric plexus of the enteric nervous system (ENS) of the small bowel in the context of intestinal adaptation. Twelve rats underwent a massive resection of the small intestine to induce SBS. Sham laparotomy without small bowel transection was performed in 10 rats. Two weeks after surgery, the remaining jejunum and ileum were harvested and studied. Samples of human small bowel were obtained from patients who underwent resection of small bowel segments due to a medical indication. Morphological changes in the muscle layers and the expression of nestin, a marker for neuronal plasticity, were studied. Following SBS, muscle tissue increases significantly in both parts of the small bowel, i.e., jejunum and ileum. The leading pathophysiological mechanism of these changes is hypertrophy. Additionally, we observed an increased nestin expression in the myenteric plexus in the remaining bowel with SBS. Our human data also showed that in patients with SBS, the proportion of stem cells in the myenteric plexus had risen by more than twofold. Our findings suggest that the ENS is tightly connected to changes in intestinal muscle layers and is critically involved in the process of intestinal adaptation to SBS.

Case Report: 2-Year-Old Boy with Grade 4 Avulsion Injury of the Hand Caused by a Conveyor Belt System. / Case report: 2-jähriger Junge mit viertgradiger Avulsionsverletzung der Hand durch Einklemmung in ein Förderband.

In the western world, mutilating hand injuries such as amputations and severe avulsions are more common in the working population than in children (Pomares G et al. Orthop Traumatol Surg Res 2018; 104: 273­276). An epidemiologic retrospective study from France identified 1715 traumatic upper-limb amputations over a 10-years period with the majority of cases involving middle-aged men (Pomares G et al. Orthop Traumatol Surg Res 2018; 104: 273­276). Systematic literature search using Pubmed on conveyor belt system injuries found few articles. A recent study analyses occupational traumatic injuries in offshore seafood processors in Alaska. Processing equipment and machinery were among the leading causes of injuries, accounting for 28% of traumata (Syron et al. J Safety Res 2018; 66: 169­178). Tiwari et al. describe a collective of six children who sustained motorized machine belt entrapment injuries (Tiwari P et al. Indian Pediatr 2020; 57: 66­68). Overall mortality and paraplegia rate were 33.3% each. Those accidents mainly occured in rural areas in India. The children were caught in the belt by their clothes while their parents were working nearby. Five patients were pulled through their torso, those with involved head were dead at the time of arrival. Only one had only his limbs involved. If a conveyor belt involves the hand, severe avulsion or crush injuries result. The outcome of reconstructive surgery in hand avulsion injuries depends mainly on the initial degree of injury (Kay et al. J Hand Surg 1989; 14: 204­213). Finger avulsion injuries are classified according to Kay's classification. In class I injuries, tissue perfusion is still normal. Kay II injuries already show inadequate blood flow but no fracture is present. In class III injuries, perfusion is restricted and there is either an associated fracture or a joint injury. Kay IV injuries cover complete digital deglovings or amputations (Kay et al. J Hand Surg 1989; 14: 204­213). Generally, replantations for sharp injuries show higher success rates than for avulsion or crush injuries (Goodman et al. J Hand Surg Am 2017;42:456­463). In general, the age of pediatric patients is critical to the feasibility and success rate of finger replantations and reconstructive hand surgery.

Genome sequencing in families with congenital limb malformations.

The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified.

BMDExpress 2: enhanced transcriptomic dose-response analysis workflow.

SUMMARY: A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses the increasing use of transcriptomic dose-response data in toxicology, drug design, risk assessment and translational research. In this new version, we have implemented additional statistical filtering options (e.g. Williams' trend test), curve fitting models, Linux and Macintosh compatibility and support for additional transcriptomic platforms with up-to-date gene annotations. Furthermore, we have implemented extensive data visualizations, on-the-fly data filtering, and a batch-wise analysis workflow. We have also significantly re-engineered the code base to reflect contemporary software engineering practices and streamline future development. The first version of BMDExpress was developed in 2007 to meet an unmet demand for easy-to-use transcriptomic dose-response analysis software. Since its original release, however, transcriptomic platforms, technologies, pathway annotations and quantitative methods for data analysis have undergone a large change necessitating a significant re-development of BMDExpress. To that end, as of 2016, the National Toxicology Program assumed stewardship of BMDExpress. The result is a modernized and updated BMDExpress 2 that addresses the needs of the growing toxicogenomics user community. AVAILABILITY AND IMPLEMENTATION: BMDExpress 2 is available at https://github.com/auerbachs/BMDExpress-2/releases. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Case report: Infant with a Fast-growing Soft Tissue Tumor on the Thumb, Revealing a PLAG1-positive Connatal Lipoblastoma.

At the age of 4 months, an infant was presented to us with a nodular subcutaneous tumor on the right thumb measuring 2cm, already seen prenatally via ultrasound. An MRI in sedation performed at the age of 4.5 months had no diagnostic specificity. By a biopsy at the age of 5 months malignancy could be excluded. Finally at the age of 16 months the tumor which had meanwhile grown to a monstrous size (5 cm of diameter) could be entirely removed by microsurgical technique maintaining the integrity of all intrinsic structures. The diagnosis of myxoid lipoblastoma was confirmed. According to literature, Lipoblastomas often present as connatal rapid growing soft tissue tumors and are benign. Total removal is essential for avoiding a local recurrence.

An Intuitive Approach for Predicting Potential Human Health Risk with the Tox21 10k Library.

In vitro-in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited. This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a three-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios. Toward lower exposure scenarios, 36 compounds of 3925 unique chemicals with curated activity in the HTS data using high-quality dose-response model fits and ≥40% efficacy gave "possible" human in vivo interaction likelihoods lower than median human exposures predicted in the United States Environmental Protection Agency's ExpoCast program. A publicly available web application has been designed to provide all Tox21-ToxCast dose-likelihood predictions. Overall, this approach provides an intuitive framework to relate in vitro toxicology data rapidly and quantitatively to exposures using either in vitro or in silico derived TK parameters and can be thought of as an important step toward estimating plausible biological interactions in a high-throughput risk-assessment framework.

A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro.

Nephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals.

Elastic Stable Intramedullary Nailing (ESIN), Orthoss® and Gravitational Platelet Separation--System (GPS®): an effective method of treatment for pathologic fractures of bone cysts in children.

BACKGROUND: The different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated. METHODS: From 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS®)--System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration. RESULTS: A cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS® and Orthoss® to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary. CONCLUSIONS: The combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS®) enhances the treatment of bone cysts in children, with no resulting complications.

A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives.

Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compounds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to January 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicology Program's Research Report 4 (NTP RR-04), "Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives". Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through January 2019. In total, there are 22, 117, and 221 human epidemiological, experimental animal, or in vitro studies included. The most frequently studied BPA analogues are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiological studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a critical need for better exposure information in order to prioritize experimental studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects in order to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA in order to consider BPA structural and functional analogues.

A hybrid gene selection approach to create the S1500+ targeted gene sets for use in high-throughput transcriptomics.

Changes in gene expression can help reveal the mechanisms of disease processes and the mode of action for toxicities and adverse effects on cellular responses induced by exposures to chemicals, drugs and environment agents. The U.S. Tox21 Federal collaboration, which currently quantifies the biological effects of nearly 10,000 chemicals via quantitative high-throughput screening(qHTS) in in vitro model systems, is now making an effort to incorporate gene expression profiling into the existing battery of assays. Whole transcriptome analyses performed on large numbers of samples using microarrays or RNA-Seq is currently cost-prohibitive. Accordingly, the Tox21 Program is pursuing a high-throughput transcriptomics (HTT) method that focuses on the targeted detection of gene expression for a carefully selected subset of the transcriptome that potentially can reduce the cost by a factor of 10-fold, allowing for the analysis of larger numbers of samples. To identify the optimal transcriptome subset, genes were sought that are (1) representative of the highly diverse biological space, (2) capable of serving as a proxy for expression changes in unmeasured genes, and (3) sufficient to provide coverage of well described biological pathways. A hybrid method for gene selection is presented herein that combines data-driven and knowledge-driven concepts into one cohesive method. Our approach is modular, applicable to any species, and facilitates a robust, quantitative evaluation of performance. In particular, we were able to perform gene selection such that the resulting set of "sentinel genes" adequately represents all known canonical pathways from Molecular Signature Database (MSigDB v4.0) and can be used to infer expression changes for the remainder of the transcriptome. The resulting computational model allowed us to choose a purely data-driven subset of 1500 sentinel genes, referred to as the S1500 set, which was then augmented using a knowledge-driven selection of additional genes to create the final S1500+ gene set. Our results indicate that the sentinel genes selected can be used to accurately predict pathway perturbations and biological relationships for samples under study.

Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data.

BACKGROUND: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. OBJECTIVES: Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. METHODS: We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and ß cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. DISCUSSION: The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. CONCLUSIONS: More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. CITATION: Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: a screening approach using ToxCast™ high-throughput data. Environ Health Perspect 124:1141-1154; http://dx.doi.org/10.1289/ehp.1510456.

Correlation between in vitro peptide binding profiles and cellular activities for estrogen receptor-modulating compounds.

Numerous biochemical and structural studies have shown that the conformation of the estrogen receptor alpha (ERalpha) can be influenced by ligand binding. In turn, the conformational state of ERalpha affects the ability of the receptor to interact with a wide variety of protein accessory factors. To globally investigate ligand-based cofactor recruitment activities of ERalpha, we have applied a flow cytometric multiplexed binding assay to determine the simultaneous binding of ERalpha to over 50 different peptides derived from both known cofactor proteins and random peptide phage display. Using over 400 ERalpha-binding compounds, we have observed that the multiplexed in vitro peptide-binding profiles are distinct for a number of compounds and that these profiles can predict the effect that ERalpha ligands have on various cellular activities. These cell-based activities include transcriptional regulation at an estrogen response element, MCF-7 cell proliferation, and Ishikawa endometrial cell stimulation. The majority of the compound-induced diversity in the peptide profiling assay is provided by the unique phage display peptides. Importantly, some of these peptides show a sequence relationship with the corepressor motif, suggesting that peptides identified via phage display might represent natural binding partners of ERalpha. These in vitro:cellular correlations may in part explain tissue-specific activities of ERalpha-modulating compounds.

Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.

Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17ß-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase.

Comparison of long-term outcomes between open and laparoscopic Thal fundoplication in children.

OBJECTIVES: In recent years laparoscopic fundoplication is increasingly performed in pediatric surgery. The aim of this study was to compare the long-term outcomes between open and laparoscopic Thal fundoplication in children. METHODS: This retrospective study includes children who underwent a Thal fundoplication between 3/1997 and 7/2009. The minimum follow-up time to enter the study was 2 years; the overall median follow-up was 77 months (range, 29-176 months). RESULTS: A total of 101 patients were included, of which 47 underwent an open and 54 a laparoscopic Thal. Intraoperative problems, early postoperative complications, time to establish enteral feeds and length of stay did not differ among both groups. The mean duration of surgery was significantly less in the open group (OPG) (108.0 (± 7.72) versus 144.1 (± 6.36) minutes; p=0.001) and this was mainly attributed to patients with neurological problems. Severe dysphagia requiring endoscopy was observed in 10 patients, but this did not differ significantly between groups (n=2 in the OPG vs. n=8 in the laparoscopic group (LAPG); p=0.10). Overall 12 patients (11.9%) (6 in each group) required a redo-fundoplication after a median of 18.7 months (range, 6-36 months). In the whole study group, 80 patients (79.2%) were classified as having surgical results being excellent, good or satisfactory and this did not differ significantly between groups. CONCLUSIONS: In the long-term open and laparoscopic Thal fundoplication have similarly good outcomes. The laparoscopic approach can be considered as an alternative, however there is not a clear superiority compared with the open counterpart.

The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.

The concordance of RNA-sequencing (RNA-seq) with microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed using a range of chemical treatment conditions. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same liver samples of rats exposed in triplicate to varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOAs). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is linearly correlated with treatment effect size (R(2)0.8). Furthermore, the concordance is also affected by transcript abundance and biological complexity of the MOA. RNA-seq outperforms microarray (93% versus 75%) in DEG verification as assessed by quantitative PCR, with the gain mainly due to its improved accuracy for low-abundance transcripts. Nonetheless, classifiers to predict MOAs perform similarly when developed using data from either platform. Therefore, the endpoint studied and its biological complexity, transcript abundance and the genomic application are important factors in transcriptomic research and for clinical and regulatory decision making.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.