Liver resection for breast cancer metastasis: Does it improve survival?

Purpose To assess the outcome and prognostic factors of liver surgery for breast cancer metastasis. Methods We retrospectively examined 16 patients who underwent partial liver resection for breast cancer liver metastasis (BCLM). All patients had been treated with chemotherapy or hormonotherapy, or both, before referral for surgery. We confirmed by preoperative radiological examinations that metastasis was confined to the liver. The survival curve was estimated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted to evaluate the role of the known factors of breast cancer survival. Results The median age of the patients was 54 years (range 38–68) and the median disease-free interval between the diagnoses of breast cancer and liver metastasis was 54 months (range 7–120). Nine major and 7 minor hepatectomies were performed. There was no postoperative death. The overall 1-, 3-, and 5-year survival rates were 94%, 61%, and 33%, respectively. The median survival rate was 42 months. Univariate analysis revealed that hormone receptor status, number of metastases, a major hepatectomy, and a younger age were associated with a poorer prognosis. The survival rate was not influenced by the disease-free interval, grade or stage of breast cancer, or intraoperative blood transfusions. The number of liver metastases was identified as a significant independent factor of survival according to the Cox proportional hazard model (P = 0.04). Conclusions Liver resection, when done in combination with adjuvant therapy, can improve the prognosis of selected patients with BCLM.     

Prevalence and risk factors of mortality and morbidity after operation for adhesive postoperative small bowel obstruction

BACKGROUND: Many factors are believed to influence the mortality and morbidity after operations for adhesive small bowel obstruction (SBO). METHODS: In a multicenter prospective cohort of 286 patients operated on for adhesive postoperative SBO, we studied the in-hospital and 30-day postdischarge mortality (early mortality) and morbidity as well as long-term mortality using univariate and multivariate analysis. RESULTS: In the present cohort, with a median follow-up of 41 months and 9% patients lost to follow-up at the end of the study, the prevalence of early postoperative mortality was 3%. All deceased patients were over 75 years old with an American Society of Anesthesiologists (ASA) class >/=III. The prevalence of long-term mortality was 7% with the following independent risk factors: age >75 years old (hazards ratio [HR] 6.6 [95% confidence interval [CI], 2.4-18.1]), medical complications (HR 7.4 [CI, 2.2-24.3]), and a mixed mechanism of obstruction (HR 4.5 [CI, 1.5-13.7]). Prevalence of medical and surgical morbidity was 8% and 6%, respectively. Independent risk factors for medical complications were ASA class >/=III (odds ratio [OR] 16.8 [CI, 2.1-133.1]) and bands (OR 14.1 [CI, 1.8-111.5]) and for the surgical complications the number of obstructive structures >/=10 (OR 8.3 [CI, 1.6-19.7]), a nonresected intestinal wall injury (OR 5.3 [CI, 1.5-18.3]), and intestinal necrosis (OR 5.6 [CI, 1.6-19.7]). Otherwise, 3 patients with "apparent" reversible ischemia developed a postoperative intestinal necrosis followed by 2 reoperations and 1 death. CONCLUSION: The early postoperative mortality is strongly linked with the age and the ASA class and the long-term mortality with postoperative complications. More frequent bowel resections might be suggested for patients featuring a number of obstructive structures >/=10 and an intestinal wall injury, especially when associated with a reversible intestinal ischemia.     

Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing

BACKGROUND: Chronic wounds continue to be a major clinical problem and novel therapeutic approaches are needed. We have previously demonstrated that treatment of diabetic mouse wounds with local application of stromal progenitor cells results in improved healing and increased production of stromal-derived growth factor-1alpha (SDF-1alpha). We hypothesized that lentiviral-mediated increased production of SDF-1alpha in the wound environment could also improve diabetic wound healing. MATERIALS AND METHODS: Full-thickness excisional wounds were created in Db-/Db- mice and immediately treated with 10(6), 10(8), or 10(9) plaque-forming units of a lentiviral construct containing GFP-SDF-1alpha or GFP alone. At 7 and 14 days post wounding, wounds were harvested for histological and molecular analysis. RESULTS: At 7 days, Db-/Db- wounds treated with lenti GFP-SDF-1alpha exhibited a decrease in wound surface area for all doses tested. Morphologically, SDF-treated wounds were more cellular with increased granulation tissue volume compared to controls (P < 0.05). GFP expression was maintained in treated tissue at 7 days post wounding, but little expression was observed at 14 days. While we did not observe a difference in the gross wound surface area at 14 days, histological analysis revealed that SDF-treated wounds were fully epithelialized (n = 6) compared to only one of six controls. CONCLUSIONS: Lentiviral-mediated overproduction of SDF-1alpha is sufficient to correct the pathophysiologic abnormalities in diabetic wound healing resulting in complete epithelialization at 2 weeks. SDF-1alpha-mediated improvement in diabetic wound healing has significant implications for the development of novel therapeutic strategies to facilitate wound closure which target progenitor cell mobilization and recruitment.     

Acute hyperglycemia induces a global downregulation of gene expression in adipose tissue and skeletal muscle of healthy subjects

To define the effects of acute hyperglycemia per se (i.e., without the confounding effect of hyperinsulinemia) in human tissues in vivo, we performed global gene expression analysis using microarrays in vastus lateralis muscle and subcutaneous abdominal adipose tissue of seven healthy men during a hyperglycemic-euinsulinemic clamp with infusion of somatostatin to inhibit endogenous insulin release. We found that doubling fasting blood glucose values while maintaining plasma insulin in the fasting range modifies the expression of 316 genes in skeletal muscle and 336 genes in adipose tissue. More than 80% of them were downregulated during the clamp, indicating a drastic effect of acute high glucose, in the absence of insulin, on mRNA levels in human fat and muscle tissues. Almost all the biological pathways were affected, suggesting a generalized effect of hyperglycemia. The induction of genes from the metallothionein family, related to detoxification and free radical scavenging, indicated that hyperglycemia-induced oxidative stress could be involved in the observed modifications. Because the duration and the concentration of the experimental hyperglycemia were close to what is observed during a postprandial glucose excursion in diabetic patients, these data suggest that modifications of gene expression could be an additional effect of glucose toxicity in vivo.     

Regional anaesthesia for orthopaedic procedures

Regional anaesthetic techniques are fundamental in the anaesthetic care of orthopaedic patients. They may be used as the primary anaesthetic technique or to provide postoperative pain relief. Compared to general anaesthesia alone, regional techniques can provide superior perioperative analgesia, fewer systemic drug adverse effects such as nausea, vomiting and confusion, and earlier mobilization which can reduce nosocomial complications and facilitate expedited hospital discharge. Disadvantages include block failure, nerve injury, unrecognised injury to the anaesthetised limb, prolonged motor blockade and local anaesthetic toxicity. Preoperative assessment should identify contraindications, document pre-existing neurological deficits, and clarify surgical and perioperative aims. Informed consent should be obtained after a clear explanation of the procedure, its risks, and potential complications. Serious and long-term neurological complications are rare and may be reduced by an awake regional technique, sonographic guidance, regular aspiration and by ensuring low pressure injections. Postoperative follow-up is essential and suspicious neurological findings should be detected, investigated, and managed in an early and timely manner.     

Removal of Protein‐Bound,Hydrophobic Uremic Toxins by a Combined Fractionated Plasma Separation and Adsorption Technique

Protein‐bound uremic toxins, such as phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate, contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, based on their protein binding, these hydrophobic uremic toxins are poorly cleared during conventional dialysis and thus accumulate in CKD‐5D patients. Therefore, we investigated whether hydrophobic and cationic adsorbers are more effective for removal of protein‐bound, hydrophobic uremic toxins than conventional high‐flux hemodialyzer. Five CKD‐5D patients were treated using the fractionated plasma separation, adsorption, and dialysis (FPAD) system for 5 h. A control group of five CKD patients was treated with conventional high‐flux hemodialysis. Plasma concentrations of phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate were measured. Removal rates of FPAD treatment in comparison to conventional high‐flux hemodialysis were increased by 130% for phenylacetic acid, 187% for indoxyl sulfate, and 127% for p‐cresol. FPAD treatment was tolerated well in terms of clinically relevant biochemical parameters. However, patients suffered from mild nausea 2 h after the start of the treatment, which persisted until the end of treatment. Due to the high impact of protein‐bound, hydrophobic uremic toxins on progression of CKD and CVD in CKD‐5D patients, the use of an adsorber in combination with dialysis membranes may be a new therapeutic option to increase the removal rate of these uremic toxins. However, larger, long‐term prospective clinical trials are needed to demonstrate the impact on clinical outcome.