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Biomedical subjects

H D Saeger

Publications and source records attributed to H D Saeger.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5-fluorouracil and folinic acid for liver metastases from colorectal carcinomas.

BACKGROUND: A multicenter phase II trial was initiated in order to evaluate the weekly, high-dose 24-hour infusion of 5-fluorouracil (5-FU) plus folinic acid (FA) in patients with unresectable colorectal cancer hepatic metastases. PATIENTS AND METHODS: A weekly hepatic arterial infusion (HAI) of FA 500 mg/m2 followed by a 24-hour infusion of 5-FU 2,600 mg/m2 (later reduced to 2,200 mg/m2) was given via a surgically implanted intra-arterial port system. One treatment cycle consisted of six weekly applications followed by a two-week rest period. Toxicity was assessed according to the WHO criteria. Chemotherapy was continued until disease progression or complete response occurred. RESULTS: A total of 50 patients (40 chemonaive, 10 pre-treated) entered this trial. An objective tumor response occurred in 28 patients (56%), while 13 patients (26%) had stable disease. The median progression free survival was 12 months, and the median survival 22.3 months. Due to a high rate of gastrointestinal side-effects in the initial phase of the trial, the dosage of 5-FU was reduced to 2,200 mg/m2 for all subsequent patients. Diarrhea and nausea led to a dose reduction in 40% of applications and 24% of patients, respectively. One patient died of cardiac insufficiency unrelated to chemotherapy before response evaluation. CONCLUSIONS: This HAI approach using high-dose 5-FU was relatively well tolerated when 2,200 mg/m2 instead of 2,600 mg/m2 was used. The activity of this regimen is promising and warrants further evaluation and modification.

Adenocarcinoma↗
PubMed2001

[The value of colour duplex sonography in the assessment of surgical resectability of pancreatic tumors].

UNLABELLED: The Value of Colour Duplex Sonography in the Assessment of Surgical Resectability of Pancreatic Tumors. AIM: The aim of this study was to evaluate the assessment by modern colour duplex imaging (CDI) concerning the relation between tumour and vessels including haemodynamic parameters in the main abdominal arteries and the portal system, and to evaluate the influence of these results on surgical decision making. METHOD: From January 1997 to October 1998, 146 patients with a tumour of the pancreas were included in a prospective study. Tumour contact to vessels and to the retroperitoneum, data on the flow in the main abdominal arteries and the portal circulation (regional topography) as well as the detection of liver metastases, enlarged lymph nodes and peritoneal carcinomatosis were defined as representing criteria of resectability. The results were compared with the intraoperative situation and with the definite histological findings. RESULTS: In 57 resectable tumours, the portal system was found to be infiltrated by the tumour up to a length of 1.5 cm. The flow velocity reached between 4 and 53 cm/s (mean flow) and 9 to 105 cm/s (maximum flow). Out of 146 pancreatic tumours, 89 were found as being non-resectable. In these cases, the measured parameters differed depending on the degree of tumour infiltration in to the portal circulation. We measured values from 0 to 96 cm/s (mean flow) and from 0 to 201 cm/s (maximum flow) with loss of breath-dependent modulation. The contact area between tumor and portal vessel was longer than 2 cm. Pathological flow in the main abdominal arteries was only found in 2 of 13 cases. The local situation was assessed correctly in 140 out of 146 cases by CDI (sensitivity of 93.0 %, specificity of 97.8 %, positive predictive value of 96.4 %, negative predictive value of 95.6 %). Regarding the complete oncological status (local situation, metastases, lymph node involvement and peritoneal carcinomatosis), a sensitivity of 82.5 % and a specificity of 92.1 % (positive predictive value of 87.0 %, negative predictive value of 89.1 %) was found. CONCLUSION: Modern CDI can reliably assess the resectability of pancreatic tumours by the evaluation of morphological and haemodynamic parameters. There are still difficulties in the assessment of lymph node involvement as well as in the detection of small liver metastases and of peritoneal carcinomatosis without ascites.

Adult↗
PubMed2001

[Jejunal reservoir for pouch. Anal reconstruction].

Jejunal reservoir for pouch. Anal reconstruction. For restaurative proctocolectomy the ileal J-pouch is a world-wide accepted procedure. In some cases the mesenteric vascular anatomy does not allow to bring the ileum down to the dentate line. In these patients a jejunal reservoir can be a good alternative. The different architecture of arteries and veins within the jejunal mesentery makes the bridging of a longer distance possible. Within a group of 38 restaurative proctocolectomies, jejunal pouch was performed in 2 cases. Failure of an ileal pouch was the reason in one patient. In the other, the ileal mesentery was too short to achieve a tension free ileal pouch-anal anastomosis. The functional result is good in both cases.

Adenomatous Polyposis Coli↗
PubMed2001

[Hereditary colorectal carcinomas - reflection on preventive surgery].

Nonpolyposis Colorectal Cancer (HNPCC) accounts for about 5% of all colorectal cancers and is the most frequent familial form; familial adenomatous polyposis coli accounts for about 1%. Prerequisitive for individually tailored surveillance is the identification of the pathogenic germline mutation. In classical FAP, surgical standard is a restorative proctocolectomy while in HNPCC there is no surgical standard other than standard oncological resection due to missing evidence. In HNPCC, prophylactic colectomy before the onset of the first colorectal cancer is not recommended. Main arguments for the extension of the resection in the case of the first colorectal carcinoma in HNPCC are the rate of metachronous colorectal carcinomas of 40-45% in a 10-year interval and rapid tumor progression. In HNPCC, in the case of first colon cancer a subtotal colectomy seems to be indicated. A proctocolectomy or, if indicated, a restorative proctocolectomy may be considered in the case of carcinomas in the lower rectum. These considerations should be evaluated in a prospective clinical trial. Counselling, molecular diagnosis and surgery in patients with hereditary colorectal cancers should only be performed in interdisciplinary centers.

Adenomatous Polyposis Coli↗
PubMed2001

[Can molecular genetic knowledge from studies of hereditary carcinoma be applied to sporadic colorectal carcinoma?].

Colorectal carcinomas without a family history are considered to be "sporadic" carcinomas, however, also have a genetic basis. Within the hereditary forms there are 15-50% of patients without a family history being carriers of de novo germline mutations. In addition, non-pathogenic polymorphisms in these tumorsyndrome-genes as well as in genes involved in the carcinogen metabolism (GST, NAT, CYP, MTHFR) are associated with an increased or decreased colorectal cancer risk. Identification of these genetic risk factors will enable individually tailored surveillance and recommendations for prophylaxis as well as individually tailored treatment.

Adenomatous Polyposis Coli↗
PubMed2000

Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer.

To evaluate the involvement of hMSH6 in colorectal cancer, the complete coding sequence and flanking intron regions of the gene were analyzed by DNA sequencing in 10 patients fulfilling Bethesda Guidelines for colorectal tumors and 10 patients with sporadic colorectal carcinoma. In addition, 10 mono- and 10 dinucleotide repeat markers were analyzed for microsatellite instability. A protein-truncating T insertion at codon 218 was identified in the index person of a hereditary non-polyposis colorectal cancer (HNPCC)-like kindred and was accompanied by a somatic T deletion in the tumor. The tumor of this patient was positive for mono- but negative for dinucleotide repeat instability and lacked allelic losses at loci frequently affected in colorectal carcinomas. A novel amino acid change, F340S, was found in a patient with sporadic colon and breast cancer and leukemia but was not detected in 246 chromosomes from healthy anonymous blood donors. In addition, we describe 2 silent and 15 intronic sequence variants not previously reported. Although the frequency is low, we present further evidence for hMSH6 germline mutations that predispose patients to HNPCC-like phenotypes and suggest that mono- and dinucleotide repeat instability testing may be useful for distinguishing between individuals harboring an hMSH2 or hMLH1 mutation and a mutation of the hMSH6 gene.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Serous cystadenoma of the pancreas].

INTRODUCTION: Serous cystadenomas of the pancreas are rare tumors and thought to be almost always benign. METHODS: We report our experience in the diagnosis and surgical treatment of 12 patients with these tumors. RESULTS: Between October 1993 and December 1998, 41 patients with cystic tumors of the pancreas underwent surgical resection; in 12 cases (11 women, 1 man) a serous cystadenoma (10 micro-cystic, 2 oligo-microcystic) was found. Only 6 (50%) patients had symptoms. The mean tumor size was 4.8 (2.7-10) cm. Ultrasound, CT and MRT usually could detect the mass, but differentiation with other cystic lesions was not reliable. All tumors were resected: 4 Whipple procedures, 7 distal pancreatectomies and 1 segmental resection were performed. No patient died after surgery and none had to be reoperated on. CONCLUSIONS: Because of the difficulty in reliably differentiating benign and malignant lesions of the pancreas, we believe that cystic tumors of the pancreas should be resected.

Adult↗
PubMed2000

Clinical consequences of molecular diagnosis in families with mismatch repair gene germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC), clinically defined by the Amsterdam criteria, is associated with mismatch repair gene germline mutations. This study was performed to evaluate the efficiency of combined clinical and molecular diagnostics in identifying carriers of a mutated gene in families meeting criteria of the Bethesda guidelines and to examine the influence of molecular diagnosis on clinical decision-making in carriers and noncarriers. Seventy-two patients meeting criteria of the Bethesda guidelines were tested for microsatellite instabilities (MSI). MSI-H tumors were found in 38 (52.8%) index patients. Complete sequencing of hMLH1 and hMSH2 in 38 MSI-H patients and of hMSH6 in one of these patients revealed 15 pathogenic germline mutations, including three novel mutations, and three novel unclassified germline variants. Twelve of the 15 pathogenic mutations were found in patients fulfilling the Amsterdam I/II criteria. Surgical and genetic counseling was offered to the affected families; as a result of molecular diagnosis in the 15 families, 26 index patients and affected carriers and 8 asymptomatic carriers of a mutated mismatch repair gene were included in the surveillance program, and 26 noncarriers were excluded from this program. Although germline mutations are detected in only 20.8% of patients fulfilling criteria of the Bethesda guidelines, family history and MSI-H tumor classification are both strong indicators for germline mutations in hMSH2, hMLH1, and hMSH6 genes, resulting in a 51.9% mutation detection rate. Identification of individual mutation status allows clear-cut decisions on whether or not inclusion in surveillance programs is indicated.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Surgery of hereditary colorectal carcinoma].

Hereditary colorectal cancer syndromes account for about 7% of all colorectal carcinomas. The most frequent form is Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Identification, cloning and sequence analysis of the predisposing genes enables identification of mutation carriers and non-mutation carriers, respectively. These genetic informations can be used in an individually tailored clinical surveillance program and may ultimately result in standard preventive surgical treatment. In classical FAP the surgical standard is performing a restorative proctocolectomy. It is still unclear now, if this procedure should be modified in attenuated forms (colectomy with ileorectostomy). Due to a high rate of synchronous and metachronous carcinomas a subtotal colectomy in the case of first colon cancer seems to be indicated in HNPCC patients. A proctocolectomy or a restorative proctocolectomy should be weighed in case of carcinomas in the lower rectum. These procedures should be performed under the precondition of identification of the pathogenic germline mutation in the patient, only. In addition, a synchronous prophylactic hysterectomy with oophorectomy should be recommended postmenopausal gene carriers. Intensive counseling of the patient should proceed these preventive procedures involving surgeons, gastroenterologists, geneticists, molecular biologists, gynecologists, physicians and psychologists. It is recommended to have patients treated exclusively in specialized centers. Currently, six interdisciplinary centers for cancer surveillance and early diagnosis in hereditary colorectal cancer are being sponsored in Germany by the Deutsche Krebshilfe since 1999. In the future clinical studies have to be conducted to evaluate the efficacy of extended colorectal resections versus efficacy of surveillance and conventional resections according to general oncological principles.

Adenomatous Polyposis Coli↗
PubMed1999

[Significance of selenium in regulation of inflammatory response by transcription factors in polytrauma patients. A clinical study].

The authors have investigated the relationship between selenium and transcription factors (NF-kappa B and AP-1) in the field of pathogenesis of polytrauma. Correlations between plasma selenium content and transcription factor binding activity have been found. The measured connecting capacitances of transcription factors have been associated with the severity of disease. To harden the results of this research a randomized double blind study with sodium selenite substitution is necessary next. This study will be to establish the therapy with sodium selenite in the treatment of polytrauma.

APACHE↗
PubMed1999

[Low T3 syndrome in multiple trauma patients--a phenomenon or important pathogenetic factor?].

BACKGROUND: Many nonthyroidal illnesses, such as major trauma, severe burn injury, sepsis or immune deficiency are associated with a reduced T3 concentration without increased serum TSH secretion. The pathopysiologic meaning of this phenomenon was controversely discussed since its investigation 20 years ago. The identification of the Type I 5-iodthyronine-deiodinase as a selenoenzyme brought many new aspects into this discussion. PATIENTS AND METHODS: To investigate the correlation of T3 blood levels and the selenium concentrations in consideration of the severity of the nonthyroidal illness 20 patients with major trauma where included in this study. In all these patients frequently T3, T4, fT3, fT4, TSH, Se (whole blood), Se (plasma) and Glasgow-Coma-Scale (GCS), APACHE II and MOF-Score where measured until the 28th day of illness. RESULTS: Five patients (20%) died during the study until the 8th day of measurement. Survivors and nonsurvivors initial showed a low T3 and fT3 level in serum. While the T3 serum concentrations of nonsurvivors remained on a low level the thyronine concentrations of survivors distinctly increased. The measured thyroid hormone concentrations were significantly correlated with MOF-score, APACHE II and inversely with GCS. There was no significant correlation between low T3/fT3 blood levels and low selenium concentrations in all observed patients. CONCLUSION: The selenium deficiency in all patients with major trauma seems to be not the single cause of the low T3 syndrome. The distinctly suppression of TSH could be caused by the action of various cytokines such as IL-6 and TNF-alpha. Further investigations should improve the effectivity of substitution of selenium and/or thyroid hormones in the therapy of patients with severe nonthyroidal illness.

APACHE↗
PubMed1999

[Redox sensitive behavior of selenite in the presence of reactive oxygen species. Are there nonenzymatic direct reaction pathways].

From extensive research over the last decade it has been known that selenium is essential as necessary component of selenoaminoacids and of specific enzymes. Among others, the redoxpair GSH/GSSG is closely connected with antioxidative processes. Moreover it inhibits and/or activates molecular key reactions with the involvement of various small reactive O- and N-species. We investigated the direct interaction of selenite with components of the respiratory burst of human blood cells, considering the redoxamphoterie of alkali-selenite. Selenite tend to redox-disproportation depending on the pH-value. Whether selenite leads to oxidation or reductation is dependent not only on the pH-value, but also on the redox-potential of the reaction partners. In in-vivo adapted in-vitro conditions (ph = 7.4; mumolar concentrations of reaction partners) we observed the following results: 1. SeO3(2-) is not oxidized by H2O2/NO or triplet-oxygen, when the oxidatives are applied alone; 2. SeO3(2-) is quantitatively oxidized from SeO4(2-) by the combination H2O2/NO2- or O2-/NO; 3. SeO3(2-) is semiquantitatively oxidized by singlett oxygen to SeO4(2-). The composition of reaction products was measured by 77Se-NMR-spectroscopy. The reactive intermediate product for the 2. reaction should be peroxynitrite (HOONO). One cannot rule out the possibility that HOONO reacts on a large scale with H2O2 to singlett oxygen. Subsequently singlett oxygen oxidizes selenite. The pathophysiological impact of singlett oxygen in processes like arteriosclerosis is now being investigated. It has been supposed, that singlett oxygen is participating in processes of lipidperoxidation invivo. Further investigations have to show, to what extent selenite is effective as direct 1O2-scavanger.

Arteriosclerosis↗
PubMed1999

[Palliative measures in the hepatobiliary-pancreatic system].

Malignant tumors of the hepatobiliopancreatic system are not curable in > 60%. For this reason, palliation plays an important therapeutic role. Indications are mainly obstructive jaundice, duodenal obstruction and pain. Assessment of the tumor's morphology and resectability is often possible only by surgical exploration. If necessary and feasible, non-curable malignancies are treated synchronously during this operation. In preoperatively proven distant metastases or local non-resectability, interventional procedures are preferred. They are efficient, at least primarily, and mostly correlated with little patient discomfort. A surgical biliary bypass obviously leads to improved long-term palliation. Especially in Klatskin tumors, palliative resection may be useful. Generally the patients benefit from palliation depends on minor therapeutic discomfort and long-lasting control of symptoms.

Biliary Tract Neoplasms↗
PubMed1999

[Crohn disease of the esophagus].

INTRODUCTION: Since the landmark report by Crohn, Ginzburg and Oppenheimer in 1932, the spectrum of involvement of Crohn's disease has expanded to include the entire digestive tract from mouth to anus. The involvement of the esophagus by Crohn's disease is very rare. METHODS: We report a 41-year-old male patient with severe Crohn's disease of the distal esophagus with a fistula to the right bronchial system. RESULTS: After a long period of nutritional support we performed a transthoracic esophagectomy and a Nissen fundoplication. Postoperatively his course was complicated by pneumonia and withdrawal symptoms. CONCLUSIONS: Esophagectomy is indicated in Crohn's disease of the esophagus with severe stricture or fistula formations.

Adult↗
PubMed1999

[Preventive surgery of inherited colorectal cancer identified through molecular diagnosis].

Numerous inherited genetic changes predisposing to cancer have already been identified and the number is increasing. Accurate prediction of individual risk by means of molecular diagnosis implies clinical consequences in the treatment of cancer-predisposing syndromes. Using familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) as an example, we present here the underlying genetic changes that contribute to tumor development. These genetic alterations can be efficiently identified through molecular diagnostic techniques. Identification of the familial germline mutation permits one to distinguish mutation carriers from non-mutation carriers within affected families and results in individually tailored surveillance and prevention. Therefore, molecular diagnosis is making a contribution to the advances in preventive surgical therapy. The indications are discussed.

Colorectal Neoplasms↗
PubMed1999

[Mammographic screening starting in the fifth or sixth decade of life].

Mammography is an established diagnostic procedure for breast cancer. Data concerning screening mammography are available from nine prospectively controlled trials, the largest series being presented from Sweden. Mammographic screening leads to a significant reduction of breast cancer of 30% in women ages 50-59 years. In younger women (40-49 years) the benefit accounts to only 20% and has not proven to be statistically significant. Nevertheless, the major advantage of mammographic screening is detection of the non-palpable tumor < or = 10 mm in size. The treatment of these small breast carcinomas leads to long-term survival rates of > or = 90%. Mammographic screening programs have been introduced in the USA, Canada, Iceland and Sweden for women in their 5th decade of life. Starting yearly lifelong mammography-screening at the age of 40, the theoretical cancer induction by radiation exposure does not exceed 0.1%. Under highly qualified conditions, it should be possible to minimize false-positive and false-negative screening results. In Germany, screening-mammography is only introduced in patients at high risk for breast cancer. Based on medical data, mammography must be a part of screening for women with an average risk--starting at the age of 40, although there are still open questions needing further clinical research.

Aged↗