Gerd Berger

Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract

Background: The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased.

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer

Objective To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. Methods The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. Results Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan–Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months’ survival for combined groups 0 and 1, and 38.9 months’ survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. Conclusion Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III–IV colorectal cancer.

Expression of SIALYL-Lex antigen defined by MAb AM-3 is an independent prognostic marker in colorectal carcinoma patients

Expression of mucin‐bound sialyl‐Lex antigen during the progression of colorectal carcinoma and its potential prognostic value were analysed in sections of tumours from 182 patients with a documented follow‐up by immunohistochemistry using the monoclonal antibody (MAb) AM‐3. Two groups of colonic carcinomas with weak (n = 79) and strong (n = 103) sialyl‐Lex expression were discerned. The percentage of strongly expressing tumours increased with the progression of the disease (UICC stage I = 10%, stage II = 46%, stage III = 63%, stage IV = 68%, p < 0.0001). Seventy‐four percent of patients with carcinomas exhibiting a strong sialyl‐Lex expression but only 34% of patients with weak sialyl‐Lex expression died of the disease (p = 0.0026). In multivariate analysis, strong sialyl‐Lex expression increased the relative risk of cancer‐related death 3.8‐fold (95% CI = 1.8–7.9, p = 0.00034). The separate analyses of patients in UICC stage II (n = 56), III (n =5 9) and IV (n = 57) revealed that strong sialyl‐Lex expression was associated with a reduction of the 5‐year overall survival rate in UICC stage II (84% vs. 54%, p = 0.0013) and in stage III patients (86% vs. 35%, p = 0.0008) after curative resection but was not relevant in patients with distant metastases. In conclusion, the strong expression of sialyl‐Lex antigen defined by the MAb AM‐3 in colorectal carcinomas is an independent unfavourable prognostic factor after curative resection in stage II and III patients. The predictive power of the sialyl‐Lex expression may be helpful to define subgroups of patients at high risk for whom preventive adjuvant therapy can be selectively applied before the occurrence of detectable metastases. Int. J. Cancer 88:281–286, 2000.

Relevance of Carbohydrate-deficient Transferrin as a Predictor of Alcoholism in Intensive Care Patients following Trauma

Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patients history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

β‐Carbolines in chronic alcoholics following trauma

In our society every second polytraumatized patient is a chronic alcoholic. A patients alcohol‐related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol‐dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post‐traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether β‐carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM‐III‐R and ICD‐10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was ≥ 60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate‐deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.

Reliability of Carbohydrate-Deficient Transferrin to Detect Chronic Alcohol Misuse in Carcinoma Patients

The patients’ history and conventional laboratory markers are often not sensitive or specific enough to detect chronic alcohol misuse, preoperatively. We investigated whether carbohydrate-deficient tr

Diagnostics and surgical treatment strategy for rectal cavernous hemangiomas based on three case examples

Abstract A 20-year-old man with a congenital vascular malformation extending from the anal canal into the distal sigmoid had had recurrent perianal blood loss as a neonate. A hemangioma was diagnosed for the first time in 1978. The patient received regular and frequent gastroenterological treatment until admission. Decisive for the indication for surgery was the patient’s need for blood infusions and shorter bleeding intervals in June 1998. Surgical therapy consisted of deep anterior rectosigmoid resection with coloanal pouch anastomosis. In a second case of a 27-year-old woman a sigmoid hemangioma was diagnosed in conjunction with emergency sigmoid resectioning. Because of recurrent hemorrhages a coloanal pouch was also established here in a second step. The third case involved a 19-year-old woman with a 12-year history of repeated perianal hemorrhages. After sigmoid discontinuity resection we carried out proctectomy with descendostoma creation due to renewed severe intractable perianal bleeding. The histological examination revealed a rectal hemangioma that had caused the repeated perianal hemorrhages. Surgical reconstruction was then achieved by coloanal pouch anastomosis. In view of the good functional and perioperative results, current surgical therapy should aim at preserving continuity and continence by coloanal pouch anastomosis.

Acquired factor VIII inhibitor.

or uncontrolled bleeding is one of the most feared consequences of any surgical procedure. Numerous factors can contribute to its etiology. Among these, both inherited and acquired disorders of coagulation and/or thrombocyte function need to be taken into account. 1,2 Acquired hemophilia can be caused by antibodies to coagulation factors. Antibodies can arise in hemophilic or non-hemophilic patients. In the former case, patients are treated with Factor VIII concentrate and develop alloantibodies. Nonhemophilic patients produce autoantibodies (mostly against Factors VIII and IX), and this is believed to be an autoimmune reaction. 3 The estimated annual incidence rate of clinically apparent bleeding caused by autoantibodies is 1.48/million inhabitants, 3 or approximately 450 patients in the United States per year. The incidence of the disease seems to be increasing; it is more prevalent in elderly patients and it can be successfully treated if diagnosed adequately and early. 3 Here, we present a case of massive and long-lasting bleeding in a nonhemophilic patient undergoing extensive visceral surgery.

β-Carbolines in alcohol-dependent intensive care patients during prophylactics and therapy of alcohol withdrawal syndrome

The primary aim of this study was to investigate whether the naturally occurring beta‐carbolines norharman and harman differed between alcohol‐dependent patients who developed alcohol withdrawal syndrome (AWS) and those who did not. The secondary aim was to determine whether different treatment regimens influenced the levels of the beta‐carbolines. Thirty chronic alcoholics with carcinoma of the upper digestive tract were included in this study. They were prophylactically treated by two different medical regimens: flunitrazepam and clonidine (FNZ regimen) and gamma‐hydroxybutyrate and clonidine (GHB regimen). Patients exceeding the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar) score of 20 were assigned to the AWS therapy group and received haloperidol in addition to their prevous prophylactic treatment. Patients without AWS remained in the prophylactic group. From days 1–4 of the intensive care unit (ICU) stay norharman, but not harman, was increased in the AWS therapy group. In the FNZ regimen, six of 16 patients (38%) and in the GHB regimen, nine of 14 patients (64%) developed AWS (p= 0.14). Norharman levels did not differ between the two regimens. However, harman levels were increased in the GHB treated regimen on days 1, 2 and 4 following admission to the ICU and correlated with the severity of alcohol withdrawal syndrome. As norharman was elevated in the therapeutically treated ICU patients, this marker appears to be involved in the pathogenesis of AWS. As harman was elevated before and during hallucinations on the GHB regimen, it seems reasonable to carry out further investigations into the potential role of harman as a hallucinatory substance.

Improvement in 5-Fluorouracil (5-FU) and 5-Fluoro-2'- Deoxyuridine (FdUrd) Concentration by 5-Fluorouracil- Polyethylene-Glycol-Liposomes in Abdominal Stop-Flow: Treatment of VX2 Liver-Tumor-Bearing Rabbits

Abstract The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration. In abdominal stop-flow therapy, a separate partial circulation with a defined flow is realized via a roller pump under hypoxic conditions. Forty chinchilla rabbits with VX-2 liver tumors were treated either intra-aortally (stop-flow therapy) or systemically with 50 mg 5-FU or 5-FU-PEG liposomes. During therapy, pH and pO2 were measured at regular intervals. After 20 minutes, concentrations of 5-FU and its metabolite FdUrd were determined by HPLC in different organs and the liver tumor. Compared to the i.v. application of monosubstances, the combination of i.a. 5-FU-PEG liposomes and flow retardation increased the concentration in tumor tissue by a factor of 44 and even 100-fold in the para-aortal lymph nodes (LN). The concentration of 5-FU and FdUrd was increased by flow reduction, intraaortal application and liposomal encapsulation of 5-FU.