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Biomedical subjects

H D Saeger

Publications and source records attributed to H D Saeger.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Early results and complications of surgery of liver metastases].

Following resection of liver metastases the overall prognosis still remains limited because of the lack of adjuvant therapy. The number of explorative laparotomies, non-radical resections and complications needs to be reduced. One hundred and ten laparotomies in 97 patients with liver metastases were performed with the intention to cure between October 1993 and February 1998. In a prospective analysis we reviewed: patient characteristics, characteristics of primary tumors and metastases, part and extent of liver resection, radicality, complications and mortality. Additionally, a prospective study about the value of ultrasonography and CT scan concerning the evaluation of preoperative liver findings was undertaken between January 1995 and February 1998. Altogether, resection of liver metastases was achieved in 75 cases (68.2%). Nineteen patients (25.3%) had postoperative complications. Two patients (2.7%) died following liver resection. Thirty-five operations (31.8%) had to be finished as only an explorative laparotomy. The major reason for these restricted operations was in 15 patients (42.9%) regional recurrence or peritoneal metastases. Preoperative determination of the liver finding (quantity, localization and size) by ultrasonography and CT scan achieved an accuracy of 68.9% each. The results of this analysis show that resection of liver metastases can be accomplished with minor morbidity and mortality. The high number of explorative laparotomies still remains a central problem in the surgery of liver metastases. By the introduction of duplex sonography and contrast-medium-enhanced helical CT scan, liver pathology can be defined more precisely in the preoperative evaluation. However, preoperative detection of regional recurrence or peritoneal metastases remains difficult.

Adult↗
PubMed1999

Hereditary colorectal cancer: clinical consequences of predictive molecular testing.

The continuing increase in knowledge about the genetic basis of carcinogenesis has led to diverse efforts to exploit this knowledge clinically, primarily in the form of predictive genetic testing. In conjunction with family history, gene tests are intended to improve individual cancer risk assessment. The objectives of predictive molecular testing are to identify the disease-causing germline mutation in an index person who has already developed the disease and to distinguish asymptomatic mutation carriers from non-mutation carriers within a given cancer-prone family. At present, genetic testing for colorectal cancer risk, primarily in form of DNA sequencing, is applied in familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). In these inherited colorectal tumor syndromes determining the genetic status may result in an individually tailored surveillance program and prophylactic treatment. The implications of genetic testing for the clinical management of disease, both of mutation and non-mutation carriers, in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer families are discussed.

Adenomatous Polyposis Coli↗
PubMed1999

Quantitative differences between aberrant transcripts which occur as common isoforms and due to mutation-based exon skipping of the mismatch repair gene hMLH1.

About one-third of hereditary non-polyposis colorectal cancer-related mutations in the mismatch repair gene hMLH1 result in the loss of entire exons from the wild type transcripts. Here we describe quantitative differences of hMLH1 transcripts without exon 15, exon 16 or exon 17 in several members of a family with hereditary non-polyposis colorectal cancer. The transcript lacking exon 15 is caused by a G to A transition affecting the last nucleotide of the respective exon and results in a truncated protein. The transcripts lacking exon 16 or exon 17, which are in-frame deletions, were also found in all tested samples of a normal population and represent common isoforms. Reverse transcription-polymerase chain reaction-based relative quantification revealed about 50 % signal intensity for the mutation-based transcript, but less than 10% for the common isoforms, if compared to the wild type. All aberrant transcripts were detected from blood-derived cDNAs but not from samples of normal colon epithelium. Although the biological significance of the common isoforms is unknown, they might lead to false risk assessment in hereditary non-polyposis colorectal cancer cases.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Therapy of deep leg vein thrombosis. When is surgical therapy indicated?].

In spite of quite a few clinical trials the benefit of venous thrombectomy is seen controversially. The primary objectives of treating venous thrombosis are survival rate, prevention of pulmonary embolism and of postthrombotic syndrome. We report our experience with 47 patients who underwent venous thrombectomy. The mortality rate was 0%. We did not observe clinically relevant pulmonary embolism. After two years 90% of thrombectomised veins were patent. The mortality rates given in the literature of conservative treatment with heparin and following oral anticoagulation are 0.4 to 1.6%. Fibrinolysis shows mortality rates of 1 to 2.4, and thrombectomy of 3.8%, respectively. Venous thrombectomy is an effective treatment to prevent pulmonary embolism. In our own experience we saw no clinically significant pulmonary event. The danger of embolism rises with the proximity of the venous thrombus. Therefore those patients may have the greatest potential benefit from thrombectomy who present with a mobile inguinal thrombus or a thrombus in the iliac vein. So far there are no statistically sufficient data to support the indication of thrombectomy to prevent a postthrombotic syndrome.

Adult↗
PubMed1999

Loss of heterozygosity accumulation in primary breast carcinomas and additionally in corresponding distant metastases is associated with poor outcome.

The occurrence of distant metastases is the most feared manifestation of breast cancer, often occurring years after the primary surgery and associated with poor survival. The dominant metastatic clone is characterized by an accumulation of genetic alterations, but it is not actually known at what stage of the metastatic cascade these alterations have occurred. We investigated allelic losses during breast cancer progression in a series of 17 primary breast carcinomas and 22 corresponding brain, liver, lung, and bone metastases (mean metastasis-free interval, 31 months) by analyzing 19 microsatellite markers on seven breast cancer- or metastasis-related chromosomal regions and correlated the incidence of combined loss of heterozygosity (LOH) with metastasis-free and postmetastatic survival. We found that, in comparison with the corresponding primary tumor, additional LOH events are frequently found in metastases and that the incidence of combined LOH in the primary tumor, plus the occurrence of additional LOH events in the distant metastases, correlated significantly with decreased postmetastatic survival. Combined LOH of the three breast cancer-related chromosomal regions alone or in combination with allelic loss at the p53 gene region seems to have a specific influence on the aggressive behavior of metastases. We hypothesize that the occurrence of additional LOH events is either involved in termination of dormancy of micrometastatic tumor cells at distant organ sites or acquired during further progression of metastases.

Bone Neoplasms↗
PubMed1999

[Management of esophageal perforation].

The majority of esophageal perforations is caused by endoscopic procedures, while the spontaneous rupture, also known as Boerhaave's syndrome, is rare. Regardless of the cause the esophageal perforation is an urgent surgical problem. The main diagnostic method is a water-soluble contrast study of the esophagus, probably supplemented by a CT-scan. In case of uncertain diagnosis or localisation eosophagoscopy should be performed. We believe that esophageal perforation should be operated, the factor "time" seems to be important for prognosis. In case of early surgical treatment (within 24 hours) a primary suture is sufficient and safe. Only after a delay in diagnosis with extended mediastinal spillage and necrosis of the esophageal wall the use of autogenous tissue to buttress the esophageal repair may be necessary. Esophagectomy should only be performed for perforated carcinomas. We treated 10 patients in a 4-years-period by primary surgical repair combined with drainage. Nine of them survived, only a 82-years old patient died because of an unresectable perforated esophageal carcinoma.

Adult↗
PubMed1999

[Hierarchy and research].

Surgical research needs structural and organizational conditions. These have to ensure, that the young surgeon finds the opportunity for scientific activities and development in a highly professional environment.

Curriculum↗
PubMed1998

Evidence that TSG101 aberrant transcripts are PCR artifacts.

Critical analysis of the data published so far concerning the TSG101 gene revealed some inconsistencies leading us to its re-evaluation in 80 breast, brain, colon, and neuroectodermal tumors and 37 normal tissue specimens. In this study, the occurrence of TSG101 cDNA aberrant transcripts was verified, but in addition we made observations that are in apparent conflict with the aberrant splicing theory supposed as the underlying mechanism for transcript formation: the location of most deletion breakpoints within exons and nonconformity of these putative splice sites with the highly conserved GT-AG rule, detection of insertions as well as nonreproducible and highly variable results in repeated RT-nested PCRs. Furthermore, we found that reamplification of full-length TSG101 cDNA products leads to the generation of deleted transcripts. In summary, for the first time we provide evidence that the acquired TSG101 transcripts are caused by PCR artifacts.

Artifacts↗
PubMed1998

Resection of pancreatic cancer--surgical achievements.

INTRODUCTION: Looking back at the initially dismal record for pancreatic cancer surgery - Whipple himself felt that a 30-35% mortality was justifiable (!) - significant progress has been made. PROGRESS: The operative mortality has fallen below 5% and the serious complications of pancretic resections such as leaks and haemorrhage have been reduced to some 10% and we are better equipped to deal with these if they occur. The 5-year-survival of patients in whom pancreatic cancer was amenable to an R0-resection has risen to 30%. These are the surgical achievements using the standard Kausch-Whipple technique alone. There has been no improvement in these results, either by increasing radicality (regional pancreatectomy) or by reducing it (pylorus-preserving pancreatoduodenectomy). The same can be said of all other modalities of oncological treatment that have been tried so far: adjuvant radiochemotherapy, regional chemotherapy, hormonal or genetic manipulations. PERSPECTIVE: This does not mean that we should reduce efforts at improving early detection of the disease and unravelling its complex molecular biology. On the contrary, the results of surgery alone in spite of all improvements seem to have reached a plateau that gives little cause for complacency.

Disease-Free Survival↗
PubMed1998

Spontaneous regression of hepatocellular carcinoma confirmed by surgical specimen: report of two cases and review of the literature.

Two cases with spontaneous regression of a histologically confirmed hepatocellular carcinoma (HCC) are presented. This rarely seen phenomenon of a spontaneous tumor involution is discussed and compared with the current literature. The clinical symptoms were very similar to that of a liver abscess. A 56-year-old male suffered from a multicentric, highly differentiated, trabecular HCC. First symptoms were epigastric pain, septic fever and arthritis. The tumor marker AFP was constantly normal and no hepatitis could be verified. A resection of the tumor was performed. In patient 2, a 74-year-old male, a multicentric, clear cell HCC was found. The patient had completely recovered from hepatitis type B and within the liver tissue no viruses could be identified. Clinical symptoms were mainly characterized by upper abdominal pain and septic fever. AFP was excessively elevated (3850 ng/ml) but returned to normal preoperatively. In both cases, the specimen showed a subtotal necrotic HCC with insignificant amounts of vital tumor cells. Neither patient had a liver cirrhosis macroscopically, however patient 2 had local periportal fibrosis histologically. After 24 and 41 months of follow-up, respectively, both patients are in good health

Aged↗
PubMed1998

[Color Doppler sonography in liver surgery. Status of perioperative monitoring].

AIM: Resection of liver tumours is not always successful despite detailed diagnostic work-up preoperatively. In our study we compared the predictive value of colour Doppler imaging of the liver with other radiological examinations for tumour staging, surgical decision making and postoperative complications. METHODS: From 1/95 to 6/1997 we investigated 76 patients with liver tumours; 60 patients with liver metastases, 13 with primary liver carcinomas and 3 with benign lesions. Resectability was defined in colour Doppler imaging by tumour localisation, distance of the tumour to the central vessels and blood flow in the portal vein. CT-scan in all patients and angiography in patients with central tumour localisation was performed. The preoperative results were compared to intraoperative ultrasound and surgical examination. RESULTS: 108 out of 118 intrahepatic lesions were found preoperatively using high-resolution ultrasound. Ultrasound and CT-scan achieve comparable results in delineating pathologic changes in the liver. Considering only the liver findings and local resectability in 76 patients, the sensitivity achieved for B-mode-ultrasound was 77.6% (59/76); for CT-scan 78.9% (61/76) and for colour Doppler imaging 86.4% (66/76). 31 out of 76 laparotomies were terminated after exploration. Resectability was correctly predicted by ultrasound in 55 (72.4%) and by CT-scan in 57 (73.7%) patients. Colour Doppler imaging improved the ultrasound results in up to 62 (81.6%) patients. Unsuspected not resectable tumour growth was found in 9 patients with local/regional recurrences, in 4 patients with peritoneal spread and in one patient with multiple bilateral liver metastases. CONCLUSIONS: Using high-resolution ultrasound systems the preoperative detection of lesions in the liver achieves the results of CT-scan. Little isoechogenic lesions, peritoneal spread and locoregional recurrences can be missed by ultrasound examination. Colour Doppler imaging shows compared with B-mode and CT-scan a higher sensitivity for the detection of the infiltration of hilar structures and can take place of more invasive methods in preoperative liver investigations. Considering functional and morphological aspects colour Doppler imaging makes an essential contribution to the planning of liver surgery. Using lung passing contrast media the determination of tumour vascularisation and perioperative quantification of liver perfusion is possible. The use of the intraoperative ultrasound is justified to determine resection limits, detection of smallest non-palpable lesions and to control perfusion after vascular reconstruction. In experienced hands colour Doppler imaging gives valuable preoperative information with excellent cost-benefit ratio.

Equipment Design↗
PubMed1998

[Surgical procedure in primary and metastatic breast carcinoma].

We know that breast cancer is already a systemic disease in the majority of patients at the time it is first diagnosed, requiring an interdisciplinary treatment concept. This fact has changed the surgical treatment approach of primary breast cancer which currently follows the principle: "As much as necessary, as little as possible". Improved early detection of breast carcinomas allows the treatment of a majority of early stage breast cancer patients with breast-conservation surgery, followed by irradiation except for a few contraindications. Although survival is not significantly different for patients who undergo breast conservation surgery plus irradiation than for those having modified radical mastectomy, the pattern and prognostic value of locoregional failure are different. Locoregional failure after breast conservation requires mastectomy, thoracic wall recurrence will be treated by (en-bloc) resection and irradiation. Following rigorous selection criteria and indications, surgical resection of distant metastases to the liver, lung or brain can improve the quality of life and prolong survival, it should therefore be taken into consideration in individual cases. Since the two breast cancer susceptibility genes, BRCA1 and BRCA2, have been detected, high-risk patients should be offered the possibility of genetic counseling and genetic testing. Based on our present knowledge, the surgical approaches for BRCA1 or BRCA2 mutation carriers with breast cancer remain unchanged. There are some indications that molecular tumor parameters can be used to identify a subgroup of primary breast cancer patients who are characterized by a poorer prognosis. The results achieved in our own patients add further evidence in favor of this theory.

Biomarkers, Tumor↗
PubMed1998

[Sequence analysis of BRCA1 gene in young breast cancer patients and/or positive family history].

We analyzed the complete coding region with adjacent intron sequences of the BRCA1 gene in eight patients with hereditary and/or early-onset breast/ovarian cancer. We detected one germline mutation in exon 5 in a 35-year-old woman with early-onset breast and ovarian cancer and 10 polymorphisms, of which one has not been published so far. To determine whether certain BRCA1 polymorphisms are associated with an increased risk for breast cancer, we will compare genotype distributions of early-onset breast cancer populations with matched controls.

Adult↗
PubMed1998

[Molecular diagnosis and clinical consequences in families with HNPCC syndrome].

Thirteen families were included in our HNPCC surveillance program, eight of which met strict and three incomplete Amsterdam criteria. Two index patients were younger than 35 years of age. Tumors of all index persons showed microsatellite instabilities in at least 50% of the ten markers studied. Immunohistochemical analysis of tumor sections was performed using antibodies against hMLH1 and hMSH2 proteins in order to identify the mutated gene, which is not expressed in the tumor. Coding regions of hMLH1 and hMSH2 genes were amplified by PCR from genomic DNA and sequenced. In nine families pathogenetic mutations all resulting in a truncated protein, could be identified. Furthermore, 21 intron and exon polymorphisms were found. Since July 1997 we have offered surgical and genetic counseling to families with hereditary cancer syndromes in a special outpatient clinic. In addition to 13 index patients three asymptomatic gene carriers were included and eight noncarriers were excluded from the HNPCC surveillance program, as recommended by the HNPCC study group of Germany. Molecular diagnosis has considerable clinical implication in hereditary nonpolyposis colorectal cancer (HNPCC) families with respect to family members who actually have the disease as well as gene carriers and noncarriers.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Multiple endocrine neoplasia type 2-associated RET proto-oncogene mutations do not contribute to the pathogenesis of sporadic parathyroid tumors.

BACKGROUND: Parathyroid disease occurs sporadically or as part of hereditary multiple endocrine neoplasia (MEN) syndrome. The aim of this study was to evaluate the possible role of the RET proto-oncogene not only in hereditary MEN 2-associated hyperparathyroidism but also in different forms of sporadic hyperparathyroidism. METHODS: We investigated 22 patients with parathyroid disease whose family history and results of laboratory and clinical examinations excluded MEN 2 syndrome. DNA extractions of histologically confirmed tumor tissue of patients with primary hyperparathyroidism (n = 18), renal hyperparathyroidism (n = 2), and parathyroid carcinoma (n = 2) were performed. Using solid phase DNA sequencing, mutation analysis of polymerase chain reaction amplified products focused on exons 10, 11, and 16 of the RET proto-oncogene. Parathyroid tissue from four patients with known MEN 2A served as positive controls. RESULTS: No mutations of the codons 609, 611, 618, 620, 634, and 918 were found in the sporadic parathyroid tumors analyzed. DNA sequencing revealed heterozygous mutations in codon 634 of the RET proto-oncogene in four parathyroid glands from four patients with MEN 2A. CONCLUSIONS: Mutations of the RET proto-oncogene contributing to MEN 2 syndromes are absent in sporadic parathyroid tumors. Our data in conjunction with the literature suggest at least three different modes of tumorigenesis in parathyroid disease.

Adenoma↗
PubMed1998

[VATS (video-assisted thoracoscopic surgery): possibilities and limits of surgical therapy of malignant lung diseases].

VATS is able to perform by minimal access all operations known in general thoracic surgery. Mortality (0.07-1.9%) is low and complications (4.3-14.2%) are rare, as published in four studies in the last two years. Especially long-term results of VATS in malignant disease are not clear. Indications and limitations for VATS in bronchial carcinoma and lung metastases are discussed. Surgical treatment in peripheral non-small cell lung cancer has best results after lobectomy. Limited resection decreases the oncological result (5-year-survival-rate) by 10 to 18% compared to lobectomy. Conservative treatment with radiotherapy in stage I carcinomas in patients who are not eligible for open lobectomy because of restricted lung function or other non oncological reasons has a bad prognosis (0-12% 5-y-survival). In these cases VATS resection of bronchial carcinoma should by considered. Detection of all lung metastases by preoperative radiological study is only in 56-75% possible. Between 10/93-2/98 we performed 52 thoracotomies for lung metastases at our surgical department. In eight cases bronchial carcinoma was confirmed by histological examination, nine patients with metastases of malignant germ-cell-tumors were excluded from the study. CT-scan of the lung was performed preoperatively. In 43% of the cases (n = 35) additional lesions were detected intraoperatively by palpation of the lungs. Histopathologic examination revealed benign lesions in 9% and malignant in 34%. The result of lung metastases resection is highly dependent on the completness of extirpation. We therefore conclude that lung metastases should be removed by open thoracotomy.

Carcinoma, Bronchogenic↗