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Biomedical subjects

H D Saeger

Publications and source records attributed to H D Saeger.

At least 73 records · Page 4Linked to original sources

[Multicenter phase II study of the Liver Metastases Study Group of weekly intra-arterial 24-hour high dose therapy with 5-FU and folinic acid (FA) in liver metastases of colorectal tumors].

This prospective multicenter trial was performed to determine the response rate, toxicity and applicability of continuous 24 h hepatic arterial infusion of high-dose 5-FU and folinic acid. An improved response rate (60.5% in non-pretreated patients) was however associated with many systemic side-effects (340/509), mainly nausea and diarrhea. Therefore this treatment should be applied only in selected patients in specialized centers.

Adult↗

Role of NFkappaB in the mortality of sepsis.

Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished from survivors by an increase in NFkappaB binding activity during the observation period (P < 0.001). The increase in NFkappaB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IkappaBalpha was used to investigate the role of members of the NFkappaB family in a mouse model of endotoxemia. In this model, increased NFkappaB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated renal NFkappaB binding activity and increased survival. Endothelial cells and monocytes/macrophages were the major target cells for somatic gene transfer, transfected with an average transfection efficiency of 20-35%. Tissue factor, a gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression, activation of the plasmatic coagulation system (decrease of thrombin-antithrombin III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with an expression plasmid with tissue factor cDNA in the antisense direction (in contrast to sense or vector alone) also increased survival. Furthermore, antisense tissue factor decreased renal tissue factor expression and the activation of the plasmatic coagulation system.

Adult↗

[Minimally invasive surgery and tumor surgery--palliative laparoscopic techniques].

The oncological principles of radical tumor surgery are not proven to be successfully applied with today's laparoscopic techniques. The value of minimal invasive surgery has to be critically evaluated for the radical (R0) resection of malignant tumors. On the other hand, there is an indication for laparoscopic palliation in order to minimize the surgical trauma. Many publications have demonstrated the technical feasibility with acceptable morbidity and mortality and a decreased hospital stay. For different reasons (previous operations, assessment of resectability, use of interventional techniques etc.) laparoscopic palliation obviously is realized only in a small number of patients. The most frequently reported operation concerns the implantation of feeding catheters into the stomach or jejunum. If noncurability is proven preoperatively, the rate of laparoscopic palliations probably could be increased, if minimal access surgery could take a more definite place in the wide spectrum of therapeutical options. The operative techniques usually can be easily performed by the laparoscopically experienced surgeon today. However, benefit for the patients after palliative laparoscopic tumor resection has not yet been proven. The best condition for laparoscopic palliation is the discovery of the incurable situation during diagnostic laparoscopy. Laparoscopic palliation should follow directly within the same session.

Enteral Nutrition↗

[Surgical therapy of esophageal perforation. A determination of current status based on 4 personal cases and the literature].

We present four cases of esophageal rupture (three iatrogenic, one Boerhaave syndrome) to demonstrate the difficulty in diagnosis and therapy. The current literature is discussed and conclusions are drawn as regards the modus operandi. All our patients were operated on. The site of esophageal rupture was always closed with a primary suture and substantial irrigation and drainage were performed. In two cases the suture line was in addition covered with fibrin glue or by an omentum flap, respectively. All patients survived and recovered was unremarkable. Our own results and a subsequent analysis of literature allow the following conclusions. At an early stage of esophageal rupture surgical intervention is indicated. The method of choice is primary closure of the rupture site by suture, possibly combined with a muscle or omentum flap. In cases of delayed diagnosis with advanced mediastinitis, suture of the rupture site should also be striven for. Additional coverage is advisable in these cases. Resection procedures with or without reconstruction should be done only in exceptional cases before of the high surgical risk.

Aged↗

[Peripheral aneurysm of the hepatic artery as the etiology of acute upper gastrointestinal hemorrhage].

We report the case of a 64-year-old female with an intrahepatic aneurysm of the right hepatic artery. Initially uncharacteristic upper abdominal symptoms were followed by repeated upper gastrointestinal bleeding and, eventually, hemorrhagic shock. Finding the cause of severe hematemesis was challenging due to a previous Billroth-II gastric resection. Delayed diagnosis of hemobilia necessitated coeliacography, whereby an intrahepatic aneurysm of the right hepatic artery was found and, during the same session, super-selective embolization was achieved. If the cause of upper abdominal complaints remains unknown after routine diagnostic measures and the origin of bleeding in the upper gastrointestinal tract cannot be identified, aneurysms of abdominal arteries should be considered. Hemobilia of unknown etiology should always be an indication for coeliacography. The superselective angiographic embolization of intrahepatic aneurysms is a promising form of treatment with low risk.

Angiography↗

[Injuries to the pancreas].

Injuries of the pancreas seldom occur in connection with abdominal trauma (12%), but they are difficult to diagnose. There is a high complication rate (35%) after such injuries. Ultrasound, CT and other means of diagnosis are only helpful in making the diagnose only in 60-80%. A clinical examination is difficult in such patients, as they often have multiple injuries. We discuss 10 cases with different grades of pancreatic injuries (Lucas), their therapy with special attention to the diagnosis, time of laparotomy, exploration of the pancreas during operative intervention, the extent of treatment and the management of complications.

Abdominal Injuries↗

An intronic germline transition in the HNPCC gene hMSH2 is associated with sporadic colorectal cancer.

The aim of this study was to determine whether an intronic germline substitution in the hereditary non-polyposis colorectal cancer (HNPCC) gene hMSH2 represents a genetic risk factor for sporadic CRC. Possible effects of this substitution were investigated by assessment of microsatellite instability and hMSH2 cDNA sequencing. Constitutional DNA from patients with sporadic CRC and healthy controls from the same region in Germany was analysed for the intronic germline T-->C transition six bases upstream of exon 13 of hMSH2. 29 of 106 patients (27%) were found to harbour the germline T-->C transition as opposed to only 13 of 125 controls (10%; P < 0.001; OR 3.2, CI 1.58-6.63). CRCs from patients with the substitution displayed neither clinical HNPCC-like features nor an increased rate of microsatellite instability. No abnormal cDNA sequence was found at the exon 12-13 border. These data suggest a 3.2-fold increased risk of sporadic CRC for individuals with the intronic hMSH2 transition. However, this substitution might not be pathogenic itself, but may be linked to a locus nearby that is.

Adult↗

[Molecular genetics of hereditary breast carcinoma].

Breast cancer is the most common malignancy among women. Genetic predisposition is considered to account for 5-10% of all cases while the majority of these cancers are sporadic and caused by complex interactions of exogenous and endogenous factors. The inherited predisposition can be due to germline mutations in one of several cancer susceptibility genes. For high risk families the two most important genes are BRCA1 on chromosome 17q, which confers a high risk of both, breast and ovarian cancer and BRCA2 on chromosome 13 associated with high penetrance of breast cancer but lower risk of ovarian cancer. A high risk of breast cancer is conferred by mutations in the p53 tumor suppressor gene as part of the rare Li-Fraumeni-syndrome, and possibly also by the estrogen receptor gene. Other cancer genes associated with a less increased risk of breast cancer are the autosomal recessive ataxia telangiectasia (AT) gene and the HRAS1 gene. Germline mutations in BRCA1 and BRCA2 account for the majority of families with multiple cases of breast and/or ovarian cancer and also at least 10% of cases below the age of 40 years. Genetic testing for BRCA1 mutations is not generally recommended except for women with a strong family history. The aim for the management of familial breast cancer should be the establishment of interdisciplinary teams to cover genetic counseling, molecular analysis, onco-surgical therapy, psychosocial support and clinical follow-up.

BRCA1 Protein↗

[Intraoperative determination of parathyroid hormone--an alternative to preoperative localization diagnosis].

The results of localization procedures in hyperparathyroidism are not satisfying and amount to 65% for ultrasonography, 63% for CT-scan, 75% for MRI, and 74% for Tc-Mibi scintigraphy. Since 1994, we have performed intraoperative measurement of PTH with a modified immunochemiluminiscence assay in 44 patients. Ten minutes after exstirpation of pathological parathyroid glands, the PTH concentration decreases to less than 40% of the starting PTH level. We think that intraoperative PTH measurement is a rapid and safe method for controlling the success of surgery in HPT and makes preoperative localization procedures unnecessary.

Adenoma↗

Lower frequency of allele loss on chromosome 18q in human breast cancer than in colorectal tumors.

Inactivation of tumor suppressor genes is thought to be a critical step in tumorigenesis. The DCC (deleted in colorectal carcinoma) gene, located on the long arm of chromosome 18, has been shown to be frequently deleted in colorectal tumors. To investigate the involvement of allelic deletions on chromosome 18q in breast cancer tumorigenesis we analyzed 28 primary breast tumors and 28 colorectal tumors (24 carcinomas, 4 adenomas) with four different polymorphic DNA markers detecting RFLPs on chromosome 18q. In breast cancer we found loss of heterozygosity (LOH) in 4 of 27 (15%) informative cases whereas 15 of 25 (60%) colorectal tumors showed allelic deletions. In all cases of allelic loss the DCC locus or its proximal vicinity (locus SSAV1) were involved. LOH on chromosome 18q occurs both in breast and colorectal cancer, yet the frequency of these deletions in breast tumors is lower than in colorectal tumors. Moreover, in breast cancer these mutations were only detected in large and undifferentiated tumors.

Adult↗

[Clinical significance of cytokines Il-6, Il-8 and C-reactive protein in serum of patients with acute pancreatitis].

The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

Acute Disease↗

Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma.

An active specific immunization (ASI) procedure with two types of autologous tumor cell vaccines (ATVs) is tested for adjuvant immunotherapy of resected colorectal carcinoma to provide preliminary information on local immunological skin responses, side effects, and 2-year survival rates. For vaccine preparation, the tumor-derived freshly isolated and cryopreserved cells were thawed, purified by Percoll density centrifugation, and depleted of tumor-infiltrating lymphocytes by immunomagnetic beads. After inactivation by 200 Gy, the cells of this ATV were either infected by Newcastle disease virus (NDV) or they were admixed with Bacillus Calmette Guérin (BCG) organisms. Vaccination was performed in the arm beginning 6-8 weeks after operation, three times at 2-week intervals. Of 57 patients that received ASI, 48 were treated by virus-infected ATV (ATV-NDV) and 9 were treated with the BCG-admixed vaccine (ATV/BCG). The mean value of delayed hypersensitivity skin reactions from ATV-NDV-treated patients was 18 mm for the first vaccination and 26 and 29 mm for the succeeding ones. Although the application of ATV-NDV was associated with only mild side effects, the ATV/BCG vaccine led to long-lasting ulcers and to more serious side effects. The 2-year survival rate obtained with ATV-NDV was 97.9%, whereas the survival rate with ATV/BCG was 66.7%. The mean survival of 661 patients from a historical control was 73.8%. These data suggest that the type and quality of the tumor vaccine for ASI treatment is important. The findings with ATV-NDV necessitate corroboration in a prospective, randomized controlled study.

Aged↗

Malignant neurofibroma of the urinary bladder.

We report a case of a large malignant neurofibroma of the urinary bladder occurring in a 33-year-old patient with Recklinghausen's neurofibromatosis. Urologic manifestations of neurofibromatosis are infrequent; a neurofibroma of the bladder with malignant degeneration is an extreme rarity. To date only 3 cases have been described in the literature.

Adult↗

[Ambulatory visceral surgery--limits and risks from the clinical viewpoint].

Visceral outpatient operations are well established in Dresden. Since 1978, 13,948 cases have been operated on in general surgery. Most patients (57.8%) had local anesthesia; only 9.2% needed general anesthesia. A total of 9,175 patients (65.8%) had visceral outpatient surgery. The conditions for these operations in outpatients are: the patient's compliance, the cooperation of the family, an operating theater with complete equipment and, last but not least, a qualified surgical team. The pre- and postoperative management must be perfectly organized. Even today there are special limitation for one-day surgery. We have not yet introduced laparoscopy into our outpatient program. Oncological surgery can be performed, provided the general standards for radical tumor surgery can be realized. With careful selection of patients and the right indication, complications are rare in outpatient surgery. In only 0.7% of all cases did wound infections occur postoperatively. None of the patients died.

Ambulatory Surgical Procedures↗

[The Whipple partial duodenopancreatectomy--its value in the treatment of chronic pancreatitis].

The surgical treatment of chronic pancreatitis is indicated only in the complicated disease. The aim is mainly the treatment of pain, of mechanical obstacles and to exclude suspicion of cancer. Between October 1972 and January 1993 713 patients with chronic pancreatitis were treated at the Surgical University Hospital in Mannheim. In 40% of the patients conservative treatment was continued or intensified. Only in 123 patients a Whipple operation was performed. The leading symptom was pain in these patients. We saw postoperative surgical complications in 14 patients (11.4%). One of them died due to an operative leak (0.8%). Late results are based on a median follow up of 4.8 years and showed a complete or substantial pain relief in 94%. 66% went back to work. 77% gained weight with an average of more than 10 kg. The rate of postoperative endocrine insufficiency was 10% (total 40%), of exocrine insufficiency 26 (total 51%). Late mortality was 11% and mostly caused by continued alcoholic abuse. Based on these results, the Whipple operation seems to be the best standardized method for surgery of the complicated chronic pancreatitis within the head of the pancreas.

Alcoholism↗

[Resection of solitary liver metastases of malignant melanoma].

Patients with solitary metastasis of melanoma may benefit from resection, although diffuse organ involvement is common. Recent results in immunotherapy of metastatic melanoma are impaired by early local recurrence, leading to consolidation surgery. Two patients with solitary liver metastasis were treated by liver resection. In one patient in January 1993, atypical resection was performed after partial remission induced by regional adoptive immunotherapy with LAK-cells and Interleukin-2. In September 1983 right hemihepatectomy was done in one patient for large metastasis without preceding therapy. Until now there is no evidence of disease in both patients. The metastasis were 14 cm without and 3.5 cm after (5.3 cm before) immunotherapy in diameter. On histologic examination we found only a slight necrosis without marked immunological reaction like mononuclear cell infiltration or fibrotic demarcation in the specimen of the patient without forgoing therapy. In the specimen of the patient after immunotherapy, the metastasis was necrotic. It was encapsulated by fibrous tissue which was infiltrated by lymphoid cells. The microscopic evaluation revealed some clots of vital tumorcells. The resection of solitary liver metastasis of melanoma with or without immunotherapy is recommended. The rational for consolidation surgery for melanoma metastases after successful immunotherapy is based on the histologically proven vital tumor cells in necrotic metastasis, which are responsible for early local recurrence.

Combined Modality Therapy↗