Paravertebral Block for Post-Operative Analgesia after Breast Cancer Surgery, Effects of Adding Morphine: Double Blind, Randomised Clinical Trial

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Introduction: Thoracic paravertebral block (PVB) block is frequently used in breast cancer surgery for postoperative pain management. Adding opioids to local anaesthetics has been shown to have beneficial effects during epidural analgesia. Our hypothesis was that adding morphine to bupivacaine for PVB would improve analgesia provided by this procedure. Methods: 60 patients (25 - 75 years) undergoing elective surgery for breast cancer were randomly assigned to one of two groups. Both groups received a single injection thoracic paravertebral block; group BAM with 20 ml 0.5% bupivacaine, epinephrine and morphine while group BA received identical block except morphine was given subcutaneously. All patients had general anaesthesia. Results: Severity of pain and nausea was low in both groups. Pain scores remained below 20/100 after the first 2 hours throughout the 72 hours of the study. There was no significant difference between the groups in pain scores, consumption of additional morphine or nausea scores. Shoulder mobility was also very good in both groups. Conclusion: Thoracic paravertebral block with bupivacaine and epinephrine was associated with good postoperative analgesic effects and low incidence of nausea and vomiting. The addition of morphine to the local anaesthetic solution in paravertebral block did not have any additional analgesic effects

Reconciling biodiversity conservation and agricultural expansion in the sub-arctic environment of Iceland

Intensified agricultural practices have driven biodiversity loss throughout the world and, although many actions aimed at halting and reversing these declines have been developed, their effectiveness depends greatly on the willingness of stakeholders to take part in conservation management. Knowledge of the willingness and capacity of landowners to engage with conservation can therefore be key to designing successful management strategies in agricultural land. In Iceland, agriculture is currently at relatively low intensity but is very likely to expand in the near future. At the same time, Iceland supports internationally important breeding populations of many ground-nesting birds which could be seriously impacted by further expansion of agricultural activities. To understand the views of Icelandic farmers towards bird conservation, given the current potential for agricultural expansion, 62 farms across Iceland were visited and farmers were interviewed, using a structured questionnaire survey in which respondents indicated a series of future actions. Most farmers intend to increase the area of cultivated land in the near future and, despite considering having rich birdlife on their land to be very important, most also report they are unlikely to specifically consider bird conservation in their management, even if financial compensation were available. However, as no agri-environment schemes are currently in place in Iceland, this concept is highly unfamiliar to Icelandic farmers. Nearly all respondents were unwilling, and thought it would be impossible, to delay harvest, but many were willing to consider sparing important patches of land and/or maintaining existing pools within fields (a key habitat feature for breeding waders). Farmers’ views on the importance of having rich birdlife on their land and their willingness to participate in bird conservation provide a potential platform for the co-design of conservation management with landowners before further substantial changes in the extent of agriculture take place in this sub-arctic landscape

Evidence against PALB2 involvement in Icelandic breast cancer susceptibility

Several mutations in the PALB2 gene (partner and localizer of BRCA2) have been associated with an increased risk of breast cancer, including a founder mutation, 1592delT, reported in Finnish breast cancer families. Although most often the risk is moderate, it doesn't exclude families with high-risk mutations to exist and such observations have been reported. To see if high-risk PALB2-mutations may be present in the geographically confined population of Iceland, linkage analysis was done on 111 individuals, thereof 61 breast cancer cases, from 9 high-risk non-BRCA1/BRCA2 breast cancer families, targeting the PALB2 region. Also, screening for the 1592delT founder mutation in the 9 high-risk families and in 638 unselected breast cancer cases was performed. The results indicate no linkage in any of the high-risk families and screening for the 1592delT mutation was negative in all samples. PALB2 appears not to be a significant factor in high-risk breast cancer families in Iceland and the 1592delT mutation is not seen to be associated with breast cancer in Iceland

Multiplex SNaPshot for detection of BRCA1/2 common mutations in Spanish and Spanish related breast/ovarian cancer families

<p>Abstract</p> <p>Background</p> <p>It is estimated that 5–10% of all breast cancer are hereditary and attributable to mutations in the highly penetrance susceptibility genes <it>BRCA1 </it>and <it>BRCA2</it>. The genetic analysis of these genes is complex and expensive essentially because their length. Nevertheless, the presence of recurrent and founder mutations allows a pre-screening for the identification of the most frequent mutations found in each geographical region. In Spain, five mutations in <it>BRCA1 </it>and other five in <it>BRCA2 </it>account for approximately 50% of the mutations detected in Spanish families.</p> <p>Methods</p> <p>We have developed a novel PCR multiplex SNaPshot reaction that targets all ten recurrent and founder mutations identified in <it>BRCA1 </it>and <it>BRCA2 </it>in Spain to date.</p> <p>Results</p> <p>The SNaPshot reaction was performed on samples previously analyzed by direct sequencing and all mutations were concordant. This strategy permits the analysis of approximately 50% of all mutations observed to be responsible for breast/ovarian cancer in Spanish families using a single reaction per patient sample.</p> <p>Conclusion</p> <p>The SNaPshot assay developed is sensitive, rapid, with minimum cost per sample and additionally can be automated for high-throughput genotyping. The SNaPshot assay outlined here is not only useful for analysis of Spanish breast/ovarian cancer families, but also e.g. for populations with Spanish ancestry, such as those in Latin America.</p

Mutation analysis of the CHK2 gene in breast carcinoma and other cancers

BACKGROUND: Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways. METHODS: We screened 139 breast tumors for loss of heterozygosity at chromosome 22q, using seven microsatellite markers, and screened 119 breast tumors with single-strand conformation polymorphism and DNA sequencing for mutations in the CHK2 gene. RESULTS: Seventy-four of 139 sporadic breast tumors (53%) show loss of heterozygosity with at least one marker. These samples and 45 tumors from individuals carrying the BRCA2 999del5 mutation were screened for mutations in the CHK2 gene. In addition to putative polymorphic regions in short mononucleotide repeats in a non-coding exon and intron 2, a germ line variant (T59K) in the first coding exon was detected. On screening 1172 cancer patients for the T59K sequence variant, it was detected in a total of four breast-cancer patients, two colon-cancer patients, one stomach-cancer patient and one ovary-cancer patient, but not in 452 healthy individuals. A tumor-specific 5' splice site mutation at site +3 in intron 8 (TTgt [a → c]atg) was also detected. CONCLUSION: We conclude that somatic CHK2 mutations are rare in breast cancer, but our results suggest a tumor suppressor function for CHK2 in a small proportion of breast tumors. Furthermore, our results suggest that the T59K CHK2 sequence variant is a low-penetrance allele with respect to tumor growth

High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.</p> <p>Methods</p> <p>The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.</p> <p>Results</p> <p>BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.</p> <p>Conclusion</p> <p>Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.</p