ObjectiveTo analyze the changing pattern in tumor type and postoperative deaths at a national referral center for esophageal cancer in the Western world and to assess prognostic factors for long-term survival after resection. Summary Background DataDuring the past two decades, the epidemiology and treatment strategies of esophageal cancer have changed markedly in the Western world. The influence of these factors on postoperative deaths and long-term prognosis has not been adequately evaluated. MethodsBetween 1982 and 2000, 1,059 patients with primary esophageal squamous cell cancer or adenocarcinoma had resection with curative intention at a single center. Patient and tumor characteristics and details of the surgical procedure and outcome were documented during this period. Follow-up was available for 95.8% of the patients. Changing patterns in tumor type and postoperative deaths were analyzed. Prognostic factors for longterm survival were assessed by multivariate analysis. ResultsThe prevalence of adenocarcinoma in patients with resected esophageal cancer increased markedly during the study period. The postoperative death rate decreased from about 10% before 1990 to less than 2% since 1994, coinciding with the introduction of a procedure-specific composite risk score and exclusion of high-risk patients from surgical resection. In addition to the well-established prognostic parameters, tumor cell type "adenocarcinoma" was identified as a favorable independent predictor of long-term survival after resection. The independent prognostic effect of tumor cell type persisted in the subgroups of patients with primary resection and patients with primary resection and R0 category.

The risk of death after oesophagectomy for oesophageal cancer can be assessed objectively before surgery and quantified by a composite risk score. This score provides a useful tool for refining the criteria of patient selection for resection or the choice of procedure.

Non-malignant tracheobronchial lesions are a serious complication of transthoracic oesophagectomy with extensive lymph node dissection, particularly in patients undergoing preoperative radiochemotherapy for locally advanced tumours.

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Altered host defense mechanisms after major surgery or trauma are considered important for the development of infectious complications and sepsis. In the present study, we demonstrate that major surgery results in a severe defect of T-lymphocyte proliferation and cytokine secretion in response to coligation of the antigen receptor complex and CD28. During the early postoperative course, reduced cytokine secretion was observed for interleukin-2 (IL-2), gamma interferon, and tumor necrosis factor alpha, which are associated with the Th1 phenotype of helper T lymphocytes, and for IL-4, the index cytokine of Th2 cells. During the late postoperative course, T-cell cytokine secretion increased to normal levels. Production of the anti-inflammatory cytokine IL-10 was altered, with different kinetics being selectively elevated during the late postoperative course. In contrast, the capacity of peripheral blood monocytes to present bacterial superantigens and to stimulate T-cell proliferation was normal or enhanced after surgery despite a significant loss of cell surface HLA-DR molecules. Thus, the level of major histocompatibility complex class II protein expression does not appear to predict the antigen-presenting capacity of monocytes obtained from surgical patients with uneventful postoperative recovery. Secretion of IL-1␤ and IL-10 by endotoxin-stimulated peripheral blood monocytes was increased at different time points after surgery. Major surgery therefore results in a distinct pattern of immune defects with a predominant defect in the T-cell response to T-cell receptor-and CD28 coreceptor-mediated signals rather than an impaired monocyte antigen-presenting capacity. Suppression of T-cell effector functions during the early phase of the postoperative course may define a state of impaired defense against pathogens and increased susceptibility to infection and septic complications.

The response to sound in the inferior colliculus was elevated in tinnitus patients compared with controls without tinnitus.

Postemetic spontaneous rupture of the esophagus is an intrathoracic disaster which is generally lethal if untreated. The tragedy seems to strike more often than commonly suspected. The current literature review focuses on publications since 1980 and includes the retrospective review of 18 additional patients treated in our hospital for spontaneous rupture of the esophagus. Frequently, a wide variety of unspecific symptoms has led to the mistaken diagnosis of an acute abdomen, pancreatitis or cardiac arrest. About 40% of the patients with spontaneous rupture of the esophagus presented a history of alcoholism or heavy drinking and 41% suffered from gastroduodenal ulcer disease. Pain (83%) and vomiting (79%) often associated with dyspnea (39%) and shock (32%) are the major symptoms. This unspecific symptomatology delayed the correct diagnosis of the Boerhaave's syndrome and resulted in a significant complication rate. The mortality rate associated with Boerhaave's syndrome was 50% from the first successful surgical repair in 1947 by Barrett to 1980. After 1980, however, the mortality rate dropped to 31%, because of earlier diagnosis, surgical repair and improvement in intensive care. When surgery is delayed, the prognosis of patients with spontaneous rupture of the esophagus is in general severe.

Therapeutic intervention for human succinic semialdehyde dehydrogenase (SSADH) deficiency (␥-hydroxybutyric aciduria) has been limited to vigabatrin (VGB). Pharmacologically, VGB should be highly effective due to 4-aminobutyrate-transaminase (GABA-transaminase) inhibition, lowering succinic semialdehyde and, thereby, ␥-hydroxybutyric acid (GHB) levels. Unfortunately, clinical efficacy has been limited. Because GHB possesses a number of potential receptor interactions, we addressed the hypothesis that antagonism of these interactions in mice with SSADH deficiency could lead to the development of novel treatment strategies for human patients. SSADH-deficient mice have significantly elevated tissue GHB levels, are neurologically impaired, and die within 4 weeks postnatally. In the current report, we compared oral versus intraperitoneal administration of VGB, CGP 35348 [3-aminopropyl(diethoxymethyl)phosphinic acid, a GABA B receptor antagonist], and the nonprotein amino acid taurine in rescue of SSADH-deficient mice from early death. In addition, we assessed the efficacy of the specific GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-[H]benzocycloheptene-5-ol-6-ylideneacetic acid) using i.p. administration. All interventions led to significant lifespan extension (22-61%), with NCS-382 being most effective (50 -61% survival). To explore the limited human clinical efficacy of VGB, we measured brain GHB and ␥-aminobutyric acid (GABA) levels in SSADH-deficient mice receiving VGB. Whereas high-dose VGB led to the expected elevation of brain GABA, we found no parallel decrease in GHB levels. Our data indicate that, at a minimum, GHB and GABA B receptors are involved in the pathophysiology of SSADH deficiency. We conclude that taurine and NCS-382 may have therapeutic relevance in human SSADH deficiency and that the poor clinical efficacy of VGB in this disease may relate to an inability to decrease brain GHB concentrations.