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Introduction: Nissen fundoplication is frequently applied in the surgical treatment of patients with gastroesophageal reflux disease (GERD). When the gastroesophageal junction remains too large or becomes too narrow, persistent GERD or dysphagia may occur. To assure a correct size of the gastroesophageal junction, the fundoplication can be created over a bougie. However, this increases the risk of esophageal perforation. Therefore, we have modified a previously described technique to create a standardized fundoplication without the use of a bougie. In this article, we describe this technique and demonstrate the initial results. Materials and Methods: We describe a technique to create a standardized Nissen fundoplication. After suture repair of the hiatal hernia, three marking sutures were placed on the gastric fundus, based on an equilateral triangle. The size of this triangle determines the final diameter of the fundoplication. With these measurements, we assure sufficient patency, minimize rotation, and create a more reproducible fundoplication that may reduce postoperative dysphagia. Results: We have operated 15 patients according to this technique. Mean operative time was 69.5 (SD 8.4) minutes, no complications occurred. There was no early dysphagia and the mean length of stay was 1.3 days (1-2). Quality of life after 1 year was excellent. Conclusions: This modified method for standardized Nissen fundoplication is safe and might reduce postoperative dysphagia. Quality of life after 1 year is excellent. The effect on postoperative dysphagia and the reproducibility of this technique should be established in a large prospective study.

The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients.All patients underwentRetrospective single-centre study.Head and neck squamous cell carcinoma patients with high-risk factors for distant metastases.Accuracy ofIn 23 (12%) of the 190 patients,In head and neck squamous cell carcinoma patients with high-risk factors

Contains fulltext : 195227.pdf (Publisher’s version ) (Open Access)

Heartburn is a very common condition. When medication fails to relieve symptoms, surgery may be considered as a treatment option. The studies in this dissertation describe the quality of life following surgery, which appears to be good in both the short term and the long term. A literature study describes the optimal surgical treatment. As the surgical techniques to treat heartburn are difficult to master, we designed a new technique that leads to more reproducible results and that is easier for novice surgeons to perform. The clinical benefits of this technique must be examined further.

INTRODUCTION: For decades, intrathoracic stomach has been an indication for surgical repair and over time laparoscopy has become standard treatment. However, there are still many aspects in the treatment of intrathoracic stomach that are subject of debate. We performed a literature review to discuss the role of laparoscopy in intrathoracic stomach repair. EVIDENCE ACQUISITION: We performed an extensive literature search in Pubmed, Embase and Cochrane and reviewed studies from the last 5 years. To provide a complete overview, references from the found studies are also used. All data was compiled into a review format. EVIDENCE SYNTHESIS: Laparoscopic surgery is proven to be superior to open hiatal hernia repair in the treatment of intrathoracic stomach. The role of hernia sac excision, short esophagus, mesh reinforcement, fundoplication, complications and future perspectives are discussed in this review. CONCLUSIONS: Laparoscopy plays a major role in the treatment of intrathoracic stomach and regarding most aspects of the treatment. All available techniques have their advantages and disadvantages, and the decision on how to repair the intrathoracic stomach, remains a tailored based decision.

Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

ObjectivesEvaluation of accuracy and interobserver variation of diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDGPET-CT) to detect residual lymph node metastases after chemoradiotherapy (CRT) in advanced staged head and neck squamous cell carcinoma (HNSCC).Materials and methodsRetrospectively, routinely performed DW-MRI (n = 73) and 18F-FDG-PET-CT (n = 58) 3 months after CRT in HNSCC-patients with advanced nodal disease (N2-N3) were assessed by two radiologists and two nuclear medicine physicians (individually and in consensus). Imaging was scored dichotomously and on a five-point Likert scale. We also explored different scenarios for the potential added value of DW-MRI to PET-CT using the consensus Likert scale. Histopathology and a follow-up of 9 months after CRT served as reference standard.ResultsFive patients (7%) had residual regional disease. DW-MRI showed a sensitivity of 60% and a specificity of 93%, vs. 100% and 84% for PET-CT, respectively. DW-MRI and PET-CT observers had ‘moderate’ and ‘substantial’ interobserver agreement (κ = 0.58 and κ = 0.64, respectively) with the dichotomous system. The combination of PET-CT and DW-MRI showed a sensitivity of 100% and a specificity of 95%.ConclusionThe high sensitivity of PET-CT authorizes a neck dissection in all patients with a positive test result and the high specificity of DW-MRI justifies avoidance of invasive neck dissections if the test is negative. Interobserver agreement varied as a function of test positivity criteria. Adding DW-MRI to PET-CT seemed to increase the specificity of PET-CT alone, thereby ensuring that less patients are exposed to unnecessary neck dissections.

Plant cells cannot rearrange their positions; therefore, sharp tissue boundaries must be accurately programmed. Movement of the cell fate regulator SHORT-ROOT from the stele to the ground tissue has been associated with transferring positional information across tissue boundaries. The zinc finger BIRD protein JACKDAW has been shown to constrain SHORT-ROOT movement to a single layer, and other BIRD family proteins were postulated to counteract JACKDAW's role in restricting SHORT-ROOT action range. Here, we report that regulation of SHORT-ROOT movement requires additional BIRD proteins whose action is critical for the establishment and maintenance of the boundary between stele and ground tissue. We show that BIRD proteins act in concert and not in opposition. The exploitation of asymmetric redundancies allows the separation of two BIRD functions: constraining SHORT-ROOT spread through nuclear retention and transcriptional regulation of key downstream SHORT-ROOT targets, including SCARECROW and CYCLIND6. Our data indicate that BIRD proteins promote formative divisions and tissue specification in the Arabidopsis thaliana root meristem ground tissue by tethering and regulating transcriptional competence of SHORT-ROOT complexes. As a result, a tissue boundary is not “locked in” after initial patterning like in many animal systems, but possesses considerable developmental plasticity due to continuous reliance on mobile transcription factors.

BACKGROUND AND PURPOSE: DWI is typically performed with EPI sequences in single-center studies. The purpose of this study was to determine the reproducibility of ADC values in the head and neck region in healthy subjects. In addition, the reproducibility of ADC values in different tissues was assessed to identify the most suitable reference tissue. MATERIALS AND METHODS: We prospectively studied 7 healthy subjects, with EPI and TSE sequences, on 5 MR imaging systems at 3 time points in 2 institutions. ADC maps of EPI (with 2 b-values and 6 b-values) and TSE sequences were compared. Mean ADC values for different tissues (submandibular gland, sternocleidomastoid muscle, spinal cord, subdigastric lymph node, and tonsil) were used to evaluate intra- and intersubject, intersystem, and intersequence variability by using a linear mixed model. RESULTS: On 97% of images, a region of interest could be placed on the spinal cord, compared with 87% in the tonsil. ADC values derived from EPI-DWI with 2 b-values and calculated EPI-DWI with 2 b-values extracted from EPI-DWI with 6 b-values did not differ significantly. The standard error of ADC measurement was the smallest for the tonsil and spinal cord (standard error of measurement = 151.2 × 10(−6) mm/s(2) and 190.1 × 10(−6) mm/s(2), respectively). The intersystem difference for mean ADC values and the influence of the MR imaging system on ADC values among the subjects were statistically significant (P < .001). The mean difference among examinations was negligible (ie

ObjectivesTo assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT).MethodsPretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0–750s/mm2 (ADC750) and 0–1000s/mm2 (ADC1000). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC750 and ADC1000. Lesion volumes and ADC-values were related to DFS using Cox regression analysis.ResultsMedian follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75–0.83, respectively; lymph node: 0.81–0.83 and 0.61–0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P

This trial is a randomized controlled, patient-blinded, multicentre, superiority trial. All patients ≥18 years with a single, symptomatic and primary umbilical or epigastric hernia (

Background: Laparoscopic cruroplasty and fundoplication have become the gold standard in the treatment of hiatal hernia and gastro-oesophageal reflux disease (GERD). The use of a mesh-reinforcement of the cruroplasty has been proven effective; although, there is a lack of evidence considering which type of mesh is superior. The aim of this study was to compare recurrence rates after mesh reinforced cruroplasty using biological versus synthetic meshes. Methods: We performed a systematic review of all clinical trials published between January 2004 and September 2015 describing the application of a mesh in the hiatal hernia repair during Nissen fundoplication for both GERD and hiatal hernia. The primary outcome was the recurrence rate, and secondary outcomes were complication rate, mortality and symptomatic outcome. Results: We included 16 studies and extracted data regarding 1089 mesh operated patients of whom 385 received a biological mesh and 704 a synthetic mesh. The mean follow-up was 53.4 months. The recurrence rate in the synthetic mesh group was 6.8% compared to 16.1% in the biological mesh group (P < 0.05). The complication rate was 5.1% and 4.6% (P = 0.694), respectively, and there were 12 mesh-related complications. No mesh-related mortality was reported. Conclusion: Mesh reinforcement of hiatal hernia repair seems safe in the short-term follow-up. The available literature suggests no clear advantage of biological over synthetic meshes. Regarding cost-efficiency and short-term results, the use of synthetic nonabsorbable meshes might be advocated.

Objective Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose (18F-FDG) uptake at the primary tumor site 3 months after (chemo)radiotherapy. Study Design For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site. Results The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residual 18F-FDG uptake, and only a positive read on both PET-CT and DWI was considered to be overall positive, sensitivity remained 80% (95% confidence interval [CI] 28%-99%), and specificity was 88% (95% CI 64%-99%). Conclusions In this pilot study of the selected patients with residual 18F-FDG uptake at the primary tumor site 3 months after (chemo)radiotherapy, we demonstrated that the addition of DWI to PET-CT has the potential to increase the specificity of the response evaluation with limited decrease in sensitivity.

Background: Retinoblastoma is the most common intraocular tumor in childhood with a good prognosis in terms of mortality, but detailed information about tumor morphology and disease extent in retinoblastoma is important for treatment decision making. Purpose: To demonstrate ultrahigh-field MRI tumor morphology and tumor extent in retinoblastoma correlating with in and ex vivo images with histopathology. Study Type: Prospective case series. Population: Six retinoblastoma patients (median age 5.5 months, range 2–14) were prospectively included in this study. Median time between diagnosis and enucleation was 8 days (range 7–19). Field Strength/Sequence: In vivo pre-enucleation at 1.5T MRI with a circular surface coil. Ex vivo imaging (FLASH T1-weighted and RARE T2-weighted) was performed at field strengths of 9.4T and 17.6T. Assessment: After ex vivo imaging, the eyes were histopathologically analyzed and morphologically matched with MRI findings by three authors (two with respectively 14 and 4 years of experience in ocular MRI and one with 16 years of experience in ophthalmopathology). Results: Small submillimeter morphological aspects of intraocular retinoblastoma were successfully depicted with higher-resolution MRI and matched with histopathology images. With ex vivo MRI a small subretinal tumor seed (300 μm) adjacent to the choroid was morphologically matched with histopathology. Also, a characteristic geographical pattern of vital tumor tissue (400 μm) surrounding a central vessel interspersed with necrotic areas correlated with histopathology images. Tumor invasion into the optic nerve showed a higher signal intensity on T1-weighted higher-resolution MRI. Data Conclusion: Higher-resolution MRI allows for small morphological aspects of intraocular retinoblastoma and extraocular disease extent not visible on currently used clinical in vivo MRI to be depicted. Level of Evidence: 4. Technical Efficacy: Stage 2. J. Magn. Reson. Imaging 2018;47:1487–1497.

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was “spin-echo planar imaging”. A median of 10.5 b-values (range, 3–17) were used. All but three studies included at least 4 b-values below b = 200 s/mm2. By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85–87% and specificity of 80–100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations.

Contains fulltext : 174260.pdf (Publisher’s version ) (Open Access) BACKGROUND: Considerable variation exists in diagnostic tests used for local response evaluation after chemoradiation in patients with advanced oropharyngeal cancer. The yield of invasive examination under general anesthesia (EUA) with biopsies in all patients is low and it may induce substantial morbidity. We explored four response evaluation strategies to detect local residual disease in terms of diagnostic accuracy and cost-effectiveness. METHODS: We built a decision-analytic model using trial data of forty-six patients and scientific literature. We estimated for four strategies the proportion of correct diagnoses, costs concerning diagnostic instruments and the proportion of unnecessary EUA indications. Besides a reference strategy, i.e. EUA for all patients, we considered three imaging strategies consisting of 18FDG-PET-CT, diffusion-weighted MRI (DW-MRI), or both 18FDG-PET-CT and DW-MRI followed by EUA after a positive test. The impact of uncertainty was assessed in sensitivity analyses. RESULTS: The EUA strategy led to 96% correct diagnoses. Expected costs were euro468 per patient whereas 89% of EUA indications were unnecessary. The DW-MRI strategy was the least costly strategy, but also led to the lowest proportion of correct diagnoses, i.e. 93%. The PET-CT strategy and combined imaging strategy were dominated by the EUA strategy due to respectively a smaller or equal proportion of correct diagnoses, at higher costs. However, the combination of PET-CT and DW-MRI had the highest sensitivity. All imaging strategies considerably reduced (unnecessary) EUA indications and its associated burden compared to the EUA strategy. CONCLUSIONS: Because the combined PET-CT and DW-MRI strategy costs only an additional euro927 per patient, it is preferred over immediate EUA since it reaches the same diagnostic accuracy in detecting local residual disease while leading to substantially less unnecessary EUA indications. However, if healthcare resources are limited, DW-MRI is the strategy of choice because of lower costs while still providing a large reduction in unnecessary EUA indications.

Contains fulltext : 153872.pdf (Publisher’s version ) (Closed access) Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response evaluation, i.e., examination under general anesthesia (EUA), 12 weeks after treatment. However, in the Netherlands there is no consensus on response evaluation in patients with advanced oropharyngeal cancer. Questionnaire on current clinical practice concerning response evaluation after CRT for advanced OPSCC in all eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group. The response rate was 100 %. Response evaluation was routinely performed with various methods in five institutions (62.5 %) and in one institute (12.5 %) only if clinical evaluation was difficult. Two centers (25 %) did not perform response evaluation. In case of suspicion of residual disease during follow-up, six centers (75 %) performed imaging prior to EUA and two centers (25 %) only if clinical evaluation was difficult. Diagnostic techniques used prior to EUA were MRI (87.5 %), diffusion-weighted MRI (37.5 %), 18F-FDG-PET-CT (75-87.5 %) and CT (37.5 %). This survey shows a substantial variation in the diagnostic policy concerning response evaluation after CRT for advanced OPSCC in the Netherlands. There is a need for guidelines for response evaluation in patients with advanced oropharyngeal cancer.

Regional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck.

Purpose To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard. Design Systematic review and meta-analysis. Participants Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies. Methods Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed. Main Outcome Measures Sensitivity and specificity of MRI and CT in detecting tumor extent. Results Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%–78%), 74% (95% CI, 52%–88%), and 88% (95% CI, 20%–100%), respectively, and specificities of 94% (95% CI, 84%–98%), 72% (95% CI, 31%–94%), and 99% (95% CI, 86%–100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses. Conclusions Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few—mostly old—studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed.

Recently, a new MRI technique was developed at 3 Tesla (T), called fluid attenuated inversion recovery* (FLAIR*). In this study, we implemented FLAIR* in an existing MS cohort at 7 T, to investigate whether we could corroborate results of previous 7 T studies that introduced specific MS lesion characteristics. Furthermore, we aimed to investigate the meaning of these lesion characteristics by relating them to clinical characteristics of the MS patient. Three-dimensional FLAIR and T2*-weighted images of 33 MS patients and 7 healthy controls were fused into FLAIR* images. Lesion type, signal intensity and morphology were analysed on FLAIR*, side-by-side with the original FLAIR and T2*, and correlated with clinical characteristics using Spearman’s rho. Three morphological features of MS lesions were visualised: (1) central vessel (CV) within lesions, present in 78 % of total MS lesions; (2) hypointense rims around MS lesions, present in eight patients; (3) FLAIR* lesions that were hypointense at T2*, present in 13 patients. The presence of hypointense (rims around) lesions was not related to clinical characteristics. The simultaneous presence of rimlike lesions and hypointense lesions within MS patients was significantly correlated (ρ = 0.52, P

Wij presenteren een casus van een 43-jarige man bij wie per toeval het zeldzame Pellegrini-Stiedafenomeen werd gevonden. Dit is een ossificatie van de mediale collaterale band van de knie. In dit artikel worden aan de hand van de huidige literatuur de diagnostiek, pathofysiologie en behandeling besproken. Tevens wordt een overzicht gegeven van de casuistiek zoals die gepubliceerd is in de afgelopen tien jaar. Het is belangrijk om te beseffen dat het Pellegrini- Stiedasyndroom een verklaring kan zijn voor pijnklachten en bewegingsbeperking van de knie.

Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulates the steady-state levels of chromatin modifications. Here we describe a novel microscopy-based screening method to identify proteins that regulate histone modification levels in a high-throughput fashion. We named our method CROSS, for Chromatin Regulation Ontology SiRNA Screening. CROSS is based on an siRNA library targeting the expression of 529 proteins involved in chromatin regulation. As a proof of principle, we used CROSS to identify chromatin factors involved in histone H3 methylation on either lysine-4 or lysine-27. Furthermore, we show that CROSS can be used to identify chromatin factors that affect growth in cancer cell lines. Taken together, CROSS is a powerful method to identify the writers and erasers of novel and known chromatin marks and facilitates the identification of drugs targeting epigenetic modifications.