Endovascular therapy in combination with conventional vascular surgery for the treatment of peripheral arterial obliterative disease

INTRODUCTION: In a prospective trial we analysed the results and the management of complications following a combined endovascular and vascular surgical therapy of peripheral occlusive arterial disease (POAD). PATIENTS AND METHODS: From November 1998 until January 2001 a total number of 61 patients with 64 extremities were included in this study. By preoperative angiography 19 patients had stenoses at three levels, 42 patients suffered from stenoses at two levels. The iliac axis was recanalized by intraluminal angioplasty (ITA) plus stent placement under general anesthesia. Simultaneously an infrainguinal bypass reconstruction and a local thrombendarterectomy (TEA) rsp. were performed. Intra- and postoperative complications and the patency rates as assessed by colour doppler ultrasound and angiography were analysed. RESULTS: The rate of conversion from endovascular to conventional surgery was 12.5 %. In 56 cases the endovascular therapy of the iliac axis was successful. In 28 patients a distal bypass was implanted, in 25 patients a local TEA was performed. Intraoperatively 6 dissections (10.7 %) were noted, dislocation of stents were seen in 4 patients (7.1 %), perforations occurred in 2 patients (3.6 %). Both perforations and 5/6 dissections were detected intraoperatively and were treated by endovascular means without complications. The early postoperative patency rate was 98.2 %, the secondary patency rate was 100 % and the cumulative patency rate after two years was 98.2 %. DISCUSSION: ITA and stent placement in the iliac axis can be established quickly and safely by the vascular surgeon. Intraoperative complications can be managed by endovascular means in most cases. Stent dislocation is avoidable in most cases. The complication rate after such combined endovascular therapy and conventional vascular surgery is determined by the surgical but not the endovascular part. Excellent early results and low complication rates lead to the conclusion that endovascular therapy in combination with conventional vascular surgery seems to be a reasonable supplement to the therapeutic options for the treatment of POAD.     

Does intraoperative nerve monitoring reduce the rate of recurrent nerve palsies during thyroid surgery?

Two different aspects of the influence of neuromonitoring on the possible reduction of post-operative recurrent laryngeal nerve palsies require critical examination: the nerve identification and the monitoring of it's functions. Due to the additional information from the EMG signals, neuromonitoring is the best method for identifying the nerves as compared to visual identification alone. There are still no randomized studies available that compare the visual and electrophysiological recurrent laryngeal nerve detection in thyroid operations with respect to the postoperative nerve palsies. Nevertheless, comparisons with historical collectives show that a constant low nerve-palsy-rate was achieved with electrophysiological detection in comparison to visual detection. The rate of nerve identification is normally very high and amounts to 99 % in our own patients. The data obtained during the "Quality assurance of benign and malignant Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve-palsy-rates are achieved with neuromonitoring as compared to solely visual detection. Following subtotal resection, this discrepancy becomes even statistically significant. While monitoring the nerve functions with the presently used neuromonitoring technique, it is possible to observe the EMG-signal remaining constant or decreasing in volume. Assuming that a constant neuromonitoring signal represents a normal vocal cord, our evaluation shows that there is a small percentage of false negative and positive results. Looking at the permanent recurrent nerve palsy rates, this method has a specificity of 98 %, a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative prognostic value of 100 %. Although an altered neuromonitoring signal can be taken as a clear indication of eventual nerve damage, an absolutely reliable statement about the postoperative vocal cord function is presently not possible with intraoperative neuromonitoring.     

Postoperative cognitive dysfunction in middle-aged patients

BACKGROUND: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent. METHODS: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living. RESULTS: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months. CONCLUSIONS: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery. It may be associated with decreased activity during this period. Subjective report overestimates the incidence of POCD. Patients may be helped by recognition that the problem is genuine and reassured that it is likely to be transient.     

Randomized clinical trial comparing quality of life after straight and pouch coloanal reconstruction

BACKGROUND: Functional results after rectal resection with straight coloanal anastomosis are poor. While most functional aspects are improved with coloanal J pouch anastomosis, it is still unclear whether this translates into better quality of life. The aim of this trial was to investigate health-related quality of life as a primary endpoint in patients undergoing sphincter-saving rectal resection. METHODS: Sixty-four patients were randomized to either straight (n = 32) or coloanal J pouch (n = 32) anastomosis. Patients were studied before operation, at the time of stoma reversal and at 3-month intervals for 1 year thereafter. Quality of life was measured using two generic (Gastrointestinal Quality of Life Index and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30) and one disease-specific (EORTC QLQ-CR38) instruments. Functional results using a standardized score as well as manometric variables were recorded. RESULTS: Thirty-nine patients (19 with a pouch and 20 with a straight anastomosis) completed the trial. There was a marked difference between the two groups with regard to quality of life profile. Patients with a pouch reconstruction had a significantly better quality of life, particularly in the early postoperative period. CONCLUSION: Patients undergoing low anterior rectal resection and coloanal J pouch reconstruction may expect not only better functional results but also an improved quality of life in the early months after surgery compared with patients who receive a straight coloanal anastomosis.     

Strychnine-blocked glycine receptor is removed from synapses by a shift in insertion/degradation equilibrium

The long-term inhibition by strychnine of glycine receptor activity in neurons provokes the receptor's selective intracellular accumulation and disappearance from synapses. This could result either from a disruption of the postsynaptic anchoring of the receptor or from an arrest of its exocytic transport. In this study we combined biochemical and fluorescence microscopy analyses to determine on a short time scale the fate of the strychnine-inactivated glycine receptor. Quantification of the cellular content of receptor showed that the rapid accumulation depends on protein synthesis. Cell surface biotinylation of neurons demonstrated that strychnine did not accelerate the turnover rate of the receptor. Labeling of endosomes indicated that, in strychnine-treated cells, the accumulated receptor is not blocked in the endosomal transport pathway. Taken together, these results indicate that strychnine does not destabilize the postsynaptic receptor but triggers its disappearance from synapses by a nondegradative sequestration of newly synthesized molecules in a nonendocytic compartment.     

A BRCA1/2 mutation,high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography

Female BRCA1/2 mutation carriers develop in up to 50% breast cancer (BC) before age 50 years. We investigated whether the specific histologic features of BRCA1/2-associated breast cancer influence imaging. We correlated the mammographic results with the histology of 34 BC in BRCA1/2 mutation carriers and 34 sporadic cancers in patients, matched for age and year of diagnosis. Mammography was significantly more frequently false-negative in carriers than controls (62% vs. 29% p = 0.01), despite comparable tumor size (mean solidus in circle 1.51 vs. 1.75) and breast density (high 41% vs. 53%). The image in carriers was significantly less as spiculated mass (6 vs. 18 p = 0.01). Cancers of BRCA1/2 mutation carriers had frequently higher mitotic counts (p < 0.0001) and prominent pushing margins around the tumor (p = 0.08) (p = 0.05 for 32 BRCA1). We also observed that prominent "pushing margins" correlated significantly with a false-negative mammography (p = 0.005) and with a mammographic image of a smooth, not a spiculated, mass (p = 0.01). False-negative mammography correlated independently with: BRCA1/2 mutation (p = 0.02), prominent pushing margins (p = 0.03) and high breast density (p = 0.01). MRI was carried out in 12 carriers, had 100% sensitivity and detected 5 cancers, still occult at physical examination and mammography. A BRCA1/2 mutation and high breast density at mammography contribute independently to false-negative mammography results. In mutation carriers any mammographic mass must be regarded with suspicion. Pushing margins of the tumor partly explain these results. For early BC detection in mutation carriers additional methods like MRI may be needed. This may not be necessary in other young women with breast symptoms.     

Allelic deletions of Rb and L-myc in urine sediments from patients with bladder tumors or carcinoma in situ

In a previous study we found allelic imbalances of Rb and L-myc associated with disease stage and disease course in bladder cancer. The primary aim of the present study was to determine whether the changes found in tumors were reflected in urine sediments. Secondly we wanted to test if Rb and L-myc were frequently lost in urine sediments from patients with carcinoma in situ and no bladder tumor at present. Based on this we examined allelic deletions of the Rb and L-myc genes in tumor and urine from 55 patients with bladder tumors or carcinoma in situ. Deletions were examined on extracted DNA from tumors and urine sediments by the use of microsatellite markers located as close to the genes as possible. Fifty-five patients and 10 controls were included. We found no strict correlation between allelic deletions in bladder tumors and urine sediments from the same patient. Allelic deletions in urine sediments were at least as common in patients with carcinoma in situ and no bladder tumor (32%) as in patients with bladder tumors (20%). It was possible to identify allelic deletions in urine sediment from 1 patient with cystitis and no history of malignant bladder disease (6%). In conclusion we found no strict correlation between allelic deletions in bladder tumors and urine sediments. Allelic deletions in urine sediments seem to be at least as common in patients with carcinoma in situ as in patients with bladder tumors.     

MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients

Allelic variants of the MDR-1 gene have been shown recently to influence protein expression and P-glycoprotein (P-gp) function in healthy volunteers. Therefore, 405 acute myeloid leukemia patients were investigated for somatic genotypes of the three most frequent single nucleotide polymorphisms (SNPs) in exons 12, 21, and 26. In all three loci, homozygous wild-type alleles were classified as genotype A, heterozygous as B, and homozygous mutant (alternative) allele as C. Patients with the C genotype in exons 12 and 26 showed a lower median age (both P < 0.05). Additionally, the C genotype in exons 12 and 26 was associated with cytogenetic poor risk aberrations (both P < 0.05). A possible regulatory impact of the SNPs on MDR1 mRNA expression was investigated by a Real time-PCR assay. MDR1 expression was strongly correlated with a decreased complete remission rate (P = 0.01) but failed to predict decreased overall survival (OS). There was a significant association of the A genotype in exons 21 (P = 0.05) and 26 (P < 0.05) with lower MDR1 expression, whereas the B variants showed highest MDR1 values at all three investigated gene loci. The A genotype in exon 26 was associated with lower OS (P < 0,01). In these patients, worse OS is likely attributable to an increased risk of relapse (P < 0.001). We were able to detect a linkage disequilibrium of the investigated SNPs, indicating combined polymorphisms that could affect the regulation of MDR1 expression. The A genotype of all SNPs demonstrated both lowest MDR1 values and significantly decreased OS (P < 0.05) with a high probability of relapses (P < 0.01). These observations indicate that allelic variants of the MDR1 gene may influence therapy outcome by additional mechanisms, different from P-gp expression on acute myeloid leukemia blasts, possibly involving pharmacokinetic effects of P-gp.     

Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter

Indole-3-carbinol (I3C) is a naturally occurring substance that shows anti-carcinogenic properties in animal models. Besides its clear anti-carcinogenic effects, some studies indicate that I3C may sometimes act as a tumor promoter. Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic environment of the stomach after intake of I3C, has a similar structure to, and shares biological effects with, the well-known tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, we hypothesized that ICZ could be responsible for the potential tumor-promoting activity of I3C. The aim of the present study was to investigate the effect of ICZ on gap junctional intercellular communication (GJIC) in primary cultured rat hepatocytes co-cultured with the rat liver epithelial cell line WB-F344. Indolo[3,2-b]carbazole inhibited GJIC in the rat hepatocytes in a dose- and time-dependent manner. Significant inhibition was observed after 8 and 12 h of treatment with 1 and 0.1 micro M ICZ, respectively. Maximum GJIC inhibition (cell-cell communication only 5% of control values) was observed after 24-48 h of ICZ treatment. Continued exposure to 1 micro M ICZ suppressed GJIC until approximately 120 h. Both ICZ and TCDD treatment reduced the Cx32 mRNA level as well as the plasma membrane Cx32 staining. Indolo[3,2-b]carbazole increased the Cyp1a1, Cyp1a2 and Cyp1b1 mRNA levels concurrently with an increase in 7-ethoxyresorufin O-deethylase (EROD) activities. Maximum EROD activity and Cyp1a1 mRNA levels were observed after approximately 12 h, whereas Cyp1a2 and Cyp1b1 mRNA levels peaked after 48 h. This study shows that ICZ may possess tumor promoter activity down-regulating GJIC by mechanisms, which seem to include activation of the Ah receptor and/or Cyp1 activity. Further studies are needed in order to clarify the anticarcinogenic/carcinogenic effects of I3C and ICZ before high doses of I3C may be recommended as a dietary supplement.