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Simple Summary: Sacrectomy represents a radical indication for bone sarcomas (e.g., osteosarcoma or chondrosarcoma) and chordomas, as well as selected carcinomas with invasion of the sacrum. Extralesional en bloc excision is surgically demanding and associated with resection-induced neurologic deficits and risks. Due to the low incidence of bone sarcomas, the rare localization in the sacrum and the complexity of the surgical procedure, studies reporting on the oncological outcome and corresponding complications in larger patient numbers are rare. The aim was to describe the oncosurgical management and the complication profile and to analyze our own treatment results after partial/total sacrectomy, with attention paid to a possible benefit by using intraoperative 3D navigation. There was a significant difference in progression-free and metastasis-free survival between sarcoma, chordoma and carcinoma patients. Complications were common, but no independently influencing causative factors could be identified. Although there was a subjective impression of improved intraoperative 3D orientation and easier identification of resection planes, the use of navigation did not significantly influence resection status or oncological patient outcome. Introduction: Bone sarcoma or direct pelvic carcinoma invasion of the sacrum represent indications for partial or total sacrectomy. The aim was to describe the oncosurgical management and complication profile and to analyze our own outcome results following sacrectomy. Methods: In a retrospective analysis, 27 patients (n = 8/10/9 sarcoma/chordoma/locally recurrent rectal cancer (LRRC)) were included. There was total sacrectomy in 9 (incl. combined L5 en bloc spondylectomy in 2), partial in 10 and hemisacrectomy in 8 patients. In 12 patients, resection was navigation-assisted. For reconstruction, an omentoplasty, VRAM-flap or spinopelvic fixation was performed in 20, 10 and 13 patients, respectively. Results: With a median follow-up (FU) of 15 months, the FU rate was 93%. R0-resection was seen in 81.5% (no significant difference using navigation), and 81.5% of patients suffered from one or more minor-to-moderate complications (especially wound-healing disorders/infection). The median overall survival was 70 months. Local recurrence occurred in 20%, while 44% developed metastases and five patients died of disease. Conclusions: Resection of sacral tumors is challenging and associated with a high complication profile. Interdisciplinary cooperation with visceral/vascular and plastic surgery is essential. In chordoma patients, systemic tumor control is favorable compared to LRRC and sarcomas. Navigation offers gain in intraoperative orientation, even if there currently seems to be no oncological benefit. Complete surgical resection offers long-term survival to patients undergoing sacrectomy for a variety of complex diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored advanced diagnostic methods that are used for identifying skin cancer in high-risk melanoma patients. A total of 410 patients were examined using a combination of three advanced imaging techniques: 3D total body photography, digital dermoscopy, and reflectance confocal microscopy. These methods were used in addition to regular skin exams. Results showed that the specialized imaging detected 16 melanomas in 39 removed pigmented lesions, while regular exams detected only 7 melanomas in 163 removed lesions. This indicates that specialized imaging was much more efficient. Each imaging method found melanomas that the others did not. The study concludes that combining these three imaging techniques improves melanoma detection and reduces unnecessary skin removals in high-risk patients. Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Functional MRI has become established in the surgery of brain metastases (BM) as a preoperative diagnostic tool to identify intact eloquent cortex areas. Evidence shows that by allowing surgeons to spare these intraoperatively, patients' postoperative outcome is improved in terms of significantly reduced mortality and morbidity. The influence specifically of BM on the fMRI signal and brain networks has scarcely been investigated, as most studies to date refer only to primary brain tumors or include various tumor entities. Our work examined how BM affect cortical activation and brain networks using task-based fMRI. We found a qualitative attenuation of patients' fMRI signal in the metastasis-affected hemisphere compared to the contralateral hemisphere and alterations in all examined brain networks of the patients compared to healthy controls, and also in the contralateral hemisphere. Thus, our results provide insights into the behavior of BM during fMRI examination and their impact on the integrity of the brain. To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage. [ABSTRACT FROM AUTHOR]

Background: In hemodynamically unstable patients, the passive leg raise (PLR) test is recommended for use as a self-fluid challenge for predicting preload responsiveness. However, to interpret the hemodynamic effects and reliability of the PLR, the method of performing it is of the utmost importance. Our aim was to determine the current practice of the correct application and interpretation of the PLR in intensive care patients. Methods: After ethical approval, we designed a cross-sectional online survey with a short user-friendly online questionnaire. Using a random sample of 1903 hospitals in Germany, 182 hospitals with different levels of care were invited via an email containing a link to the questionnaire. The online survey was conducted between December 2021 and January 2022. All critical care physicians from different medical disciplines were surveyed. We evaluated the correct points of concern for the PLR, including indication, contraindication, choice of initial position, how to interpret and apply the changes in cardiac output, and the limitations of the PLR. Results: A total of 292 respondents participated in the online survey, and 283/292 (97%) of the respondents completed the full survey. In addition, 132/283 (47%) were consultants and 119/283 (42%) worked at a university medical center. The question about the performance of the PLR was answered correctly by 72/283 (25%) of the participants. The limitations of the PLR, such as intra-abdominal hypertension, were correctly selected by 150/283 (53%) of the participants. The correct effect size (increase in stroke volume ≥ 10%) was correctly identified by 217/283 (77%) of the participants. Conclusions: Our results suggest a considerable disparity between the contemporary practice of the correct application and interpretation of the PLR and the practice recommendations from recently published data at German ICUs. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most commonly diagnosed cancers worldwide with a high probability of developing metastasis over the course of the disease. Only certain patients with colorectal liver metastases can be treated by surgical resection. Different interventional treatments such as laser-induced thermotherapy, microwave ablation, as well as transarterial chemoembolization can be applied for treating colorectal liver metastases. These therapies have been discussed in various studies. However, the current medical literature is still lacking research from large long-term studies. This retrospective monocentric study includes 2140 patients with colorectal liver metastases treated by different locoregional treatments. It is based upon data collected over a period of more than 26 years at the University Hospital Frankfurt of Goethe University. The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 outbreak necessitated physical distancing, as part of secondary prevention, at a personal and professional level. Working from home (WFH) became increasingly important. In this study, the impact of the COVID-19 pandemic restrictions on physical and mental health is investigated, compared with pre-pandemic data, and with employees who WFH and are on-site. Methods: Data from the German Saxon longitudinal study population were used. Attitudes towards WFH as well as mental and physical health assessments during the COVID-19 pandemic were examined. Comparisons were made with corresponding pre-pandemic scores and between employees WFH and on-site in 2022. Results: In total, 319 participants with equal gender distribution were included. Of those, 86 worked from home stating better organizability of their work, more time for partnership, less stress, and greater work satisfaction. Compared to pre-pandemic data, the D-score, PHQ-4, G-Score, and PHQ-SSS-8 showed a significant increase. No difference in physical or mental health between employees WFH and on-site was observed. Conclusion: In general, COVID-19 restrictions had a negative impact on mental and physical health. Although WFH is well accepted, it did not show significant health benefits. [ABSTRACT FROM AUTHOR]

Background: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. Methods: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. Results: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). Conclusions: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Hyperthermic intrathoracic chemotherapy (HITOC) is an intraoperative treatment after a surgical cytoreduction of pleural malignancies. The pleural cavity is perfused with high doses of cytostatic drugs that are consequentially excreted via various body fluids. These are potential occupational health risk factors for medical staff and safety measurements must be established based on scientific evidence. Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin. [ABSTRACT FROM AUTHOR]

Simple Summary: This opinion paper describes the regulatory hurdles for a clinical oncologist and physician scientist to activate an Investigator-Initiated Trial (IIT) before and after 2004 with German regulation as an example. Changes in legal framework with impacts on time and costs to activate a clinical trial are described. Evidence needed to reach the objective of higher patient safety and trial quality by European Union (EU) Clinical Trial Directive (CTD) 2001/20 is discussed. Shortly after the beginning of the year 2000, multiple legal changes with impacts on the regulatory framework of clinical trials became effective almost simultaneously. They included the European Union (EU) Clinical Trial Directive (CTD) 2001/20 followed by major changes in national drug laws, the change in the legal status of German University Hospitals (1998), and a new disease-related groups (DRG)-based reimbursement system for hospitals in Germany (2000). Together, these changes created enormous bureaucratic and financial inhibition of activation and conduct of academic investigator-initiated clinical trials (IIT). Examples for activating clinical trials in oncology before and after 2004 are outlined and discussed, focussing on extended time frames, the establishment of centralized responsibility structures and the exploding financial consequences. In addition, the evolution of trial numbers and the distribution of trial initiators between "commercial" and "academic" over time are discussed together with the occurrence of clinical registries. At the same time, progress in molecular biology led to a plethora of new targets for effective pharmacological therapy of life-threatening diseases such as cancer, and the overall number of clinical trials has not decreased. Yet, judging the regulatory and administrative hurdles between scientific study design and first-patient on trial before and after 2004 and weighing these against the lack of evidence that this regulation has achieved its goal to enhance patient safety and trial quality, the necessity to completely overhaul this CTD becomes obvious. A main goal of such an initiative should be to minimize bureaucracy. For the specific situation in Germany, relocation of responsibility and freedom to operate in University Hospitals and Medical Faculties back to the physician–scientists and reduction in interference by legal divisions should be a goal as well as increasing the public financial support for IITs. [ABSTRACT FROM AUTHOR]

Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer from reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients' quality of life. A total of 489 advanced rectal cancer patients from the University Hospital Erlangen in Germany were surveyed between May 2010 and March 2022 and asked to fill out the EORTC QLQ-C30 and QLQ-CR38 questionnaires over eight different time points: at the beginning, during and after radiochemotherapy, right before surgery, and in yearly intervals after surgery for up to four years. Answers were converted to scores to compare the COVID-19 period to the time before March 2020, focusing on the follow-ups, the developments over time—including by sex and age—and the influence of the TNM cT-stage. Overall, a trend of impaired functional and symptom scores was found across all surveys with few significances (body image −10.6 percentage points (pp) after one year; defecation problems +13.5 pp, insomnia +10.2 pp and weight loss +9.8 pp after three years; defecation problems +11.3 pp after four years). cT4-stage patients lost significantly more weight than their cT1-3-stage counterparts (+10.7 to 13.7 pp). Further studies should be conducted to find possible causes and develop countermeasures for future major infectious diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) association is the most important predictor of survival in squamous cell carcinomas in the head and neck region (HNSCC). The role of HPV in cancer of unknown origin at this anatomic site (CUPHNSCC) is less well understood. The objective of this study was to identify prognostic classification markers in CUPHNSCC. Therefore, we investigated a consecutive cohort by multivariate modeling and testing for HPV DNA, mRNA, and p16INK4a (p16) expression. In 31% of CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%) of them, which was mostly consistent with mRNA detection. In contrast to oropharyngeal cancer, detection of p16 without additional detailed HPV testing appears to be more appropriate for the classification of CUPHNSCC. Three risk groups can be stratified based on performance status and p16, but additional factors may become important in future data or for cases with particular risk profiles. Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. Methods: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000–2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. Results: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. Conclusions: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles. [ABSTRACT FROM AUTHOR]

Background: Satisfaction with care is an important indicator of health care quality. However, if this process measure is associated with patients' outcomes in real-world data is largely unknown. We, therefore, aimed to evaluate if satisfaction with physician- and nurse-related care is associated with quality of life and self-rated health among inpatients at the University Hospital Hamburg-Eppendorf in Germany. Method: We used standard hospital quality survey data of 4925 patients treated at various departments. We used multiple linear regressions to examine an association between satisfaction with staff-related care and quality of life as well as self-rated health, adjusted for age, gender, mother tongue, and treating ward. Patients rated their satisfaction with physician- and nurse-related care from 0 "not at all" to 9 "very much". The outcomes regarding quality of life and self-rated health were evaluated on five-point Likert scales ranking from 1 "bad" to 5 "excellent". Results: We found that satisfaction with physician-related care was positively associated with quality of life (ß = 0.16; p < 0.001) as well as with self-rated health (ß = 0.16; p < 0.001). Similar findings were observed for satisfaction with nurse-related care and the two outcomes (ß = 0.13; p < 0.001 and ß = 0.14; p < 0.001, respectively). Conclusion: We show that patients who are more satisfied with staff-related care report better quality of life and self-rated health than patients less satisfied with care. Thus, patient satisfaction with care, is not only a process measure indicating the quality of care but is also positively associated with patient-reported outcomes. [ABSTRACT FROM AUTHOR]

This study aims at evaluating the use case potential of breast cancer care for artificial intelligence and blockchain technology application based on the patient data analysis at Marburg University Hospital and, thereupon, developing a digital workflow for breast cancer care. It is based on a retrospective descriptive data analysis of all in-patient breast and ovarian cancer patients admitted at the Department of Gynecology of Marburg University Hospital within the five-year observation period of 2017 to 2021. According to the German breast cancer guideline, the care workflow was visualized and, thereon, the digital concept was developed, premised on the literature foundation provided by a Boolean combination open search. Breast cancer cases display a lower average patient case complexity, fewer secondary diagnoses, and performed procedures than ovarian cancer. Moreover, 96% of all breast cancer patients originate from a city with direct geographical proximity. Estimated circumference and total catchment area of ovarian present 28.6% and 40% larger, respectively, than for breast cancer. The data support invasive breast cancer as a preferred use case for digitization. The digital workflow based on combined application of artificial intelligence as well as blockchain or distributed ledger technology demonstrates potential in tackling senological care pain points and leveraging patient data safety and sovereignty. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is frequently seen in elderly patients. The aim of our retrospective study was to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. Our data confirm that pancreatic resections can be performed with equal short-term outcomes even in older age. However, patient age significantly influenced the overall and disease-free survival of patients with PDAC undergoing primary resection in curative intent. Therefore, the choice of the optimal therapy concept for each patient should be individualized taking into account the patient's age. (1) Purpose: to evaluate the impact of age on postoperative short-term and long-term outcomes in patients undergoing curative pancreatic resection for PDAC. (2) Methods: This retrospective single-center study comprised 213 patients who had undergone primary resection of PDAC from January 2000 to December 2018 at the University Hospital of Erlangen, Germany. Patients were stratified according the age into two groups: younger (≤70 years) and older (>70 years) patients. Postoperative outcome and long-term survival were compared between the groups. (3) Results: There were no significant differences regarding inhospital morbidity (58% vs. 67%, p = 0.255) or inhospital mortality (2% vs. 7%, p = 0.073) between the two groups. The median overall survival (OS) and disease-free survival (DFS) were significantly shorter in elderly patients (OS: 29.2 vs. 17.1 months, p < 0.001, respectively; DFS: 14.9 vs. 10.4 months, p = 0.034). Multivariate analysis revealed that age was a significant independent prognostic predictor for OS and DFS (HR 2.23, 95% CI 1.58–3.15; p < 0.001 for OS and HR 1.62, 95% CI 1.17–2.24; p = 0.004 for DFS). (4) Conclusion: patient age significantly influenced overall and disease-free survival in patients with PDAC undergoing primary resection in curative intent. [ABSTRACT FROM AUTHOR]

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling. [ABSTRACT FROM AUTHOR]

Her2 overexpression and amplification can be found in a significant subset of esophageal adenocarcinomas. The activity of Her2 has been shown to be modulated by molecular chaperones such as HSP90. We analyzed expression/amplification data for HSP90 and Her2 on 127 primary resected esophageal adenocarcinomas in order to evaluate a possible relationship between these two molecules. HSP90 expression determined by immunohistochemistry was observed in various levels. Thirty nine (39) tumors (30.7%) were classified as Her2-positive according to their immunoreactivity and amplification status. There was a significant correlation between HSP90 expression and Her2-status (p = 0.008). This could also be demonstrated by quantitative protein expression analysis with reverse phase protein arrays (r = 0.9; p < 0.001). Her2-status was associated withpT-category (p = 0.041), lymph node metastases (p = 0.049) and tumor differentiation (p = 0.036) with a higher percentage of cases with negative Her2 status in lower tumor stagesA negative Her2-status was also associated with better survival in univariate and multivariate analysis (p = 0.001 and p = 0.014). For HSP90, no associations between clinical and pathological parameters were found. The observed association between HSP90 expression and Her2 suggests a co-regulation of these molecules in at least a subset of esophageal adenocarcinomas. Anti-HSP90 drugs, which recently have been introduced in cancer treatment, may also be an option for these tumors by targeting HSP90 alone or in combination with Her2. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether prematurity and associated factors affect the anterior chamber angle (ACA) width in adulthood. Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination of adults (age 18–52 years) in Germany. All participants were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany) using linear regression analysis to assess the associations of ACA in the different sectors with gestational age (GA), birth weight, birth weight percentile, retinopathy of prematurity (ROP), ROP treatment, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 516 eyes of 319 preterm and full-term individuals (aged 28.9 ± 8.8 years, 188 females) were examined. ROP treatment was associated with smaller ACA width in the nasal (B = −9.6 [95%CI: −14.7; −4.5] degree; p < 0.001) and temporal positions (B = −11.5 [95%CI: −17.7; −5.3] degree; p = 0.001), whereas non-treated individuals with ROP had an unaltered ACA width, as did individuals with low gestational age without ROP. Conclusion: Advanced stages of ROP following treatment with laser- and cryocoagulation lead to a smaller ACA width until adulthood, and hence may increase the risk of angle closure in later life. [ABSTRACT FROM AUTHOR]

Simple Summary: Differentiated thyroid cancer includes papillary (PTC) and follicular thyroid cancer (FTC). Eighty-five percent of patients are cured by thyroidectomy and one single radioiodine treatment. Relapse is rare and can mostly be cured by a second radioiodine therapy. Between 5% and 10% of differentiated thyroid cancers are, or become, unresponsive to radioiodine treatment during the course of disease. For these patients repeated surgery is the only curative option: chemotherapy and external beam radiation play a minor role, targeted therapy is started in a palliative setting for rapidly progressing tumors. In most studies on radioiodine refractory differentiated thyroid cancer, there is a predominance of PTC, due to its higher incidence compared to FTC. In the present study we critically evaluate indications and outcome of repetitive cervical surgery for radioiodine refractory FTC at our university clinic. Compared to its more common counterpart papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) has a less favorable outcome, due to its higher incidence of distant metastases and advanced stages at diagnosis. Despite radioiodine (RAI) avidity, metastatic FTC often progresses after radioiodine treatment (RAIT). We aimed at evaluating the indications and outcomes of surgery for cervical relapse of radioiodine refractory FTC. Patients receiving RAIT between 2005 and 2015 at the University Hospital of Cologne, Germany, were screened. Patients with FTC were identified. Demographics, clinic-pathologic characteristics, treatment, and outcome of patients diagnosed with RAI refractory FTC, who underwent cervical surgery in the course of disease, were analyzed. FTC accounted for 8.8% of all thyroid carcinomas undergoing RAIT. In 35.2% of FTC patients, disease persisted or recurred despite a cumulative mean RAI activity of 18.7 GBq ± 11.6 (follow-up 83.5 ± 56.7 months). Distant metastases were diagnosed in 75% of these patients, as bone (57.6%), lung (54.6%), and liver metastases (12.1%). Cervical relapse occurred in 63.6% of these patients and was treated in 57.1% with surgery with, and without, external beam radiation therapy (EBRT). Despite surgery and EBRT, in 75% of patients, cervical relapse recurred again. In conclusion, surgery for cervical radioiodine refractory FTC relapse is often performed in metastatic setting. With and without EBRT, cure is rare, although metastases can appear radioiodine avid. Early biological marker and systemic treatments for these patients are still needed. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a common medical problem in patients worldwide, with an increasing prevalence of patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT). In patients requiring RRT for more than two weeks or those who develop ESKD, tunneled hemodialysis catheter (HDC) insertion is preferred, based on a lower risk for infectious complications. While the efficacy of ultrasound (US)-guided tip positioning in antegrade-tunneled HDCs has previously been shown, its application for the insertion of retrograde-tunneled HDCs has not been described yet. This is especially important, since the retrograde-tunneled technique has several advantages over the antegrade-tunneled HDC insertion technique. Therefore, we here report our first experience of applying the rapid atrial swirl sign (RASS) for US-guided tip positioning of retrograde-tunneled HDCs. Methods: We performed a cross-sectional study to assess the feasibility of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs. We performed a total number of 24 retrograde-tunneled HDC insertions in 23 patients (requiring placement of a HDC for the temporary or permanent treatment of ESKD) admitted to our Department of Nephrology and Rheumatology at the University Medical Center Göttingen, Germany. Results: The overall success rate of applying the RASS for US-guided tip positioning of retrograde-tunneled HDCs was 24/24 (100%), with proper tip position in the right atrium in 18/23 (78.3%), or cavoatrial junction in 5/23 (21.7%) when RASS was positive and improper position when RASS was negative in 1/1 (100%), confirmed by portable anterior-posterior chest radiography, with only minor post-procedural bleeding in 2/24 (8.3%). In addition, this insertion technique allows optimal HDC flow, without any observed malfunction. Conclusion: This is the first study to investigate the efficacy of the RASS for US-guided tip positioning of retrograde-tunneled HDCs in patients with ESKD. Application of the RASS for US-guided tip positioning is an accurate and safe procedure for the proper placement of retrograde-tunneled HDCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Regular tumor follow-up care provided by ear-nose-throat specialists ends when patients reach 5-year survival, but radio-toxicity is a lifelong process. In this study, long-term head-and-neck cancer survivors undergoing tumor FU-care exceeding five years were analyzed for late onset symptoms after radio-(chemo-)therapy. Almost one third of these patients developed new radiation associated symptoms beyond the common 5-year tumor follow-up margin. Previous radiotherapy led to a two-fold increase for late-onset new complaints, especially after irradiation of the lymphatic pathways in the neck. These findings underline the need for a life-long tumor-follow-up care for long-term head-and-neck cancer survivors. Regular tumor follow-up care provided by ear-nose-throat (ENT) specialists ends when patients reach 5-year survival, but radiotoxicity is a continuous lifelong process. In this study, long-term head-and-neck cancer (HNC) survivors undergoing tumor follow-up (FU) care exceeding five years in a certified HNC center of a German university hospital were analyzed for newly diagnosed late sequelae after radio-(chemo-)therapy. Patients diagnosed with squamous cell carcinoma (SCC) of the oral cavity, larynx or oro-/hypopharynx receiving treatment between 1990 and 2010 with a tumor FU care beyond five years were reviewed retrospectively for signs of late sequelae after radio-(chemo-)therapy (R(C)T) including carotid artery stenosis, stenosis of the cranial esophagus, dysphagia, osteoradionecrosis, and secondary malignancies. Long-term survivors that solely received surgical treatment served as control. Of 1143 analyzed patients we identified 407 patients with an overall survival beyond five years, 311 with R(C)T and 96 patients without R(C)T. Furthermore, 221/1143 patients were lost to FU and the mortality rate within the first 5-years was 45%. Moreover, 27.7% of the long-term survivors were diagnosed with new onset late sequelae within the following five years. RT was significantly associated with a two-fold risk increase for newly diagnosed symptoms, especially after RT of the lymphatic pathways (LP) which showed a hazard ratio of 23.3 to develop alterations on the carotid arteries. Additional chemotherapy had no statistical correlation with any late onset toxicity nor did the mode of R(C)T (adjuvant/definitive). Although the validity of this study might be limited due to its retrospective nature and the dependence on the voluntary participation in a prolonged tumor FU, the results nevertheless provide the need to offer and encourage a tumor FU by ENT specialists exceeding the common 5-year margin. This could prevent secondary morbidities and improve quality of life for long-term cancer survivors. [ABSTRACT FROM AUTHOR]