Detection of disseminated tumor cells in the lymph nodes of colorectal cancer patients using a real-time polymerase chain reaction assay

Introduction Postoperative treatment for colorectal cancer depends on tumor stage as defined by the International Union Against Cancer (UICC). Adjuvant chemotherapy is not recommended in patients without lymph node involvement (UICC stages I and II). As many as 20–30% of these patients, however, will develop recurrence. Aims and objectives We conducted this study to determine the presence of disseminated tumor cells in the lymph nodes by quantitative real-time polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to provide supplementary information compared to histopathological findings. Materials and methods Using a standard QRT-PCR assay, we examined primary tumors and 391 lymph nodes from 31 patients with completely resected colorectal cancer. Results Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR. Discussion An examination of the lymph nodes from the 29 patients with CK20-positive primary tumors revealed that 35 (92.1% sensitivity) of the 38 histopathologically positive lymph nodes and 54 (16.7%) of the 324 histopathologically negative lymph nodes were positive by molecular analysis. CK20 expression was detected in 10 (100%) of 10 patients with a histopathologically positive lymph node status (pN1). In 9 (47.4%) of 19 patients with negative histopathological results (pN0), we detected a CK20 mRNA signal in at least one lymph node. Whereas eight patients with histopathologically negative lymph nodes could be upstaged on the basis of the molecular findings, no patient would be downstaged. Conclusion Our results suggest that QRT-PCR for CK20 is a useful tool for the quantitative detection of micrometastases in the regional lymph nodes. We introduce a standardized procedure that integrates a molecular diagnostic technique in the clinical staging.     

An Unusual Complication of Gastric Bypass: Perforated Duodenal Ulcer

Peptic ulcer in the excluded segment of a gastric bypass has been reported in the literature in only 17 cases.We report a 54-year-old woman with a perforated duodenal ulcer, who had undergone laparoscopic Roux-en-Y gastric bypass surgery for morbid obesity 15 months previously. She was successfully treated by a laparoscopic repair of the perforated duodenal ulcer.     

Impact of polysol, a newly developed preservation solution, on cold storage of steatotic rat livers.

Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 degrees C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728+/-824 in HTK vs. 3107+/-718 in Polysol; P < 0.001) but also mitochondrial (GLDH (IU/L); 3189+/-773 vs. 1282+/-365; P < 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9+/-2.7 vs. 7.8+/-1.5 mmHg; P < 0.05), hepatic O2 consumption (0.291+/-0.047 vs. 1.056+/-0.053 micromol/g liver/min; P < 0.001), tissue ATP content (0.695+/-0.086 vs. 1.340+/-0.157 micromol/g dry-liver; P < 0.005), bile production (0.79+/-0.11 vs. 4.08+/-0.66 microL/g liver/45-min; P < 0.001), malondialdehyde into the perfusate (1.922+/-0.198 vs. 0.573+/-0.094 nmol/L; P < 0.0001) and wet/dry-weight ratio of the liver tissues (5.20+/-0.31 vs. 3.85+/-0.15; P < 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs.     

Endothelial cell dysfunction after coronary artery bypass grafting with extracorporeal circulation in patients with type 2 diabetes mellitus.

OBJECTIVE: Type 2 diabetes mellitus is a well-known risk factor in patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG). The aim of the study was to analyze the endothelial dysfunction in these patients by evaluating postoperative soluble inflammatory cytokines. METHODS: Patients undergoing CABG without (n=15, group A) and with (n=14, group B) diabetes mellitus were analyzed for their release of E-selectin, interleukin-6 (IL-6), and tumor necrosis factor (TNF) up to 3 days postoperatively. A pharmacokinetic quantitative kinetic evaluation (Kinetica 2000) of maximum concentrations (c(max)), time to reach c(max) (t(max)), area under the curve (AUC(0-inf)), and terminal elimination half time (t(1/2)) was performed using a non-compartmental model. RESULTS: There was no difference in preoperative plasma concentrations of the cytokines and in the postoperative kinetic analyses of TNF when comparing both groups. However, the release of IL-6 was restricted with c(max) of 1055+/-543 pg/ml for group B versus 2112+/-1532 pg/ml for group A (p< or =0.05), paralleled by a decrease in the absolute amount (AUC(0-inf)) of IL-6. The t(1/2) remained unaffected (13.9+/-6.6h and 12.7+/-4.6h, respectively). The AUC(0-inf) of E-selectin decreased by a factor of 1.7 (p< or =0.05) with unchanged c(max) but reduced t(1/2) (12.9+/-10h for group B vs 33.1+/-20.4h for group A; p< or =0.01) referring to an augmented endothelial uptake and degradation of E-selectin. CONCLUSIONS: CABG with extracorporeal circulation could be used to verify a specific endothelial dysfunction in diabetic patients characterized by an impaired release of IL-6 and an increased turnover of E-selectin.     

Die Ulnaverkürzungsosteotomie

Objective Ulnar shortening to unload the ulnocarpal ligamentous complex. Indications Clinically relevant ulnar impaction syndrome, be it congenital or posttraumatic. Contraindications Concomitant pronounced malunion of the radius.Osteoarthritis of the distal radioulnar joint. Surgical Technique Ulnopalmar approach. Oblique osteotomy of the ulna in its distal third. Removal of a bony wafer of predetermined thickness. Internal fixation with a 7-hole LD-DC plate or special plate and lag screw. Results 29 patients (14 men, 15 women, average age 42 years) underwent an ulnar shortening osteotomy for a therapy-resistant ulnar impaction syndrome.Follow-up after an average of 25 (7–37) months. Average amount of shortening 4.5 (1.5–13) mm. 72% reduction of pain as determined with a visual analog scale. The range of motion was improved by 7% in extension/flexion, by 8% in abduction/adduction and by 11% in pronation/supination. Grip strength measured with a vigorimeter (balloon size 5) increased by 12%.Complications: three malunions, effectively treated by revision of internal fixation.     

A comparison of laparoscopic pyeloplasty performed with the daVinci robotic system versus standard laparoscopic techniques: initial clinical results

PURPOSE: Laparoscopic pyeloplasty is an accepted therapy for primary ureteropelvic junction obstruction (UPJO), however difficulty associated with intracorporeal suturing has limited widespread clinical application. We report our initial experience of laparoscopic pyeloplasty performed with the daVinci robotic system matched to procedures performed with standard laparoscopic techniques. PATIENTS AND METHODS: From June 2001 until August 2001, six patients underwent definitive management of primary UPJO using the daVinci robotic system. In four patients an Anderson-Hynes pyeloplasty was performed, while in two patients Fengerplasty was performed. Using demographic and preoperative information, each patient in the daVinci-assisted group was matched to a corresponding patient with primary UPJO undergoing laparoscopic pyeloplasty with standard techniques between November 1999 and June 2001. Perioperative results and follow-up data were subsequently compared. RESULTS: Treatment groups were identical with regard to surgical procedure, gender, and side of UPJO. The length of hospitalization was 4 days for all patients, regardless of treatment group. Estimated blood loss was <50 cc in all cases. For Anderson-Hynes pyeloplasty, the mean overall operative and suturing times were 140 and 70 min using the daVinci system and 235 and 120 min using standard techniques, respectively. For the Fengerplasty, the mean overall operative and suturing times were 78 and 13 minutes using the daVinci system and 100 and 28 minutes using standard techniques, respectively. No complications were observed and there were no open conversions. CONCLUSION: Anderson-Hynes pyeloplasty and Fengerplasty are feasible using either conventional laparoscopic techniques or the daVinci robotic system. In this initial pilot study, procedures performed with the daVinci robotic system resulted in overall decreased operative time, however factors responsible for the decreased operative time remain to be defined. Long-term prospective follow-up of procedures performed with or without the daVinci robotic system for surgeons with limited experience in laparoscopic management of UPJO is warranted to delineate the true efficacy of the device.     

A Commentary on Real-Time Biofeedback to Augment Neuromuscular Training for ACL Injury Prevention in Adolescent Athletes

Anterior cruciate ligament injury and the associated long-term sequelae, such as immediate reductions in physical inactivity, increased adiposity and increased risk of osteoarthritis throughout adulthood, are a major health concern for adolescent athletes. Current interventions for injury prevention may have limited effectiveness, are susceptible to issues of compliance and have not achieved the widespread acceptance necessary to promote full adoption. Neuromuscular training (NMT) is a well-established training intervention introduced to affect change in modifiable biomechanical risk factors to reduce the risk of injury in these athletes. Despite moderate success, neuromuscular training is still limited by its reliance on subjective feedback and after the fact (i.e., offline) objective feedback techniques. The purpose of this commentary is to discuss technological tools that could be used to enhance and objectify targeted biofeedback interventions to complement NMT. Electromyography, force plates, motion sensors, and camera-based motion capture systems are innovative tools that may have realistic feasibility for integration as biofeedback into NMT programs to improve training outcomes. Improved functional deficit identification and corrective analysis may further improve and optimize athletic performance, and decrease the risk of sports-related injury during sport performance.

Key points

• Specific, targeted interventions that isolate injury risk factors and can help correct modifiable neuromuscular deficits are essential.
• Current training interventions for anterior cruciate ligament (ACL) injury prevention have only demonstrated limited effectiveness and have not achieved the widespread acceptance necessary to promote full adoption to reduce ACL injury rates.
• The paper provides an overview of innovative strategies and technological tools that could be used to enhance and objectify targeted biofeedback interventions to complement neuromuscular training (NMT) including electromyography, force plates, motion sensors, and camera-based motion capture systems.
• These strategies utilize biomechanical, physiological, or neuromotor variables for training, automate the quantitative measurement of those variables through a variety of technological modalities, and then feed those measured variables via software to provide information in simplified form for online, visual biofeedback displays.

Key words: Neuromuscular training, anterior cruciate ligament injury, biofeedback, electromyography, force platforms, motion sensors, 3D motion capture     

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years

BackgroundMetal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.MethodsAt a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.ResultsWe found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.ConclusionThis study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.Level of EvidenceTherapeutic Level III     

Photodynamic Diagnosis in Non–Muscle-Invasive Bladder Cancer: A Systematic Review and Cumulative Analysis of Prospective Studies

Context

The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially.

Objective

To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non–muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection.

Evidence acquisition

An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction.

Evidence synthesis

The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8–35) more tumour-positive patients were detected with PDD in all patients with non–muscle-invasive tumours and 39% (CI, 23–57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15–0.52; p < 0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002).

Conclusions

PDD detects more bladder tumour–positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.     

Ankle and first metatarsophalangeal joint dorsiflexion in children with clubfoot.

It has been hypothesised that the stiffness of the plantar aponeurosis after clubfoot surgery affects push-off. Because the first metatarsophalangeal (MTP) joint motion relies on the plantar aponeurosis, it was important to determine whether there was a lack of first MTP joint motion in children with clubfoot that also affected push-off. By examining the motion of the first MTP joint using a motion analysis system and passive motion techniques, then correlating these with gait characteristics, the authors found that the first MTP joint was not affected in children with clubfoot. The authors found that a motion analysis system could be used to determine range of motion accurately.