Solitary iliac branch endoprosthesis placement for iliac artery aneurysms.

BACKGROUND: Isolated iliac artery aneurysms (IAAs), accounting for 2% to 7% of all abdominal aneurysms, are often treated with the use of iliac branched endografts. Although outside the manufacturer's instructions for use, iliac branched devices can be used solely, without the adjunctive placement of an endovascular aneurysm repair device, for the treatment of an isolated IAA. In the present study, we have described the outcomes of the use of the Gore iliac branched endoprosthesis (IBE; W.L. Gore & Associates, Flagstaff, Ariz), without the support of an infrarenal endovascular aneurysm repair device, for the exclusion of an isolated IAA. The present study was an international multicenter retrospective cohort analysis. METHODS: All the patients who had undergone treatment with a solitary IBE for IAA exclusion from January 11, 2013 to December 31, 2018 were retrospectively reviewed. The primary outcome was technical success. The secondary outcomes included mortality, intraoperative and postoperative complications, and reintervention. RESULTS: A total of 18 European and American centers participated, with a total of 51 patients in whom 54 IAAs were excluded. The technical success rate was 94.1%, with an assisted technical success rate of 96.1%. No 30-day mortality occurred, with 98.1% patency of the internal and external iliac artery found at 24 months of follow-up. At 24 months of follow-up, 81.5% of the patients were free of complications and 90% were free of a secondary intervention. CONCLUSIONS: Treatment with a solitary IBE is a safe and, at midterm, an effective treatment strategy for selected patients with a solitary IAA.

Insect Immunity to Entomopathogenic Nematodes and Their Mutualistic Bacteria.

Entomopathogenic nematodes are important organisms for the biological control of insect pests and excellent models for dissecting the molecular basis of the insect immune response against both the nematode parasites and their mutualistic bacteria. Previous research involving the use of various insects has found distinct differences in the number and nature of immune mechanisms that are activated in response to entomopathogenic nematode parasites containing or lacking their associated bacteria. Recent studies using model insects have started to reveal the identity of certain molecules with potential anti-nematode or antibacterial activity as well as the molecular components that nematodes and their bacteria employ to evade or defeat the insect immune system. Identification and characterization of the genes that regulate the insect immune response to nematode-bacteria complexes will contribute significantly to the development of improved practices to control insects of agricultural and medical importance, and potentially nematode parasites that infect mammals, perhaps even humans.

Jump Squat is More Related to Sprinting and Jumping Abilities than Olympic Push Press.

The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise.

Treatment of Aortoiliac Occlusive Disease with the Endologix AFX Unibody Endograft.

OBJECTIVE/BACKGROUND: Aorto-bifemoral bypass remains the gold standard for treatment of aortoiliac occlusive disease (AIOD) in patients with advanced (TASC D) lesions, but has significant associated morbidity and mortality. Treatment with a unibody stent-graft positioned at the aortic bifurcation is a potential endovascular option for the treatment of AIOD. The current study examines the safety, efficacy, and early patency rates of the Endologix AFX unibody stent-graft for treatment of AIOD. METHODS: A multicenter retrospective review was conducted of patients treated exclusively for AIOD with the AFX device. Primary, assisted primary, and secondary patency rates were noted. Clinical improvement was assessed using Rutherford classification and ankle brachial index. Mean duration of follow-up was 22.2 ± 11.2 months. Ninety-one patients (56 males [62%]) were studied. RESULTS: Sixty-seven patients (74%) presented with lifestyle-limiting intermittent claudication and the remaining 24 (26%) had critical limb ischemia. Technical success was 100%. Complications included groin infection (n = 4 [4%]), groin hematoma (n = 4 [4%]), common iliac rupture (n = 4 [4%]), iliac dissection (n = 4 [4%]), and thromboembolic event (n = 3 [3%]; one femoral, one internal iliac artery, and one internal iliac with bilateral popliteal/tibial thromboemboli). Thirty-day mortality was 1% (1/91) resulting from a case of extensive pelvic thromboembolism. At 1 year, 73% of patients experienced improvement in Rutherford stage of -3 or greater compared with baseline. Nine patients (10%) required 16 secondary interventions. At all time points, primary patency rates were > 90%, assisted patency rates were > 98%, and secondary patency rates were 100%. CONCLUSION: This is the largest study to examine the use of the Endologix AFX unibody stent-graft for the treatment of AIOD. Use of the AFX stent-graft appears to be a safe and effective endovascular treatment for complex AIOD.

Descripción de la ecografía de los pectorales II (pectorales I modificados): un nuevo enfoque de la cirugía mamaria / Ultrasound description of Pecs II (modified Pecs I): A novel approach to breast surgery

Objetivo. El bloqueo Pecs es un bloqueo regional superficial sencillo que se inspira en el abordaje del bloqueo infraclavicular y en el bloqueo TAP (plano del transversus abdominis). Una vez identificados los músculos pectorales distales a la clavícula disecamos el plano fascial entre ambos para alcanzar los nervios pectorales lateral (LPM) y medial (MPN). La indicación principal del bloqueo Pecs es para expansores subpectorales y en prótesis submamarias donde la distension muscular produce un dolor extremo. Material y método En este artículo describimos una segunda modificación del bloqueo Pecs. Lo llamamos bloqueo Pecs modificado o bloqueo Pecs II. Es un abordaje original que pretende alcanzar los nervios pectorales, nervios intercostobraquial, intercostales III-IV-V-VI y el torácico largo. Estos nervios son esenciales a la hora de proporcional analgesia completa en la cirugía oncológica de mama y se posiciona como una alternativa o un bloqueo de rescate de los bloqueos paravertebrales y epidurales torácicas. En el ultimo año hemos estado usándolo en nuestro centro en tumorectomias, ampliaciones de bordes y para vaciamientos axilares además de las indicaciones del Pecs I. Resultados y conclusiones Mostraremos la secuencia ecográfica para poder realizar este bloqueo junto con imágenes con contraste radiográfico y resonancia magnética con gadolinium para poder entender los beneficios de este bloqueo(AU)

Objective. The Pecs block (pectoral nerves block) is an easy and reliable superficial block inspired by the infraclavicular block approach and the transversus abdominis plane blocks. Once the pectoralis muscles are located under the clavicle the space between the two muscles is dissected to reach the lateral pectoral and the medial pectoral nerves. The main indications are breast expanders and subpectoral prosthesis where the distension of these muscles is extremely painful. Material and methods. A second version of the Pecs block is described, called "modified Pecs block" or Pecs block type II. This novel approach aims to block at least the pectoral nerves, the intercostobrachial, intercostals III-IV-V-VI and the long thoracic nerve. These nerves need to be blocked to provide complete analgesia during breast surgery, and it is an alternative or a rescue block if paravertebral blocks and thoracic epidurals failed. This block has been used in our unit in the past year for the Pecs I indications described, and in addition for, tumorectomies, wide excisions, and axillary clearances. Results and conclusions. The ultrasound sequence to perform this block is shown, together with simple X-ray dye images and gadolinium MRI images to understand the spread and pathways that can explain the benefit of this novel approach(AU)

Ultrasound description of Pecs II (modified Pecs I): a novel approach to breast surgery.

OBJECTIVE: The Pecs block (pectoral nerves block) is an easy and reliable superficial block inspired by the infraclavicular block approach and the transversus abdominis plane blocks. Once the pectoralis muscles are located under the clavicle the space between the two muscles is dissected to reach the lateral pectoral and the medial pectoral nerves. The main indications are breast expanders and subpectoral prosthesis where the distension of these muscles is extremely painful. MATERIAL AND METHODS: A second version of the Pecs block is described, called "modified Pecs block" or Pecs block type II. This novel approach aims to block at least the pectoral nerves, the intercostobrachial, intercostals III-IV-V-VI and the long thoracic nerve. These nerves need to be blocked to provide complete analgesia during breast surgery, and it is an alternative or a rescue block if paravertebral blocks and thoracic epidurals failed. This block has been used in our unit in the past year for the Pecs I indications described, and in addition for, tumorectomies, wide excisions, and axillary clearances. RESULTS AND CONCLUSIONS: The ultrasound sequence to perform this block is shown, together with simple X-ray dye images and gadolinium MRI images to understand the spread and pathways that can explain the benefit of this novel approach.

Left subclavian artery coverage during TEVAR: is revascularization necessary?

Thoracic endovascular aortic repair (TEVAR) has rapidly become a viable and accepted treatment option for atherosclerotic aortic aneurysms as well as a variety of other aortic pathologies including ulcers, dissection, coarctation and disruption. Left subclavian artery (LSA) coverage is often necessary to achieve proximal seal in up to 40% of patients treated with TEVAR. The management of the LSA in this cohort of patients remains controversial. Studies in support of routine pre-operative LSA revascularization show that coverage of the LSA during TEVAR is associated with an increased risk of stroke, paraplegia and arm ischemia. Other studies show that intentional coverage of the LSA without revascularization is not associated with increased morbidity and lends support to those who advocate more selective LSA revascularization during TEVAR (i.e. in those patients with patent LIMA-coronary bypass, dominant or isolated left vertebral artery, or a functioning left upper extremity (LUE) dialysis arteriovenous fistula). This paper is intended to review the literature comparing routine and selective LSA revascularization after TEVAR to determine the best management strategy.

Complications of endovenous lasers.

Endovenous laser ablation (EVLA) and radiofrequencey ablation have become the procedures of choice for the treatment of superficial venous insufficiency. Their minimally invasive technique and safety profile when compared with operative saphenectomy have led to this change. As EVLA has replaced saphenectomy as the procedure of choice, the distribution of complications has changed. We evaluated the most common and most devastating complications in the literature including burns, nerve injury, arterio-venous fistula (AVF), endothermal heat-induced thrombosis and deep venous thrombosis. The following review will discuss the most frequently encountered complications of treatment of superficial venous insufficiency using EVLA. The majority of the complications described can be avoided with the use of good surgical technique and appropriate duplex ultrasound guidance. Overall, EVLA has an excellent safety profile and should be considered among the first line for treatment of superficial venous reflux.

Percutaneous drainage of aortic aneurysm sac abscesses following endovascular aneurysm repair.

PURPOSE: To report preliminary experiences with the treatment of aortic aneurysm sac abscesses following prior endovascular aortic aneurysm repair (EVAR) using computerized tomography (CT)-guided percutaneous drainage. CASE REPORTS: Three patients aged 73 to 78 years with aortic aneurysm sac infections following prior EVAR, 2 of which were associated with aortoduodenal fistula, underwent CT-guided percutaneous drainage and catheter placement. One patient had complete resolution of the aortic aneurysm sac abscess following percutaneous drainage; 1 patient was stabilized to eventual extraanatomic bypass, graft explantation, and fistula repair; and 1 patient was temporized to debridement and fistula repair with endograft preservation. CONCLUSION: CT-guided percutaneous drainage may be a helpful therapy in selected patients for the treatment of aortic aneurysm sac infections following EVAR.

The coronary technique for complex carotid artery stenting in the setting of complex aortic arch anatomy.

Carotid artery stenting (CAS) remains a viable option for treating carotid artery lesions in high surgical risk patients. We retrospectively reviewed our experience in performing CAS in patients with complex aortic arch anatomy. The ''coronary technique'' uses an AL1 guiding catheter to engage the origin of the common carotid artery permitting delivery of protection device and stent. In total, 12 patients had complex arch anatomy which precluded access using the standard technique as determined on preoperative imaging. A total of 8 patients with such anatomy underwent femoral artery catheterization with placement of an Amplatz AL1 guide catheter into the common carotid artery. All were able to be successfully treated, with no dissection, neurovascular deficit, or other major complication. Based on this case series, we describe the coronary technique as a safe and viable method for CAS in the setting of complex anatomy which might otherwise preclude CAS.

Experience and technique for the endovascular management of iatrogenic subclavian artery injury.

BACKGROUND: Inadvertent subclavian artery catheterization during attempted central venous access is a well-known complication. Historically, these patients are managed with an open operative approach and repair under direct vision via an infraclavicular and/or supraclavicular incision. We describe our experience and technique for endovascular management of these injuries. METHODS: Twenty patients were identified with inadvertent iatrogenic subclavian artery cannulation. All cases were managed via an endovascular technique under local anesthesia. After correcting any coagulopathy, a 4-French glide catheter was percutaneously inserted into the ipsilateral brachial artery and placed in the proximal subclavian artery. Following an arteriogram and localization of the subclavian arterial insertion site, the subclavian catheter was removed and bimanual compression was performed on both sides of the clavicle around the puncture site for 20 min. A second angiogram was performed, and if there was any extravasation, pressure was held for an additional 20 min. If hemostasis was still not obtained, a stent graft was placed via the brachial access site to repair the arterial defect and control the bleeding. RESULTS: Two of the 20 patients required a stent graft for continued bleeding after compression. Both patients were well excluded after endovascular graft placement. Hemostasis was successfully obtained with bimanual compression over the puncture site in the remaining 18 patients. There were no resultant complications at either the subclavian or the brachial puncture site. CONCLUSION: This minimally invasive endovascular approach to iatrogenic subclavian artery injury is a safe alternative to blind removal with manual compression or direct open repair.

Multidimensional characterization of carotid artery stenosis using CT imaging: a comparison with ultrasound grading and peak flow measurement.

PURPOSE: Clinical decision making for carotid surgery depends largely upon stenosis grade. While digital subtraction angiography remains the gold standard for stenosis grading, many physicians use less invasive modalities. The purpose of this study was to compare the results of multidimensional Computed tomography (CTA) with ultrasound (US) grading and peak flow velocity (PSV). METHODS: 37 stenosed carotid arteries were studied retrospectively in 36 consecutive patients. US grading and PSV were compared to multidimensional CTA analysis (diameter, area and volumetric measurements), performed by a medical software company. Calculations of stenosis percentage on CTA were made using the NASCET and ECST methodology. Diameter measurements were also performed by a neuroradiologist. RESULTS: All CTA diameter, area and volume measurements had only modest correlation with PSV (r<0.5) and ultrasound grading (p<0.5). There was concordant classification of stenosis grades in only 40-60% of cases. CTA diameter, area and volume measurements had good correlation (0.69

Regional nerve block allows for optimization of planning in the creation of arteriovenous access for hemodialysis by improving superficial venous dilatation.

Durable vascular access for hemodialysis remains a critical issue in end-stage renal disease patients. Creation of an autogenous arteriovenous (AV) fistula in the most distal location of the nondominant extremity is the preferred technique and provides superior patency over an AV graft. Others have shown that regional anesthesia in the form of axillary block results in the dilatation of the native veins and allows for their increased utilization in creating AV fistulae. We report on 26 patients undergoing creation of a vascular access for hemodialysis. Regional anesthesia consisting of axillary nerve block was used in all cases. All surgical plans with regard to the site and type of access were made based on the physical exam and ultrasound vein measurements taken prior to surgery. On the day of surgery patients were reevaluated with venous ultrasound using tourniquet before and after administration of the regional block. The previously determined operative plan either remained unchanged or was modified depending on the venous dilatation noted after administration of regional block. Among 26 patients, average vein diameter increased from 0.29 +/- 0.12 cm to 0.34 +/- 0.11 cm (P = 0.008). Twenty-one of 26 patients had no modification in operative plan (group 1). Five had some modification of the original operative plan (group 2): AV graft to a brachial vein transposition (n = 2), AV graft to a Cimino fistula (n = 2), and brachiocephalic to a Cimino (n = 1). The average follow-up for all patients was 82.6 +/- 75.6 days and did not differ between the groups. There was one failure in a patient from group 1, and there was no significant difference in the patency rate between study groups (P = 0.29). Following regional nerve block, operative plans in patients undergoing AV access surgery were modified in 29.4% of patients undergoing creation of an AV access for hemodialysis; either from graft to fistula creation or from the proximal to more distal fistula site. The routine use of regional anesthesia as well as intraoperative ultrasound during AV access surgery can lead to improved site selection and increased opportunity for AV fistula creation.

An alloantibody to a high-prevalence MNS antigen in a person with a GP.JL/Mk phenotype.

The low-prevalence MNS blood group antigenTSEN is located at the junction of glycophorin A (GPA) to glycophorin B (GPB) in several hybrid glycophorin molecules. Extremely rare people have RBCs with a double dose of the TSEN antigen and have made an antibody to a high-prevalence MNS antigen. We report the first patient who is heterozygous for GYP.JL and Mk. During prenatal tests,an alloantibody to a high-prevalence antigen was detected in the serum of a 21-year-old Hispanic woman. The antibody detected an antigen resistant to treatment by papain, trypsin, alpha-chymotrypsin, or DTT. The antibody was strongly reactive by the IAT with all RBCs tested except those having the MkMk, GP.Hil/GP.Hil, or GP.JL/GP.JL phenotypes. The patient's RBCs typed M+N-S+/-s-U+, En(a+/-), Hut-, Mi(a-), Mur-, Vw-, Wr(a-b-), and were TSEN+, MINY+. Reactivity with Glycine soja suggested that her RBCs had a decreased level of sialic acid. Immunoblotting showed the presence of monomer and dimer forms of a GP(A-B) hybrid and an absence of GPA and GPB. Sequencing of DNA and PCR-RFLP using the restriction enzyme RsaI confirmed the presence of a hybrid GYP(AB). The patient's antibody was determined to be anti-EnaFR. She is the first person reported with the GP.JL phenotype associated with a deletion of GYPA and GYPB in trans to GYP.JL.

Successful limb reperfusion using prolonged intravascular shunting in a case of an unstable trauma patient--a case report.

When peripheral vascular injuries present in conjunction with life threatening emergencies, controlling hemorrhage from a peripheral blood vessel may take initial priority, however, sacrificing a limb to preserve life is a well-established dictum. The use of intravascular shunts has allowed arterial and venous injuries to be controlled and temporized while treating other injuries. Typically, intravascular shunts are used for short time periods while orthopedic injuries are repaired or other life threatening injuries are managed. The following case demonstrates the long-term use of an intravascular arterial shunt to treat a traumatic transection of the common femoral artery and vein in a patient with an open pelvic fracture from blunt trauma. A 20-year-old woman fell between a subway platform and an oncoming train. She sustained a crush injury to her lower extremity and pelvis as she was pinned between the train and platform. The patient presented with active hemorrhage from a groin laceration, quickly became hemodynamically unstable, and was brought to the operating room. In addition to a pelvic fracture with massive pelvic hematoma she sustained a complete transection of the bifurcation of the common femoral artery (CFA), the common femoral vein (CFV), and associated orthopedic injuries. Vascular shunts were placed in the common femoral artery and vein. The patient became hypotensive from an expanding retroperitoneal hematoma. Pelvic bleeding was controlled with angioembolization and the venous injury was repaired. At this time the patient became cold, acidotic, and coagulopathic. It was thought unsafe to proceed with the arterial repair and it was elected to keep her arterial shunts in place and perform a planned reexploration in 24 hours after correcting her physiologic status. The patient returned to the operating room for an elective repair of her CFA the following day. Her shunt had remained patent throughout this time. She underwent a reverse saphenous vein graft from her CFA to her SFA. After a prolonged hospital course she was ultimately transferred to a rehabilitation center with intact pulses in both lower extremities. This case demonstrates the effectiveness of prolonged (>6 hours) use of an intravascular shunt as part of damage control surgery for peripheral arterial and venous injuries. In a patient who would otherwise undergo an amputation for their injury, the risk of shunt thrombosis, or infection, during damage control resuscitation may not be a contraindication for placement.

Initial successful management of type I endoleak after endovascular aortic aneurysm repair with n-butyl cyanoacrylate adhesive.

OBJECTIVE: Transcatheter embolization with coils and other agents has been described as a treatment method for type II endoleak after endovascular aortic aneurysm repair (EVAR). Type I endoleak has not been treated commonly with such therapies, although most investigators believe they warrant definitive intervention. The liquid adhesive n-butyl 2-cyanoacrylate (n-BCA) is often used to treat congenital arteriovenous malformations. The objective of this study is to report our initial experience in treating type I endoleak with n-BCA and with a variety of other interventions. METHODS: A retrospective review was performed of 270 patients who underwent EVAR at our institution between January 1994 and December 2002. Of these, 24 patients had type I endoleak (8.9%), diagnosed either intraoperatively (n = 13, 52%) or during follow-up (n = 12, 48%). Among these 24 patients, 17 had proximal leaks and the remaining 8 patients had distal leaks. These cases form the focus of this study. RESULTS: Twenty-two leaks required endovascular intervention, with the following success rate: n-BCA, 12 of 13 cases (92.3%); extender cuffs, 4 of 5 cases (80%); coils with or without thrombin, 3 of 4 cases (75%). In one patient with persistent endoleak despite attempted endovascular intervention the device ultimately was surgically explanted, and the patient did well. Of six patients with endoleak initially managed expectantly, two eventually underwent attempts at definitive intervention, both with n-BCA. Three sealed spontaneously before definitive intervention could be performed; and in one 97-year-old patient who refused intervention, the aneurysm subsequently ruptured and the patient died. In total, 13 patients with type I endoleak underwent n-BCA transcatheter embolotherapy. No serious complications were directly related to this therapy. Colon ischemia developed in one patient, and was believed to be a result of thromboembolism during wire and catheter manipulation rather than n-BCA treatment. Twelve of these 13 leaks remain sealed at mean follow-up of 5.9 months (range, 0-19 months). CONCLUSION: Our initial use of n-BCA occlusion suggests that it may be an effective and safe method of treatment of type I endoleak after EVAR. In particular, n-BCA embolotherapy may be especially useful in treating type I endoleak not amenable to placement of extender cuffs. Larger case series and longer follow-up are needed before this treatment is more broadly recommended. Type I endoleak after EVAR can be treated successfully with a variety of endovascular methods, and surgical explantation is rarely required.

An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting.

It is unclear whether cleft palate formation is attributable to intrinsic biomolecular defects in the embryonic elevating palatal shelves or to an inability of the shelves to overcome a mechanical obstruction (such as the tongue in Pierre Robin sequence) to normal fusion. Regardless of the specific mechanism, presumably embryonic palatal shelves are ultimately unable to bridge a critical distance and remain unapproximated, resulting in a clefting defect at birth. We propose to use a palate organ culture system to determine the critical distance beyond which embryonic palatal shelves fail to fuse (i.e., the minimal critical intershelf distance). In doing so, we hope to establish an in vitro cleft palate model that could then be used to investigate the contributions of various signaling pathways to cleft formation and to study novel in utero treatment strategies. Palatal shelves from CD-1 mouse embryos were microdissected on day 13.5 of gestation (E13.5; term = 19.5 days), before fusion. Using a standardized microscope ocular grid, paired palatal shelves were placed on a filter insert at precisely graded distances ranging from 0 (in contact) to 1.9 mm (0, 0.095, 0.19, 0.26, 0.38, 0.48, 0.57, 0.76, 0.95, and 1.9 mm). A total of 68 paired palatal shelves were placed in serum-free organ culture for 96 hours (n = 68). Sample sizes of 10 were used for each intershelf distance up to and including 0.48 mm (n = 60). For intershelf distances of 0.57 mm and greater, two-paired palatal shelves were cultured (n = 8). All specimens were assessed grossly and histologically for palatal fusion. Palatal fusion occurred in our model only when intershelf distances were 0.38 mm or less. At 0.38 mm, eight of 10 palates appeared grossly adherent, whereas six of 10 demonstrated clear fusion histologically with resolution of the medial epithelial seam and continuity of the palatal mesenchyme. None of the 18 palates fused when placed at intershelf distances of 0.48 mm or greater. Using our selected intershelf distances as a guideline, we have established an approximate minimal critical intershelf distance (0.48 mm) at which we can reliably expect no palatal fusion. Culturing palatal shelves at intershelf distances of 0.48 mm or greater results in nonfusion or clefting in vitro. This model will allow us to study biomolecular characteristics of unfused or cleft palatal shelves in comparison with fused shelves. Furthermore, we plan to study the efficacy of grafting with exogenous embryonic mesenchyme or candidate factors to overcome clefting in vitro as a first step toward future in utero treatment strategies.

Retinoid signaling directs secondary lineage selection in pancreatic organogenesis.

BACKGROUND/PURPOSE: Retinoid signaling plays an important role in many differentiation pathways. Retinoid signaling has been implicated in the induction of differentiation by pancreatic ductal cancer cell lines and in patients with pancreatic cancer. The authors wished to better understand the role of retinoid signaling in pancreatic development. METHODS: Embryonic pancreas was harvested from mice at serial gestational ages and immunohistochemical analysis was performed for retinoic acid receptors (RAR-alpha, RAR-beta, RAR-gamma), and retinoid X receptors (RXR-alpha, RXR-beta, and RXR-gamma). Also, early embryonic pancreases were cultured for 7 days with exogenous 9-cis retinoic acid (9cRA) or all-trans retinoic acid (atRA) and analyzed histologically and immunohistochemically. RESULTS: Retinoid receptors were expressed in a lineage-specific distribution, with stronger expression for many in the exocrine compartment. The receptors were not often expressed until late gestation. Exogenous 9cRA induced predominantly ducts instead of acini, plus more mature endocrine (islet) architecture. Exogenous atRA induced predominantly acini instead of ducts, with no apparent endocrine effect. CONCLUSIONS: Retinoids may have an important role in pancreatic differentiation, with a particular effect on secondary lineage selection between ductal and acinar phenotype. Because the control of ductal versus acinar differentiation has been implicated strongly in the pathogenesis of pancreatic ductal carcinoma, these results may lay the groundwork for studies in the mechanism of induced differentiation of pancreatic ductal cancer by retinoids.