| 1. |
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Phillips, Helen R. P., et al.
(författare)
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Global distribution of earthworm diversity
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
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Tidskriftsartikel (refereegranskat)abstract
- Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
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| 4. |
- Enajat, Morteza, et al.
(författare)
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Aesthetic Refinements and Reoperative Procedures Following 370 Consecutive DIEP and SIEA Flap Breast Reconstructions : Important Considerations for Patient Consent
- 2010
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Ingår i: Aesthetic Plastic Surgery. - : Springer Science and Business Media LLC. - 0364-216X .- 1432-5241. ; 34:3, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- Breast reconstruction often requires multiple operations. In addition to potential complications requiring reoperation, additional procedures are frequently essential in order to complete the reconstructive process, with aesthetic outcome and breast symmetry shown to be the most important factors in patient satisfaction. Despite the importance of these reoperations in decision-making and the consent process, a thorough review of the need for such operations has not been definitively explored. A review of 370 consecutive autologous breast reconstructions (326 patients) was undertaken, comprising 365 deep inferior epigastric artery perforator (DIEP) flaps and 5 superficial inferior epigastric artery (SIEA) flaps. The need for additional procedures for either complications or aesthetic refinement following initial breast reconstruction was assessed. Overall, there was an average of 1.06 additional interventions for every patient carried out after primary reconstructive surgery. Of 326 patients, 46 underwent early postoperative operations for surgical complications (0.17 additional operations per patient as a consequence of complications). Procedures for aesthetic refinement included those performed on the reconstructed breast, contralateral breast, or abdominal donor site. Procedures for aesthetic refinement included nipple reconstruction, nipple-areola complex tattooing, dog-ear correction, liposuction, lipofilling, scar revision, mastopexy, and reduction mammaplasty. While DIEP flap surgery for breast reconstruction provides favorable results, patients frequently require additional procedures to improve aesthetic outcomes. The need for reoperation is an important part of the consent process prior to reconstructive surgery, and patients should recognize the likelihood of at least one additional procedure following initial reconstruction.
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| 5. |
- Acosta, Rafael, et al.
(författare)
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Performing two DIEP flaps in a working day : an achievable and reproducible practice
- 2010
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Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 63:4, s. 648-654
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Tidskriftsartikel (refereegranskat)abstract
- Background: While the deep inferior epigastric artery perforator (DIEP) flap is a reliable technique for autologous breast reconstruction, the meticulous dissection of perforators may require lengthy operative times. In our unit, we have performed 600 free flaps for breast reconstruction over 8 years and have reduced operative times with a combination of preoperative computed tomographic angiography (CTA), various anastomotic techniques and the Cook-Swartz implantable Doppler probe for perfusion monitoring. We sought to assess the feasibility of performing two DIEP flaps within the working hours of a single day. Methods: A review of 101 consecutive patients undergoing DIEP flap breast reconstruction in a 12-month period was performed, comparing one DIEP flap per day (n=43) to two DIEP flaps per day (n=58). Complications, outcomes and techniques used were critically analysed. For cases of two DIEP flaps per day, a comparison was made between the use of two separate operating theatres (n=44) and a single consecutive theatre (n=14). Results: Complications did not increase when two DIEP flaps were performed in a single working day. The use of vascular closure staple (VCS) sutures and ring couplers resulted in statistically significant reductions in anastomotic times. The use of two separate theatres for performing two DIEP flaps resulted in a reduction of 59 min in operative time per case (p=0.004). Conclusion: Two DIEP flaps can be safely and routinely performed within the hours of a single working day. By minimising operative times, these techniques can improve productivity and substantially decrease surgeon fatigue.
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| 6. |
- Enajat, Morteza, et al.
(författare)
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A single center comparison of one versus two venous anastomoses in 564 consecutive diep flaps : Investigating the effect on venous congestion and flap survival
- 2010
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 30:3, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: Venous complications have been reported as the more frequently encountered vascular complications seen in the transfer of deep inferior epigastric artery (DIEA) perforator (DIEP) flaps, with a variety of techniques described for augmenting the venous drainage of these flaps to minimize venous congestion. The benefits of such techniques have not been shown to be of clinical benefit on a large scale due to the small number of cases in published series. Methods: A retrospective study of 564 consecutive DIEP flaps at a single institution was undertaken, comparing the prospective use of one venous anastomosis (273 cases) to two anastomoses (291 cases). The secondary donor vein comprised a second DIEA venae commitante in 7.9% of cases and a superficial inferior epigastric vein (SIEV) in 92.1%. Clinical outcomes were assessed, in particular rates of venous congestion. Results: The use of two venous anastomoses resulted in a significant reduction in the number of cases of venous congestion to zero (0 vs. 7, P = 0.006). All other outcomes were similar between groups. Notably, the use of a secondary vein did not result in any significant increase in operative time (385 minutes vs. 383 minutes, P = 0.57). Conclusions: The use of a secondary vein in the drainage of a DIEP flap can significantly reduce the incidence of venous congestion, with no detriment to complication rates. Consideration of incorporating both the superficial and deep venous systems is an approach that may further improve the venous drainage of the flap.
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| 7. |
- Enajat, Morteza, et al.
(författare)
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The deep inferior epigastric artery perforator flap for autologous reconstruction of large partial mastectomy defects
- 2011
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 31:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast conservation surgery in the treatment of early stage breast cancer has become increasingly utilized as a means to avoiding mastectomy. While partial mastectomy defects (PMDs) may often be cosmetically acceptable, some cases warrant consideration of reconstructive options, and while several reconstructive options have been described in this role, a series of deep inferior epigastric perforator (DIEP) flaps has not been reported to date. Methods: A cohort of 18 patients undergoing PMD reconstruction with a DIEP flap were included. Patient-specific data, operation details, cosmetic results, and complication rates were assessed. Oncologic outcomes, in particular recurrence rates, were also evaluated. Results: In our series there were no cases of partial or total flap necrosis, and overall complications were low. There were two cases of wound infection (both had undergone radiotherapy), managed conservatively, and one case of reoperation due to hematoma. There were no cancer recurrences or effect on oncologic management. Cosmetic outcome was rated as high by both patients and surgeon. The results were thus comparable with other reconstructive options. Conclusion: Although autologous reconstruction has an established complication rate, our results suggest that the DIEP flap may be of considerable value for delayed reconstruction of selected larger partial mastectomy defects.
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| 8. |
- Whitaker, Iain S., et al.
(författare)
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Peritoneo-cutaneous perforators in deep inferior epigastric perforator flaps : a cadaveric dissection and computed tomographic angiography study
- 2009
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 29:2, s. 124-127
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cutaneous perforators that do not originate from the deep inferior epigastric artery (DIEA) are rare, but may significantly affect operative outcome. Peritoneal-cutaneous perforators have been described as a source for augmenting the blood flow to a deep inferior epigastric perforator (DIEP) flap, however if unrecognized, may compromise flap survival. METHODS: We reviewed 375 DIEA perforator (DIEP) flaps (325 with preoperative CTA and 50 cadaveric dissections) to investigate the incidence of this anomaly. RESULTS: We detected this variation in 3/325 (1%) of DIEP flaps following preoperative computed tomography. In 1/50 (2%) of the cadaveric specimens, a peritoneal-cutaneous perforator was found and injected with lead oxide contrast. It was shown to fill the cutaneous veins of the majority of the lower abdominal integument. CONCLUSION: Peritoneal-cutaneous perforators are rare anatomical variations (4/375: 1.1%) that may have significant ramifications for surgery utilizing the vasculature of the abdominal wall. CTA was significantly able to detect this anomaly and aid operative planning. Preoperative CTA helps to safely identify individual vascular anatomy including rare variations.
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| 9. |
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| 10. |
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| 11. |
- Audolfsson, Thorir, et al.
(författare)
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A Reliable and Aesthetic Technique for Cephalic Vein Harvest in DIEP Flap Surgery
- 2009
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Ingår i: Journal of reconstructive microsurgery. - : Georg Thieme Verlag KG. - 0743-684X .- 1098-8947. ; 25:5, s. 319-321
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Tidskriftsartikel (refereegranskat)abstract
- The need for a secondary source of venous drainage in deep inferior epigastric artery perforator flaps is common, with the cephalic vein Commonly utilized as an alternative venous recipient vessel. In using the cephalic vein, previous studies have described the deltopectoral groove or the infraclavicular fossa as the site for harvest. We describe the use of an anterior axillary skin crease, which can improve aesthetic outcome, reduce the time needed for harvest, enable a greater length of vein to be transposed, and minimize surgical insult to the upper breast/chest wall. An anterior axillary-line skin fold can be used as the site for cephalic vein harvest, and using the methodology described, the technique can be fast and highly reliable and result in a final scar that is barely visible.
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| 12. |
- Chubb, Daniel, et al.
(författare)
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The Efficacy of Clinical Assessment in the Postoperative Monitoring of Free Flaps : A Review of 1140 Consecutive Cases
- 2010
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Ingår i: Plastic and reconstructive surgery (1963). - 0032-1052 .- 1529-4242. ; 125:4, s. 1157-1166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective postoperative monitoring of the vascular pedicle to a free flap can potentiate rapid return to the operating room in the setting of compromise, allowing for the potential to salvage the flap. The only ubiquitous method for postoperative monitoring of free flaps is clinical bedside monitoring, but although the use of clinical monitoring may be inferred in large reported series of free flaps, there has been little discussed in the literature of specific clinical outcome measures. Methods: The authors present their experience with 1140 consecutive cases of free tissue transfer and the use of clinical monitoring as a sole method of monitoring, and subgroup analysis of different recipient sites. Results: There were 94 take-backs, four of which had no pedicle compromise (false-positives) and there were four false-negatives. The overall flap salvage rate was 62.8 percent and the false-positive rate was 0.4 percent. Subgroup analyses demonstrated statistically significant differences between recipient sites for the false-positive rates: fewer false-positives with breast reconstruction cases (p < 0.05) and significantly more false-positives in the extremity group (p < 0.05). There was an improved flap salvage rate in cases of venous compromise compared with arterial compromise (69 percent versus 51 percent, p = 0.015). Conclusions: This largest reported series to date provides an outcome-based analysis of postoperative monitoring for free flaps, providing a benchmark standard against which adjunctive monitoring techniques can be compared. Future studies need to be assessed in the context of individual recipient sites, with significant differences in monitoring outcomes between sites.
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| 13. |
- Enajat, Morteza, et al.
(författare)
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How long are fasciocutaneous flaps dependant on their vascular pedicle : A unique case of SIEA flap survival
- 2010
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Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 63:4, s. E347-E350
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Tidskriftsartikel (refereegranskat)abstract
- Background: While it has long been held that muscle flaps maintain their dependency on their vascular pedicle for the long term, fasciocutaneous flaps have been less well investigated. Recent studies of the deep inferior epigastric artery perforator (DIEP) flap have suggested that these flaps may maintain long term dependence on their vascular pedicles for survival. There is no literature concerning these effects in the superficial inferior epigastric artery (SIEA) flap. Case report: We describe a unique case in which the pedicle of a superficial inferior epigastric artery (SIEA) flap for breast reconstruction was avulsed 11 days postoperatively, with the flap surviving on its inferior wound edge alone. Conclusion: Fasciocutaneous flaps may lose dependency on their vascular pedicles in the short term following transfer, developing alternative pathways for vascular supply and ultimately survival. A conservative approach early in the course of flap compromise due to perforator ligation or avulsion, in cases where immediate re-anastomosis may not be feasible, is thus supported.
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| 14. |
- Enajat, Morteza, et al.
(författare)
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Thermal injuries in the insensate deep inferior epigastric artery perforator flap : case series and literature review on mechanisms of injury
- 2009
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 29:3, s. 214-217
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Forskningsöversikt (refereegranskat)abstract
- With the increasing use of the deep inferior epigastric artery perforator (DIEP) flap, complications that are particularly rare (less than 1%) may start to become clinically relevant. During DIEP flap harvest, cutaneous nerves innervating the flap are necessarily sacrificed, resulting in reduced sensibility This impaired sensibility prevents adequate thermoregulatory reflexes, like vasodilatation, sweating, and protective behaviors, leaving the reconstructed breast considerably more susceptible to thermal insult. We present four DIEP flap cases who sustained postoperative thermal injury to the reconstructed breast. All four cases were operated on between 2001 and 2008, over the course of 600 DIEP flaps in our unit (an incidence of 0.7%). The injuries occurred between 2 and 18 months after reconstruction. Two patients sustained thermal injury while sunbathing, one while staying in a warm environment, and one sustained the injury while taking a shower. No flap losses ensued, but these were not without morbidity. A literature review discusses other similar cases in the literature and describes the mechanisms for these findings. As a majority of patients will regain both fine-touch and heat sensation by 3 years postoperatively, it is pertinent that prophylactic measures be instituted during this period, such as the avoidance of sunbathing and the use of cooler shower temperatures for the first 3 years postoperatively. While performing sensory nerve coaptation is the gold standard for maximizing the success of sensory regeneration, this is not always sought and the 0.7% incidence of thermal injury we have encountered suggest the role for greater consideration of such injury.
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| 15. |
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| 18. |
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| 19. |
- Rozen, Warren M., et al.
(författare)
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Postoperative monitoring of lower limb free flaps with the Cook-Swartz implantable Doppler probe : A clinical trial
- 2010
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 30:5, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free flaps to the lower limb have inherently high venous pressures, potentially impairing flap viability, which may lead to limb amputation if flap failure ensues. Adequate monitoring of flap perfusion is thus essential, with timely detection of flap compromise able to potentiate flap salvage. While clinical monitoring has been popularized, recent use of the implantable Doppler probe has been used with success in other free flap settings. Methods: A comparative study of 40 consecutive patients undergoing microvascular free flap reconstruction of lower limb defects was undertaken, with postoperative monitoring achieved with either clinical monitoring alone or the use of the Cook-Swartz implantable Doppler probe. Results: The use of the implantable Doppler probe was associated with salvage of 2/2 compromised flaps compared to salvage of 2/5 compromised flaps in the group undergoing clinical monitoring alone (salvage rate 100% vs. 40%, P = 0.28). While not statistically significant, this was a strong trend toward an improved flap salvage rate with the use of the implantable Doppler probe. There were no false positives or negatives in either group. One flap loss in the clinically monitored group resulted in limb amputation (the only amputation in the cohort). Conclusion: A trend toward early detection and salvage of flaps with anastomotic insufficiency was seen with the use of the Cook-Swartz implantable Doppler probe. These findings suggest a possible benefit of this technique as a stand-alone or adjunctive tool in the clinical monitoring of free flaps, with further investigation warranted into the broader application of these devices.
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| 20. |
- Rozen, Warren M, et al.
(författare)
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The efficacy of postoperative monitoring : A single surgeon comparison of clinical monitoring and the implantable Doppler probe in 547 consecutive free flaps
- 2010
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 30:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: An important element in achieving high success rates with free flap surgery has been the use of different techniques for monitoring flaps postoperatively as a means to detecting vascular compromise. Successful monitoring of the vascular pedicle to a flap can potentiate rapid return to theater in the setting of compromise, with the potential to salvage the flap. There is little evidence that any technique offers any advantage over clinical monitoring alone. Methods: A consecutive series of 547 patients from a single plastic surgical unit who underwent a fasciocutaneous free flap operation for breast reconstruction [deep inferior epigastric artery perforator (DIEP) flap, superficial interior epigastric artery l flap, or superior gluteal artery perforator (SGAP) flap] were included. A comparison was made between the first 426 consecutive patients in whom flap monitoring was performed using clinical monitoring alone and the subsequent 121 patients in whom monitoring was achieved with the Cook-Swartz implantable Doppler probe. Outcome measures included flap salvage rate and false-positive rate. Results: There was a strong trend toward improved salvage rates with the implantable Doppler probe compared with clinical monitoring (80% vs. 66%, P = 0.48). When combined with the literature (meta-analysis), the data prove statistically significant (P < 0.01). There was no statistical difference between the groups for false-positive rates. Conclusion: Flap monitoring with the implantable Doppler probe can improve flap salvage rates without increasing the rate of false-positive takebacks.
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| 21. |
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| 22. |
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| 23. |
- Rozen, Warren M., et al.
(författare)
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Venous Coupler for Free-Flap Anastomosis : Outcomes of 1,000 Cases
- 2010
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:4, s. 1293-1294
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Tidskriftsartikel (refereegranskat)abstract
- Since the advent of microvascular free tissue transfer, adjunctive surgical techniques have become sought as a means to improving overall surgical time and outcomes in oncological surgery. Anastomotic devices have provided one such avenue, with staples and coupling devices suggested as an alternative to traditional suturing. We describe our experience with two such devices, automatic staples and the anastomotic ring coupler, in 1,000 cases of free tissue transfer. In 1,400 anastomoses, there was a significant reduction in anastomotic time from suturing (22 minutes) with the use of staples (15 minutes) or the ring coupler (4 minutes), p<0.01. This was without any increase in complication rates. These findings support the use of these devices and suggest an increasing role for modern devices in microvascular surgery.
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| 24. |
- Wagstaff, Marcus J. D., et al.
(författare)
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Perineal and posterior vaginal wall reconstruction with superior and inferior gluteal artery perforator flaps
- 2009
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 29:8, s. 626-629
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Tidskriftsartikel (refereegranskat)abstract
- Perineal and posterior vaginal wall reconstruction following abdominoperineal and local cancer resection entails replacement of volume between the perineum and sacrum and restoration of a functional vagina. Ideal local reconstructive options include those which avoid functional muscle sacrifice, do not interfere with colostomy formation, and avoid the use of irradiated tissue. In avoiding the donor site morbidity of other options, we describe a fasciocutaneous option for the reconstruction of the perineum and posterior vaginal wall. We present our technique of superior and inferior gluteal artery perforator (SGAP or IGAP) flaps to reconstruct such defects. Fourteen patients between 2004 and 2008 underwent 11 SGAP and three IGAP flaps. There were no flap failures or partial flap losses and no postoperative hernias. All female patients reported resumption of sexual intercourse following this procedure. Our experience in both the immediate and delayed setting is that this technique produces a good functional outcome with low donor-site morbidity.
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| 25. |
- Whitaker, Iain S., et al.
(författare)
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Postoperative Monitoring of Free Flaps in Autologous Breast Reconstruction : A Multicenter Comparison of 398 Flaps Using Clinical Monitoring, Microdialysis, and the Implantable Doppler Probe
- 2010
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Ingår i: Journal of reconstructive microsurgery. - : Georg Thieme Verlag KG. - 0743-684X .- 1098-8947. ; 26:6, s. 409-416
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Tidskriftsartikel (refereegranskat)abstract
- Many techniques for flap monitoring following free tissue transfer have been described; however, there is little evidence that any of these techniques allow for greater rates of flap salvage over clinical monitoring alone. We sought to compare three established monitoring techniques across three experienced microsurgical centers in a comparable cohort of patients. A retrospective, matched cohort study of 398 consecutive free flaps in 347 patients undergoing autologous breast reconstruction was undertaken across three institutions during the same 3-year period, with a single form of postoperative monitoring used at each institution: clinical monitoring alone, the Cook-Swartz implantable Doppler probe, or microdialysis. Both objective and subjective measures of efficacy were assessed. Clinical monitoring alone, the implantable Doppler probe, and microdialysis showed statistically similar rates of flap salvage. False-negative rates were also statistically similar (only seen in the clinically monitored group). However, there was a statistically significant increase in false-positive alarms causing needless take-backs to theater in the microdialysis and implantable Doppler arms, p < 0.001. This study did not find any technique superior to clinical monitoring alone. New monitoring technologies should be compared objectively with clinical monitoring as the current standard in postoperative flap monitoring.
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| 26. |
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