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Biomedical subjects

U Laffer

Publications and source records attributed to U Laffer.

At least 19 recordsLinked to original sources
PubMed2003

Infrequent mutation of the tumour-suppressor gene Smad4 in early-stage colorectal cancer.

Smad4 is a candidate tumour-suppressor gene identified recently on chromosome 18q21.1. Both alleles are inactivated in nearly one-half of pancreatic carcinomas, but its role in the tumorigenesis of other tumours is still unknown. The aim of this study was to investigate the potential involvement of the Smad4 locus in early-stage colorectal cancers (stages I-III) in tumour samples from a randomised multicentre trial. Of a large collection of DNA samples, 73 with a loss of one allele of the Smad4 gene were analysed for the presence of point mutations in the remaining gene. Patients, from whom biopsies were isolated, were part of a previous randomised multicentre study of the Swiss Group for Clinical Cancer Research on the benefit of adjuvant chemotherapy (SAKK study 40/81). Mutation analysis was restricted to the highly conserved C-terminal domain (exons 8, 9, 10 and 11) of Smad4, using PCR and single-strand conformational variant analysis. Two of the 73 patients (3%) with loss of one allele of Smad4 had a point mutation in the remaining allele. These results indicate that whereas Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer.

Clinical Trials as Topic↗
PubMed2002

SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer.

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer.

Antimetabolites, Antineoplastic↗
PubMed2001

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7.

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta-mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Chromosome Deletion↗
PubMed2000

[Is appendectomy really performed too frequently? Results of the prospective multicenter study of the Swiss Society of General Surgery].

Scientific publications and provoking criticism from the lay press have recently pointed out, that appendices may be surgically removed too frequent and without indisputable necessity. In an attempt to verify these questionable statements, the Swiss Society for General Surgery (SGAC) initiated a prospective controlled multi center trial. From September 1997 to December 1998, hundred and twenty-five institutions documented 4603 appendectomies performed due to a suspected appendicitis. Histological investigation of all specimens revealed a 7% rate of normal appendices, 7.2% for patients with national health service (NHS) and 5.9% for patients with private insurances respectively. Compared to the results of the literature, where a frequency of normal appendices around 15% is judged as standard, these results are excellent. In 17.2% of the patients (15.9% NHS and 23.6% privately insured patients) an "appendicitis perforata" was observed. This percentage remains in the range reported by other authors. The analysis of time of admission (i.e. day or night) and the delay from admission to surgery shows a distribution independent to the insurance of the patients. Therefore, the planned appendectomy for patients with private insurances does not exist. A different choice of the surgical technique could be observed depending on the insurance status. In 30.4% of the private insured patients a laparoscopic appendectomy was performed as compared to 22.6% of patients with NHS. Surprisingly, an identical median hospitalization time can be observed for both groups (laparoscopic 5.5 days, open surgery 5.5 days).

Adolescent↗
PubMed2000

[Transfusion use in curatively operated patients with colorectal carcinomas. Swiss Study Group for Clinical Cancer Research].

OBJECTIVE: Is there an improvement of the behaviour for restrective blood transfusions after the data in the literature and especially the preliminary data of the SAKK 40/81 study have been published? They have shown a worsening of the prognosis in patients with colorectal cancer after pre-/postoperative blood transfusions have been given. MATERIAL AND METHODS: Analysis of the retrospective transfusion data of the SAKK 40/81 study in comparison with the prospective transfusion data of the study SAKK 40/87. RESULTS: The analysis of the data showed that in the SAKK 40/81 study more patients received blood transfusions than in the SAKK 40/87 study (77% versus 49%). Especially there was a diminution from 90% in the SAKK 40/81 to 59% in the SAKK 40/87 study for the rectal cancer patients respectively from 70% to 44% in the colon cancer patients having received blood transfusions. The mean value of hemoglobin of the patients not having received transfusions has decreased from 11.2 (7.8-15) g/100 ml in the SAKK 40/81 to 10.6 (5.4-15) g/100 ml in the SAKK 40/87 study (p = 0.0001). CONCLUSION: The data of the two SAKK studies showed that in Switzerland the donation of blood transfusions in patients with colorectal cancer has continuously been handled more and more restrictive. An even more restrective use may be possible in future due to new operation techniques and the possibility of preoperative administration of erythropoetin to increase the hemoglobin level.

Blood Transfusion↗
PubMed1999

Quality of life as subjective experience: reframing of perception in patients with colon cancer undergoing radical resection with or without adjuvant chemotherapy. Swiss Group for Clinical Cancer Research (SAKK)

PURPOSE AND BACKGROUND: We examined whether patients with colon cancer undergoing surgery with or without adjuvant chemotherapy change the internal standards on which they base their quality-of-life (QL) estimation, and, if they do so, whether this reframing alters interpretation of QL findings. These questions were addressed within a randomized clinical trial of the Swiss Group for Clinical Cancer Research (SAKK 40/93). PATIENTS AND METHODS: After radical resection of adenocarcinoma of the colon (pT1-4pN > 0M0 and pT3-4pN0M0) and perioperative chemotherapy, patients were randomized to three treatment arms: observation only (A), 5-FU 450 mg/m2 plus Levamisol (B), or 5-FU 600 mg/m2 (C). QL was measured by linear analogue self-assessment indicators. Patients estimated their pre-surgery QL both before surgery and retrospectively thereafter, and their pre-adjuvant QL both at the beginning of randomly assigned chemotherapy or observation and retrospectively about two months later. Thereafter, current QL was assessed. Paired t-tests were used to test the hypotheses of no change. RESULTS: Overall, 187 patients with at least one pair of corresponding questionnaires were analyzed. Patients estimated their pre-surgery QL after surgery significantly lower than before and their pre-adjuvant QL under treatment or observation also lower than at the beginning. In the adjuvant phase, in contradiction to our hypothesis, chemotherapy had almost no impact on these changes attributed to reframing. Conventionally assessed changes indicated an improvement in QL. Patients with treatment C reported less improvement in functional performance than those with B or those under observation (P = 0.04). Patients with treatment B indicated a greater worsening in nausea/vomiting than those with C, whereas patients with observation only showed an improvement (P = 0.0009). After adjustment of current QL scores under treatment or observation to patients' retrospective estimation, the treatment effects were diluted but the overall improvement was substantially amplified in most QL indicators. CONCLUSIONS: Patients with colon cancer substantially reframe their perception in estimating QL both under radical resection and under adjuvant chemotherapy or observation. This effect is an integral part of patients' adaptation to disease and treatment. An understanding of this phenomenon is of particular relevance for patient care. Its role in evaluating QL endpoints in clinical trials needs further investigation.

Adenocarcinoma↗
PubMed1999

[Systematic scientific quality improvement in surgical specialties. The AQS mode].

BACKGROUND: How can the new legal requirements (Law on Statistics 1992 with its corresponding regulations of 1993: minimum data record of the Federal Department of Statistics (BFS) with ICD codification and the law on medical insurance 1995 with its corresponding regulations of 1996: necessity of documenting quality and efficiency) be integrated into the daily hospital routine with reasonable expenditure of time and costs? METHOD: The BFS minimum data record was combined with additional information on quality improvement on one single questionnaire. The surgical departments of the Hospital Limmattal in Schlieren and the Regional Hospital Bienne founded the Association for Quality Improvement in Surgery (AQC) in 1995 and have tested the AQC system for two years. RESULTS: Until the end of 1997 data from 15,115 surgical procedures were collected in our database. In addition to the more time consuming collection of the "minimal data set of the Federal Department of Statistics (BFS)" which requires between 3 to 10 minutes, the collection of the additional AQC-data will take 1 to 3 minutes. DISCUSSION: There is an increasing expenditure of time and costs as a result of legal requirements. Expenditure may, however, be kept within manageable limits if a single questionnaire serves several purposes simultaneously. The AQC system does not only meet the legal requirements as to systematic quality improvement and BFS statistics, but can also be used for the annual statistics of the clinic, the statistics of individual surgeons, and for hospital comparisons provided other clinics adopt the system as well. There are no standards, reference areas or indicators as yet, but such tools may now be developed much more easily with comprehensive data available through the AQC system. CONCLUSIONS: The AQC system has proved to be a manageable tool in the hospital routine; it could thus be implemented as a wide-area system to provide systematic quality improvement and to meet other statistical requirements.

Humans↗
PubMed1998

[Ischemic colitis and mesenteric ischemia after abdominal aortic reconstruction].

Ischemic colitis is quite a rare condition, which can be subdivided into two categories, a so-called occlusive form as a complication of various vascular diseases, and a non-occlusive form caused by exogenous administration of drugs, or i.e. higher cocentrations of various endotoxines or cytokines. Besides the most serious cases with transmural ischemia, needing operation and resection, over 50% of all cases suffer from non-transmural or mucosal ischemia which can be treated conservatively. These cases usually show a rather favourable outcome. A part of these patients will suffer from bowel stenosis or strictures later on and may need secondary resections. Ischemic colitis following aorto-iliac reconstructive surgery is a rare but well known complication. Although it should be suspected much more frequently, only 1 to 2% of the patients will present a condition of clinical importance. The complication is more frequent in patients who undergo surgery as an emergency, especially reconstruction for aneurysmal disease, and it is less frequent in patients who undergo aorto-iliac reconstruction for occlusive disease; probably because the latter have already developed collateral vessels in the visceral area. A preoperative evaluation of this specific risk is rarely possible by angiography. Intraoperative strong pulsating backflow from the inferior mesenteric artery is considered as a quite reliable prognostic factor for a sufficient mesenteric circulation. Measurement of inferior mesenteric stump pressure, fluoresceine instillation and doppler ultrasound have been proposed as more reliable predictive elements. Wherever mesenteric circulation seems to be doubtful, inferior mesenteric replantation is advisable. In the postoperative course, a thorough clinical surveillance and probably systematic sigmoidoscopy especially on patients with prolonged intubation in strongly advisable in order to detect ischemic lesions in an early stage. Early operations on transmural lesions will help to improve this otherwise very serious and life threatening complication.

Aortic Diseases↗
PubMed1997

[Breast preserving therapy of breast carcinoma: analysis of over 1,300 patients treated in the Basel region].

From 1977 to 1994 a total of 1329 breast cancer patients have been treated with breast conserving surgery in the region of Basel. This analysis is based on 832 patients treated from 1977 to 1990 according to a prospective treatment protocol, which was adjusted only once (1985). In comparison with the most known international publications this analysis represents one of the greatest homogeneous series of breast conserving treatment. We observe an overall 5-year survival of 91% and a 10-year survival rate of 77%. 94% of the women remain locally recurrence free at 5 years and 86% at 10 years respectively. At 5 years, freedom of local recurrence totals to 97% in patients without (pN0) and to 89% in patients with tumor involvement of the axillary lymph nodes (pN+) (p = 0.00008), as well as to 96% for pT1 and 91% for pT2-tumors (p = 0.08328). In our analysis the R0-resection significantly influences local recurrence free survival.

Adult↗
PubMed1995

[Local treatment of breast carcinoma: when is breast-saving therapy not indicated?].

Conservative treatment of breast cancer is now an accepted oncological procedure. It further allows a good functional and cosmetic result. This treatment needs more skills and time than mastectomy, as it does not only include a surgical excision but also a postoperative local radiotherapy and a sometimes difficult follow-up during many years. The contraindications for conservative breast cancer therapy are numerous and depend on factors as tumor, patient and radiotherapy. As more than 1100 patients have been treated since 1977 in our area at a single radiooncological center by a breast conserving procedure. We have confirmed or defined criteria which lead to a good local tumor control as well as to good functional and cosmetic results.

Breast Neoplasms↗
PubMed1994

Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer.

A randomized double-blind trial has shown that, in 160 women with breast cancer undergoing lumpectomy or mastectomy with axillary clearance, perioperative and postoperative administration of tranexamic acid 1 g three times daily resulted in a significant reduction in the mean postoperative drainage volume compared with patients given placebo (283 versus 432 ml, P < 0.001). The frequency of postoperative seroma formation was also decreased by tranexamic acid administration (27 versus 37 per cent, P = 0.2). Haematoma formation was infrequent in both groups and was not altered by administration of tranexamic acid. No infectious complications occurred. Age over 60 years was a significant risk factor for overall wound complications but tumour size and regional lymph node metastases were not. Tranexamic acid may be used to reduce the frequency of postoperative wound complications following surgery for breast cancer.

Age Factors↗
PubMed1994

[Status of portal perfusion in colorectal cancer. Swiss Study Group for Clinical Cancer Research].

533 patients with diagnosis of operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C (MMC) and 5-Fluorouracil (5-FU) starting immediately after operation, or no adjuvant treatment. Of these, 505 (94%) were evaluable. Over the median follow-up of 8 years, the adjuvant therapy reduced the risk of recurrence by 22% (Hazard ratio = 0.78%, 95% CI 0.61-0.99; P = 0.045). The relative reduction of relapse on death was similar in all subgroups (i.e. nodal status, localization). However, adjuvant portal chemotherapy proved to be most efficient in the subgroups of patients with tumor involvement of the regional lymph nodes (Dukes C) and of patients with colon cancer. Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (i.e. local relapses, liver metastases and/or other distant metastases) in the treated group, rather than to liver relapses alone. We conclude therefore, that part of significant benefit obtained for patients with operable colorectal carcinoma treated with a single course of adjuvant chemotherapy via the portal vein might be due to the additional systemic effects of the portal chemotherapy and further study of perioperative treatment with and without prolonged chemotherapy appears worthwhile.

Adenocarcinoma↗
PubMed1993

[Developments in the surgical therapy of colonic diverticulitis].

All patients admitted to our department with diverticulitis of the left sided colon between 1980 and 1990 were retrospectively evaluated. Staging was performed according to the Hinchey classification. Altogether, 263 patients were evaluated; 71% had complicated diverticulitis and 29% simple diverticulitis. Of those patients with complicated diverticulitis, 68% required surgery due to abscess formation and/or perforation, 19% because of obstruction, 10% because of fistula formation, and 3% due to intestinal hemorrhage. While primary resection (primary reanastomosis in 82% or Hartmann procedure in 13%) was carried out in 250 patients (95%), 13 patients (5%) did not obtain this result (colostomy) following the initial operation. None of the patients who presented with simple diverticulitis died in the postoperative period. The total operative mortality and mortality for complicated diverticulitis amounted to 6.5% and 9%, respectively. In comparison to a former analysis from our department, resection of the primary focus during the initial operation led to a significant decrease in morbidity and mortality. In patients with complicated diverticulitis and peritonitis, primary resection and anastomosis also achieved favourable results in 78%.

Abscess↗
PubMed1992

[Prevention of thromboembolism in hip traumatology: low molecular weight heparin versus dextran].

A prospective, randomized trial has been undertaken to evaluate the prophylactic effects of low molecular weight heparin (LMWH) and dextran-70 in 216 patients with hip fracture during a postoperative period of ten days. Deep vein thrombosis (DVT) was diagnosed using the 125Iodine fibrinogen uptake test, confirmed by ascending venography. 113 patients received LMWH and 103 dextran-70. The frequency of DTV of 14.2% in the LMWH group was significantly lower compared with the 30.1% in the dextran group (p less than 0.003). During the first 10 days postoperative there were no fatal pulmonary embolism (PE). After this period PE occurred in 2 patients (1.8%) in the LMWH group and 1 patient (1.0%) in the dextran group. In each group one patient died from PE. There was no major bleeding in either group. The frequency of local complications was slightly higher in the dextran group (10.7%) compared with the LMWH group (3.5%). The postoperative hemoglobin level was significantly lower in dextran treated patients than in patients receiving LMWH (p less than 0.0001).

Adult↗