Use of magnetic resonance imaging for the evaluation of vascular malformations of the lower extremity

Vascular malformations are anatomically subdivided according to the predominant channel anomaly into either capillary, arterial, venous, lymphatic, or combinations. They can be further subdivided into high- or low-flow malformations. Any lesion that has an arterial component is considered a high-flow malformation. Once the diagnosis of a vascular malformation is made, it is of paramount importance to define not only the flow characteristics but also the full range of extension, because the prognosis and appropriate treatment vary substantially for each type of anomaly. The two most useful noninvasive imaging techniques for assessing vascular malformations are magnetic resonance imaging (MRI) and ultrasonography. The aim of this review is to give surgeons involved in treating patients with vascular malformations an opportunity to gain some background on MRI scans when assessing vascular malformations. Although MRI is a powerful modality for assessing vascular malformations, we will also discuss some of the limitations of MRI. We further suggest a diagnostic flow chart developed on the basis of MRI features designed to help determine the composition of a vascular birthmark when intervention is anticipated.     

Eversion with four sutures: an easy, fast, and reliable technique for microvascular anastomosis

In this study, a microvascular anastomosing technique called "eversion with four sutures" is introduced. For microvascular anastomosis, this technique requires fishmouth incisions at both vessel ends and the completion of four sutures. In 120 Wistar-Albino rats, 120 eversion and 120 conventional anastomoses were done in 240 femoral arteries. Each rat received both treatments. Operating time, bleeding time, number of sutures used, patency rates, and pseudoaneurysm formation were analyzed statistically; healing was evaluated with both light and electron microscopy. When compared with the conventional technique using nine sutures, the eversion with four sutures technique was found to be a faster and easier method of anastomosis and as reliable as the conventional technique. Without compromising patency rates, bleeding time, or rates of pseudoaneurysm formation, anastomosis time and amount of suture material exposed to the lumen were significantly reduced when using this technique. In conclusion, the authors think that eversion with four sutures is a reliable alternative to the conventional suturing technique, especially for emergency cases that require multiple microvascular anastomoses.     

Antimicrobial characteristics and biocompatibility of the surgical sutures coated with biosynthesized silver nanoparticles

Surgical sutures play important role during the wound healing of the surgical sites which are known to be sensitive to microbial infections. Silver nanoparticles (AgNPs) have been recently used as promising agents against multiple-drug resistant microorganisms. This study was designed to coat the sutures with silver nanoparticles obtained via a green synthesis approach. Microbial-mediated biological synthesis of AgNPs were carried out ecofriendly using Streptomyces sp. AU2 cell-free extract and deposited on silk sutures through an in situ process. Sutures coated with biosyntehsized AgNP (bio-AgNP coated sutures) were characterized using Scanning Electron Microscopy (SEM) and elemantal analysis were carried out using Energy Dispersive X-ray Spectroscopy (EDS). The silver amount released by the bio-AgNP coated sutures was calculated by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) throughout a degradation process. Antimicrobial potential of the bio-AgNP coated sutures was determined against common pathogenic microorganisms Candida albicans, Escherichia coli and Staphylococcus aureus. To determine the biocompatibility/cytotoxicty of the bio-AgNP coated sutures, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay was used through an indirect test method; that the elutions obtained by the extraction of the sutures at 1, 4, 8 and 10. days and were placed in contact with 3T3 fibroblast cell culture. To best of our knowledge, this is the first report about coating of the nonabsorbable silk sutures with silver nanoparticles biosynthesized using a microbial extract.     

Balanced auricular reconstruction in dystopic microtia with the presence of the external auditory canal

This article presents a new repositioning method in dystopic microtia (low-set microtia, anteriorly tilted microtia, or both) with the presence of the external auditory canal. In the case of low-set malformations, the dystopic auricular canal complex was freed from adjacent bony structure, shifted upward, and anchored to the thick periosteum of the suprameatal triangle or the adjacent superior portion of the temporal bone with nonabsorbable sutures. When the auricular vestige was large and dystopia was severe, the complex was shifted with attachment of the temporoparietal fascia on its cranial part. Meanwhile, when the auricular vestige was small and dystopia was mild, the complex was shifted without attachment of the temporoparietal fascia. Then, the ear framework fabricated with autogenous costal cartilage was positioned and wrapped with the temporoparietal fascial flap. In the case of anteriorly tilted malformations, the dystopic complex was freed, shifted posteriorly, and anchored to the periosteum of the suprameatal triangle. Preauricular dead space, resulting from shifting the complex, was obliterated with pieces of costal cartilage. Simultaneously, the ear framework was placed and wrapped with the temporoparietal fascial flap. No skin necrosis of the shifted complexes occurred in any of the cases. In one case, the facial nerve was transected during dissection and reanastomosed. Upward repositioning distances in low-set microtias were between 1 and 3.5 cm. Posteriorly repositioning distances in anteriorly tilted microtias were 2 and 3 cm. Thirteen patients with low-set malformations, two patients with anteriorly tilted malformations, and three patients with low-set and anteriorly tilted malformations underwent reconstructive operations. The new repositioning method is relatively simple, safe, and effective.     

In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods

BACKGROUND: The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS: Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS: Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS: An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk.     

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.     

A technique for the quantification of the 3D connectivity of thin articulations in Bony sutures

The anatomy and development of cranial and facial sutures have been studied in detail using histological sections, 2D radiographs and more recently CT imaging. However, little attention has been paid to evaluating and quantifying the connectivity of these thin cortical bone articulations. More recent technological advances such as micro-CT imaging has the potential to be used to provide quantitative measurements of 3D connectivity in bony articulations. This study presents a new technique for quantifying the connectivity of bony projections inside cranial and facial sutures using a combination of skeletonization, thinning algorithms and 3D intensity mapping. The technique is demonstrated in five sutures through semi-automated analysis and image processing of μCT scans. In the sagittal, coronal and frontozygomatic sutures an average bone connectivity of 6.6–11.6% was found with multiple bony projections providing an interlocking structure between adjacent bones. Much higher bone connectivity was present in the zygomaticotemporal and zygomaticomaxillary sutures (22.7–37.4%) with few bony projections. This method combining μCT scanning and image processing techniques was successfully used to quantify the connectivity of thin bone articulations and allowed detailed assessment of sutural fusion in 3D. The wider application of this technique may allow quantification of connectivity in other structures, in particular fracture healing of long bones.     

Associated malformations in cases with congenital diaphragmatic hernia

The etiology of congenital diaphragmatic hernia (CDH) is unclear and its pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with CDH, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 115 patients with the most common type of CDH, the posterolateral, or Bochdalek-type hernia, 70 (60.8%) had associated malformations. These included: chromosomal abnormalities (n = 21, 30.0%); non-chromosomal syndromes (Fryns syndrome, fetal alcohol syndrome, De Lange syndrome, CHARGE syndrome, Fraser syndrome, Goldenhar syndrome, Smith-Lemli-Opitz syndrome, multiple pterygium syndrome, Noonan syndrome, and spondylocostal dysostosis); malformation sequences (laterality sequence, ectopia cordis); malformation complexes (limb body wall complex) and non syndromic multiple congenital anomalies (MCA) (n = 30, 42.9%). Malformations of the cardiovascular system (n = 42, 27.5%), urogenital system (n = 27, 17.7%), musculoskeletal system (n = 24, 15.7%), and central nervous system (n = 15, 9.8%) were the most common other congenital malformations. We observed specific patterns of malformations associated with CDH which emphasizes the need to evaluate all patients with CDH for possible associated malformations. Geneticists and pediatricians should be aware that the malformations associated with CDH can often be classified into a recognizable malformation syndrome or pattern (57.1%).     

Dislocation and/or congenital malformation of the shoulder joint. Observations on a Mediaeval skeleton from Denmark

The purpose of this paper is to present a Mediaeval skeleton of an approximately 16 year old boy, which was excavated at a Danish cemetery containing ca. 150 graves. The skeleton reveals several pathologic changes, probably due to congenital malformation. The most intriguing find is seen at both scapulae, and the changes are bilateral symmetric. Both the glenoid cavities are placed posterior but at the normal height of the bone. The joints are almost perpendicular to their normal direction. The size of the glenoid cavities is normal and the shape is rather flat in accordance to the development stage of the skeleton, where the epiphysis of the rim has not yet appeared to form the gently concave fossa as normally seen in adults. Both the surface and the borderlines of the glenoid cavities are, however, more irregular than normally at that age. The position of the joints may be caused by dislocation and/or congenital malformation which is discussed. Due to the shape of the cavities, to the symmetric bilaterality, and to the minor congenital malformations, it is primarily believed to be caused by congenital malformation. Probably the young man was not much affected by the malformation of the shoulder joints, which is indicated by the normal form and size of the humeri and the well-developed muscle attachments of the bones. The claviculae seem shorter and more twisted than normal, which may be caused by a twisting of the scapulae. So the glenoid cavities may have pointed almost in the normal direction in spite of the malformation. Other minor malformations are spina bifida of the atlas and the 5. lumbar vertebra, multiple minor changes of the joints of both feet and malformations of one metatarsal bone in both feet. Agenesi of the praemolars is also seen. Although our study of the literature, we have not succeeded in correlation our finds with any known congenital syndrome, and as far as we know no similar case has been described in clinical observation or in skeletal finds.     

CHARGE Association in newborns: a registry-based study

The CHARGE Association is a nonrandom occurrence of congenital malformations that has been described in clinical series. Reported patients have been selected on the basis of certain prior criteria. In this article, we try to identify a congenital malformation pattern corresponding to the CHARGE Association, using statistical methods and analyzing 5,260 infants with multiple malformations collected from four large registries of congenital malformations. Care was taken to identify a number of confounding characteristics that can influence the ascertainment and registration of specific congenital malformations. We have identified a cluster of malformations that generally agreed with the current clinical definition of the CHARGE Association and have added some further malformations (e.g., facial clefts). We demonstrate that others (e.g. , esophageal atresia) are probably not part of the pattern. Heart defects (H in the acronym) seems to be less helpful in identifying infants with the association. We suggest a method to select infants who probably represent the CHARGE Association for analyses of possible risk factors.     

Histologic investigation of vascular malformations of the face after transarterial embolization with ethibloc and other agents

Twenty-one vascular malformations located in the facial area, 11 high-flow arteriovenous malformations and 10 slow-flow malformations, underwent combined treatment by embolization and later surgery. Embolization was performed simultaneously with superselective angiography of the branches of the external carotid artery. The new biodegradable fibrosing agent Ethibloc was used in 16 cases. Histologic examination of the surgical specimens confirmed the good target orientation by the transarterial injection of Ethibloc. Limitations of this technique are discussed. The agent proved to have thrombogenic and fibrogenic properties. Some of the vascular walls degenerated and ruptured following the embolization, but there were no instances of necrosis of interstitial tissue or skin. Embolization treatment of vascular malformations of the face was not curative, but it facilitated subsequent surgery in all examined cases.     

Effects of magnetic resonance imaging on eye development in the C57BL/6J mouse

An investigation was undertaken to ascertain the potential teratogenicity of magnetic resonance imaging (MRI) fields. The C57BL/6J mouse was chosen as the experimental model with eye malformations (microphthalmia and morphologic anomalies) designated as the biological end point. This mouse strain is genetically predisposed to this type of malformation as a 10% spontaneous incidence occurs. Dams in groups of 15 were subjected to MRI imaging conditions on gestational day (Gd) 7 for 36 minutes to a spin-echo T-2-weighted scan by using a 1.5 Tesla magnetic field and a radiofrequency (RF) field of 64 MHz. One group was exposed at the magnetic isocenter while another was exposed at the entrance to the magnet lumen. There was also a sham control group. The dams were sacrificed at Gd 14. Assessment of eye abnormality was determined by, 1) a veterinary ophthalmologist, 2) a computer-based method comparing eye areas, and 3) a methodology combining both the above subjective and quantitative methods. MRI fields were found to produce malformation rates (15-37%) higher than controls (2-19% P less than or equal to .05, Kruskal-Wallis Test) for both isocenter and lumen entrance groups. The malformation rates and degree of statistical significance varied somewhat with analytical methodology and the unit of measure (right eye, left eye, or fetus). The results suggest for the first time the potential of MRI fields to produce developmental malformations in an animal model utilizing clinically realistic exposure conditions. (However, the reader is remained that the mouse strain utilized in this investigation was genetically prone to malformations).     

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged Shh and BMP signaling is correlated with severe anorectal malformations in both mouse and humans.KEY WORDS: Anorectal malformation, Cloaca, Patterning, Epithelial differentiation, Sonic hedgehog     

"Staying power"--absorbable vs. nonabsorbable

An experiment was designed to compare the "holding power" or "staying power" of absorbable (polyglycolic acid and polyglactin 910) and nonabsorbable (nylon) suture. The aim of this experiment was to determine what provides the lasting strength of the bond between soft tissues that are approximated or plicated. When correcting the rectus diastasis during abdominoplasty, we used nylon sutures in 15 patients and absorbable synthetic sutures in 15 other patients. We then marked the closed folds of the rectus sheath with small metal vascular clips. Two days later and approximately 6 months after operation an upright anteroposterior abdominal x-ray was taken and the position of the metal clips was compared in the test groups. Although there was usually slight separation of the clips after 6 months, no significant difference between the two groups was noted, thereby indicating that holding power is not related to type of suture material but more likely to fibroplasia.     

Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF

Giant congenital melanocytic nevi may be symptomatically isolated or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71‐year‐old patient with a giant congenital melanocytic nevus (CMN) of the lower back, buttocks, and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts then developed within it. Imaging and biopsy showed a large, non‐pulsatile venous malformation intermingled with the deep nevus. A low‐abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both gluteal and occipital congenital nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS, or PIK3CA were undetectable. This is the first demonstration of a recurrent BRAF mutation in multiple large congenital nevi from the same individual, confirming that this malformation can have multiple genetic origins. Early constitutive activation of BRAF can therefore cause unusual associations of giant nevi with vascular malformations, indicating that both pigment and endothelial cell physiology may be affected by mosaic RASopathies.     

Absorbable versus nonabsorbable sutures to prevent postoperative stretching of wound area

In surgery it is not uncommon to demand considerable tensile strength of sutures, at least for the time it takes the scar to gain sufficient strength to resist wound-shearing forces without the help of sutures. There is controversial thinking as to whether absorbable or nonabsorbable sutures should be used in this situation. By tattooing two pairs of marks on each side of the wound after a midline sagittal excision of the scalp for correction of androgenetic alopecia and suturing 13 patients with Dexon (polyglycolic acid) and 8 with Prolene (polypropylene), the authors were able to measure a 48 to 59 percent larger postoperative stretching of the wound area in the Dexon group 2 months postoperatively. In addition, the scar width was 60 to 76 percent larger in the Dexon group 3 months postoperatively. These differences were highly significant. Differences in scar depression also supported the idea of more stretching in the Dexon group. This indicates the importance of careful choice of suture material in situations where problems are to be expected, such as in wide scars or wound failure.     

Using ICD‐9 codes to establish prevalence of malformations in newborn infants

BACKGROUND The International Classification of Disease (ICD‐9) codes are used to identify, after discharge, diagnoses from a review of the medical record and provide the basis for reimbursement. These codes have been used to establish the prevalence of malformations and to assess potential teratogens. We have analyzed the accuracy of codes 740 to 759.9 to identify newborn infants with malformations. METHODS The diagnoses and ICD‐9 codes in the medical records of 1000 consecutive live‐born and stillborn infants were compared to the information provided in the medical records of those infants. RESULTS One hundred twenty‐seven of the 1000 infants had ICD‐9 codes between 740 and 759.9. 67 (52.8%) of the codes identified minor features, such as birth marks and minor anomalies. Twenty‐three (18.1%) of the codes designated a malformation and were correct. Two types of errors were identified in another 33 infants (26%) whose codes designated a malformation: either the pediatricians' notes described a less severe finding or the fact that there was no such abnormality. In addition, four malformed infants were missed in pregnancies that were either terminated electively or stillborn, as they did not have medical records. CONCLUSION The ICD‐9 codes 740 to 759.9 identified accurately some infants ( 18% ) with malformations, but identified incorrectly many others. The accuracy of the coding for identifying malformations would be improved if (1) the findings of the examining pediatricians were considered; (2) normal features of prematurity, such as patent foramen ovale and patent ductus arteriosus, were not considered malformations; (3) minor physical features were not assigned ICD‐9 codes within the 740 to 759.9 sequence. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.     

A chromosomal deletion map of human malformations.

Malformations are common causes of pediatric morbidity and mortality, and genetic factors are a significant component of their etiology. Autosomal deletions, in almost all cases, cause a nonspecific embryopathy that presents after birth as growth failure, mental retardation, and multiple malformations. We have constructed a chromosome map of autosomal deletions associated with 47 different congenital malformations, using detailed clinical and cytogenetic information on 1,753 patients with nonmosaic single contiguous autosomal deletions. The 1,753 deletions involved 258 (89%) of 289 possible autosomal bands (by the use of ISCN 400-band nomenclature), giving a total of 4,190 deleted autosomal bands for analysis. We compared the band distributions of deletions associated with common major malformations with the distribution of all 1,753 deletions. We noted 283 positive associations between deleted bands and specific malformations, of which 199 were significant (P<.05, P>.001) and 84 were highly significant (P<.001). These "malformation-associated bands" (MABs) were distributed among 137 malformation-associated chromosome regions (MACRs). An average of 6 MABs in 2.9 MACRs were detected per malformation studied; 18 (6%) of 283 MABs contain a locus known to be associated with the particular malformation. A further 18 (6%) of 283 are in seven recognized specific malformation-associated aneuploid regions. Therefore, 36 (26%) of 137 of the MACRs contain an MAB coinciding with a previously recognized locus or malformation-associated aneuploid region. This map should facilitate identification of genes important in human development.     

Nigrocaudate and nigroputaminal projections in the monkey.

Following injections of tracers into the caudate nucleus, the putamen or into both structures of the same cerebral hemisphere, retrograde cell labeling in the nigral complex of the squirrel monkey has been analyzed. Our goal was to investigate a possible relation of the retrograde neuronal labeling in the substantia nigra pars compacta (SNc) with the histochemical compartmentalization of this structure detected with the aid of the acetylcholinesterase (AChE) technique. Our results confirmed that in the squirrel monkey there was a very precise topography in the nigrostriatal projection system as a whole, and also in the nigrocaudate and nigroputaminal projection systems considered separately. In the cases with injections of two different tracers, we were not able to find any double-labeled nigral cell. Nigrocaudate and nigroputaminal projecting cells generally formed independent groups which at some nigral levels clearly interdigitated, as shown by the group of Parent. However, the presence of nigral cells labeled either by one or another tracer within the same histochemical compartment of the SNc confirmed that the segregation of nigroputaminal and nigrocaudate projecting cells did not explain the AChE compartmentalization of the SNc. Based on our experiments and on the literature we suggest that the histochemical compartmentalization of the SNc could be related, at least in part, to the subdivision of the striatum into AChE-poor striosomes and an AChE-rich extrastriosomal matrix.