Instrumentation for laparoscopic renal surgery--Padron Endoscopic Exposing Retractor (PEER) and Endoholder: point of technique

During laparoscopic surgery, as in open surgery, exposure is critical. However, this can be difficult during laparoscopy due to limited haptic feedback and the loss of 3-dimensional visualization. Excessive force may be inadvertently applied by assistants when anatomic structures are retracted; similarly, the retractors may be unknowingly moved because the limited field of view with the laparoscope precludes constant visualization of the retracting instrument. To overcome these problems, we have been using a 5- or 10-mm PEER retractor in combination with an articulating arm instrument holder (Endoholder) to aid laparoscopic renal surgery. The adjustable spring-loaded articulating instrument holder (Endoholder) consists of 4 components, including table attachment, a base rod, flexible extension arm, and precision clamp. The clamp accommodates variously sized instruments, and the flexible extension arm rotates 360 degrees to aid in positioning. The instrument holder is clamped to the table via the base rod over a sterile drape. A PEER Retractor, Roto-lok ratchet (5- or 10-mm diameter and 32-cm length) is placed intracorporeally to retract and position the kidney for hilar, upper, and lower pole dissection. The PEER retractor's handle is secured in place using the precision clamp of the instrument holder. The articulating instrument holder and PEER retractor are used for our renal, adrenal, and ureteral laparoscopic procedures. Placement of the retractor through a 5- or 10-mm port and deployment can be done quickly. Adequate and stable positioning of the retractor provides excellent and secure visualization of the operative field. These instruments have been used in more than 200 cases without any complication except 1 minor liver laceration. The articulating instrument holder with the PEER retractor is a very useful aid during laparoscopic renal surgery. This instrument reduces the chances of inadvertent injury to viscera by the assistant while maintaining an excellent anatomic view throughout the procedure. This will have a significant impact on the advancement of laparoscopy and its acceptance by every urologist.     

Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model

This study reports the preclinical evaluation of the bone and muscle protective potential of the synthetic androgen 7alpha-methyl-19-nortestosterone (MENTtrade mark), as assessed in the aged orchidectomized rat model. Aged (13-month-old) orchidectomized Wistar rats were treated with different doses of MENT (4, 12 or 36 microg/day) subcutaneously for 16 weeks via mini-osmotic pumps. Analysis of the effects of androgen deficiency versus MENT replacement was performed using quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DEXA) and biochemical markers of bone turnover. At the end of the study period, prostate weight in orchidectomized rats treated with low- (4 microg/day) or mid-dose (12 mug/day) MENT remained significantly lower compared to the sham-operated animals (-47% and -25%, respectively). High-dose MENT (36 microg/day), on the other hand, induced prostate hypertrophy (+21% versus sham). Low-, mid- and high-dose MENT were found to be effective in suppressing the acceleration of bone remodeling following orchidectomy, as assessed by osteocalcin and deoxypyridinoline. In addition, low-, mid- and high-dose were able to prevent the orchidectomy-induced bone loss, as evaluated by DEXA at the femur and total-body and by pQCT at the femur. Compared to sham-operated animals, the low- and mid-dose MENT groups showed no decline in lean body mass and no muscle atrophy (as measured by m. quadriceps weight) at 16 weeks, whereas high-dose MENT was associated with a significant decline in lean body mass (-8.5% versus sham) and quadriceps weight (-10.6%). We conclude that, in the aged orchidectomized rat model, low- and mid-doses of the synthetic androgen MENT have bone and muscle protective effects and do not induce prostate hypertrophy. The bone protective action of high-dose MENT, however, occurs at the expense of muscle wasting and prostate hypertrophy. Our findings support the need for human studies to explore the potential of MENT as an option for androgen replacement in aging men.     

Evaluation of hydrogel tissue sealant in porcine laparoscopic partial-nephrectomy model

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) is technically challenging with a steep learning curve, primarily because techniques used to control bleeding on the cut surface of the kidney can be ineffective, inconsistent, or challenging. Hemostatic techniques can include intracorporeal suturing, vascular coagulation (argon-beam coagulator, bipolar cautery, laser), and application of various tissue sealants. There is no uniformity of opinion regarding which hemostatic technique is optimal for this application. CoSeal, a hydrogel (Baxter Healthcare Corp, Deerfield, IL), has been effective following vascular surgery but has not been applied to a partial-nephrectomy model. We evaluated the effectiveness of this hydrogel in controlling bleeding and sealing the collecting system by comparing it with intracorporeal suturing and fibrin sealant (Tisseel; Baxter) in a porcine laparoscopic partial-nephrectomy model. MATERIALS AND METHODS: Bilateral synchronous upper-pole partial nephrectomies were performed in two groups of 18 farm pigs, and the three hemostatic techniques (suturing, Tisseel, CoSeal) were applied. In the first group, partial nephrectomies were performed and the pigs sacrificed 3 days postoperatively (acute group). In the second group, the pigs were euthanized 6 weeks postoperatively (chronic group). In both groups, weight, blood pressure, estimated blood loss, weight of the partial and completion nephrectomy specimen, presence/ absence of urinary leak on retrograde study, histopathologic findings, and complications were recorded. RESULTS: The mean weight, blood pressure, estimated blood loss, histopathology findings, and weight of the partial and completion nephrectomy specimens were similar in the three groups. CoSeal did not adhere well to the renal parenchyma compared with Tisseel. All three animals in the acute CoSeal group and three of the six pigs in the sutured group had small urinary leaks during retrograde ureteral study, whereas none of the pigs in the fibrin-glue cohort had urinary leaks. There was one complication (urinary leak) in the CoSeal group, necessitating sacrifice of the animal on postoperative day 8 because of sepsis. CONCLUSIONS: CoSeal is not as effective as fibrin glue in adhering to the cut renal surface and sealing the collecting system during laparoscopic partial nephrectomy.     

The limitations of magnetic resonance angiography in the diagnosis of renal artery stenosis: comparative analysis with conventional arteriography

PURPOSE: Gadolinium-enhanced magnetic resonance angiography (MRA) is commonly used as a screening modality for the detection of renal artery stenosis. However, evidence supporting its utility in clinical practice is lacking; few rigorous studies have compared MRA with contrast arteriography (CA). After making anecdotal clinical observations that MRA sometimes overestimated the degree of renal artery stenosis, we decided to determine the interobserver variability, sensitivity, specificity, and diagnostic accuracy of MRA compared with CA. METHODS: From September 1999 to April 2003, we evaluated 68 renal arteries in 34 patients with clinically suspected renal artery stenosis using both MRA and CA. All studies were independently reviewed by four blinded observers. Renal arteries were categorized by MRA as normal, <50%, and >50% stenosis/occlusion. The sensitivity, specificity, and accuracy of MRA detection of renal artery stenosis were compared to CA as the gold standard. Interobserver variability (kappa) was also calculated. RESULTS: MRA demonstrated 87% sensitivity, 69% specificity, 85% accuracy, 95% negative predictive value, and 51% positive predictive value for the diagnosis of renal artery stenosis. Interobserver agreement was moderate for MRA (kappa = 0.53) and good for CA (kappa = 0.76). In 21 arteries (31%), MRA was falsely positive. CONCLUSIONS: In patients with a high clinical suspicion of renal artery stenosis, MRA is 87% sensitive in the detection of >50% stenosis. However, MRA is relatively nonspecific compared with CA and results in significant overestimation of renal artery stenosis in nearly one third of patients. To reduce unnecessary CA, clinicians should consider supplemental studies.     

Adeno-associated virus-mediated delivery of a mutant endostatin in combination with carboplatin treatment inhibits orthotopic growth of ovarian cancer and improves long-term survival

A human ovarian cancer cell line, which migrates to mouse ovaries and establishes peritoneal carcinomatosis, was used to evaluate the cooperative effect of an antiangiogenic gene therapy combined with chemotherapy. The ovarian carcinoma cell line MA148 was genetically modified by "Sleeping Beauty" transposon-mediated delivery of DsRed2 fluorescent protein. Stable, high-level expression of DsRed protein enabled in vivo imaging of peritoneal dissemination of ovarian cancer. Both external and internal imaging, along with histopathology, showed migration of i.p. injected human ovarian cancer cell line to mouse ovaries. Using this model, we evaluated the effect of adeno-associated virus (AAV)-mediated expression of a mutant endostatin either alone or in combination with carboplatin treatment. A single i.m. injection of recombinant AAV (rAAV)-mutant human endostatin with P125A substitution (P125A-endostatin) showed sustained expression of mutant endostatin. Antiangiogenic gene therapy inhibited orthotopic growth of ovarian cancer and resulted in 33% long-term tumor-free survival. A single cycle of carboplatin treatment combined with mutant endostatin gene therapy resulted in 60% of the animals remaining tumor free for >200 days, which was significantly better than rAAV-LacZ and/or carboplatin. Combination treatment delayed tumor appearance in 40% of the animals, wherein the residual tumors were smaller in size with limited or no peritoneal metastasis. These studies suggest that AAV-mediated gene therapy of P125A-endostatin in combination with carboplatin is a useful method to inhibit peritoneal dissemination of ovarian carcinoma.     

Radiologic case study. Acute calcific retropharyngeal tendinitis

Knowledge of the characteristic clinical spectrum and imaging features of this disorder are crucial for a correct diagnosis of this uncommon cause of odynophagia and dysphagia.     

The case: your diagnosis? Calcific tendonitis of the fibular collateral ligament

This article describes calcific tendonitis within the fibular collateral ligament, presumably from hydroxyapatite deposition, a rare cause of acute, severe lateral knee pain. Imaging findings confirmed calcifications in an intact but thickened fibular collateral ligament with adjacent soft-tissue reaction, consistent with calcific tendonitis. Magnetic resonance imaging can appear aggressive, and therefore the findings often can be mistaken for other knee abnormalities; specifically, the presentation following a twisting injury that requires avulsion fracture or ligamentous injury be excluded. Confirmation of crystal deposition with thin-section CT is helpful when suspected on MRI because it is unequivocal in depicting calcifications and bony detail.     

Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra

Blood vessel plays a crucial role in solid tumor development. It has been suggested that blocking of angiogenesis and the action of the cytokine VEGF could be possible in cancer therapy. In a screen for naturally occurring angiogenic inhibitors, we have identified an extract from the roots of Glycyrrhiza glabra, which has potent antiangiogenic and antitumor activity. The aqueous extract inhibits the in vivo and in vitro proliferation of Ehrlich ascites tumor cells. The angioinhibitory activity of G. glabra was confirmed by its inhibition of angiogenesis in in vivo assays, peritoneal and chorioallantoic membrane assay. Reduction in the levels of the cytokine VEGF and microvessel density count in the peritoneum of mice treated with G. glabra indicated that the plant extract decreased VEGF production and the cytokine induced neovascularization. Our results suggest that the extract from the roots of G. glabra may be a potential supplemental source for cancer therapy.     

Addition of an aminopeptidase N-binding sequence to human endostatin improves inhibition of ovarian carcinoma growth

BACKGROUND: Blood vessels in tumors express higher level of aminopeptidase N (APN) compared with normal tissues. It has been reported that peptides that contain asparagine-glycine-arginine (NGR) sequence home to APN in tumor vasculature. Increased expression of APN in tumor vascular endothelium, therefore, offers an opportunity to target NGR peptide-linked therapeutic reagents to tumors. METHODS: To determine whether an additional NGR sequence could improve endothelial homing and biologic activity, human endostatin was modified genetically to introduce an NGR motif (NGR-endostatin) and was expressed in yeast. In vitro biologic activity of NGR-endostatin was compared with the native protein in endothelial cell proliferation and migration. NGR-modified endostatin was used in tumor localization studies. Finally, the effects of endostatin and NGR-endostatin on tumor growth were determined in two model systems. RESULTS: Human endostatin has an internal NGR sequence, which is not accessible to bind APN. However, the addition of an NGR-sequence at the amino terminus resulted in strong binding and inhibition of endothelial cell APN. NGR-endostatin showed increased binding to endothelial cells compared with the native protein. Increased binding of endostatin also coincided with improved antiangiogenic properties of endostatin. NGR modification improved tumor localization and, as a consequence, effectively inhibited ovarian carcinoma growth in athymic nude mice. CONCLUSIONS: These studies demonstrated that human endostatin can be modified genetically to improve its ability to inhibit tumor growth.