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  • Junginger, Theodor  (52)
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  • 1
    In: American Journal of Gastroenterology, 2008, Vol.103(4), pp.856-864
    Description: BACKGROUND: The etiology of achalasia is still unknown. The current theories of chronic inflammation leading to autoimmune response with destruction and loss of the inhibitory myenteric ganglion cells enlighten its pathogenesis in a limited way only. Interstitial cells of Cajal (ICC) have been shown to be involved in nitrergic neurotransmission of the lower esophageal sphincter (LES). AIM: To investigate the significance of ICC and neuronal nitric oxide synthase (n-NOS) in esophageal wall tissue of patients undergoing surgery for achalasia. METHODS: In 53 patients with a median age of 45 (6–78) yr undergoing surgery for achalasia, the immunoreactivity of ICC (CD117/c-kit) and n-NOS was assessed. In 42 patients, biopsies were taken from the LES high-pressure zone during Heller myotomy, whereas in 11 patients with end-stage achalasia and a decompensated megaesophagus, the complete esophagus was resected. A semiquantitative analysis was carried out and ICC and n-NOS impairments were classified into four grades. Staining intensity was correlated with preoperative clinical, radiologic, and manometric findings and with long-term postoperative Eckardt score. RESULTS: Grade III/IV ICC reduction (severe reduction to complete loss) was seen in 59.5% of all biopsy specimens of the LES high-pressure zone. Patients with grade III/IV ICC reduction had a significantly longer duration of achalasia symptoms (3 [0–43] yr) than patients with minor to marked (grade I/II) impairment (1 [0–16] yr, P= 0.028). A majority (72.5%) of tissue samples revealed severe reduction to complete loss of n-NOS immunoreactivity. The preoperative Eckardt score was statistically significantly different between patients with grade I/II and those with grade III/IV n-NOS reductions (P= 0.031). CD117 (c-kit) positivity was statistically significantly correlated with n-NOS staining intensity (correlation coefficient r= 0.781, P 〈 0.0001). CONCLUSION: The present results suggest that in the pathogenesis of achalasia, especially in the development of the LES high-pressure zone, depletion of ICC networks and potential changes in the electrical activity of smooth muscle cells may play a crucial role. The reduction in CD117-positive ICC in a few patients also seemed to be of relevance, even if the cells of Auerbachʼs plexus were unscathed. The associated reduced NOS release might underlie the profound ICC impairment and could possibly be responsible for the lack of LES relaxation, because of missing inhibitory neurotransmission. It is unclear, however, whether the ICC loss is primarily caused by the accelerated attrition of mature cells or their impaired regeneration.
    Keywords: Achalasia -- Development And Progression ; Achalasia -- Care And Treatment ; Neurons ; Nitric Oxide;
    ISSN: 0002-9270
    E-ISSN: 15720241
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  • 2
    Language: English
    In: BMC Cancer, Feb 15, 2012, Vol.12, p.70
    Description: Background 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. Methods 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). Results 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 (P = 0.027), tumor localization (P = 0.019), and type of therapy (P = 0.005), respectively, in univariate analysis. Treatment modality (P = 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 (P [less than] 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 (P = 0.069 and P = 0.059, respectively). Conclusions 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.
    Keywords: Chemotherapy -- Health Aspects ; Chemotherapy -- Patient Outcomes ; Chemotherapy -- Comparative Analysis ; Esophageal Cancer -- Care And Treatment ; Esophageal Cancer -- Patient Outcomes ; Esophageal Cancer -- Research ; Radiotherapy -- Health Aspects ; Radiotherapy -- Patient Outcomes ; Radiotherapy -- Comparative Analysis
    ISSN: 1471-2407
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: BMC Cancer, Feb 15, 2012, Vol.12, p.70
    Description: Background 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. Methods 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). Results 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 (P = 0.027), tumor localization (P = 0.019), and type of therapy (P = 0.005), respectively, in univariate analysis. Treatment modality (P = 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 (P [less than] 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 (P = 0.069 and P = 0.059, respectively). Conclusions 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.
    Keywords: Chemotherapy -- Health Aspects ; Chemotherapy -- Patient Outcomes ; Chemotherapy -- Comparative Analysis ; Esophageal Cancer -- Care And Treatment ; Esophageal Cancer -- Patient Outcomes ; Esophageal Cancer -- Research ; Radiotherapy -- Health Aspects ; Radiotherapy -- Patient Outcomes ; Radiotherapy -- Comparative Analysis
    ISSN: 1471-2407
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Gastroenterology, May 2012, Vol.142(5), pp.S-1094-S-1094
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
    Source: ScienceDirect Journals (Elsevier)
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  • 5
    Language: English
    In: The Annals of Thoracic Surgery, November 2013, Vol.96(5), pp.1840-1845
    Description: There is an increasing trend to include patients with esophageal carcinoma invading the muscularis propria (pT2) in neoadjuvant therapy regimens. But it is unclear which patients have prognostic benefit from this strategy. The aim of this study was to assess the prognosis and prognostic factors in patients with pT2 esophageal adenocarcinoma to further optimize treatment strategies. Included were patients with pT2 esophageal adenocarcinoma treated operatively at three centers specializing in upper gastrointestinal surgery. There were 159 patients (139 male) without induction therapy; median age was 64.5 years. Survival was analyzed by univariate and multivariate analysis. In 37% of patients (n = 59), no lymph node involvement (pN0) was detected. Overall 5-year survival rate for all patients was 37%; for pN0 patients it was 62%, and for patients with lymph node metastases (pN+) it was 24%. Median number of examined lymph nodes was 26. Extracapsular lymph node involvement (ELNI) was evident in 55 of 100 pN+ patients with a 5-year survival rate of 14%. Patients without ELNI had a 5-year survival rate of 36% (  = 0.041). Results were comparable in all participating hospitals. Thirty-day and 90-day mortality rates of the entire collective were 2.6% and 3.8%, respectively. Multivariate analysis of prognosis revealed the lymph node ratio ( 〈 0.001) and the pN-ELNI category (  = 0.005) as significant parameters (pN0 hazard ratio 1 [reference]; pN+ without ELNI hazard ratio 2.2, 95% confidence interval: 1.2 to 3.8); pN+ with ELNI hazard ratio 2.5, 95% confidence interval: 1.5 to 4.5). The prognosis of patients with esophageal adenocarcinoma invading the muscularis propria without lymph node metastasis is very good. However, in this study, about 30% had extracapsular lymph node involvement, which reflects particularly aggressive biological tumor behavior.
    Keywords: 7;
    ISSN: 0003-4975
    E-ISSN: 1552-6259
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  • 6
    Language: English
    In: Annals of Surgical Oncology, 2013, Vol.20(7), pp.2428-2433
    ISSN: 1068-9265
    E-ISSN: 1534-4681
    Source: Springer Science & Business Media B.V.
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  • 7
    Language: English
    In: The Thoracic and cardiovascular surgeon, September 2013, Vol.61(6), pp.470-8
    Description: The aim of our study was to develop a prognostic index score for patients undergoing surgical resection for esophageal cancer that accurately determines survival with specific clinicopathological characteristics. Clinical, histological, and demographical variables of 475 patients were entered in an univariate and multivariate regression model, followed by individual calculation of the Prognostic Indicator Score and model validation via simulation. Significant variables included in the scoring system were number of positive lymph nodes, pT, pL, R, obesity, and American Society of Anesthesiologist classification. Survival probability and its associated hazard function was significantly different between the scores, with an increase of hazard ratio ranging from 2.56 (score 2) to 20 (score 6 or higher). Comparing histological cancer entities revealed statistical significance only between stage IIA versus IIB in squamous cell and stage IIIA versus IIIB in adenocarcinoma. According to our methodology, an individualized follow-up by each possible score might allow interdisciplinary selection of patients for treatments based on expected survival. This may represent a breakthrough in patient selection for currently available treatments and clinical studies.
    Keywords: Decision Support Techniques ; Esophagectomy ; Adenocarcinoma -- Surgery ; Carcinoma, Squamous Cell -- Surgery ; Esophageal Neoplasms -- Surgery
    ISSN: 01716425
    E-ISSN: 1439-1902
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  • 8
    Language: English
    In: Journal of Gastrointestinal Surgery, 2006, Vol.10(10), pp.1400-1408
    Description: Myotomy has proved to be an efficient primary therapy in patients with achalasia, especially in younger patients (〈40 years of age). The results of laparoscopic myotomy cannot be finally assessed, on account of the shorter postoperative follow-up. Thus, there are considerable data regarding intermediate-term outcomes after laparoscopic myotomy. The aim of our study was a 20-year analysis of the conventional cardiomyotomy as the underlying basis assessing the results of minimal-invasive surgery. Within 20 years (September 1985 through September 2005), 161 operations for achalasia were performed in our clinic. Enrolled in this study were 108 patients with a conventional, transabdominal myotomy in combination with an anterior semifundoplication (Dor procedure) and a minimal follow-up of 6 months. All patients were prospectively followed and, in addition to radiologic and manometric examinations of the esophagus, the patients were asked for their clinical symptoms by structured interviews in 2-year intervals. The median age at the time of surgery was 44.5 (range, 14–78) years, and 72.2% of the patients were males. The median length of the preoperative symptoms was 3 years (3 months to 50 years), and the postoperative follow-up was 55 (range, 6-206) months. In 70 (64.8%) patients, a pneumatic dilation had been performed. The preoperative Eckardt score of 6 (range, 2–12) could be reduced to 1 (range, 0–4) after myotomy ( P 〈0.0001). Consequently, with 97.2% of all patients, a good-to-excellent result was achieved in the long-term follow-up, corresponding to a clinical stage I-II. Postoperatively, 69 patients (63.9%) gained weight. The radiologically measured maximum diameter of the esophagus decreased from preoperatively 45 (range, 20–75) mm to postoperatively 30 (range, 20–60) mm, while the minimum diameter of the cardia increased from 3.4 (range, 1–10) mm to 10 (range, 5–15) mm. The resting pressure of the lower esophageal sphincter could be reduced from 28.4 (range, 9.4–56.0) mm Hg to 8.6 (range, 3.0–22.5) mm Hg. Conventional myotomy leads in the long run with high efficiency to an improvement of the symptoms evident in achalasia. These results may be regarded as the basis for assessment of the minimal-invasive procedure.
    Keywords: Achalasia ; conventional myotomy ; prospective 20-year analysis ; basis for assessing the laparoscopic procedure
    ISSN: 1091-255X
    E-ISSN: 1873-4626
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  • 9
    In: Journal of Magnetic Resonance Imaging, June 2014, Vol.39(6), pp.1436-1442
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/jmri.24301/abstract Byline: Andre Lollert, Theodor Junginger, Carl Christoph Schimanski, Stefan Biesterfeld, Ines Gockel, Christoph Duber, Katja Oberholzer Purpose To evaluate correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinicopathologic data as well as immunostaining of the markers of angiogenesis epidermal growth factor receptor (EGFR) and CXC-motif chemokine receptor 4 (CXCR4) in patients with rectal cancer. Materials and Methods Presurgical DCE-MRI was performed in 41 patients according to a standardized protocol. Two quantitative parameters (k.sub.21, A) were derived from a pharmacokinetic two-compartment model, and one semiquantitative parameter (TTP) was assessed. Standardized surgery and histopathologic examinations were performed in all patients. Immunostaining for EGFR and CXCR4 was performed and evaluated with a standardized scoring system. Results DCE-MRI parameter A correlated significantly with the N category (P = 0.048) and k.sub.21 with the occurrence of synchronous and metachronous distant metastases (P = 0.029). A trend was shown toward a correlation between k.sub.21 and EGFR expression (P = 0.107). A significant correlation was found between DCE-MRI parameter TTP and the expression of EGFR (P = 0.044). DCE-MRI data did not correlate with CXCR4 expression. Conclusion DCE-MRI is a noninvasive method which can characterize microcirculation in rectal cancer and correlates with EGFR expression. Given the relationship between the dynamic parameters and the clinicopathologic data, DCE-MRI data may constitute a prognostic indicator for lymph node and distant metastases in patients with rectal cancer. J. Magn. Reson. Imaging 2014;39:1436-1442. [c] 2013 Wiley Periodicals, Inc.
    Keywords: Rectal Cancer ; Dce‐Mri ; Tumor Microcirculation ; Egfr ; Cxcr4 ; Prognosis ; Histopathology ; Immunohistochemistry
    ISSN: 1053-1807
    E-ISSN: 1522-2586
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  • 10
    In: American Journal of Gastroenterology, 2006, Vol.101(1), pp.202-203
    Description: TO THE EDITOR: A cascade of inflammatory events, leading to myenteric plexus alteration, following an initial insult to the esophagus, possibly a viral infection or an unknown environmental factor, was stated the possible pathophysiologic mechanism in achalasia by Park and Vaezi (1). The inflammation then leads to an autoimmune response in a susceptible population possibly genetically predisposed.
    Keywords: Medicine;
    ISSN: 0002-9270
    E-ISSN: 15720241
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