23 Another area of the brain associated with theory of mind and perspective taking that has been activated in both groups is the left anterior cingulate (BA 32).23 Both groups also show intense activation in the right insula, a region associated with visceral processing, but specifically in the context of emotional self-awareness and non-language vocalizations such as laughing and crying.24 Figure 1. Patterns of activation during an fMR word Fedratinib chemical structure association task performed by artists (Figure 1a) and scientists (Figure 1b) show strikingly similar patterns

Inhibitors,research,lifescience,medical of activation in multiple regions of association cortex and areas involved in socioaffective processing. … The bilateral visual cortices have also been invoked Inhibitors,research,lifescience,medical in imagery processing in this task in both groups, involving the cuneus and the lingual gyrus. While the involvement of this region is to be expected in visual imagery

associated with verbal stimuli, there is increasing evidence that sensory cortices (such as the cuneus and lingual gyrus) are also involved in multimodal higher-order sensory processing (similar to the Inhibitors,research,lifescience,medical association cortices) as would be relevant to the creative generation of verbal responses.25 Discussion This small group of “big C” individuals includes a diverse group of artists and scientists. When the activations in the two groups are compared, the findings give no support for the notion that the artists and scientists Inhibitors,research,lifescience,medical represent “two cultures.” Rather, they suggest that very gifted artists and scientists have association cortices that respond in similar ways. Both groups display a preponderance of activation in brain circuits involved in higher-order socioaffective processing and REST/the default mode network. This is to be expected, given that the artist group is comprised of storytellers working with various media. However, it is novel to report this similar

pattern of activation in a group of scientists, stereotyped to be less verbal in their creative genius. One plausible explanation is that all Inhibitors,research,lifescience,medical highly creative geniuses, the “big C’s,” are unique and unified in their experience Terminal deoxynucleotidyl transferase of high affectivity, vivid imagery, and ability to intuit feelings and thoughts that occur in the minds of others. Perhaps this intensity of feeling and rich imagination contributes to their passion, creativity, and discovery of new frontiers. Acknowledgments This study was funded by a Senior Investigator Award to Dr Andreasen from NARSAD.
To encourage scientists to break free of categorical diagnostic constraints and realign mental illness research with the knowledge gained from the accelerating pace of findings regarding the relationship of genetic and neural factors to behavior, the National Institute of Mental Health has initiated the Research Domain Criteria (RDoC) project. This initiative represents the implementation of Strategy 1.

139 While overexpression of the ε4 allele might be expected in MCI compared with normal controls,

its frequency would not be likely to reach the levels seen in AD, since MCI cases comprise not only preclinical AD, but also other more benign conditions predisposing to TAE684 cognitive impairment. In one large study, the prevalence of nondemented persons with at least one copy of the £4 allele was 22%, while in AD the frequency was 64%.140 Values intermediary between these estimates were found in several studies of nondemented memory impaired individuals who appear to satisfy criteria for the diagnosis of MCI14,18,141,142 Two large population-based studies found that ε4 status was a significant risk factor for Inhibitors,research,lifescience,medical MCI.143,144 Most studies have found e4 to exert a cognitive impact on nondemented older adults. In community samples of nondemented elderly, although one cross_sectional study did

not find a significant relationship between £4 status and cognition,145 other longitudinal Inhibitors,research,lifescience,medical studies found ε4 to be a predictor of accelerated cognitive decline.146-148 According to one report,149 nondemented subjects who carried an e4 allele were more likely to have subjective memory Inhibitors,research,lifescience,medical complaints than those without ε4. In studies of cognitively normal persons with high MMSE scores, the impact of age on memory performance (and memory change over time) was more pronounced in e4 homozygotes relative to those without ε4.150-152 These latter reports indicate that ε4 may subtly influence cognitive Inhibitors,research,lifescience,medical performance even before the onset of MCI; it is unknown whether this influence can precede the emergence of AD pathology. Although epidemiological and longitudinal clinical

data support ε4 as a risk factor for dementia Inhibitors,research,lifescience,medical and cognitive decline, its utility as a predictor of clinical outcome in MCI populations needs to be compared with imaging, biomarker, and neuropsychological variables. Treatment of MCI The treatment of MCI is reviewed in detail by Gauthier later in this issue.153 Currently, there are no pharmacological treatments for MCI with proven efficacy or regulatory approval. However, clinically there appears to be growing use in MCI of the marketed AD treatments, donepezil, rivastigmine, galantamine, and memantine. A number of clinical trials in MCI patients have been conducted, thus far with Ketanserin mixed results. For example, a 6-month, placebo-controlled trial of donepezil failed to show significant efficacy on the primary end points, but did show efficacy on some secondary cognitive measures.154 Since a high proportion of “amnestic” MCI patients (presumably representing cases of prodromal AD) progress to an AD diagnosis within several years, 2- to 4-year “survival” clinical trial designs have been conducted with MCI patients in which “conversion” to AD is the primary outcome. Such studies are used to determine if a treatment can slow the progression of symptoms.

Hypothermia may then be applied immediately after exercise, while high dosages of anti-inflammatory nutrients such as green tea extract may be taken as additional support on these exercise days. If available, massage treatments could then be added on ‘non exercise days’ in order to complement the overall antifibrotic treatment. However, any exercise regimen should be accompanied by regular assessment of antioxidant stress levels as well as the on-going development of fibrotic tissue changes (see below). General considerations for clinical treatment Fibrosis in

DMD is a complex cascade Inhibitors,research,lifescience,medical involving mechanical, humoral and cellular factors. Originating from wounded myofibres, muscle cell necrosis and inflammatory processes are present in DMD. Muscular recovery is limited due to the limited number and capacity of satellite cells.

Inhibitors,research,lifescience,medical Hence, a proactive and multimodal approach is necessary in order to activate protective mechanisms and to hinder catabolic and tissue degrading pathways. Fibrotic changes in muscle are not confined to DMD muscle. Back in the 1980s, Michelsson developed an animal model to study the effects that develop after forceful exercise of immobilised limbs. He concluded that autoinflammatory processes lead to myositis and secondarily Inhibitors,research,lifescience,medical to fibrosis and even calcification with heterotopic bone formation (73). Two main points can be extracted for DMD. First of all, Inhibitors,research,lifescience,medical immobilisation is not advisable and second forceful overstrain should be avoided. Corticosteroids are frequently used in myofascial inflammation. Corticosteroids generally reduce gene expression and inhibit the proliferation and activity of myofibroblasts, Inhibitors,research,lifescience,medical which mainly leads to suppression of collagen production. Additionally myofibroblast migration, which is fundamental in fibrosis, is delayed after corticosteroid injection. These corticoid-associated disturbances on tendon cell metabolism

may affect the structural Farnesyltransferase integrity of the tendon and weaken its mechanical properties. There are many side effects of corticosteroids, which include a risk of diabetes, disturbance of hormonal glands and metabolism, suppression of angioneogenesis, immune function and coagulation. Hence, therapeutic VEGFR inhibitor protocols that lower the use of corticosteroids are desirable. Stiffening of pulmonary and pericardial connective tissues Mortality in DMD patients is often due to respiratory or cardiac problems. In both body areas – the pulmonary and the pericardial connective tissues – the fibrotic changes in muscular dystrophy tend to be very severely expressed and they tend to influence strongly muscular function (74, 75). An increased stiffening of related tissues can impair muscular function.

Firstly they tap into a number of cognitive domains: working memory, executive ARN-509 supplier function and sustained attention, and represent functions involved in a wide range of real world activities [Ritter et al. 2007]. Secondly these tasks have previously been demonstrated to be sensitive to the impact of herbal and dietary based interventions [e.g. Reay et al. 2006; Scholey et al. 2010], and they have been identified as possessing different

degrees of cognitive demand based on participants’ self reports [Scholey et al. 2001; Scholey and Kennedy, 2002]. This was considered potentially important as Inhibitors,research,lifescience,medical some interventions have been shown to differentially affect task performance based on cognitive load [e.g. Kennedy et al. 2002]. Subjective mood Inhibitors,research,lifescience,medical measures Mood was assessed using the Bond-Lader visual analogue scales

[Bond and Lader, 1974]. The scales were developed for use in medical psychology and psychopharmacology research, with the original paper cited in more than 1000 peer reviewed publications including clinical trials worldwide. A critical review has described them as ‘A simple technique for measuring subjective experience. They have been established as valid and reliable in a range of clinical and research applications’ [McCormack et al. 1988, p. 1007]. The Bond–Lader mood scales have also been used widely Inhibitors,research,lifescience,medical in aroma and other herbal intervention studies where they have been demonstrated to be sensitive to changes in subjective state [e.g. Moss et al. 2003, 2006, 2008, 2010; Scholey et al. Inhibitors,research,lifescience,medical 2010; Kennedy et al. 2002]. The 16 visual analogue scales of the Bond-Lader assessment were combined as recommended by the authors to form three mood factors: ‘alert’, ‘calm’ and ‘content’. Procedure Ethical clearance was granted by the School of Psychology and Sport Sciences Ethics Committee. Recruitment took place 1 week prior to testing and at this point participants were told the aims of the study and given a time to attend the laboratory. All testing took place in the same cubicle between 9:00 am and 12:00 noon. Participants were asked to read a brief Inhibitors,research,lifescience,medical for the study and instructions

for task completion prior to providing informed consent. A pre-test mood scale was completed prior to entering the aroma-infused cubicle. The cognitive tasks were completed followed by a second (post-test) mood scale. Finally, a sample of venous blood was taken by a trained phlebotomist. The participants were then debriefed, thanked for their participation and Calpain any questions answered. Blood sampling and analysis One 5 ml blood sample was taken per participant, by venous puncture into a serum gel monovette. All samples were immediately centrifuged at 3000g for 10 min at 20°C using an Allegra X-22 centrifuge (Beckman Coulter Ltd, High Wycombe, UK). The serum was then decanted into a 1.5 ml microtube and stored in a freezer at −80°C until all the samples were ready for analysis.

Subsequently, the investigators used MRI spectroscopy to measure the effect of SNP 4 on NAA, an indirect measure of prefrontal glutamate neurotransmission, synaptic abundance, and prefrontal extracellular glutamate. NAA has been previously shown to be lower in DLPFC and hippocampus in

schizophrenia.53 In this study right and left, DLPFC NAA was lower in risk allele homozygotes than other genotypes, as would be expected from the cognitive and fMRI results. Group-by-genotype Inhibitors,research,lifescience,medical interaction was not significant; even so, there was scant effect of genotype on NAA in the sibling group. Finally, in postmortem human prefrontal cortex, risk allele homozygotes had significantly lower mRNA levels of the glial glutamate transporter EAAT2.The authors suggest these convergent data reflect a specific molecular pathway Inhibitors,research,lifescience,medical by which GRM3 genotype may alter glutamate neurotransmission, and thus prefrontal and hippocampal physiology and cognition, thereby increasing risk for schizophrenia. Nevertheless, the authors cautiously point out the weakness of GRM3 Inhibitors,research,lifescience,medical effects on intermediate phenotypes in this study, particularly due to the multiple statistical testing, which is unavoidable

in a study of such complexity. This study is paradigmatic of the opportunities and the impediments encountered in a combined multimodal effort to identify genes underlying the neurobiology Inhibitors,research,lifescience,medical of cognitive functions in schizophrenia. Conclusions In many respects, it is eminently reasonable to search for intermediate phenotypes

in complex disorders such as schizophrenia, particularly because the matrix of risk alleles shaping the clinical phenotype will likely turn out to be far more complex than might have been expected. Nevertheless, emerging evidence suggests that, in order to more finely parse the genetic infrastructure, it will be necessary to more finely parse and validate the most relevant functional phenotypes. This conjunction of aims may not be easy to achieve. For example, despite a substantial literature on eye-tracking Inhibitors,research,lifescience,medical dysfunctions in schizophrenia and unaffected siblings,1,114,115 and increasingly INCB018424 cost precise understanding of the physiology of eye movement, it would seem at first glance difficult to imagine how therapeutic these normalization would improve the psychosocial outcome for patients with schizophrenia. In essence, that is precisely the reason to identify intermediate phenotypes and the genes modulating their functions; we do not have sufficient evidence to predict which intermediate phenotypes we should ignore. For this reason, it will be important to develop an operational definition of relevance that assigns primacy to putative phenotypes most likely to impact clinical outcome. The apparently incongruent sensory ERP (P50 and P300) data appears in part to be due to the inherent sensitivity of ERP experiments to methodological diferences.

Scores for each parameter ranges from 5 to 25, and the total scores ranges

from 20 (severely impaired) to 100 (normal).21 Spearman and correlation tests were used to examine the correlation between CT scores, pulmonary function tests and Shwachman-Kulczycki scores. The analysis of data was performed using Statistical Package for Social Sciences software (SPSS version.16). A P value of 0.05 Inhibitors,research,lifescience,medical or less was considered as statistically significant. Results Twenty three (nine females and 14 males) patients with CF entered this prospective study. The range of the patients’ age was 5-23 years (mean: 13.42 years). The 5FU overall CT score for all patients was 57.6±24.2. The most common findings in patients’ Inhibitors,research,lifescience,medical HRCT were bronchiectasia (100%), peribronchial thickening (100%), mucus plugging (95%) and air trapping (90%). A prototype of bronchiechtasia, peribronchial wall thickening and mucus plugging in patients’ HRCT are shown in figures 1-​-33. Figure 1 Computed tomography from a 13-year-old girl. Bronchiectasia, peribronchial wall thickening, mucus plugging can be seen in both lungs. Figure Inhibitors,research,lifescience,medical 3 Computed tomography of a 14-year-old boy. Mucus plugging and bronchiectasia can be seen in the right lung. Figure 2 Computed

tomography of a 9-year-old boy. Bronchiectasia is seen in right and left lungs. A significant positive correlation was observed between the patients’ age, and air trapping, bronchiectasis and total score. The results of PFT showed that the severity of restrictive pattern increased with the advancing age. In other words, the PFT results worsened significantly (P=0.006) with the increase of patients’ ages. The overall Shwachman-Kulczycki Inhibitors,research,lifescience,medical score was 53.48±13.8. There was no correlation between the Shwachman-Kulczycki scores and the patients’ age (P=0.136). Tables 1 and ​and22 summarize the PFT findings and Shwachman-Kulczycki Inhibitors,research,lifescience,medical scores. There was a significant (P=0.015) correlation between the total

CT scores and Shwachman-Kulczycki scores; however, there was no significant (P=0.481) correlation between total CT score and the results of PFT (table 3). Table 1 The Electron transport chain results of pulmonary function test in patients with cystic fibrosis. Table 2 Schwachman-Kulczycki scores from patients with cystic fibrosis. Table 3 Spearman Rank Correlation test results showing the correlation between high resolution computed tomography (HRCT) scores obtained by Brody’s scoring system and pulmonary function test or Shwachman–Kulzcycki (S-K) score Discussion Cystic fibrosis is known as the most common fatal genetic disease among the white population.1,2 The evaluation of the disease progression by means of a routine monitoring will reduce the mortality and morbidity rates of the patients. This study evaluated the progression of lung disease in CF patients by means of assessing the relation between HRCT scoring system and non imaging parameters such as PFT and clinical scoring system.

In addition,

the period of diagnosis was also important, as patients in our cohort diagnosed after 2000 had higher LNCs. While this suggests some change over time, we cannot readily identify the source of that change. We suspect that increased awareness among treating physicians and pathologists might have contributed to the selleck screening library improvement in LNCs. Another potential explanation for the increase in LNCs could be a shift in the operative techniques being employed. We did not observe any increase in the frequency of TME performance but noticed an increase in LNCs in those patients undergoing a TME. As suggested earlier, we believe the impact of surgical Inhibitors,research,lifescience,medical techniques of rectal resection on LNCs deserves more attention. Unfortunately, larger, population-based data sets do not provide this level of detail. Another potentially important factor in rectal cancer and LNCs is the delivery of preoperative, pelvic radiotherapy. Inhibitors,research,lifescience,medical Neoadjuvant radiotherapy is known to decrease LNCs in the resected rectal cancer specimen. Since neoadjuvant chemoradiotherapy has been accepted

as a standard treatment for node positive and Stage II rectal cancers, efforts to use LNCs as a quality indicator will have to consider the impact of this approach on this metric. One would assume that minimum LNCs would necessarily be adjusted downward. Other clinical factors, such as the clinical and or pathologic Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical response to the preoperative therapy might also have an impact on LNCs. Prior studies have not considered

patients who had undergone neoadjuvant therapy (14,15). In the current study, there did not appear to be any difference in LNCs between patients who received preoperative chemoradiotherapy and those who did not. One possible explanation for this negative result might be that more patients received neoadjuvant chemoradiatherapy in the later period, during which LNCs increased. It is possible, therefore, that the negative impact on LNCs expected because of preoperative radiotherapy was masked by improved identification during the later period Inhibitors,research,lifescience,medical of the study. Another possible explanation is that our study simply lacked the power to detect a difference in LNCs caused by preoperative radiotherapy. In either case, future population-based studies should attempt to characterize LNCs in patients who have undergone preoperative radiotherapy and to determine whether LNCs in this clinical crotamiton setting carry the same importance as they appear to carry in untreated patients. While the improvement in staging accuracy with increasing LNCs has been firmly established, the relationship between lymph node counts and survival is less settled. In the current study, no statistically significant improvement in 5-yr OS was detected with increasing LNCs. In fact, in Kaplan Meier analysis, higher lymph node counts correlated with worse survival, albeit not statistically significant either.

Bipolar disorder There have been few CNV studies of bipolar disorder.59-61 Lachman et al investigated a mixed cohort of Caucasian patients (n=227) and controls (n=276) from the Czech Republic and the United States, and found that CNVs involving the gene glycogen synthase kinase 3 beta (GSK3beta) were significantly increased in patients compared with controls.59 Using a European American sample of 1001 BD patients

and 1034 controls, Zhang et al investigated singleton microdeletions (ie, those occurring only once in the total dataset of patients and controls) of more than 100 kb and found that they were overrepresented in patients.60 The effect was strongest in a subgroup Inhibitors,research,lifescience,medical of patients with an early onset of mania (<8 years of age). A recent study of a three-generation Older Amish pedigree with segregating affective disorder61 identified Inhibitors,research,lifescience,medical a set of 4 CNVs on chromosomes 6q27,9q21,12p13, and 15q11 that were enriched in affected family members and which altered the expression of neuronal genes. No CNV with a genetic effect comparable to those identified

for neuropsychiatric disorders such as schizophrenia or autism has yet been identified for bipolar disorder. In view of the limited number of studies performed, Inhibitors,research,lifescience,medical it is not possible to evaluate the influence of CNVs on disease development. Outlook The first GWASs of schizophrenia and bipolar disorder have recently been published, and many more are in progress. Large international Inhibitors,research,lifescience,medical collaborations have been initiated to combine GWAS data sets in order to increase statistical power, the largest being the Psychiatric GWAS Consortium, which is expected to publish its first results in 2010 (The Psychiatric GWAS Consortium Steering Committee 2009). Currently

available research findings suggest that the variants identified through GWASs confer only small individual risks. The major limitation of GWASs is that they are only able to investigate common variants. If a large fraction of the genetic contribution is conferred by rare variants, other FK506 approaches Inhibitors,research,lifescience,medical will be necessary to identify them. A successful first step in this direction has been the identification of associations between rare CNVs and psychiatric diseases, in particular schizophrenia. However, due to methodological constraints, this approach remains restricted to the investigation of aberrations and of at least several thousand base pairs. Continuing technological developments will provide future studies with increasing resolution, and the availability of low-cost whole genome sequencing technology will ultimately make it possible to obtain the complete genomic sequences of large patient samples for comparison with controls. In principle, this will allow the systematic identification of rare variants that are associated with disease risk, although the existence of a myriad of rare variants in the human genome will render this a complex task.

The CA 19-9 serum levels normalize after treatment of benign cholestasis, whereas it remains elevated in malignant obstruction due to persistent production of CA 19-9 by proliferating tumor cells (31). In an effort to increase the specificity and accuracy of CA 19-9 serum evaluation in the setting of hyperbilirubinemia, several authors have suggested using higher cut-off levels

for serum CA 19-9 or choosing a level determined by receptor operator characteristic (ROC) curves associated with higher specificity. Marrelli et al. evaluated an increased serum CA 19-9 cut-off level of 90 U/mL, and noted that the specificity increased to 95%, while Inhibitors,research,lifescience,medical the sensitivity declined to 61% (78). Similarly, using a CA 19-9 serum cut-off level of >1,000 U/mL in the presence of hyperbilirubinemia, Kim et al. reported a specificity of nearly 100%, but a sensitivity of less than 50% (25). Ortiz-Gonzalez et al. studied 26 patients Inhibitors,research,lifescience,medical with resectable pancreatic

cancer Inhibitors,research,lifescience,medical and found that the median adjusted CA 19-9 serum level was significantly lower (P=0.01) among patients with normal biliary excretion than those with bilirubin levels >2 mg/dL (79). Kang et al. assessed the value of adjusted CA 19-9 serum levels to predict post-operative recurrence in 61 patients who underwent pancreatic resection. Adjusted preoperative CA 19-9 serum levels were significantly lower compared to selleck chemicals baseline CA 19-9 serum levels (129.4±225.2 U/mL vs. 442.1±645.5 U/mL, P<0.0001). Inhibitors,research,lifescience,medical In this study an adjusted preoperative CA 19-9 serum level of ≥50 U/mL (P=0.027) was an independent predictive factor for tumor recurrence (67). Contrary to the above Inhibitors,research,lifescience,medical findings, a recent article reported no effect of hyperbilirubinemia on CA 19-9 serum levels. Maithel et al. studied 491 patients in whom preoperative CA 19-9 serum level was evaluated to predict presence of sub-radiographic unresectable

disease at the time of staging laparoscopy. These authors failed to find any significant correlation between second CA 19-9 serum levels and elevated bilirubin levels (Pearson correlation coefficient 0.12) irrespective of tumor location (pancreatic head or body/tail) (35). Despite the anomalous report cited above, CA 19-9 serum levels are often significantly elevated in the setting of obstructive jaundice, resulting in a further increase in false positives in benign conditions thereby reducing the overall accuracy and specificity of CA 19-9 as a diagnostic marker. The use of adjusted CA 19-9 serum levels or using higher CA 19-9 cut-off levels in the setting of hyper-bilirubinemia and re-evaluation of CA 19-9 serum levels following the treatment of obstruction should improve the diagnostic utility.

There were

more local recurrences with surgery alone (35% versus 13% with CRT, p=0.09) (38). Overall survival was significantly improved with postoperative CRT, and median survival was 47.5 months with CRT versus 14.1 months with surgery alone. Similarly, Rice et al, on retrospective analysis, demonstrated a 28-month with CRT versus 14-month median Inhibitors,research,lifescience,medical survival with surgery alone (37),(39). In modern day practice, it would reasonable to add chemotherapy to postoperative radiation therapy as per NCCN guidelines, to maximize the benefit of radiosensization with systemic therapy, especially if the patient could tolerate such a course. The available data do suggest that postoperative RT alone also would be appropriate. For adenocarcinomas of the GEJ, the MacDonald protocol is reasonable. Postoperative chemoradiation versus Inhibitors,research,lifescience,medical postoperative radiation therapy alone A non-randomized prospective study from Taiwan evaluated postoperative patients with T3-4 and N0-1 esophageal carcinoma who were assigned to mTOR inhibitor either CRT with weekly cisplatin followed by adjuvant chemotherapy consisting

of cisplatin and 5-FU for four cycles (n=30) or postoperative RT alone (n=30) (39). RT was delivered to 55-60 Gy in both arms. A significantly better overall survival was seen with CRT (31 months vs 21 months) and Inhibitors,research,lifescience,medical 3-year survival was improved to 70% with CRT versus 34% with RT alone (p=0.003). Radiation therapy field design Patients undergo a simulation with a Inhibitors,research,lifescience,medical contrast-enhanced computed tomographic (CT) scan, in the treatment position along with an immobilization device, usually in a supine position. Many investigators are utilizing four-dimensional CT scans (40). Appreciation of how the post-resection esophageal conduit moves with respiration, will aid the radiation oncologist in developing portals that cover sites at highest risk for loco-regional recurrence. In pathological analysis of patients with esophageal Inhibitors,research,lifescience,medical and GEJ carcinoma, Gao et al prospectively collected and evaluated 34 squamous cell carcinomas and 32 carcinomas of the GEJ to assess

microscopic spread both proximally and distally in the specimens (41). For squamous cell GPX6 carcinomas, mean microscopic tumor extension beyond the gross tumor was found to be 10.5 ± 13.5 mm proximally (<30 mm in 94%) and 10.6 ± 8.1 mm distally (<30 mm in 97%). In GEJ adenocarcinomas, the spread was 10.3 ± 7.2 mm proximally (<30 mm in all cases) and 18.3 ± 16.3 mm distally (<30 mm in 84%). Lymph node metastases were observed in 35% of patients with middle and lower esophageal squamous cell carcinomas and 47% of patients with GEJ carcinomas. The recommended Clinical Target Volume (CTV) margin was <30 mm in about 94% of esophageal cancers (pleural), except for distal microscopic spread in GEJ adenocarcinomas (pleural), in which 50 mm was needed to cover 94% of cases.