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Purpose MicroRNA-218 (miR-218) is a key regulator of numerous processes relevant to tumor progression. In the present study, we aimed to characterize the relationship between miR-218 and the Epidermal Growth Factor Receptor (EGFR) as well as to understand downstream effects in triple-negative breast cancer (TNBC). Methods We assessed miR-218 and EGFR expression in cell lines and publicly available primary breast cancer gene expression data. We then overexpressed miR-218 in two TNBC cell lines and investigated effects on EGFR and downstream mitogen-activated protein (MAP) kinase signaling. Luciferase reporter assay was used to characterize a direct binding interaction between miR-218 and EGFR mRNA. Digital holographic microscopy helped investigate cell migration and dry mass after miR-218 overexpression. Cell division and invasion were assessed microscopically, while radiation response after miR-218 overexpression alone or combined with additional EGFR knockdown was investigated via clonogenic assays. Results We found an inverse correlation between EGFR expression and miR-218 levels in cell lines and primary breast cancer tissues. MiR-218 overexpression resulted in a downregulation of EGFR via direct binding of the mRNA. Activation of EGFR and downstream p44/42 MAPK signaling were reduced after pre-miR-218 transfection. Cell proliferation, motility and invasiveness were inhibited whereas cell death and mitotic catastrophe were upregulated in miR-218 overexpressing cells compared to controls. MiR-218 overexpressing and EGFR siRNA-treated cells were sensitized to irradiation, more than miR-218 overexpressing cells alone. Conclusion This study characterizes the antagonistic relationship between miR-218 and EGFR. It also demonstrates downstream functional effects of miR-218 overexpression, leading to anti-tumorigenic cellular changes.

Purpose While the stem cell marker Musashi-1 (MSI-1) has been identified as a key player in a wide array of malignancies, few findings exist on its prognostic relevance and relevance for cancer cell death and therapy resistance in breast cancer. Methods First, we determined prognostic relevance of MSI-1 in database analyses regarding multiple survival outcomes. To substantiate findings, MSI-1 was artificially downregulated in MCF-7 breast cancer cells and implications for cancer stem cell markers, cell apoptosis and apoptosis regulator p21, proliferation and radiation response were analyzed via flow cytometry and colony formation. Radiation-induced p21 expression changes were investigated using a dataset containing patient samples obtained before and after irradiation and own in vitro experiments. Results MSI-1 is a negative prognostic marker for disease-free and distant metastasis-free survival in breast cancer and tends to negatively influence overall survival. MSI-1 knockdown downregulated stem cell gene expression and proliferation, but increased p21 levels and apoptosis. Similar to the MSI-1 knockdown effect, p21 expression was strongly increased after irradiation and was expressed at even higher levels in MSI-1 knockdown cells after irradiation. Finally, combined use of MSI-1 silencing and irradiation reduced cancer cell survival. Conclusion MSI-1 is a prognostic marker in breast cancer. MSI-1 silencing downregulates proliferation while increasing apoptosis. The anti-proliferation mediator p21 was upregulated independently after both MSI-1 knockdown and irradiation and even more after both treatments combined, suggesting synergistic potential. Radio-sensitization effects after combining radiation and MSI-1 knockdown underline the potential of MSI-1 as a therapeutic target.

Background/aim Heparanase (HPSE) is relevant to therapy resistance in many malignancies yet is largely unstudied in Hodgkin's lymphoma. Here, we investigated links between HPSE, cancer stem cell (CSC) features and radioresistance in KM-H2 and L428 Hodgkin's lymphoma cells. Materials and methods Firstly, HPSE expression in unsorted and sorted CSCs was assessed. Post-irradiation, HPSE and CSC-related gene expression changes were then quantified. Clonogenic ability was investigated with and without artificial changes in HPSE expression pre and post irradiation. Results HPSE was highly expressed in L428 but barely present in KM-H2 cells. HPSE was overexpressed in sorted L428 CSCs. Irradiation induced HPSE and expression of CSC markers. High HPSE-expressing L428 cells showed higher clonogenic ability than low HPSE-expressing KM-H2 cells after irradiation. Down-regulation of HPSE in L428 cells reduced their clonogenic capability post-radiation, whilst overexpression of HPSE in KM-H2 cells increased colony formation. Conclusion HPSE expression is associated with CSC features and contributes to radioresistance in Hodgkin's lymphoma cells.

Radiation resistance represents a major challenge in the treatment of breast cancer. As heparan sulfate (HS) chains are known to contribute to tumorigenesis, we aimed to investigate the interplay between HS degradation and radiation response in triple-negative breast cancer (TNBC) cells.HS chains were degraded in vitro as TNBC cells MDA-MB-231 and HCC1806 were treated with heparinase I and III. Subsequently, radioresistance was determined via colony formation assay after doses of 2, 4 and 6 Gy. Cell cycle profile, stem cell characteristics, expression of HS, activation of beta integrins, and apoptosis were determined by flow cytometry. Additionally, cell motility was analyzed via wound-healing assays, and expression and activation of FAK, CDK-6, Src, and Erk1/2 were quantified by western blot pre- and post-irradiation. Finally, the expression of cytokines was analyzed using a cytokine array.Radiation promoted cell cycle changes, while heparinase treatment induced apoptosis in both cell lines. Colony formation assays showed significantly increased radio-resistance for both cell lines after degradation of HS. Cell migration was similarly upregulated after degradation of HS compared to controls. This effect was even more prominent after irradiation. Interestingly, FAK, a marker of radioresistance, was significantly activated in the heparinase-treated group. Additionally, we found Src to be dysregulated in MDA-MB-231 cells. Finally, we observed differential secretion of GRO, CXCL1, IGFBP1, IL8, Angiogenin, and Osteoprotegerin after HS degradation and radiotherapy.Our results suggest an influence of HS chains on the development of radioresistance in TNBC.

Background Although CT-based body composition (BC) metrics may inform disease risk and outcomes, obtaining these metrics has been too resource intensive for large-scale use. Thus, population-wide distributions of BC remain uncertain. Purpose To demonstrate the validity of fully automated, deep learning BC analysis from abdominal CT examinations, to define demographically adjusted BC reference curves, and to illustrate the advantage of use of these curves compared with standard methods, along with their biologic significance in predicting survival. Materials and Methods After external validation and equivalency testing with manual segmentation, a fully automated deep learning BC analysis pipeline was applied to a cross-sectional population cohort that included any outpatient without a cardiovascular disease or cancer who underwent abdominal CT examination at one of three hospitals in 2012. Demographically adjusted population reference curves were generated for each BC area. The

Objective To investigate the impact of thoracic body composition on outcomes after lobectomy for lung cancer. Summary and background data Preoperative identification of patients at risk for adverse outcomes permits treatment modification. The impact of body composition on lung resection outcomes has not been investigated in a multicenter setting. Methods A total of 958 consecutive patients undergoing lobectomy for lung cancer at 3 centers from 2014 to 2017 were retrospectively analyzed. Muscle and adipose tissue cross-sectional area at the fifth, eighth, and tenth thoracic vertebral body was quantified. Prospectively collected outcomes from a national database were abstracted to characterize the association between sums of muscle and adipose tissue and hospital length of stay (LOS), number of any postoperative complications, and number of respiratory postoperative complications using multivariate regression. A priori determined covariates were forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide predicted, age, sex, body mass index, race, surgical approach, smoking status, Zubrod and American Society of Anesthesiologists scores. Results Mean patient age was 67 years, body mass index 27.4 kg/m and 65% had stage I disease. Sixty-three percent underwent minimally invasive lobectomy. Median LOS was 4 days and 34% of patients experienced complications. Muscle (using 30 cm increments) was an independent predictor of LOS (adjusted coefficient 0.972; P = 0.002), any postoperative complications (odds ratio 0.897; P = 0.007) and postoperative respiratory complications (odds ratio 0.860; P = 0.010). Sarcopenic obesity was also associated with LOS and adverse outcomes. Conclusions Body composition on preoperative chest computed tomography is an independent predictor of LOS and postoperative complications after lobectomy for lung cancer.

Endometrial carcinoma is the most common gynecological cancer in Europe. Musashi-1 is known to be a key regulator of endometrial cancer stem cells and a negative prognostic marker. In the present study, we aimed to understand growth and gene expression patterns in endometrial carcinoma after Musashi-1 knockdown in vitro and in vivo. Changes in therapeutic resistance were also assessed.First, we performed analyses to understand Musashi-1 expression patterns using The Cancer Genome Atlas database. We then proceeded to assess effects of small interfering RNA-based Musashi-1 targeting in two endometrial carcinoma cell lines, Ishikawa and KLE. After quantifying baseline changes in cell metabolism, we used MTT tests to assess chemotherapy effects and colony formation assays to understand changes in radioresistance. For mechanistic study, we used quantitative polymerase chain reaction (qPCR) and western blotting of key Musashi-1 target genes and compared results to primary tissue database studies. Finally, xenograft experiments in a mouse model helped understand in vivo effects of Musashi-1 knockdown.Musashi-1 is aberrantly expressed in primary tumor tissues. In vitro, silencing of Musashi-1 resulted in a strong decline in cell proliferation and radioresistance, while chemoresistance remained unchanged. Loss of Musashi-1 led to downregulation of telomerase, DNA-dependent protein kinase, the Notch pathway and overexpression of cyclin-dependent kinase inhibitor p21, the latter of which we identified as a key mediator of Msi-1 knockdown-related anti-proliferative signaling. In vivo, the anti-proliferative effect was confirmed, with Msi-1 knockdown tumors being about 40% reduced in size.Musashi-1 knockdown resulted in a strong decrease in endometrial cancer proliferation and a loss of radioresistance, suggesting therapeutic potential.

Introduction Glioblastoma multiforme (GBM) carries a strongly unfavorable prognosis despite intensive multidisciplinary therapy. Physical exercise is rarely offered to patients for fear of adverse events such as falls, epileptic seizures, or bleeding, despite little supporting evidence. Here, we report a study of high-level and long-term exercise in a GBM patient. Methods A 33-yr-old male, diagnosed with a large cystic GBM, was included in our institution's Personal Training Program after initial tumor resection and adjuvant radiochemotherapy. The program was designed to facilitate individual long-term high-intensity exercise. Supervised by a certified personal trainer, it consisted of at least four weekly training sessions and intermittent performance diagnostics. An activity tracker quantified training intensity. Results In this setting, the patient exercised at high intensity without adverse events for 87 continuous weeks (21 months). He averaged 43.7 metabolic equivalent of task hours per week (MET·h·wk), well above the 75th percentile of healthy males the same age, while undergoing multiple surgeries, chemotherapy, and radiation therapy regimens. The patient completed two marathons averaging less than 5 min·km both times, despite tumor progression. Performance diagnostics indicated a gain of fitness even during continuous GBM treatment. Due to multiple intraventricular lesions and increasing intracranial pressure, training was stopped 6 wk before the patient passed away 2 yr after initial diagnosis. Conclusions This study demonstrates that high-intensity, long-term physical training regimens are feasible in GBM patients during full multidisciplinary therapy. In this patient, the exercise was pursued without adverse events and led to a gain of fitness despite tumor progression and intensive multiple therapies. We conclude that, in GBM patients, exercise regimens require further study instead of general discouragement.

Purpose While the stem cell marker Musashi-1 (MSI-1) has been identified as a key player in a wide array of malignancies, few findings exist on its prognostic relevance and relevance for cancer cell death and therapy resistance in breast cancer. Methods First, we determined prognostic relevance of MSI-1 in database analyses regarding multiple survival outcomes. To substantiate findings, MSI-1 was artificially downregulated in MCF-7 breast cancer cells and implications for cancer stem cell markers, cell apoptosis and apoptosis regulator p21, proliferation and radiation response were analyzed via flow cytometry and colony formation. Radiation-induced p21 expression changes were investigated using a dataset containing patient samples obtained before and after irradiation and own in vitro experiments. Results MSI-1 is a negative prognostic marker for disease-free and distant metastasis-free survival in breast cancer and tends to negatively influence overall survival. MSI-1 knockdown downregulated stem cell gene expression and proliferation, but increased p21 levels and apoptosis. Similar to the MSI-1 knockdown effect, p21 expression was strongly increased after irradiation and was expressed at even higher levels in MSI-1 knockdown cells after irradiation. Finally, combined use of MSI-1 silencing and irradiation reduced cancer cell survival. Conclusion MSI-1 is a prognostic marker in breast cancer. MSI-1 silencing downregulates proliferation while increasing apoptosis. The anti-proliferation mediator p21 was upregulated independently after both MSI-1 knockdown and irradiation and even more after both treatments combined, suggesting synergistic potential. Radio-sensitization effects after combining radiation and MSI-1 knockdown underline the potential of MSI-1 as a therapeutic target. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03743-y.

OBJECTIVE. CT-based body composition analysis quantifies skeletal muscle and adipose tissue. However, acquisition parameters and quality can vary between CT images obtained for clinical care, which...

The COVID-19 pandemic is associated with significant morbidity, mortality, and restrictions on everyday life worldwide. This may be especially challenging for brain tumor patients given increased vulnerability due to their pre-existing condition. Here, we aimed to investigate the quality of life (QoL) in brain tumor patients and relatives in this setting. Over twelve weeks during the first wave of the pandemic (04–07/2020), brain tumor patients and their families from two large German tertiary care centers were asked to complete weekly questionnaires for anxiety, depression, distress, and well-being. Information regarding social support and living conditions was also collected. One hundred participants (63 patients, 37 relatives) completed 729 questionnaires over the course of the study. Compared to relatives, patients showed more depressive symptoms (p &lt, 0.001) and reduced well-being (p = 0.013). While acceptance of lockdown measures decreased over time, QoL remained stable. QoL measures between patients and their families were weakly or moderately correlated. The number of social contacts was strongly associated with QoL. Age, living conditions, ongoing therapy, employment, and physical activity were other predictors. QoL is correlated between patients and their families and heavily depends on social support factors, indicating the need to focus on the entire family and their social situation for QoL interventions during the pandemic.

Context.—Lesion localization during intraoperative frozen section of lung resection specimens can be challenging. Imaging could aid lesion localization while enabling 3-dimensional specimen analysis.Objective.—To assess the feasibility of integrating micro–computed tomography (micro-CT) into the perioperative evaluation of fresh surgical lung resection specimens.Design.—Fresh lung specimens from patients with a presumptive diagnosis of lung cancer were imaged with micro-CT prior to routine histopathologic and molecular analysis. Micro-CT images were assessed to determine image quality, lesion size, and distance from lesion to the nearest surgical margin. Micro-CT measurements were compared to pathologic measurements using Bland-Altman analysis.Results.—A total of 22 specimens from 21 patients were analyzed (mean image acquisition time, 13 ± 6 minutes). Histologic quality of imaged specimens was indistinguishable from a control group of nonimaged lung specimens. Artifacts, most commonly from specimen deflation (n = 8), obscured fine detail on micro-CT images of 10 specimens. Micro-CT could successfully localize the target lesion in the other 12 specimens. Distance to the nearest surgical margin was determined in 10 specimens. Agreement of micro-CT with final pathology was good, with a mean difference of −2.8% (limits of agreement −14.5% to 20.0%) for lesion size and −0.5 mm (limits of agreement −4.4 to 3.4 mm) for distance to nearest surgical margin.Conclusions.—Micro-CT of fresh surgical lung specimens is feasible and has the potential to evaluate the size and location of lesions within resection specimens, as well as distance to the nearest surgical margin, all without compromising specimen integrity.

Background Assessment of risk associated with lung cancer resection is primarily based on evaluation of cardiopulmonary function and remains imprecise. We investigated the relationship between thoracic muscle and early outcomes after lobectomy. Methods Cross-sectional area of skeletal muscle was measured at the level of the fifth thoracic vertebra on computed tomography in 135 consecutive patients before lobectomy for lung cancer. Patients were stratified into low and high muscle groups using the sex-specific muscle median. Primary outcome was a composite of any postoperative complication as per The Society of Thoracic Surgeons General Thoracic Surgical Database. Secondary outcomes included postoperative respiratory complications, postoperative intensive care unit admission, hospital length of stay, and hospital readmission within 30 days of hospital discharge. The χ2 test, adjusted multivariable regression analysis, and likelihood ratio test were performed. Results Patients with low muscle were significantly more likely to have any postoperative complication and respiratory postoperative complications. Although postoperative intensive care unit admission was similar for low muscle and high muscle groups, low muscle patients had longer hospital length of stay and a higher rate of hospital readmission. Adjusted multivariable regression revealed the independent association of thoracic muscle with all outcomes. The likelihood ratio test suggested that thoracic muscle adds predictive capability to information captured by preoperative pulmonary function testing. Conclusions Low thoracic muscle is independently associated with increased postoperative complications and health care utilization among patients undergoing lobectomy for lung cancer. Evaluation of thoracic muscle may enhance risk prediction models.

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.

Cancer cachexia and sarcopenia can occur frequently in patients with advanced cancer, and may negatively affect treatment outcomes. This article highlights the importance of assessing sarcopenia and describes the relationship between sarcopenia and patients' quality of life in patients with newly diagnosed, incurable cancer., Background. Patients with advanced cancer often experience muscle wasting (sarcopenia), yet little is known about the characteristics associated with sarcopenia and the relationship between sarcopenia and patients’ quality of life (QOL) and mood. Materials and Methods. As part of a randomized trial, we assessed baseline QOL (Functional Assessment of Cancer Therapy‐General [FACT‐G]) and mood (Hospital Anxiety and Depression Scale [HADS]) in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer, and prior to randomization. Using computed tomography scans collected as part of routine clinical care, we assessed sarcopenia at the level of the third lumbar vertebra with validated sex‐specific cutoffs. We used logistic regression to explore characteristics associated with presence of sarcopenia. To examine associations between sarcopenia, QOL and mood, we used linear regression, adjusted for patients’ age, sex, marital status, education, and cancer type. Results. Of 237 participants (mean age = 64.41 ± 10.93 years), the majority were male (54.0%) and married (70.5%) and had lung cancer (56.5%). Over half had sarcopenia (55.3%). Older age (odds ratio [OR] = 1.05, p = .002) and education beyond high school (OR = 1.95, p = .047) were associated with greater likelihood of having sarcopenia, while female sex (OR = 0.25, p

Aim Research has identified patients with chronic liver disease as a risk group for colorectal neoplasia. In this study, we aimed to identify liver disease subgroups at enhanced risk of developing colorectal neoplasia, as well as causal factors. Methods The present retrospective study included patients with chronic liver disease undergoing colonoscopy during liver transplantation evaluations, and liver-healthy patients as part of the German screening protocol. We assessed inflammatory laboratory values, Model for End-stage Liver Disease score, portal hypertension, and liver disease etiologies as explanatory variables. Outcomes included polyps, adenomas, high-risk situations, and colorectal cancer, tested in uni- and multivariable analyses. Results A total of 1046 patients were included, 407 with liver disease, 639 without. Alcohol-toxic, metabolic, cryptogenic, non-alcoholic fatty liver disease, and hepatocellular carcinoma were significantly associated with colorectal neoplasia, as were low compared with high Model for End-stage Liver Disease scores. Portal hypertension showed no associations with neoplasia. Inflammatory markers were associated with colorectal neoplasia, independent of liver disease severity. Conclusions Low Model for End-stage Liver Disease score, inflammatory markers, and certain etiologies were associated with colorectal neoplasia. Our findings suggest that inflammation may play an important role in the development of colonic adenomas in patients with chronic liver disease. Findings need to be confirmed in prospective studies, but may allow risk stratification and, possibly, development of prophylactic treatments.

Body composition analysis, also referred to as analytic morphomics, morphomics, or morphometry, describes the measurement of imaging biomarkers of body composition such as muscle and adipose tissue, most commonly on computed tomography (CT) images. A growing body of literature supports the use of such metrics derived from routinely acquired CT images for risk prediction in various patient populations, including those with lung cancer. Metrics include cross-sectional area and attenuation of skeletal muscle and subcutaneous, visceral, and intermuscular adipose tissue. The purpose of this review is to provide an overview of the concepts, definitions, assessment tools, segmentation techniques and associated pitfalls, interpretation of those measurements on chest and abdomen CT, and a discussion of reported outcomes associated with body composition metrics in patients with early-stage and advanced lung cancer.

Background Sarcopenia represented by low psoas muscle area is associated with increased hospital length of stay (LOS), postoperative complications, and mortality. We studied whether thoracic skeletal muscle area (TSMA) derived from computed tomography (CT) predicts morbidity after pneumonectomy for lung cancer. Methods Consecutive patients who underwent pneumonectomy for lung cancer from 2005 to 2017 were retrospectively analyzed. TSMA was defined as the sum of muscle area at the level of the eighth and the 12th thoracic vertebral bodies on preoperative CT. Patients were stratified into sex-specific TSMA quartiles for univariate time-to-event analyses. The effect of continuous TSMA measurements on operative complications, hospital and intensive care unit (ICU) LOS, discharge disposition, and hospital readmission within 90 days was estimated using multivariable models adjusted for age, sex, body mass index, forced expiratory volume in 1 second, Zubrod score, and pneumonectomy type. Results Standard (n = 102, 78.5%) or high-risk (n = 28, 21.5%; extrapleural: n = 3, 2.3%; carinal: n = 9, 6.9%; completion: n = 16, 12.3%) pneumonectomy was performed in 130 patients (60.8 ± 10.6 years; 43.1% women). Major complications occurred in 33.1% (n = 43 of 130) and readmission in 17.7% (n = 23 of 130) of patients. In multivariable models, patients with high TSMA experienced fewer overall (odds ratio [OR], 0.87; P = .04) and cardiopulmonary (OR, 0.86; P = .04) complications, and fewer readmissions (OR, 0.78; P = .01). Associations with ICU LOS (hazard ratio, 1.08; P = .051) and hospital LOS (hazard ratio, 1.05; P = .18) did not reach significance. Conclusions TSMA predicts adverse outcome after pneumonectomy for lung cancer. This marker, readily derived from standard chest CT, identifies patients at increased risk for postoperative complications and may help select patients appropriate for focused rehabilitation before pneumonectomy.

A brain tumor diagnosis poses a significant psychological burden and it severely impacts quality of life (QOL), both in patients and relatives. However, comprehensive strategies addressing QOL in this setting remain rare. Here, we aim to share our findings of a one-week ski exercise intervention, with emphasis on feasibility, safety, QOL, and physical exercise. The intervention consisted of week-long daily ski sessions with professional ski guides as well as dedicated physicians present. The participants were handed questionnaires, including distress and QOL items before, during, and after the intervention. Using fitness watches, exercise intensity was also tracked at these timepoints. During the intervention, patients were checked for adverse events daily. Fifteen participants, nine patients after multidisciplinary treatment, and six relatives were included in the study. Additionally, 13 children participated in the exercise, but not in the study. All of the participants completed the entire program. No severe adverse events were documented during daily checks. There was a strong increase in quantified activity and QOL with a corresponding decrease in distress during the intervention, and, partly, afterwards. This prospective brain tumor rehabilitation study demonstrates the feasibility and safety of challenging ski exercise in brain tumor patients. The findings also underline the exercise-mediated QOL benefits, emphasizing the need for more comprehensive brain tumor rehabilitation programs.

Background Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy. Objective The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence. Methods This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program. Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed. Results In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients. Conclusion Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.

Objectives To assess the prognostic role of thoracic muscle as quantified on preoperative computed tomography (CT) for the estimation of overall survival (OS) following pneumonectomy. Methods Muscle cross-sectional area (CSA) at the level of the fifth (T5) and eighth (T8) thoracic vertebra was measured on CT scans of consecutive patients with lung cancer prior to pneumonectomy. We stratified patients into high and low muscle groups using the gender-specific median of muscle CSA as separator and estimated associations of muscle CSA and OS using the Kaplan-Meier analysis. Multivariable logistic regression adjusted for body mass index, Charlson comorbidity index (includes age), forced expiratory volume in the first second as a % of predicted, sex, race, smoking status, tumour stage and prior lung cancer treatment was performed. Results A total of 128 patients were included (61.0 ± 10.6 years of age, mean body mass index of 26.9 kg/m2, 55.5% men). The T8 level showed fewer artefacts and strong correlation with the T5 level (Pearson's rho = 0.904). T8 CSA was therefore used for subsequent analyses. Mean T8 CSA was 118.5 cm2 (median 115.3 cm2) in men and 75.2 cm2 (median 74.0 cm2) in women. During a median follow-up of 23.6 months (interquartile range 39.3), 65 patients (50.8%) died, of whom 41 were in the low muscle group. The Kaplan-Meier analysis showed significantly longer OS in the high muscle group (log-rank P = 0.02). Multivariable analysis showed an independent association of muscle CSA and OS (P = 0.02) with a hazard ratio of 0.80 (confidence interval 0.67-0.98) per 10-cm2 increment. Conclusions Thoracic muscle is independently associated with long-term overall survival following pneumonectomy for lung cancer and may contribute to refined survival estimates in this population. Irb protocol Protocol #2017P000650, approved 21 April 2017.

In his editorial “ Sarcopenia is a potential factor for optimized treatment selection for elderly patients with early stage non-small-cell lung cancer recent retrospective analysis” Dr. Matsuo comments on our study “Thoracic Skeletal Muscle Is Associated With Adverse Outcomes After Lobectomy for Lung Cancer ” (1). We appreciate the opportunity to reply to his comments and discuss how body composition metrics derived from routine computed tomography (CT) images of the thorax could improve lung cancer care.

Sarcopenia, the loss of muscle mass, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about change in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Cross-sectional areas of lean muscle, subcutaneous adipose tissue, and visceral adipose tissue were measured on CT at the level of the third lumbar vertebral body before HCT, 1-year post-HCT, and 2.5 years post-HCT. The incidence of sarcopenia before HCT was 47% in the autologous HCT (auto-HCT) cohort (n = 218) and 55% in the allogeneic HCT (allo-HCT) cohort (n = 97). Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.04; P .001) and male sex (OR, 4.59; 95% CI, 1.42 to 4.93; P .001) were associated with sarcopenia before HCT. Increasing body mass index (OR, .78; 95% CI, .73 to .84; P .001) was protective against sarcopenia before HCT. A significant decline in total lean body mass (β = 1.96; 95% CI, .79 to 3.13; P = .001) and increased sarcopenia incidence (OR, 1.72; 95% CI, 1.13 to 2.62, P = .012) was observed over time for patients in the allo-HCT cohort when compared with the trend in the auto-HCT cohort. Both auto-HCT and allo-HCT recipients experienced an increase in total body fat mass over time (β = 3.75; 95% CI, 2.77 to 4.73; P .001). In multivariate analysis of patients undergoing allo-HCT, the presence of sarcopenia on baseline imaging before HCT was associated with a lower risk of acute graft-versus-host disease (OR, .30; 95% CI, .09 to .98; P = .047). In conclusion, we found that total body fat mass increases after both auto-HCT and allo-HCT. Following allo-HCT, total lean body mass significantly decreases corresponding to increased incidence of sarcopenia. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes.

Background Computed tomography (CT)-based fat and muscle measures are associated with outcome in large populations. We tested if muscle and fat characteristics are associated with long-term outcomes after TAVR. Methods We included 403 clinical CTs performed prior to TAVR at our center between 2008 and 2016, measuring area (cm2) and density (Hounsfield units, HU) of both psoas muscles (PM), subcutaneous adipose (SAT), and visceral adipose tissue (VAT). Area measures were indexed to height, log-transformed and both area and density were standardized for analysis. We assessed the association of each measure with all-cause mortality (adjusted for age, sex, body mass index (BMI), and the Society of Thoracic Surgeons (STS) risk score. Results Of the 403 individuals (83 ± 8 years; 52% female), 167 (41.4%) died during a median follow-up of 458 days (interquartile range IQR 297–840). Fat measures were feasible and rapid. Fat area was available in 242 (60%) patients with an adequate field of view. Individuals with the lowest PM area, SAT area or VAT area exhibited the highest hazard of mortality. In addition, greater SAT density was associated with a higher mortality hazard (adjusted HR per standard deviation increase in density = 1.35, 95%CI 1.10–1.67, P = 0.005). Conclusion Rapid CT-based tissue characterization is feasible in patients referred for TAVR. Decreased PM area and increased SAT density are associated with long-term mortality after TAVR, even after accounting for age, sex, BMI, and STS score. Further studies are necessary to interrogate sex-specific relationships between CT tissue metrics and mortality and whether CT measures are incremental to well-established frailty metrics.