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[Salvage of amputated digits by temporary ectopic implantation].

We present two clinical cases with complete amputation of multiple digits that were salvaged after having been successfully implanted on ectopic sites. The first case concerns a 73-year-old patient, who suffered a severe crush injury of his right hand that resulted in amputation of all four long fingers and an extensive tissue loss of the palm and the dorsum of the hand. Two of the amputated digits, that were considered to be replantable, were implanted on the dorsum of the left foot. The hand defect was covered with a pedicle groin flap. After six weeks, the two ectopically implanted fingers were transferred to their proper anatomical site. Several reconstructive procedures were performed later, in order to lengthen the first ray of the injured hand, and to deepen the first web space. Satisfactory functional results were recorded after eighteen months of follow-up. The second patient concerns a 45-year-old male patient, who had a gun shot accident of his right hand. The injury resulted in a composite tissue loss of the hand with complete amputation of his four long fingers. All fingers were implanted on the left forearm, while the hand defect was reconstructed using an osteocutaneous free flap of the iliac crest. Six weeks after the initial procedure, the ectopically implanted digits were transferred - as a single free flap - to the hand. We described with details the local conditions of the injured hands in both cases, and discuss the reasons we decided to perform this sophisticated method in order to preserve the viability and function of those totally amputated fingers. The recipient sites were selected in a distance from the injured area, always considering the availability and size of appropriate recipient vessels, and the safety of the surgical procedure. We agree that the whole concept of this procedure is very demanding, and requires several microsurgical operations with high risk of complications. However, it does deserve special consideration in reconstructive microsurgery, since it offers the possibility to salvage multiple amputated digits, by preserving the anatomy and restoring the function of severely injured hands.

Aged↗

Ectopic expression of von Hippel-Lindau tumor suppressor induces apoptosis in 786-O renal cell carcinoma cells and regresses tumor growth of 786-O cells in nude mouse.

The von Hippel-Lindau (VHL) is a known tumor suppressor that binds to alpha-subunits of hypoxia-inducible factors and induces ubiquitin-mediated degradation of the protein in an oxygen-dependent manner. VHL is also involved in the regulation of tumor angiogenesis, glycolysis, cell cycle regulation, and apoptosis. In the present study, we showed that ectopic expression of VHL induces apoptosis in renal cell carcinoma 786-O cells which contain only the mutant VHL, evidenced by TUNEL assay and DAPI staining. Furthermore, biochemical studies indicated that expression of VHL in 786-O cells results in both PARP and CPP32 cleavage, suggesting that VHL-induced apoptosis in 786-O cells is caspase dependent. Moreover, we also observed that apoptosis induced by ectopic VHL expression was associated with up-regulation of p27 as well as Bax, implicating the roles of these two proteins in VHL-induced apoptosis. The up-regulation of p27 and Bax by VHL was specific since we did not detect any changes in the level of other apoptotic factors including Fas and Bcl2 by the expression of VHL. We next examined the effect of VHL expression on the tumor growth of 786-O renal cell carcinoma cells in nude mouse. The results showed that injection of Ad.VHL adenovirus regresses the tumor growth of 786-O cells in nude mouse. The analysis by TUNEL assay as well as DAPI staining of 786-O tumors injected with Ad.VHL showed clear evidence of apoptosis. These results suggest that ectopic VHL expression induces apoptotic response in 786-O VHL mutant cells both in vitro and in vivo.

Animals↗

Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered constructs in goats.

Despite decades of extensive research, the application of cell-based bone tissue engineering in clinically relevant models remains challenging. To improve effectiveness, a better understanding of how the technique should work is crucial. In the current study, we investigated the onset time, rate, location and direction of bone formation in ectopically and orthotopically implanted clinically sized tissue-engineered constructs to gain insight the mechanism behind it. Bone marrow stromal cells (BMSCs) were obtained from 10 goats, culture expanded and cryopreserved. Porous biphasic calcium phosphate (BCP) disks of 17mmx6mm were per-operatively seeded with BMSCs or left empty. Both conditions were implanted intramuscularly and in bilateral critical-sized iliac wing defects. Fluorochromes were administered at 3, 5 and 7 weeks and samples were retrieved after 9 weeks. Histology showed abundant and homogeneous bone formation throughout the intramuscular BMSC samples and little bone in the controls. Histomorphometry and measurements of the fluorochrome labels of the ectopical BMSC samples indicated that osteogenesis started at the periphery and subsequent osteoconduction filled the whole scaffold within 7 weeks. In the orthotopically implanted disks, there was good integration with the surrounding bone, but minimal bone in the center of the implants, in both conditions. Bone was only derived from the interface with the surrounding bone, there was no early bone at the surfaces in contact to soft tissue as was seen in the ectopical samples. Apparently cell survival was minimal and insufficient for relevant additional bone formation. However, the speed of integration with surrounding bone and subsequent bone apposition on the BMSC-seeded orthotopic scaffolds were found to be significantly enhanced, which may be relevant especially in challenging environments.

Animals↗

Low dose fibroblast growth factor-2 (FGF-2) enhances bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation in mice.

To examine how fibroblast growth factor-2 (FGF-2) affects the BMP signaling pathway during bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation, we implanted type I collagen disks containing constant amounts of BMP-2 (5 micrograms) and varying amounts of FGF-2 onto the back muscles of adult male mice. We then performed histological analyses and histomorphometry, and measured bone mineral density and radiopaque area on the discs 1, 2, and 3 weeks after implantation. We also determined the expression profiles of several genes involved in bone formation and the BMP signaling pathway in the muscle that had been adjacent to the implanted disc and in muscle-derived primary culture cells that had similarly been treated with a constant concentration of BMP-2 and a varying concentration of FGF-2. In the presence of a constant amount of BMP-2, we confirmed that low doses of FGF-2 increased ectopic bone formation in vivo and high doses inhibited bone formation. Northern and/or Western blots of recovered muscle from the in vivo experiment and treated muscle-derived primary culture cells from the in vitro experiment revealed that low doses of FGF-2, but not high doses, increased the expression BMP receptor (BMPR)-1B, phosphorylated Smad1, Noggin, and Osteocalcin. Our results indicate that low-dose FGF-2 may facilitate BMP-2-induced ectopic bone formation by altering the expression of BMPRs on the surface of bone forming progenitor cells. They also indicate that the inhibitory effect of high-dose FGF-2 is not mediated via increased expression of the BMP inhibitor Noggin.

Animals↗

Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles.

Calcium phosphate ceramics are widely used in bone reconstructive surgery because of their osteconductive properties. However, these materials generally lack osteoinductive properties required to support bone healing in large defects. In this article, we study the osteoinductive potential of calcium phosphate ceramic particles implanted for 6 months into the dorsal muscles of eight adult female sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1-2 mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450 microm, micropores of 0.43 microm, and a specific surface area of 1.8 m(2)/g. After 6 months in the back muscles of sheep, the explants composed of MBCP granules were hard and encapsulated by normal muscle tissue. Ectopic bone formation with Haversian structures was observed in close contact with the MBCP granules in histological sections. Back-scattered electron microscopy and micro-computed tomography indicated that approximately 10% of well-mineralized bone with mature osteocytes had formed between or upon the granules. The ectopic bone showed trabeculae bridging the MBCP granules. Both the number and thickness of the trabeculae formed between the MBCP particles were comparable to those measured in spongious bone. The overall results therefore confirmed the presence of mature bone after intramuscular implantation of MBCP granules. The different hypotheses explaining ectopic bone formation induced by MBCP granules are discussed. Synthetic bone substitutes with osteoinductive properties could be used in bone reconstructive surgery.

Animals↗

Ectopic vaginal insertion of an obstructed duplicated ureter in an adult female: demonstration by magnetic resonance imaging.

The usual presentation of an ectopically inserted vaginal ureter is continuous dribbling of urine in an otherwise healthy girl. This case did not present with the usual symptomatology, as there was severe stenosis of the ectopically located ureteric orifice. Conventional imaging failed to show the vaginal insertion of an ectopic ureter. However, a magnetic resonance urogram readily depicted the collecting system from the kidney to the point of ureteric insertion.

Adolescent↗

Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores.

The centromere-specific histone variant CENP-A (CID in Drosophila) is a structural and functional foundation for kinetochore formation and chromosome segregation. Here, we show that overexpressed CID is mislocalized into normally noncentromeric regions in Drosophila tissue culture cells and animals. Analysis of mitoses in living and fixed cells reveals that mitotic delays, anaphase bridges, chromosome fragmentation, and cell and organismal lethality are all direct consequences of CID mislocalization. In addition, proteins that are normally restricted to endogenous kinetochores assemble at a subset of ectopic CID incorporation regions. The presence of microtubule motors and binding proteins, spindle attachments, and aberrant chromosome morphologies demonstrate that these ectopic kinetochores are functional. We conclude that CID mislocalization promotes formation of ectopic centromeres and multicentric chromosomes, which causes chromosome missegregation, aneuploidy, and growth defects. Thus, CENP-A mislocalization is one possible mechanism for genome instability during cancer progression, as well as centromere plasticity during evolution.

Animals↗

Ectopic pregnancy in a preexisting hydrosalpinx during a spontaneous pregnancy.

OBJECTIVE: To discuss the possible role of abnormal embryo migration as a cause of ectopic pregnancy during IVF with hydrosalpinges. DESIGN: Case report. SETTING: University-based reproductive endocrinology and fertility clinic. PATIENT(S): A patient presenting with a tubal ectopic pregnancy after spontaneous conception in a preexisting hydrosalpinx. INTERVENTION(S): Laparoscopic salpingectomy. MAIN OUTCOME MEASURE(S): Ultrasound and operative findings. RESULT(S): Case demonstration of abnormal embryo migration into a surgically documented preexisting hydrosalpinx during a spontaneous conception. CONCLUSION(S): The mechanism of increased tubal ectopic pregnancy rates during IVF with hydrosalpinges remains unexplained. This case supports abnormal embryo migration due to the hydrosalpinx as a contributing factor.

Fallopian Tube Diseases↗

Effects of ectopic expression of Drosophila DNA glycosylases dOgg1 and RpS3 in mitochondria.

The main purpose of this study was to determine whether enhancement of repair capacity would attenuate mitochondrial DNA oxidative damage and result in greater cell survival under stressful conditions. The repair of oxidative damage is initiated by DNA glycosylases, which catalyze the excision of oxidized bases, such as 8-hydroxydeoxyguanosine (8-oxodG). Drosophila DNA glycosylases, dOgg1 and RpS3, were ectopically expressed within the mitochondrial matrix in Drosophila S2 cells, causing a severalfold decrease in the levels of 8-oxodG in mitochondrial DNA. Unexpectedly, cells did not show increased resistance to oxidative stress, but instead became more susceptible to treatment with hydrogen peroxide or paraquat. Even in the absence of oxidative challenge, cells expressing RpS3 or dOgg1 in mitochondria exhibited increased apoptosis relative to controls, as determined by flow-cytometric analysis of Annexin V and DNA degradation measured by the Comet assay. Another notable finding was that ectopic expression of either dOgg1 or RpS3 in mitochondria increased cell survival after exposure to the nitric oxide donor SNAP. These results suggest that ectopic expression of one of the constituents of the DNA repair system in mitochondria may cause a perturbation in the base excision repair pathway and lower, rather than enhance, survivability.

Animals↗

Controlled release of rhBMP-2 from collagen minipellet and the relationship between release profile and ectopic bone formation.

The purpose of this study was to examine the effects of various additives on the profiles of rhBMP-2 release from minipellet, which is a sustained release formulation for protein drugs using collagen as a carrier, and to examine the influence of varying release profiles on ectopic bone formation. When the amount of rhBMP-2 remaining in the preparation after subcutaneous implantation to mice was examined, it was found that the addition of sucrose, glucose, PEG4000, alanine (Ala) or acacia in a concentration of 20% (w/w) to the minipellet with 5% (w/w) of rhBMP-2 did not accelerate the drug release in a noticeable manner, while the addition of sodium chondroitin sulfate, glutamic acid (Glu) or citric acid accelerated the release of rhBMP-2 markedly. When two types of minipellets (a fast release type added with 20% Glu and 20% Ala and a slow release type without additives) containing varying amounts of rhBMP-2 were implanted subcutaneously to mice, the soft X-ray observation, histological examination and measurement of calcium formation 3 weeks after implantation revealed extensive ectopic bone formation in mice implanted with the fast release type preparation. Ectopic bone formation was dose-dependent. The result of this study exhibited that the effects of controlled release formulation of rhBMP-2 on bone formation vary depending on their release profiles, and suggested that combination of initial burst and sustained release was effective for bone formation. It was also shown that minipellet is useful as a controlled release formulation which can release rhBMP-2 to areas around the implanted site with various release profiles.

Animals↗

Ectopic salivary tissue of the tonsil: a case report.

To report one patient with an ectopic salivary tissue tag on the tonsil, and review the embryology, management, and implications of this benign disorder. Case report with literature review. Ectopic salivary tissue presented on the tonsil of a child as a painless, growing, unilateral pale exophytic mass. Tonsillectomy was performed to provide diagnosis, and was curative. Ectopic salivary tissue of the tonsil is a rare finding. Tonsillectomy allows for definitive diagnosis and treatment.

Adolescent↗

Pancreatic pseudocyst arising from ectopic pancreas and isolated intestinal duplication in mesocolon caused hydronephrosis in a girl with horseshoe kidney.

Ectopic pancreas is a relatively common congenital anomaly and is usually asymptomatic. Pancreatitis in the ectopic site and pseudocyst formation is extremely rare. To date, only 2 cases have been reported. We present a case of a 3-year-old girl with recurrent pancreatitis and unilateral hydronephrosis of the horseshoe kidney, which was produced by pancreatic pseudocyst arising from ectopic pancreas and isolated intestinal duplication in mesocolon. This is the first case of pancreatic pseudocyst that expanded to the retroperitoneal space and caused urinary tract obstruction.

Child, Preschool↗

Dose-response effects of ectopic agouti protein on iron overload and age-associated aspects of the Avy/a obese mouse phenome.

Isogenic and congenic offspring from matings of inbred black a/a dams by sibling (or non-sibling from another inbred strain) yellow agouti Avy/a sires provide an animal model of obese yellow agouti Avy/a and isogenic lean pseudoagouti Avy/a mice exhibiting two different in vivo concentrations (high, very low) of ectopic agouti protein (ASP) with congenic lean black a/a mice as null controls. This makes it possible to differentiate between the high and very low dose levels of ectopic ASP with respect to interactions with diverse physiological and molecular pathways. Assay of differential responses to 12 or 24 months of carbonyl iron overload assessed the possible suitability of this animal model for the study of hemochromatosis. Agouti A/a B6C3F1 mice were used as non-congenic null controls. The age-related waxing and waning of body weight, food consumption, and caloric efficiency, as well as associated changes in pancreatic islets and islet cells, and formation of liver tumors were assayed. While the hypothesis that these mice might serve as a tool for investigating hemochromatosis was not confirmed, the data did provide evidence that even the very low levels of ASP in pseudoagouti Avy/a mice affect the network of molecular/metabolic/physiological response pathways that comprises the yellow agouti obese phenome. We suggest that the combination of yellow agouti Avy/a, pseudoagouti Avy/a, and black a/a congenic mice provides a practical tool for applying a dose-response systems biology approach to understanding the dysregulatory influence of ectopic ASP on the molecular-physiological matrix of the organism.

Aging↗

Percutaneous nephrolithotomy for ectopic kidneys: over, around, or through.

OBJECTIVES: The treatment of patients with complex urolithiasis in ectopic kidneys can be challenging. Because the location of an ectopic kidney can vary, each case requires a unique and, at times, unconventional approach. We reviewed the techniques we have developed to treat such patients, including laparoscopic-assisted tubeless, transhepatic, and transiliac percutaneous nephrolithotomy (PNL). METHODS: We performed a retrospective analysis of all patients with congenital pelvic kidneys who underwent PNL at our institution. Six patients underwent laparoscopic-assisted PNL, one underwent transiliac PNL, and one underwent transhepatic PNL. All laparoscopic-assisted procedures were performed tubeless, with an internalized ureteral stent placed at the conclusion of the procedure. RESULTS: All patients underwent successful PNL. On computed tomography, performed on the morning of postoperative day 1, all patients who underwent laparoscopic-assisted PNL were stone free. The patients who underwent transiliac PNL and transhepatic PNL required secondary procedures to attain a stone-free status. The mean length of hospitalization was 3 days for the laparoscopic-assisted cohort, 1 day for the transhepatic patient, and 3 days for the transiliac patient. CONCLUSIONS: For the patient with a large or complex stone burden in an ectopic kidney, laparoscopic-assisted PNL is the optimal treatment. Performing such a procedure tubeless may be associated with a reduced hospital stay. For those patients with a hostile peritoneal cavity owing to prior surgical exploration, consideration should be given to a more individualized approach.

Adult↗

Single vaginal ectopic ureter of fetal metanephric duct origin, ipsilateral kidney agenesis, and ipsilateral rudimentary uterine horn of the bicornuate uterus.

BACKGROUND: Congenital anomalies arising from the urogenital tracts are common. We experienced two cases of specific urogenital anomalies. CASE: Two Japanese women had a single ectopic ureter opening in the central wall of the vagina, ipsilateral kidney agenesis, and ipsilateral rudimentary uterine horn of the bicornuate uterus. One had squamous cell carcinoma of the uterine cervix, and the other had adenocarcinoma of the vagina arising from the ectopic ureter meatus, which was histologically confirmed as fetal metanephric duct remnant. One had vesico-vaginal fistula postoperatively, resulting from separating the ureter-like duct from the bladder. CONCLUSION: Concomitant occurrence of anomalies suggests the common genetic backgrounds, which are not well known. Clinically, the ectopic vaginal ureter is important as a possible background of vaginal adenocarcinoma, and information on the ureter-like duct course is required during surgery.

Adenocarcinoma↗

Hysterosalpingographic evaluation of tubal patency after ectopic pregnancy.

In the period 1983 to 1985, hysterosalpingography was performed in 76 women after laparotomy to manage ectopic gestations. Clinical characteristics of these women, including their operative findings, were then correlated with the follow-up hysterosalpingography. Study participants were classified into five groups according to surgical management of the ectopic gestation. In each of the five groups, a substantial percentage of those women with a nonpatent fallopian tube (contralateral to the tube bearing the ectopic gestation) on hysterosalpingography had a normal-appearing fallopian tube at laparotomy. Approximately 50% of women with a history of previous pelvic inflammatory disease were found to have nonpatent contralateral fallopian tubes on follow-up hysterosalpingography.

Adolescent↗

Methotrexate pneumonitis after systemic treatment for ectopic pregnancy.

Pneumonitis is an infrequent complication of methotrexate therapy. Described is a case of pneumonitis after treatment of an ectopic pregnancy. A 20-year-old white woman, gravida 3, para 0, ectopic pregnancy 2, was treated for her third ectopic pregnancy with 88 mg (50 mg/m2) of intramuscular methotrexate. Four days later acute dyspnea, tachypnea, fever, patchy infiltrates on chest x-ray films, and a PO2 of 30 mm Hg developed. Respiratory distress resolved over 48 hours. Pneumonitis should be suspected in any patient treated with methotrexate who has unexplained dyspnea.

Adult↗