Current results of left gonadal vein transposition to treat nutcracker syndrome.

OBJECTIVE: Nutcracker syndrome can cause disabling chronic pain requiring surgical intervention. At present, data describing a straightforward management approach are lacking. Transposition of the left gonadal vein is one of the surgical therapeutic alternatives. The aim of the present study was to describe our clinical results with gonadal vein transposition. METHODS: All 11 patients from three centers who had undergone left gonadal vein transposition for nutcracker syndrome from 2016 to 2019 were retrospectively included. The surgical cases were mainly selected according to the morphologic criteria of the left gonadal vein. The diameter and length dictated the type of approach (laparotomy or retroperitoneal) and the transposition level. A minimally invasive retroperitoneal approach was preferred. Pain was assessed using a numeric rating scale. RESULTS: We included 11 patients (10 women) with a median age of 35 years (range, 25-69). Preoperative computed tomography angiography showed anterior nutcracker syndrome in 10 patients (91%). All 11 patients had experienced lower back and/or pelvic pain, which was associated with pelvic congestion syndrome in 6 patients (55%) and hematuria in 5 patients (45%). The median preoperative numeric rating scale score for pain was 7.0 (range, 3.5-10.0) and 6.0 (range, 3.5-8.0) for lower back pain and pelvic pain, respectively. At the level of the iliac vein crossing (external or common), the median diameter of the left gonadal vein was 7.87 mm (range, 6.45-11.28). The left gonadal vein was transposed to the inferior vena cava in one case (9%), the left external iliac vein in five (45%), and the left common iliac vein in five cases (45%). The median in-hospital stay was 4 days (range, 2-20 days). Two early complications (18%) requiring surgical revision occurred: one of active bleeding and one hematoma. The median follow-up was 15 months (range, 6-44 months). The median postoperative pain score was 1.0 (range, 0.0-4.0) and 0.0 (range, 0.0-6.0) for lower back and pelvic pain, respectively. Incisional and/or neuropathic pain was noted, with a median score of 3.5 (range, 1.0-6.0) in seven patients (64%). Two late complications (18%) were observed: one case of thrombosis and one case of anastomotic stenosis. The hematuria had disappeared in all patients who had presented with it initially. CONCLUSIONS: Left gonadal vein transposition can be proposed as a first approach if the diameter of the left gonadal vein is sufficient to perform the anastomosis. It is an easily achievable, minimally invasive alternative that achieves satisfactory results without the use of foreign material.

Comparative analysis of the efficacy and safety of endovascular and endoscopic interventions on the gonadal veins in the treatment of pelvic congestion syndrome.

OBJECTIVE: Comparison of the efficacy and safety of endovascular and endoscopic interventions on the gonadal vein in the treatment of patients with pelvic congestion syndrome (PCS). METHODS: We evaluated the treatment outcomes in 95 patients with PCS who underwent endovascular embolization of gonadal veins (EEGV) (group 1, n = 67) or endoscopic resection of the gonadal veins (ERGV) (group 2; n = 28). A comparative analysis of the efficacy and safety of EEGV and ERGV in the treatment of PCS included assessments of their effects on pelvic venous pain, pelvic venous reflux, diameter of the pelvic veins, and restoration of daily activity, as well as treatment safety assessment. Clinical examinations and ultrasound studies of the pelvic veins were repeated at 1, 10, and 30 days, and 36 months after EEGV and ERGV. Pain was assessed using a visual analogue scale and the Von Korff questionnaire. RESULTS: A decrease in pelvic venous pain intensity was observed at 3.6 ± 1.4 days after EEGV and 2.5 ± 0.8 days after ERGV (P = .49 between the groups). At 1 month after the intervention, a complete relief of pelvic pain was reported by 52 and 25 patients in the EEGV and ERGV groups, respectively. The rates of valvular incompetence of the uterine veins were decreased from 85% in both groups at baseline to 3% in group 1 and 0% in group 2 at 36 months after the intervention, respectively. In the early postprocedural period, pain in the femoral or jugular vein puncture site was reported by eight patients (12%) who underwent EEGV (2.2 ± 0.7 scores). Postembolization syndrome was diagnosed in 13 patients (19.4%). After ERGV, all patients experienced pain in the area of the surgical wound, with a severity of 3.9 ± 0.5 scores. Hematoma at the puncture site of the main vein was observed in 6% of patients after EEGV. Protrusion of coils was identified in three patients (4.5%). The VTE incidence was four times greater in group 1 vs group 2 (14 vs 3 patients; P < .05). The relative risk of this complication after EEGV was 1.4 (95% confidence interval, 1.146-1.732). In two patients (7.1%) after the bilateral laparoscopic resection of the gonadal veins, an ileus developed. No complications of anesthesia were observed in either group. CONCLUSIONS: Endovascular and endoscopic techniques for decreasing blood flow through the gonadal veins are effective and safe in treating the PCS. The obvious advantages of EEGV are minimal injury and possibility to perform procedure under local anesthesia. The ERGV is associated with at least similar and, in some cases, even superior outcomes, in the terms of significantly (P < .05) shorter time to the postprocedural pain relief and avoiding postembolization syndrome.

Gonadal vein transposition is a safe and effective treatment of nutcracker syndrome.

BACKGROUND: Nutcracker syndrome (NCS) is a pelvic venous disorder that results from outflow obstruction of the left renal vein, most often due to a decreased aortomesenteric angle, leading to gonadal vein reflux, pain, and varices. Although a number of open and minimally invasive procedures to treat NCS have been described, the optimal management of this condition remains uncertain. To the best of our knowledge, we have presented the largest case series to date using gonadal vein transposition (GVT) to treat NCS. METHODS: Patients considered for intervention to treat NCS underwent a rigorous and standardized workup, including axial imaging studies, catheter-based diagnostic procedures, and urinalysis. GVT has been the institutional first-line treatment of NCS for appropriate patients. With institutional review board approval, a retrospective review of patients who had undergone GVT for NCS was conducted. RESULTS: From 2014 to 2019, 18 GVTs had been performed. Of the 18 patients, none had died or required reintervention, although 2 had required readmission. During a median follow-up of 178 days, complete symptom relief was achieved in 11 patients (61.1%), with 4 patients (22.2%) reporting partial symptom relief and 2 (11.1%) reporting transient symptom relief. CONCLUSIONS: GVT is a safe and effective procedure to treat NCS in appropriately selected patients with outcomes that compare favorably with those of other described procedures. Appropriate patient selection for this procedure is critical and requires a rigorous and standardized approach to diagnosis and management.

CT findings after left renal vein division during abdominal aortic surgery.

BACKGROUND: The rationale behind left renal vein division (LRVD) is the assumption that adequate collateral draining channels will develop. PURPOSE: To describe computed tomography (CT) findings after LRVD during aortic surgery. MATERIAL AND METHODS: Among 61 consecutive patients who underwent LRVD during aneurysm repair or revascularization for aortic occlusive disease between January 2003 and December 2017, 51 patients (40 men, mean age 71.4 ± 8.4 years) were enrolled. Contrast-enhanced CT images were analyzed to evaluate collateral drainage, patency, left renal vein diameter, and left renal parenchymal thickness. A total of 115 radiologic reports were reviewed to check whether these findings were accurately mentioned. RESULTS: The median time period of the first postoperative follow-up CT was 36 days (range 7-1351 days). The gonadal vein (n = 47) was the most common collateral draining channel, followed by the retroperitoneal veins (n = 42) and adrenal vein (n = 33). Thrombosis occurred in five patients between postoperative days 7 and 17 in the remnant renal vein (n = 3), remnant renal vein plus gonadal and adrenal veins (n = 1), and gonadal vein (n = 1). There was a significant decrease in renal vein diameter (-0.48 ± 2.12 mm, P = 0.006). There was no significant difference in parenchymal thickness (-0.25 ± 1.27 mm, P = 0.193). Neither LRVD nor any associated findings were correctly stated on radiologic reports. CONCLUSION: Postoperative contrast-enhanced CT can delineate collateral draining channels and complications following LRVD. However, these findings tend to be either missed or misinterpreted.

Common iliac vein obstruction in a symptomatic population is associated with previous deep venous thrombosis, and with chronic pelvic pain in females.

OBJECTIVE: The objectives of this study were to determine the incidence of common iliac vein obstruction, gonadal vein incompetence, and renal vein compression/stenosis and to ascertain which referral reasons were associated with common iliac vein obstruction and gonadal vein incompetence in a population symptomatic for chronic venous insufficiency. METHODS: Data were obtained from patients, at least 18 years old, who were referred to a private vascular laboratory for venous duplex ultrasound examination between 2016 and 2017. Transabdominal ultrasound was used to assess the iliac, gonadal, and renal veins in a dedicated protocol. Demographic data, referral reasons (varicose veins, lower limb pain, lower limb edema, lower limb ulcers, chronic pelvic pain [CPP]) and history of previous deep venous thrombosis (DVT) were recorded. RESULTS: Among 421 patients (78.6% female; 57.7 ± 16.7 years), 46.7% had iliac vein obstruction, 40.1% had gonadal vein incompetence, and 29.9% had renal vein compression/stenosis. Venous disorders were significantly more prevalent among female patients and on the left side. The most common referral reasons were varicose veins for both sexes, followed by lower limb pain for females and lower limb edema for males, none of which were associated with any venous obstruction or incompetence. Previous DVT was significantly associated with common iliac vein obstruction for all patients (ß = .189; P = .001), despite its being a previous known diagnosis for only 11.4% of patients. Among females, CPP was also significantly associated with common iliac vein obstruction and gonadal vein incompetence (ß = .246 [P < .001] and ß = .201 [P = .012], respectively). Among those with CPP in this study, common iliac vein obstruction, with and without gonadal vein incompetence (33% and 35%, respectively), was more prevalent than gonadal vein incompetence alone (14%). CONCLUSIONS: History of DVT, as well as CPP among females warrants investigations of common iliac vein obstruction. Common iliac vein obstruction is likely to be a more significant contributor to CPP than gonadal vein incompetence.

Five veins at the deep inguinal ring: can they reduce the chances of indirect inguinal hernia and increase the chances of varicocele? / Cinco venas en el anillo inguinal profundo. ¿pueden reducir las probabilidades de una hernia inguinal indirecta y aumentar las posibilidades de varicocele?

Complete duplication of testicular veins is a rare phenomenon. However, a few cases of duplication of gonadal veins have been reported. Here, I report a case of unusual formation and termination of the right testicular vein in an adult male cadaver. Five veins arose from the pampinniform plexus and entered the abdomen through the deep inguinal ring. The most medial among the five was large (3 mm in diameter) and it continued as a testicular vein and opened into the right edge of the inferior vena cava, 1 cm above the union of the common iliac veins. The other four veins were about 1 mm in diameter and they united to form two veins in front of the lower part of the right psoas and iliacus muscles (about 2 cm above the deep inguinal ring) and the two veins united to form upper testicular vein, 4 cm above the deep inguinal ring. This testicular vein was 3 mm in diameter and it opened into the inferior vena cava, 4 cm above the union of common iliac veins. Having five veins at deep inguinal ring might increase the chances of varicocele and decrease the chances of indirect inguinal hernia.

La duplicación completa de las venas testiculares es un fenómeno raro. Sin embargo, se han reportado algunos casos de duplicación de venas gonadales. En el presente trabajo se informa un caso de formación y terminación inusual de la vena testicular derecha en un cadáver de un hombre adulto. Cinco venas surgieron del plexo pampiniforme y penetraron en el abdomen a través del anillo inguinal profundo. El más medial entre los cinco fue de gran tamaño (3 mm de diámetro) y continuó como una vena testicular y se abrió hacia el margen derecho de la vena cava inferior, 1 cm por encima de la unión de las venas ilíacas comunes. Las cuatro venas restantes eran de 1 mm de diámetro aproximadamente, y se unieron para formar dos venas frente a la parte inferior de los músculos psoas e ilíaco derechos (aproximadamente 2 cm por encima del anillo inguinal profundo). Se unieron dos venas para formar la vena testicular superior, la cual medía 3 mm de diámetro y se abría hacia la vena cava inferior, 4 cm por encima de la unión de las venas ilíacas comunes. Cinco venas en el anillo inguinal profundo podrían aumentar las posibilidades de varicocele y disminuir las posibilidades de una hernia inguinal indirecta.

RUG technique: replacement of the ureter with gonadal vein. A cadaveric study.

BACKGROUND: Ureteral defect lesions may result from retroperitoneal fibrosis, radiation damage, tumors, or surgical procedures; the management of long-segment ureteral defects is a challenge for urologists. Total or partial replacement of the ureter is sometimes required, with consequent ileal interposition, but this technique may lead to several complications, such as severe urinary infections. In a few cases, nephrectomy may be required. Starting from the above considerations, we can postulate the RUG technique (replacement of the ureter with gonadal vein), using the gonadal vein (GoV) as an autologous graft to substitute the ureter. For this reason, we decided to test this novel idea on an experimental model. METHODS: We tested the above technique on a cadaveric model, performing complete procedure (RUG #1), segmental replacement of the ureter (RUG #2), and ureteroplasty with a GoV patch (RUG #3). All the procedures involved an open approach. After RUG #3, the treated segment of the ureter was sampled for histologic analysis. RESULTS: Four RUGs were performed (two RUG #1, one RUG #2, one RUG #3). All anatomic structures were easily identified, and all procedures were completed successfully. The dimensions of the ureters were comparable to those of the GoV in all cases, as usual. Histologic analysis demonstrated perfect adherence of the two anastomosed structures. CONCLUSIONS: The RUG technique resulted in an adequate, safe and easy-to-perform surgical alternative.

Kidney Transplantation Using Gonadal Vein for Venous Anastomosis in Patients With Iliac Vein Thrombosis or Stenosis: A Series of Cases.

BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. The standard surgery uses the recipient's iliac vessels for vascular anastomosis. Thrombosis and/or stenosis of the iliac vein, which are possible complications of multiple vascular access points for dialysis, can be detected intraoperatively, constituting a surgical challenge. An infrequently reported option is the use of the gonadal vein. OBJECTIVES: This study aims to evaluate the outcomes of venous anastomosis in the gonadal vein in patients with iliac vein thrombosis and/or stenosis submitted to kidney transplantation. METHODS: We reviewed the records of five adult recipients with iliac vein thrombosis and/or stenosis detected intraoperatively during emergency kidney transplantation with deceased donor due to vascular access failure from February 2013 to December 2014. Antithrombotic prophylaxis was not performed. We evaluated the postoperative complications, length of stay, early graft echo-Doppler, and renal function during the first year postoperatively. RESULTS: Delayed graft function occurred in three cases. Two patients developed postoperative infection requiring antibiotics. One patient required reoperation due to post-renal biopsy complications. The mean length of stay was 31.2 days and the mean serum creatinine levels at discharge, at 6 months, and at 12 months postoperatively were 1.42 mg/dL, 0.86 mg/dL, and 0.82 mg/dL, respectively. All patients had normal ultrasonography. There were no losses of graft or deaths during follow-up. CONCLUSION: Venous anastomosis using the gonadal vein in kidney transplantation for patients with iliac vein thrombosis and/or stenosis showed good clinical and surgical results, showing this method to be a viable alternative to venous drainage in these complex patients.

Laparoscopic inferior mesenteric-gonadal vein bypass for the treatment of nutcracker syndrome.

Nutcracker syndrome is a rare entity caused by extrinsic compression on the left renal vein (LRV) crossing between the superior mesenteric artery and the aorta. This article reports the treatment of two cases of nutcracker syndrome using laparoscopic inferior mesenteric-gonadal vein bypass, knowing that this treatment option would avoid renal reperfusion injury and LRV hypertension. In addition, it is easier to operate compared with laparoscopic splenorenal venous bypass and laparoscopic transposition of LRV into the inferior vena cava.

Bilateral Duplication of Gonadal Veins: a Case Report / Duplicación Bilateral de las Venas Gonadales: Reporte de Caso

The duplication of gonadal vessels is mainly found on the left side, with less numbers of bilateral cases. The objective of this work is describing a case of bilateral duplication of gonadal veins, where two veins were draining to inferior vena cava, being that the closest vein of kidney medial margin had a thickness of 2.68mm and was distant 64.41 mm of the organ. The second vessel had a thickness of 1.43mm and was distant 73.76mm. Two veins follow to left renal vein, being that the first vessel had a thickness of 2.7mm and was distant 21.8mm of the kidney medial margin; the other had a thickness of 1.64mm and was distant 35.13mm of the organ. The presence of variations on the local of drainage of gonadal vessels has clinical importance for comprehension of origin of varicocele cases, as well as the recurrence of them after surgical procedures.

La duplicación de las venas gonadales es más común en el lado izquierdo, con pocos casos bilaterales. El propósito de este reporte fue describir el caso de una duplicación bilateral de las venas gonadales, dos de las cuales desembocaban en la vena cava inferior. El vaso próximo del margen medial del riñon tenía un diámetro de 2,68mm y una longitud de 64,41 mm. La segunda vena tenía un diámetro de 1,43 mm y una longitud de 73,76 mm. Los dos vasos desembocaban en la vena renal izquierda. La primera vena tenía un diámetro de 2,7 mm y estaba a 21,8 mm del margen medial del riñon. La otra tenía un diámetro de 1,64 mm y se se localizaba a 35,13 mm del margen medial del riñon. La presencia de variaciones donde se produce el drenaje de los vasos gonadales tiene importancia clínica para la comprensión del origen del varicocele y la recurrencia del mismo, después de procedimientos quirúrgicos.

The inferior mesenteric vein to the left gonadal vein shunt for gastroesophageal varices and extrahepatic portal vein thrombosis after living donor liver transplantation: a case report.

This 59-year-old woman underwent living donor liver transplantation using a left lobe graft as an aid for autoimmune hepatitis in 2003. Splenectomy was also performed because of blood type incompatibility. Follow-up endoscopic and computed tomography examinations showed gastroesophageal varices with extra hepatic portal vein thrombosis in 2007 that increased (esophageal varices [EV]: locus superior [Ls], moderately enlarged, beady varices [F2], Blue varices [Cb], presence of small in number and localized red color sign [RC1] and telangiectasia [TE+], gastric varices [GV]: extension from the cardiac orifice to the fornix [Lg-cf], moderately enlarged, beady varices [F2], white varices [Cw], absence of red color sign [RC-]). Portal venous flow to the gastroesophageal varices was also confirmed from a large right gastric vein. The splenic vein was thrombosed. Blood flow to the liver graft was totally supplied from the hepatic artery. The graft was functioning well. Because these gastroesophageal varices had a high risk of variceal bleeding, we decided to proceed with a portal reconstruction of a surgical portosystemic shunt in 2008. Severe adhesions were observed around the portal vein. It was impossible to perform portal reconstruction. There were relatively fewes adhesious in the left lower side of the abdominal cavity. We decided to create an inferior mesenteric vein to left gonadal vein shunt. The portal vein pressure decreased from 31.0 to 21.5 cm H2O thereafter. The postoperative course was smooth without any complication. This patient was discharged on the postoperative day 15. Follow-up endoscopic study showed the improvement in the gastroesophageal varices (EV: Ls, F2, Cb, RC(-), GV: Lg-c, F2, Cw, RC-) at 3 months after the operation. We also comfirmed the patency of the shunt by serial computed tomography examinations.

Hematopoietic stem cell activity in the aorta-gonad-mesonephros region enhances after mid-day 11 of mouse development.

The E11.5 aorta-gonad-mesonephros (AGM) region is a site of hematopoietic stem cell (HSC) development prior to colonisation of the embryonic liver. The generation of HSCs in the embryo starting from E11 is very rapid. Here, we have assessed hematopoietic development in the AGM region during E11 at precise somitic ages. Although the numbers of committed hematopoietic precursors fluctuate throughout the day, the repopulation activity in the AGM region noticeably increases from mid (44 s.p.) to end (48 s.p.) day 11 of gestation. While prior to mid day 11 two thirds of AGM regions contain no definitive HSCs, shortly prior to liver colonisation, all older day 11 embryos contain definitive HSC. Nevertheless, all E11 AGM regions even at early somitic stages have the capacity to expand numbers of definitive HSCs ex vivo. Quantitative anatomical analysis confirmed preferential localization of intra-aortic clusters (IACs) to the ventral domain of the dorsal aorta during entire day 11 of development. No clear correlation was established between IAC numbers and the presence of definitive HSCs.

Mpl receptor defect leads to earlier appearance of hematopoietic cells/hematopoietic stem cells in the Aorta-Gonad-Mesonephros region, with increased apoptosis.

In a previous study, we underlined the functional role of the TPO receptor, Mpl, in the establishment of definitive mouse hematopoiesis, by demonstrating that the lack of Mpl led to a delayed production of definitive hematopoietic cells in the aorta-gonad-mesonephros (AGM) region, and resulted in the production of hematopoietic stem cells (HSCs) with an impaired activity at E11.5. In order to more accurately estimate the role of Mpl during generation of HSCs in the aorta, we performed an analysis of these AGMs at the time of the first HSC emergence (E10.5). Our results indicated that while Mpl-/- AGMs were found to contain more hematopoietic cells (HC) than C57Bl6 AGMs at E10.5, a defect in the expansion process of the HC/HSCs was detected in explant cultures of these AGMs, likely due to an increased apoptosis of these cells. To determine the molecular mechanisms by which invalidation of Mpl receptor affects the temporal distribution and expansion of HC/HSCs in the AGM, a study of the transcription level of of Mpl target genes was conducted. Expression of Runx1, a master transcription factor for the formation of hematopoietic progenitor (HP) cells and HSCs from the vasculature, as well as expression of Meis1 and HoxB4, known to play a role in self-renewal and expansion of HSCs, were found to be down regulated in E10.5 Mpl-/- AGMs. Our data indicate that Mpl is an active player during the first steps of definitive hematopoiesis establishment through direct regulation of the expression of transcription factors or genes important for the self-renewal, proliferation and apoptosis of HSCs.

Three rare variations in the course of the gonadal artery / Tres raras variaciones en el trayecto de la arteria gonadal

The gonadal arteries, lateral branches of the abdominal aorta, usually arise distal to the renal vessels. Knowledge of the origin and course of them, particularly their relationships with renal vessels, are important for uncomplicated surgical procedures on the posterior abdominal wall. So the relationship of the testicular artery and renal vessels were studied in 80 cadavers in Calcutta National Medical College, India and detected three rare variations. We have discussed the possible clinical implications and embryological explanation with review of literature of those variations.

Las arterias gonadales, ramas laterales de la aorta abdominal, usualmente surgen distales a los vasos renales. El conocimiento del origen y trayecto de estas, particularmente sus relaciones con los vasos renales, son importantes para procedimientos quirúrgicos sin complicaciones en la pared posterior del abdomen. La relación de la arteria testicular y los vasos renales fueron estudiados en 80 cadáveres en la Escuela Nacional de Medicina de Calcuta, India y se detectaron tres variaciones raras. Se discuten las posibles implicancias clínicas y explicaciones embriológicas, con la revisión de la literatura de estas variaciones.

Impact of ligating gonadal or adrenal collateral veins with the left renal vein on renal function and histology in right-nephrectomized rats.

BACKGROUND: In cases of trauma to the left renal vein (LRV), its ligation near the inferior vena cava (IVC) is considered, but the consequences are not always good. We investigated the role of collateral venous drainage after ligation of the LRV by studying the renal function and histology after ligation of the LRV near the IVC alone or with ligation of the gonadal or adrenal collaterals, in right-nephrectomized (RN) rats. MATERIAL AND METHODS: Ligation of the LRV near the IVC alone (group 1) or with ligation of the adrenal (group 2) or gonadal (group 3) collaterals was studied in RN Wistar rats (n=18 per group). The renal histopathology (ischemic cortical necrosis) and functional status (urea, creatinine, sodium, and potassium) were compared. RESULTS: In RN rats, the results were better when ligating the LRV near the IVC alone or with the adrenal collaterals [mortality 4/18 (22.2%) and 3/18 (16.7%), respectively] than when ligating the LRV near the IVC plus the gonadal collaterals [mortality 15/18 (83.3%)] (p<0.0001). All early deaths occurred within three days and resulted from serious histopathological (ischemic cortical necrosis) and functional (increased urea, creatinine, and potassium; decreased sodium) renal damage. CONCLUSION: In right-nephrectomized rats, the LRV near the IVC and the adrenal collateral can be ligated, while the gonadal collateral should be preserved.

Reconstruction of the portal and hepatic veins using venous grafts customized from the bilateral gonadal veins.

BACKGROUND: Surgical resection for pancreatic and hepatic cancer sometimes involves combined resection and reconstruction of the major veins using venous grafts. Autologous venous grafts made from the bilateral gonadal veins (BGVs) have never been utilized or discussed. MATERIALS AND METHODS: We reconstructed the portal vein (PV), superior mesenteric vein (SMV), and middle hepatic vein (MHV) using cylindrical or patch grafts customized from the BGVs in two female patients and in one male patient. In order to assess the sexual difference in the availability of the cylindrical graft to replace these major veins, we measured the diameters of the BGVs, PV, SMV, and MHV on computed tomography in 50 male and 50 female patients, and estimated the diameter-ratios (DRs) of the cylindrical graft made from BGVs/PV, SMV, and MHV. We assumed that the cutoff value of the DR would be 0.8, for replacing of major veins using cylindrical grafts. RESULTS: The reconstructed PV, SMV, and MHV presented sufficient patency, and the postoperative courses were uneventful. The DRs of BGVs graft/PV, graft/SMV, and graft/MHV were significantly larger in female patients than those in male patients (0.82 vs. 0.54, p < 0.01, 0.96 vs. 0.61, p < 0.01, 1.39 vs. 0.95; p < 0.01) and were larger than 0.8 in 50%, 70%, and 92% in female patients, respectively, and 0%, 8%, and 68% in male patients, respectively. CONCLUSIONS: The present newly customized cylindrical and patch grafts made from the BGVs showed sufficient feasibility. A cylindrical graft made from the BGVs would be better utilized in female patients than in male patients.

Identification of high proliferative potential precursors with hemangioblastic activity in the mouse aorta-gonad- mesonephros region.

Hemangioblast, a precursor possessing hematopoietic and endothelial potential, is identified as the blast colony-forming cell in the murine gastrulating embryos (E7.0-E7.5). Whether hemangioblast exists in the somite-stage embryos is unknown, even though hemogenic endothelium is regarded as the precursor of definitive hematopoiesis in the aorta-gonad-mesonephros (AGM) region. To address the issue, we developed a unique three-step assay of high proliferative potential (HPP) precursors. The AGM region contained a kind of HPP precursor that displayed hematopoietic self-renewal capacity and was able to differentiate into functional endothelial cells in vitro (i.e., incorporating DiI-acetylated low-density lipoprotein, expressing von Willebrand factors, and forming network structures in Matrigel). The clonal nature was verified by cell mixing assay. However, the bilineage precursor with high proliferative potential-the HPP-hemangioblast (HA)-was not readily detected in the yolk sac (E8.25-E12.5), embryonic circulation (E10.5), placenta (E10.5-E11.5), fetal liver (E11.5-E12.5), and even umbilical artery (E11.5), reflective of its strictly spatial-regulated ontogeny. Expression of CD45, a panhematopoietic marker, distinguished hematopoietic-restricted HPP-colony-forming cell from the bipotential HPP-HA. Finally, we revealed that basic fibroblast growth factor, other than vascular endothelial growth factor or transforming growth factor-beta1, was a positive modulator of the HPP-HA proliferation. Taken together, the HPP-HA represents a novel model for definitive hemangioblast in the mouse AGM region and will shed light on molecular mechanisms underlying the hemangioblast development. Disclosure of potential conflicts of interest is found at the end of this article.

Less calcemic Vitamin D analogs enhance creatine kinase specific activity and modulate responsiveness to gonadal steroids in the vasculature.

Vitamin D receptors are widely expressed in the cardiovascular system, in which Vitamin D and its metabolites exert a variety of biological activities such as regulation of cellular proliferation and differentiation, cell calcium transients and cell energy metabolism in vitro. The latter is mediated through the control of the brain type creatine kinase specific activity (CK), which serves to provide a readily available reservoir for ATP generation under increased work-load. In the present study we undertook to assess the role of Vitamin D on energy metabolism in the rat heart and aorta in vivo by using CK, which is a key energy metabolizing enzyme and compare Vitamin D depleted and repleted animals. Vascular tissues from female or male Vitamin D-depleted rats showed 61-80% lower CK activity in the aorta (Ao) and left ventricle of the heart (Lv) than control, Vitamin D-replete rats. Moreover, neither estradiol-17beta (E2) nor dihydrotestosterone (DHT), which increases CK specific activity in Ao and Lv of intact female or male rats, respectively, were able to stimulate CK in Vitamin D-depleted rats. Treatment of intact female rats for 2 weeks or 2 months with the less-calcemic Vitamin D analogs JKF 1624F2-2 (JKF) or QW 1624F2-2 (QW) (Fig. 1), did not significantly affect CK specific activity. However, after pretreatment with these analogs, there was an up regulation of the E2-induced CK response in Ao and Lv. In intact female rats, all Vitamin D analogs also potentiated the in vivo CK response to the SERMs raloxifene (Ral) and tamoxifen (TAM) in Ao and Lv. However the inhibitory effect of Ral or TAM on E2-induced CK activity was lost after pretreatment with Vitamin D analogs. The non-calcemic analog CB 1093 (CB) induced a significant increase in estradiol receptor alpha (ERalpha) protein in both myocardial and aortic tissue from intact and from ovariectomized female rats. Collectively, these results indicate that Vitamin D analogs modulate cell energy homeostasis in vascular tissues through induction of CK and up regulation of the response and sensitivity of CK in vascular tissues to E2 and to SERMs, possibly through via an increase in ERalpha protein in female derived organs. These results corroborate our previous in vitro studies in human vascular cells and further suggest that the Vitamin D system plays an important physiological role in maintaining normal cell energy reservoir in the vasculature.