Sentinel node biopsy for the individualization of surgical strategy for cure of early-stage colon cancer.

INTRODUCTION: The requirement for nodal analysis currently confounds the oncological propriety of focused purely endoscopic resection for early-stage colon cancer and complicates the evolution of innovative alternatives such as natural orifice transluminal endoscopic surgery (NOTES) and its hybrids. Adjunctive sentinel node biopsy (SNB) deserves consideration as a means of addressing this shortfall. METHODS: Data from two prospectively maintained databases established for multicentric studies of SNB in colon cancer that employed similar methodologies were pooled to establish technique potency selectively in T1/T2 disease (both overall and under optimized conditions) and to project potential clinical impact. RESULTS: Of 891 patients with T1-4, M0 intraperitoneal colon cancer, 225 had T1/T2 disease. Sentinel nodes were either not found or were falsely negative in 18 patients with T1/T2 cancers (8%) as compared with 17% (112/646) in those with T3/T4 disease (P = 0.001). Negative predictive value (NPV) in the former exceeded 95%, while sensitivity [including immunohistochemistry (IHC)] was 81%. In the 193 patients with T1/T2 disease recruited from those centers contributing >22 patients, sensitivity was 89% and NPV 97%. Thus, in this cohort, SNB could have correctly prompted localized resection (obviating en bloc mesenteric dissection) in 75% (144) of patients, including 59 with T1 lesions potentially amenable to intraluminal resection alone as their definitive treatment. Forty-four patients (23.4%) would still have conventional resection, leaving three patients (1.6% overall) understaged (11% false-negative rate). CONCLUSION: These findings support the further investigation of SNB as oncological augment for localized resective techniques. Specific prospective study should pursue this goal.

A multicenter trial of sentinel lymph node mapping in colorectal cancer: prognostic implications for nodal staging and recurrence.

BACKGROUND: Sentinel lymph node (SLN) mapping (M) for staging in colorectal cancer (CRCa) remains controversial and needs to be validated. This study analyzes results of SLNM at a multi-institutional level for CRCa. METHODS: Group A patients underwent SLNM with 1 to 3 mL of 1% lymphazurin. First 1 to 4 blue lymph nodes were designated as SLNs and had focused analysis. Group B had standard resection and nodal staging. Patients with a minimum of 2 years of follow-up were analyzed for recurrence. RESULTS: Overall nodal metastasis were 50% for 500 group A patients versus 35% for 368 group B patients. In SLNM patients success, accuracy, sensitivity, and negative predictability values were 98%, 96%, 90%, and 93%, respectively. With a 2-year minimum follow-up, 153 group A patients had 7% recurrences compared with 25% in 162 group B patients. CONCLUSION: SLNM is highly feasible and accurate for staging CRCa with higher detection of nodal metastasis and lower recurrences.

Sentinel lymph node mapping technique in colon cancer.

Current conventional surgical and pathological techniques substantially understage colon cancer. This is evidenced by the fact that a significant subset of patients who are stage I and II at the time of colectomy return with distant metastases and ultimately succumb to the disease within the next 5 years. The identification of more nodes within a specimen and the detailed analysis of lymph nodes with advanced pathological techniques such as immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) can improve the staging of colon cancer, but are also associated with tremendous financial, time, and labor constraints. Sentinel lymph node (SLN) mapping has provided an avenue of staging colon cancer with high success rates and accuracy rates, while maintaining cost- and time-effectiveness. The ability to reproduce these results is dependent on adherence to the technical details of the procedure, and thereby providing the pathologist with the true SLNs, upon which the advanced pathological studies can be applied. We report our experience of SLN mapping for colon tumors in 209 patients, elaborating on the materials used, technical details, pitfalls, and results of the procedure. Our results show a success rate of 100% (209/209) and an overall accuracy rate for predicting positive or negative metastatic disease of 96.2% (201/209). Nodal metastases were identified in 46.2% (85/184) of patients with invasive disease (stage T1 to T4). The SLN was the exclusive site of metastases in 38.8% (33/85) of these patients, and the nodal disease was detected only as micrometastases in 22.4% (19/85). The skip metastases rate (false negatives) was 9.4% (8/85). SLN mapping is a powerful tool for accurate staging of colon cancer with a high success rate. The upstaging associated with this procedure may reveal disease that might otherwise go undetected by conventional surgical and pathological methods. Those patients who are upstaged can then benefit from adjuvant chemotherapy, which has been shown to improve survival of colon cancer patients with nodal disease by at least 33%.

Comparison of nodal positivity between SLNM vs conventional surgery in colon cancer patients with <12 and ≥12 lymph nodes harvested.

BACKGROUND: Examination of ≥12 lymph nodes (LNs) ensures accurate staging in colon cancer. The aim of this study was to compare nodal positivity between sentinel LN mapping (SLNM) and conventional surgery in patients with <12 and ≥12 LNs harvested. METHODS: From 1993 to 2008, 407 and 380 patients with colon cancer underwent SLNM and conventional surgery, respectively. Total LNs harvested and nodal positivity were analyzed. Patients were grouped according to number of LNs harvested: 2 to 11, 12 to 25, or >25. RESULTS: The average numbers of LNs harvested in the groups with 2 to 11, 12 to 25, and >25 LNs harvested for SLNM and conventional surgery, respectively, were 8.3 and 7.1 (P < .0001), 17.2 and 16.5 (P = .09), and 34.2 and 32.1 (P = .40). Nodal positivity for SLNM and conventional surgery in the groups with <12 and ≥12 LNs harvested was 42% and 29% (P = .01) and 50% and 36% (P = .003), respectively. Overall nodal positivity was 47% for SLNM and 32% for conventional surgery (P < .0001). When SLNM with 2 to 11 LNs was compared with conventional surgery with 12 to 25 LNs, nodal positivity was 42% versus 36% (P = .35). CONCLUSIONS: SLNM possessed higher nodal positivity compared with conventional surgery. SLNM is a valuable adjunct to accurate nodal staging in colon cancer.

Basic principles of CAOS.

The term computer aided orthopedic surgery (CAOS) stands for approaches that aim to improve visibility to the surgical field and increase application accuracy by means of so-called navigation systems alone or in combination with smart end-effectors when carrying out surgical actions. These goals achieved by linking the bony anatomy being operated on with a virtual representation, such as an image dataset. This article introduces the basic principles of CAOS. Surgical navigation systems that use modern tracking technology are introduced and classified according to the chosen virtual representation of the surgical object, ie, image-free and image-based (preoperative and intraoperative) technology. Within the latter class in particular, CT-and fluoroscopy-based (2-D and 3-D) systems have successfully made their way into the operating room (OR). Challenges during the development of the underlying enabling technologies are presented and references to orthopedic applications in different anatomical areas are given.

Downregulation of the epidermal growth factor receptor by human cytomegalovirus infection in human fetal lung fibroblasts.

Epidermal growth factor plays a key role in late fetal lung development and differentiation as well as in regulating surfactant protein A synthesis, which is involved in innate immunity of the lung. Here we show that human cytomegalovirus (HCMV), a known lung pathogen in connatal and postnatal infection of neonates as well as transplant recipients, completely down-regulates EGF receptor (EGF-R) on the surface of human fetal lung fibroblasts. Inhibition of EGF-R synthesis occurs on the transcriptional rather than on the posttranscriptional level. The effect essentially depends on expression of viral immediate early and/or early genes, as binding of ultraviolet light-inactivated virus to the cells had no effect on EGF-R expression. Furthermore, the anti-HCMV drug ganciclovir, which blocks HCMV DNA replication and late gene expression, cannot overcome HCMV-mediated inhibition of EGF-R, suggesting that immediate early or early gene products may be responsible for down-regulation of EGF-R. Interestingly, the glucocorticoid dexamethasone, which is used for its antiinflammatory action to prevent chronic lung disease in preterm infants, promotes HCMV-associated downregulation of the EGF-R by stimulation of viral gene expression. From these data it can be hypothesized that the pathogenesis of HCMV lung infection involves down-regulation of EGF-R and that congenital HCMV infection may cause retardation in lung maturation and surfactant protein synthesis.

Kinematic response of lumbar functional spinal units to axial torsion with and without superimposed compression and flexion/extension.

Experimental data suggest that lumbar torsion contributes to lumbar disc degenerative changes, such as instability, spondylolisthesis and spinal canal stenosis. However, some basic mechanical characteristics of the lumbar spine under torsional loading have not yet been reported in detail. For example, the function of the facet joints under combined mechanical loads such as torsion with superimposed flexion or extension postures is an area of interest about which little biomechanical data have been reported. In this study, the kinematic response to axial torsion with superimposed axial compression (200 N), compression-flexion (3 and 6 Nm) and compression-extension (3 and 6 Nm) was investigated in 10 cadaveric lumbar functional spinal units. Range of motion (ROM), and helical axes of motion (HAM), were analyzed. There was no difference in ROM between no preload, pure compressive and flexion-compression preload conditions. The ROM was significantly reduced by both extension-compression preload conditions (11% reduction for 3 Nm and 19% reduction for 6 Nm of extension) compared to the pure compressive preload. For no preload, the average HAM position in the transverse plane of the intervertebral disc was near the posteriormost part of the disc and located laterally on the side contralateral to the applied torsional moment. In the transverse plane, the HAM position showed a discrete trend towards the posterior part of the specimens during extension. Kinematic data were visualized using computer animation techniques and CT-based reconstructions of the respective specimens. This information may be used for identifying and characterizing physiologic and pathologic motion and for specifying conservative and surgical treatment concepts and, thus, may find application to identifying indications for spinal fusion or in evaluating the effect of future semi-flexible instrumentation.

A new prosthetic design for proximal humeral fractures: reconstructing the glenohumeral unit.

A new shoulder prosthesis design for proximal humeral fractures has been developed. The rim of the articular component of this prosthesis has several holes to which the bone-tendon junction of the rotator cuff is fixed, to allow an anatomic reconstruction of the glenohumeral unit. The strength of the tuberosity fixation to this prosthesis is investigated in a cadaveric study. Artificial 4-part fractures were created in 18 human, fresh-frozen, paired shoulder joints with intact rotator cuffs. Two methods of tuberosity fixation were used in a matched-pair fashion. In group I the tuberosities were sutured to the rim of the prosthetic head, and in group II the tuberosities were circumferentially tension band-wired. Strength testing was performed on a material-testing machine, and displacement was recorded with an opto-electronic device. Both fixation methods proved to be equally reliable in the forces exerted during activities of daily living without significant displacement of the fracture fragments.

Biomechanical comparison of the sandblasted and acid-etched and the machined and acid-etched titanium surface for dental implants.

To make a direct biomechanical comparison between the sandblasted and acid-etched surface (SLA) and the machined and acid-etched surface (MA), a well-established animal model for implant removal torque testing was employed, using a split-mouth experimental design. All implants had an identical cylindrical solid-screw shape with the standard ITI thread configuration, without any macroscopic retentive structures. After 4, 8, and 12 weeks of bone healing, removal torque testing was performed to evaluate the interfacial shear strength of each surface type. Results showed that the SLA surface was more powerful in enhancing the interfacial shear strength of implants in comparison with the MA surface. Removal torque values of the SLA-surfaced implants were about 30% higher than those of the MA-surfaced implants (p = 0.002) except at 4 weeks, when the difference was at the threshold of statistical significance (p = 0.0519). The mean removal torque values for the SLA implants were 1.5074 Nm at 4 weeks, 1.8022 Nm at 8 weeks, and 1.7130 Nm at 12 weeks; and correspondingly, 1.1924 Nm, 1.3092 Nm, and 1.3226 Nm for the MA implants. It can be concluded that the SLA surface achieves a better bone anchorage than the MA surface, and that sandblasting before acid etching has a beneficial effect on the interfacial shear strength. As regards the bone-implant interfacial stiffness calculated from the torque-rotation curve, the SLA implants showed an overall more than 5% higher stiffness compared with the MA implants, although the difference did not reach the statistical significance level.

Comparative analysis of nodal upstaging between colon and rectal cancers by sentinel lymph node mapping: a prospective trial.

PURPOSE: Sentinel lymph node mapping accurately predicts nodal status in > 90 percent of melanoma and breast and colorectal cancers. However, because of anatomic differences, sentinel lymph node mapping of rectal cancers has been considered inaccurate and difficult relative to colon. A prospective study was undertaken to identify differences in sentinel lymph node mapping between patients with colon cancer and those with rectal cancer. METHODS: At operation 1 to 3 ml of 1 percent isosulfan blue dye was injected subserosally around colon cancers. The first to fourth blue-staining nodes seen within ten minutes of injection were marked as sentinel lymph nodes. For cancer of the mid-rectum to low rectum, the dye was injected submucosally via rigid scope and spinal needle. The mesorectum was dissected ex vivo to identify blue nodes nearest the tumor as sentinel lymph nodes. Multilevel microsections of sentinel lymph nodes were stained with hematoxylin and eosin and immunostained for cytokeratin, and standard examination of the entire specimen was performed. RESULTS: There were 407 consecutive patients (336 with colon and 71 rectum). The sentinel lymph nodes were identified in 99.1 percent of colon and 91.5 percent of rectal patients (P < 0.0001). Skip metastases were found in 3.6 percent of colon vs. 2.8 percent of rectal patients (P = 0.16). Occult micrometastases were found in 13.4 percent of colon vs. 7.0 percent of rectal patients (P = 0.24). Except for success rates, no other parameters were statistically different between colon and rectum. Lower success in sentinel lymph node identification in rectal cancer may have been related to neoadjuvant chemoradiation received in all six of the patients with sentinel lymph node mapping failures. CONCLUSION: Despite higher success rates in sentinel lymph node identification for colon patients, sentinel lymph node mapping was highly successful (91.5 percent) in rectal patients. Nodal upstaging, skip metastases, and occult metastases were similar.