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  • 1
    In: The American Journal of Gastroenterology, 2008, Vol.103(4), p.856
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1572-0241.2007.01667.x Byline: Ines Gockel (1), Juergen R.E. Bohl (2), Volker F. Eckardt (3), Theodor Junginger (1) Abstract: 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 Auerbach's 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. Author Affiliation: (1)Department of General and Abdominal Surgery, Johannes Gutenberg-University, Mainz, Germany (2)Institute of Neuropathology, Johannes Gutenberg-University, Mainz, Germany (3)Department of Gastroenterology, German Diagnostic Clinic, Wiesbaden, Germany Article History: Received June 17, 2007; accepted October 5, 2007. Article note: Reprint requests and correspondence: Ines Gockel, M.D., Ph.D., Department of General and Abdominal Surgery, Johannes Gutenberg-University, Langenbeckstr. 1, D-55131 Mainz, Germany.
    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: 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 ( 〈 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 ; Medicine
    ISSN: 1091-255X
    E-ISSN: 1873-4626
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  • 3
    In: Journal of Gastroenterology and Hepatology, April 2006, Vol.21(4), pp.727-733
    Description: The etiology of achalasia is still unknown. The aim of the present study was to illucidate its underlying pathologies and their chronology by investigation of esophageal specimens in patients undergoing surgery (esophageal resection or myotomy) for achalasia. In 17 patients with achalasia, histopathologic examinations of the esophageal wall focussing on the myenteric plexus were performed. Preoperative diagnosis was based on clinical evaluation, esophagogastroscopy, barium esophagogram in all, and esophageal manometry in eight patients. The median age at the time of surgery was 54 years (range: 14–78 years). In eight cases, the complete esophageal, body and in nine cases a smooth muscle biopsy including parts of the myenteric plexus from the distal part of the esophagus (high pressure zone) was available. The tissue specimens were fixed in formalin and embedded in paraffin. The staining procedures were hematoxylin and eosin (HE), Elastica van Gieson (EvG), and periodic acid–Schiff (PAS) reaction. Immunohistochemical examinations were performed with antibodies against B and T ymphocytes, neurofilament, protein gene‐related product (PGP 9.5), S‐100 protein, myosin, desmin, smooth muscle actin and substance P. In 13 of 17 patients, a significant reduction of the number of intramural ganglion cells was present. Common findings were a severe fibrosis of the smooth muscle layer (10/17) and obvious myopathic changes of the smooth muscle cells (5/17). Staining for B and T lymphocytes found signs of inflammation in mucosal and muscular areas. Three patients exhibited a marked invasion of eosinophilic granulocytes of the muscularis propria (eosinophilia). Esophageal carcinoma had developed in three patients (squamous cell carcinoma in two and carcinoma in another patient with Barrett's esophagus and high‐grade dysplasia). Severe inflammatory reactions (neural, eosinophilic and mucosal) dominated in patients with a longstanding history of achalasia (〉10 years) as well as a marked endomysial fibrosis. The histopathological investigations of the esophageal wall in 17 patients undergoing esophageal resection or myotomy for achalasia suggest that the reduction of intramural ganglion cells might be a secondary change, probably due to inflammation triggered by autoimmune mechanisms or a chronic degenerative process of the central and/or peripheral part of the vagal nerve. The primary lesion could also be a severe myopathy of the smooth muscle cells.
    Keywords: Achalasia ; Auerbach'S Plexus ; Autoimmunity ; Intramural Inflammation ; Smooth Muscle Myopathy
    ISSN: 0815-9319
    E-ISSN: 1440-1746
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  • 4
    Language: English
    In: Hepato-gastroenterology, 2010, Vol.57(99-100), pp.507-12
    Description: Previous investigations of esophageal tissue and serum probes failed to identify a common etiologic agent predisposing to, triggering or causing achalasia. In order to further examine the detailed pathologic processes resulting in achalasia we performed electron-microscopic studies of muscle biopsies taken from the LES high pressure zone in patients undergoing surgery--either Heller myotomy or esophageal resection. Smooth muscle biopsies with a 20 x 15-mm longitudinal segment of the myenteric plexus from the distal esophagus (lower border of the esophageal incision) in patients undergoing Heller myotomy for achalasia were taken. In patients with end-stage achalasia and mega-esophagus with esophageal resection, the complete esophageal body was available. For electron microscopy, ultrathin sections were contrasted with uranyl-acetate and plumbic citrate. The photographs were taken by a digitalized electron-microscope (ZEISS, Leo 905). A striking finding was the large number of mast cells in the region of the smooth muscle layers as well as in the surrounding connective tissue and also in close vicinity to the nerve cells and to the nerve fibres. The smooth muscle cells in these regions were very often stained less intensively, and they showed signs of an acute degenerative process. Our electron microscopic studies suggest that mast cells may play an important role in the secondary pathogenesis of achalasia. Esophageal retention and bacterial overgrowth with stasis esophagitis causing mucosal injury may be a mechanism of increased antigen exposure.
    Keywords: Esophageal Achalasia -- Pathology ; Esophagus -- Ultrastructure
    ISSN: 0172-6390
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    Language: English
    In: Gastroenterology, 2009, Vol.136(5), pp.A-928-A-928
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
    Source: ScienceDirect Journals (Elsevier)
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  • 6
    Language: English
    In: Gastroenterology, April 2015, Vol.148(4), pp.S-1105-S-1105
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0016-5085(15)33763-X Byline: Martin E. Kreis, Reinhard Ruppert, Henry Ptok, Joachim Strassburg, Theodor Junginger, Susanne Merkel
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
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  • 7
    Language: German
    In: coloproctology, 2007, Vol.29(3), pp.139-149
    Description: In früheren Studien wurde die lokale Exzision vorwiegend als Eingriff bei „low-risk“ pT1-Rektumkarzinomen propagiert. Die Ergebnisse bei T2-Tumoren sind unklar; es wurden Rezidivraten von 0–67% berichtet. Diese Studie wurde durchgeführt, um den Wert der lokalen Exzision bei T2-Rektumkarzinomen, prognostische Faktoren sowie die Notwendigkeit von Nachoperationen zu bestimmen.Nach einer lokalen Exzision bei 649 Patienten mit Rektumkarzinomen wurden bei 44 Patienten pT2-Karzinome gefunden. Im Allgemeinen wurde eine sofortige Nachoperation empfohlen; allerdings lehnten 24 Patienten eine weitere Operation ab oder wurden aufgrund von Begleiterkrankungen nicht operiert. Die Ergebnisse wurden getrennt analysiert für lokale R0-Resektionen von „low-risk“ Karzinomen sowie für prognostisch ungünstige Kriterien (R1/RX/R ≤ 1 mm/G3–4/L1/V1). Nachoperationen wurden innerhalb von 4 Wochen durchgeführt. Rezidive wurden außerdem entsprechend einer vorausgehenden lokalen R0-Resektion von „low-risk“ Tumoren wie auch ungünstiger Ergebnisse differenziert und in einer Langzeit-Follow-up-Studie analysiert. Patienten mit palliativer Therapie wurden ausgeschlossen, das Follow-up wurde bei 90% erreicht (20 ausschließlich transanale endoskopische mikrochirurgische Exzisionen, 17 transanale endoskopische mikrochirurgische Exzisionen und Nachoperationen).Die lokalen Rezidivraten nach ausschließlicher lokaler R0-Resektion von „low-risk“ T2-Karzinomen betrugen 29%, wohingegen Patienten mit ungünstigen Kriterien zu 50% Rezidive entwickelten. Nach einer sofortigen Nachoperation war das lokale Rezidivrisiko bei Patienten ohne Lymphknotenmetastasen signifikant reduziert auf 7%.Die lokale R0-Resektion bei „low-risk“ pT2-Karzinomen stellt eine unzureichende Therapie dar. Bei pT2N0M0-Rektumkarzinomen kann die Rezidivrate durch sofortige Nachoperation auf ein Level ähnlich einer primären Radikaloperation reduziert werden. Ein primär schlechtes lokales Resektionsergebnis (R1/RX/R ≤ 1 mm/ G3–4/L1/V1) hat keinen negativen Einfluss auf das weitere onkologische Ergebnis.In previous studies, local excision was predominantly established for “low-risk” pT1 rectal cancer. The results obtained with T2 tumors are unclear; recurrence rates of 0 to 67 percent were reported. This study was designed to determine the value of local excision for T2 rectal carcinomas, prognostic factors, and the need for reoperation.After local excision of 649 patients with rectal tumors, pT2 carcinoma was found in 44 patients. In general, immediate reoperation was recommended; however, 24 patients declined further surgery or were not reoperated because of comorbidities. The results were analyzed separately for local R0 resection of low-risk carcinomas and for prognostically unfavorable criteria (R1/RX/R ≤ 1 mm/G3–4/L1/V1). Reoperation was performed within four weeks. Recurrences also were divided by previous local R0 resection of low-risk tumors as well as by unfavorable results and were analyzed in a long-term, follow-up study. Patients with palliative therapy were excluded, and follow-up was obtained in 90 percent (20 transanal endoscopic microsurgical excision alone, 17 transanal endoscopic microsurgical excision and reoperation).Local recurrence rates after local R0 resection alone of low-risk T2 carcinomas were 29 percent, whereas patients with unfavorable criteria developed recurrences in 50 percent. After immediate reoperation, the local recurrence risk in patients without lymph node filiae was significantly reduced to 7 percent.Local R0 resection of low-risk pT2 carcinomas represents an inadequate therapy. In pT2N0M0 rectal carcinomas, the recurrence rate can be reduced through immediate reoperation to a level similar to primary radical surgery. An initial poor local resection result (R1/RX/R ≤ 1 mm/G3–4/L1/V1) has no negative influence on further oncologic outcome.
    Keywords: T2 rectal cancer ; Local excision ; Recurrence risk ; Immediate reoperation
    ISSN: 0174-2442
    E-ISSN: 1615-6730
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  • 8
    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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  • 9
    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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  • 10
    Language: English
    In: Archives of surgery (Chicago, Ill. : 1960), November 2007, Vol.142(11), pp.1093-7
    Description: Two groups of patients with inadequate therapeutic success after surgical treatment for achalasia can be identified, patients with type 1 recurrence (early recurrence after technical failure of myotomy or a scarring process requiring remyotomy) and patients with type 2 recurrence (late recurrence with irreversible progression of the disease and development of megaesophagus requiring esophagectomy). Prospective study. University-based tertiary care center. One hundred sixty-three patients undergoing surgery for achalasia during 20.3 years. Conventional remyotomy for type 1 recurrence (group 1) and esophagectomy (transhiatal or transthoracic) for type 2 recurrence (group 2). Long-term results after reoperation, including Eckardt score, body mass index, reflux esophagitis, manometric lower esophageal sphincter resting pressure, and radiologic maximum diameter of the esophageal body and minimum diameter of the cardia. After reoperation, a postoperative Eckardt score of 1 (corresponding to clinical stages 1 to 2) was calculated in 92.3% of group 1 patients and in 80.0% of group 2 patients. In group 1 patients, the maximum diameter of the esophagus decreased to a median value of 25 mm (range, 20-60 mm), while the minimum diameter of the cardiac sphincter increased to a median value of 10.0 mm (range, 5.0-12.0 mm). After surgery, the resting pressure of the lower esophageal sphincter was reduced to a median value of 8.3 mm Hg (range, 4.0-10.0 mm Hg). Reoperation for achalasia yields good long-term symptomatic outcomes, with relief of dysphagia. Subjective, radiographic, and manometric findings after remyotomy duplicate the good results reported for primary open myotomy.
    Keywords: Digestive System Surgical Procedures ; Esophageal Achalasia -- Surgery ; Esophagus -- Surgery
    ISSN: 00040010
    E-ISSN: 1538-3644
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