Mikrosatellitenanalyse zur Detektion der genetischen Instabilität bei monofokalen und bifokalen Prostatatumoren

In dieser Studie wurden mittels Mikrosatellitenanalyse 10 ausgewählte genetische Marker von 92 Patienten mit Prostatakarzinom auf einen LOH untersucht. Ziel war es, genetische Veränderungen auf bestimmten Markern oder Markerkombinationen ausfindig zu machen, die mit anderen Untersuchungsgrößen die Erkennung und Prognose des Prostatakrebses verbessern können. Das Gesamtkollektiv setzte sich aus 76 Patienten mit monofokalen und 16 Patienten mit bifokalen Tumoren zusammen. Die Ergebnisse zeigten, daß die hier eingesetzten Marker zur genetischen Untersuchung von Prostatakarzinomen geeignet sind. In dieser Studie haben sich die Marker D8S258, D10S541, D13S153, und p53 als die relevantesten gezeigt. Beim Prostatakarzinom handelt es sich vermutlich um eine polygene Erkrankung. Die Kombination verschiedener genetischer Alterationen scheint bei der Tumorgenese eine Rolle zu spielen. Für die bifokalen Tumoren konnte gezeigt werden, daß sich eine Vielzahl der Foci als genetisch heterogen erweisen

Combined indocyanine green and quantitative perfusion assessment with hyperspectral imaging during colorectal resections

Anastomotic insufficiencies still represent one of the most severe complications in colorectal surgery. Since tissue perfusion highly affects anastomotic healing, its objective assessment is an unmet clinical need. Indocyanine green-based fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have received great interest in recent years but surgeons have to decide between both techniques. For the first time, two data processing pipelines capable of reconstructing an ICG-FA correlating signal from hyperspectral data were developed. Results were technically evaluated and compared to ground truth data obtained during colorectal resections. In 87% of 46 data sets, the reconstructed images resembled the ground truth data. The combined applicability of ICG-FA and HSI within one imaging system might provide supportive and complementary information about tissue vascularization, shorten surgery time, and reduce perioperative mortality

Developments in esophageal surgery for adenocarcinoma: a comparison of two decades

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine outcomes in patients undergoing esophageal resection for adenocarcinoma at our institution during a 20-year period and, in particular, to address temporal trends in long-term survival.</p> <p>Methods</p> <p>Out of 470 patients who underwent esophagectomy for malignancy between September 1985 and September 2005, a total number of 175 patients presented with esophageal adenocarcinoma. Patients enrolled in this study included AEG (adenocarcinoma of the esophagogastric junction) type I tumors only. Time trends were studied comparing two decades, 9/1985 to 9/1995 (DI) and 10/1995 to 9/2005 (DII).</p> <p>Results</p> <p>The overall survival was significantly more favourable in patients undergoing esophageal resection for adenocarcinoma in the recent time period (DII, 10/1995 to 9/2005) as compared to the early time period (DI, 9/1985 to 9/1995) (log rank test: p = 0.0329). Significant differences in the recent decade were seen based on lower ASA-classifications, earlier tumor stages, and the operative procedure with a higher frequency of transhiatal resections (p < 0.05). 30-day mortality improved from 8.3% to 3.1% during the 20-year time-interval, thus without statistical significance.</p> <p>Conclusion</p> <p>Based on our experience, overall survival is improving over time for adenocarcinoma of the esophagus. Factors that may play an important role in this trend include early diagnosis and improved patient selection through better preoperative staging, improved surgical technique with a tailored approach carefully evaluated by physiologic patient status, comorbidity and tumor extent.</p

Survival after chemotherapy and/or radiotherapy versus self-expanding metal stent insertion in the setting of inoperable esophageal cancer: a case-control study

<p>Abstract</p> <p>Background</p> <p>Our aim was to compare survival of the various treatment modality groups of chemotherapy and/or radiotherapy in relation to SEMS (self-expanding metal stents) in a retrospective case-control study. We have made the hypothesis that the administration of combined chemoradiotherapy improves survival in inoperable esophageal cancer patients.</p> <p>Methods</p> <p>All patients were confirmed histologically as having surgically non- resectable esophageal carcinoma. Included were patients with squamous cell carcinoma, undifferentiated carcinoma as well as Siewert type I--but not type II - esophagogastric junctional adenocarcinoma. The decision to proceed with palliative treatments was taken within the context of a multidisciplinary team meeting and full expert review based on patient's wish, co-morbid disease, clinical metastases, distant metastases, M1 nodal metastases, T4-tumor airway, aorta, main stem bronchi, cardiac invasion, and peritoneal disease. Patients not fit enough to tolerate a radical course of definitive chemo- and/or radiation therapy were referred for self-expanding metal stent insertion. Our approach to deal with potential confounders was to match subjects according to their clinical characteristics (contraindications for surgery) and tumor stage according to diagnostic work-up in four groups: SEMS group (A), Chemotherapy group (B), Radiotherapy group (C), and Chemoradiotherapy group (D).</p> <p>Results</p> <p>Esophagectomy was contraindicated in 155 (35.5%) out of 437 patients presenting with esophageal cancer to the Department of General and Abdominal Surgery of the University Hospital of Mainz, Germany, between November 1997 and November 2007. There were 133 males and 22 females with a median age of 64.3 (43-88) years. Out of 155 patients, 123 were assigned to four groups: SEMS group (A) n = 26, Chemotherapy group (B) n = 12, Radiotherapy group (C) n = 23 and Chemoradiotherapy group (D) n = 62. Mean patient survival for the 4 groups was as follows: Group A: 6.92 ± 8.4 months; Group B: 7.75 ± 6.6 months; Group C: 8.56 ± 9.5 months, and Group D: 13.53 ± 14.7 months. Significant differences in overall survival were associated with tumor histology (<it>P </it>= 0.027), tumor localization (<it>P </it>= 0.019), and type of therapy (<it>P </it>= 0.005), respectively, in univariate analysis. Treatment modality (<it>P </it>= 0.043) was the only independent predictor of survival in multivariate analysis. The difference in overall survival between Group A and Group D was highly significant (<it>P </it>< 0.01) and in favor of Group D. As concerns Group D versus Group B and Group D versus Group C there was a trend towards a difference in overall survival in favor of Group D (<it>P </it>= 0.069 and <it>P </it>= 0.059, respectively).</p> <p>Conclusions</p> <p>The prognosis of inoperable esophageal cancer seems to be highly dependent on the suitability of the induction of patient-specific therapeutic measures and is significantly better, when chemoradiotherapy is applied.</p

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future

International consensus on the management of metastatic gastric cancer:step by step in the foggy landscape: Bertinoro Workshop, November 2022

Background: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. Methods: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. Results: The assembly agreed to define oligometastases as a “dynamic” disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. Conclusion: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.</p

Physiological responses to low-force work and psychosocial stress in women with chronic trapezius myalgia

<p>Abstract</p> <p>Background</p> <p>Repetitive and stressful work tasks have been linked to the development of pain in the trapezius muscle, although the underlying mechanisms still remain unclear. In earlier studies, it has been hypothesized that chronic muscle pain conditions are associated with imbalance in the autonomic nervous system, predominantly expressed as an increased sympathetic activity. This study investigates whether women with chronic trapezius myalgia show higher muscle activity and increased sympathetic tone at baseline and during repetitive low-force work and psychosocial stress, compared with pain-free controls.</p> <p>Methods</p> <p>Eighteen women with chronic trapezius myalgia (MYA) and 30 healthy female controls (CON) were studied during baseline rest, 100 min of repetitive low-force work, 20 min of psychosocial stress (Trier Social Stress Test, TSST), and 80 min recovery. The subjects rated their pain intensity, stress and energy level every 20 min throughout the experiment. Muscle activity was measured by surface electromyography in the trapezius muscle (EMGtrap) and deltoid muscle (EMGdelt). Autonomic reactivity was measured through heart rate (HR), skin conductance (SCL), blood pressure (MAP) and respiration rate (Resp).</p> <p>Results</p> <p>At baseline, EMGtrap, stress ratings, and HR were higher in MYA than in CON. Energy ratings, EMGdelt, SCL, MAP and Resp were, however, similar in the two groups. Significant main group effects were found for pain intensity, stress ratings and EMGtrap. Deltoid muscle activity and autonomic responses were almost identical in MYA and CON during work, stress and recovery. In MYA only, pain intensity and stress ratings increased towards the end of the repetitive work.</p> <p>Conclusion</p> <p>We found increased muscle activity during uninstructed rest in the painful muscle of a group of women with trapezius myalgia. The present study could not confirm the hypothesis that chronic trapezius myalgia is associated with increased sympathetic activity. The suggestion of autonomic imbalance in patients with chronic local or regional musculoskeletal pain needs to be further investigated.</p

International consensus on the management of metastatic gastric cancer:step by step in the foggy landscape: Bertinoro Workshop, November 2022

Background: Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible. Methods: A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement. Results: The assembly agreed to define oligometastases as a “dynamic” disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy. Conclusion: As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.</p

The Plastid Genome of Eutreptiella Provides a Window into the Process of Secondary Endosymbiosis of Plastid in Euglenids

Euglenids are a group of protists that comprises species with diverse feeding modes. One distinct and diversified clade of euglenids is photoautotrophic, and its members bear green secondary plastids. In this paper we present the plastid genome of the euglenid Eutreptiella, which we assembled from 454 sequencing of Eutreptiella gDNA. Comparison of this genome and the only other available plastid genomes of photosynthetic euglenid, Euglena gracilis, revealed that they contain a virtually identical set of 57 protein coding genes, 24 genes fewer than the genome of Pyramimonas parkeae, the closest extant algal relative of the euglenid plastid. Searching within the transcriptomes of Euglena and Eutreptiella showed that 6 of the missing genes were transferred to the nucleus of the euglenid host while 18 have been probably lost completely. Euglena and Eutreptiella represent the deepest bifurcation in the photosynthetic clade, and therefore all these gene transfers and losses must have happened before the last common ancestor of all known photosynthetic euglenids. After the split of Euglena and Eutreptiella only one additional gene loss took place. The conservation of gene content in the two lineages of euglenids is in contrast to the variability of gene order and intron counts, which diversified dramatically. Our results show that the early secondary plastid of euglenids was much more susceptible to gene losses and endosymbiotic gene transfers than the established plastid, which is surprisingly resistant to changes in gene content