MicroRNA signature predicts survival and relapse in lung cancer.

We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.

Intra-abdominal adhesion formation induces anti-oxidative injury, enhances cell proliferation, and prevents complement-mediated lysis.

Whether the alteration of gene expression is accompanied with intra-abdominal adhesion formation is unclear. The aim of this study was to analyze the dynamic gene expression patterns in an animal model of intra-abdominal adhesion formation. The mRNA was extracted from the jejunums of sham control mice and jejunum-abrading mice at 1, 3, 7, and 14 days postsurgery. The mouse cDNA microarray was used to monitor the dynamic changes of the tested genes and up-regulated and down-regulated genes were calculated. Quantitative real-time RT-PCR, and immunohistochemistry staining were used to confirm the accuracy of microarray results at RNA and protein levels. The top 100 genes with the greatest change across all studied mice groups were identified and 93 of them were correct after sequencing verification. Of the 93 genes, 74 genes were up-regulated and 19 were down-regulated following jejunal abrasion. Gene expressions of complement-mediated lysis, anti-oxidative response, and cell proliferation were significantly induced during adhesion formation. Intra-abdominal adhesion induces several genes to eliminate overfilled complement-mediated lysis, prevent oxidative injuries, and enhance cell proliferation. These findings may provide insights into the pathogenesis of intra-abdominal adhesion formation and might also help to identify some new target genes for specific diagnostic tools and novel therapeutic strategies.

Influence of age and gender on surveillance for colorectal tumors in low-risk asymptomatic population.

BACKGROUND: We tried to find the possible "downstream" approach for the low-risk asymptomatic population surveillance for colorectal tumors by fecal occult blood test (FOBT) and flexible sigmoidoscopy (FS) with the factors of age and gender. PATIENTS AND METHODS: Retrospectively, 2187 asymptomatic low-risk cases received complete FOBT and FS. These cases also received complete colonoscopy (CF) for definite diagnosis and were separated into two groups by age (age < or = 49 vs. age > or = 50 groups) and gender (male and female groups). RESULTS: The sensitivity and specificity to FOBT and FS were 44% and 98%, and 65% and 100% respectively for all cases. Significant positive FOBT, FS and CF results were noted in the age > or = 50 group (p=0.002, <0.001, <0.001, respectively). Positive FS and CF results were significantly noted in the male group (p=0.012, 0.009, respectively). After combination of age and gender factors, a positive FOBT result was significant in female cases with age > or = 50 years (p =0.006). Positive FS and CF results were significant in male cases with age > or = 50 (both p<0.001). CONCLUSION: In the surveillance of a low-risk asymptomatic population for colorectal tumor, repeated FOBT might be considered in people of age < or = 49 years regardless of gender. In female and age > or = 50 years, FOBT might be considered first and then FS could be performed in positive FOBT cases. In male and age > or = 50 cases, FS was considered first without FOBT for the surveillance.

The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty.

BACKGROUND: Bone mineral density around the knee is related to the mechanical properties of bone. Alendronate has been shown to be effective for the treatment of osteoporosis and for reducing the rate of osteoporotic fractures. The purpose of the present study was to investigate the effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty in women. METHODS: Ninety-six women with an average age of seventy years who were undergoing total knee arthroplasty were randomly divided into two groups. Patients in the study group received oral alendronate at a dose of 10 mg/day for six months, whereas patients in the control group did not. The bone mineral density in the distal part of the femur and proximal part of the tibia was determined preoperatively and at six and twelve months postoperatively. RESULTS: In the control group, the bone mineral density showed significant decreases of 13.8% (p < 0.001) and 7.8% (p = 0.003) in the distal part of the femur and of 6.5% (p = 0.002) and 3.6% (p = 0.141) in the proximal part of the tibia at six and twelve months, respectively. In the study group, however, the bone mineral density showed significant increases of 10.0% (p = 0.010) and 1.9% (p = 0.049) in the distal part of the femur and of 9.4% (p < 0.001) and 5.4% (p = 0.032) in the proximal part of the tibia at six and twelve months, respectively. The overall differences in bone mineral density between the study and control groups were significant (p = 0.011 for the proximal part of the tibia, and p = 0.033 for the distal part of the femur). CONCLUSIONS: We found significant postoperative decreases in bone mineral density in the distal part of the femur and proximal part of the tibia in women who had undergone total knee arthroplasty. Oral administration of alendronate for six months postoperatively significantly improved the bone mineral density. While the clinical benefits of alendronate after total knee arthroplasty remain unproven and the duration of follow-up in the present study was quite short, the improvement in bone mineral density may have a clinically important effect on prosthetic fixation and the rate of periprosthetic fractures after total knee arthroplasty.

Shock wave therapy for patients with lateral epicondylitis of the elbow: a one- to two-year follow-up study.

BACKGROUND: The results of both nonoperative and surgical treatments for lateral epicondylitis of the elbow have been inconsistent. Shock wave therapy has been shown to have a favorable short-term effect in treating this condition. HYPOTHESIS: Shock wave therapy is an effective treatment for patients with lateral epicondylitis of the elbow and long-term results will be as favorable as short-term ones. STUDY DESIGN: Case series. METHODS: The effect of shock wave therapy was investigated in 57 patients with lateral epicondylitis of the elbow. Forty-three patients (24 men and 19 women with an average age of 46 years) with 1 to 2 years of follow-up were included in this study. In addition, six patients were treated with a sham procedure as a control group. Each patient was treated with 1000 impulses of shock wave therapy at 14 kV to the affected elbow. A 100-point scoring system was used for evaluating pain, function, strength, and elbow range of motion. RESULTS: Twenty-seven elbows (61.4%) were free of complaints, 13 (29.5%) were significantly better, 3 (6.8%) were slightly better, and 1 (2.3%) was unchanged. In the control group, the results were unchanged in all six patients. There were no device-related problems and no systemic or local complications. CONCLUSIONS: Shock wave therapy is a safe and effective modality in the treatment of patients with lateral epicondylitis of the elbow.

Effects of knee position, graft tension, and mode of fixation in posterior cruciate ligament reconstruction: a cadaveric knee study.

PURPOSE: Many knees exhibit residual ligament laxity after posterior cruciate ligament (PCL) reconstruction, which is believed to be technique related. The purpose of this study was to investigate the optimal graft tension, the best angle of knee flexion, and the mode of fixation in PCL reconstruction. TYPE OF STUDY: Anatomic biomechanical study. METHODS: A testing apparatus with frictionless bearing that allows other degrees of freedom except for flexion and extension of the knee joint was designed. The normal PCL tension at different angles of knee flexion was measured with a force transducer, and the optimal tension of the PCL graft that allows full range of knee motion was studied with a tensiometer in 12 cadaver knees. The modes of fixation failure between interference screw fixation and post fixation were studied with an Instron (Canton, MA) machine in 8 cadaver knees. RESULTS: The lowest PCL tension in normal knees was noted at 20 degrees to 30 degrees of knee flexion and the highest at 90 degrees. The optimal tension of PCL graft, which allows full range of knee motion, was 15 lb (68 N). The average load of graft failure was 417 (179-730) N with interference screw fixation and 367 (149-701) N with post fixation when the patellar bone-tendon-bone graft was tested. There was no statistical difference in the failure load between interference screw fixation and post fixation (P =.753); however, the modes of failure differ. The sites of failure for interference screw fixation were 25% caused by rupture of ligament substance and 75% bone plug pullout; those of post fixation were 25% caused by rupture of ligament substance, 37.5% caused by fracture, and 37.5% as a result of suture breakage. CONCLUSIONS: The results of this study suggested that a 15-lb tension to the graft at 20 degrees to 30 degrees of knee flexion is optimal in PCL reconstruction. There was no statistical difference in the failure load between interference fixation and post fixation despite different modes of fixation failure.

Clinical outcome and patient satisfaction in aseptic and septic revision total knee arthroplasty.

This study compares clinical outcome and patient satisfaction in 33 aseptic and 15 septic revision total knee arthroplasties across a 30-130-month follow-up. Aseptic revisions included only knees in which the femoral, tibial and patellar components had been exchanged, and excluded knees in which only isolated patellar components had been revised or only the tibial insert exchanged. Septic revisions included only knees in which there had been successful revision for chronic infection without recurrence of infection for at least 2 years from the index revision. The evaluation included pain scores, knee scores, functional scores, SF-12 functional surveys and radiographs of the knee. The results for the aseptic group were excellent in 26 (78.8%), good in 3 (9.0%), fair in 2 (6.1%) and poor in 2 (6.1%); those for the septic group were excellent in 5 (33.3%), good in 7 (46.7%), fair in 2 (13.3%) and poor in 1 (6.7%). The overall results of septic revision were less satisfactory than for aseptic revision. Aseptic revisions achieved significantly better knee scores and ranges of motion than septic revisions, but their pain and functional scores were similar. Despite the difference in knee scores, 85% of the patients from both groups were equally satisfied with the results of treatment. There was no discernible radiographic difference between the two groups, including radiolucency.

Shockwave therapy for patients with plantar fasciitis: a one-year follow-up study.

The effect of shockwave therapy was investigated in 79 patients (85 heels) with plantar fasciitis with one-year follow-up. There were 59 women and 20 men with an average age of 47 (range, 15-75) years. Each patient was treated with 1000 impulses of shockwave at 14 kV to the affected heel. A 100-point scoring system was used for evaluation including 70 points for pain and 30 points for function. The intensity of pain was based on a visual analogue scale from 0 to 10. The overall results were 75.3% complaint-free, 18.8% significantly better, 5.9% slightly better and none unchanged or worse. The effect of shockwave therapy seemed cumulative and was time-dependent. The recurrence rate was 5%. There were no device-related problems, systemic or local complications. Shockwave therapy is a safe and effective modality in the treatment of patients with plantar fasciitis.

Comparing cruciate-retaining total knee arthroplasty and cruciate-substituting total knee arthroplasty: a prospective clinical study.

BACKGROUND: This prospective clinical study was performed to compare the clinical outcomes and radiographic changes between patients with cruciate-retaining (CR) and cruciate-substituting (CS) total knee arthroplasty (TKA). METHODS: From 1997 through 1998, 228 patients (183 females and 45 males) with a total of 267 knees with an average age of 55 years (range, 20 to 83 years) were enrolled in this study. Patients were randomly divided into two groups including group I of 137 patients underwent 157 CR TKA, and group II of 91 patients underwent 110 CS total knee arthroplasties. The evaluation parameters included knee scores, functional scores, radiographs of the knees and SF-12 surveys. The average follow-up period was 42 months (range, 24 to 66 months). RESULTS: The overall results for group I were 74.3% excellent, 17.7% good, 7.1% fair and 0.9% poor for; and 76.9% excellent, 19.2% good and 3.8% fair for group II. No significant differences were noted in the overall results between the two groups. The radiographic changes showed no discernable differences. CONCLUSIONS: Cruciate-retaining and cruciate-substituting total knee arthroplasties function equally well at 2 to 5 years postoperatively. The ultimate differences between the patients who underwent CR TKA and CS TKA need to be examined after long-term follow up.

Outcome of arthroscopic single bundle reconstruction for complete posterior cruciate ligament tear.

PURPOSE: To evaluate the clinical outcome and correlate the results and degenerative change of the affected knees with the duration of injury, ligament laxity and follow-up time in 30 patients with 31 knees undergoing arthroscopic single bundle reconstruction for complete posterior cruciate ligament (PCL) tear with 2-9-year follow-up. MATERIALS AND METHODS: This series included 22 men and 8 women with an average age of 32 years. High-energy trauma accounts for 93.5% of PCL injury, while only 6.5% are sports related. Arthroscopic single bundle PCL reconstruction was performed in all knees. The average follow-up time was 40 (range: 24-108) months. The methods of evaluation included functional assessment, ligament laxity and radiograph of the knee. RESULTS: The overall clinical results showed 77.4% satisfactory (61.3% excellent and 16.1% good) and 22.6% unsatisfactory (16.1% fair and 6.5% poor). Complete restoration of ligament stability was noted in 52% of the knees with one third showing mild (0-5 mm) and 9.7% moderate (5-10 mm) ligament laxity. The incidence of radiographic degenerative changes was 52% (16/31), and it correlated with the duration of injury, severity of ligament laxity and length of follow-up time. CONCLUSION: Arthroscopic single bundle reconstruction produced 77.4% satisfactory clinical results in medium term follow-up. Despite good clinical results, complete restoration of ligament stability was achieved in only 52% of the knees. The incidence of degenerative changes of the affected knees was 52% that correlated with the duration of injury, ligament laxity and follow-up time.

Outcome of surgical reconstruction for posterior cruciate and posterolateral instabilities of the knee.

PURPOSE: To evaluate the clinical outcome and the incidence of degenerative changes in 25 patients with 25 knees undergoing surgical reconstruction for combined posterior cruciate ligament (PCL) and posterolateral instabilities of the knee with 2-5-year follow-up. MATERIALS AND METHODS: This series included 16 men and 9 women with an average age of 28 years. The average time from injury to surgery was 10 (range 2-24) months, and the average follow-up time was 40 (range 32-60) months. The mechanisms of injury were 88% due to trauma, and 12% sports related. Arthroscopic single bundle posterior cruciate reconstruction and reconstruction of the posterolateral structures were performed in all cases. Clinical evaluations included functional assessment, ligament laxity and radiograph of the knee. The results were correlated with the duration of injury, the severity of ligament laxity and the follow-up time. RESULTS: The overall results were 68% satisfactory (28% excellent and 40% good) and 32% unsatisfactory (20% fair and 12% poor). Despite functional improvement, complete restoration of ligament stability was observed in only 44% of the knees, while 36% of the knees showed mild (<5 mm), and 20% moderate (5-10 mm) ligament laxity. There was no correlation of the clinical outcome with the duration from injury to surgery. The incidence of degenerative changes of the affected knee was 44%, and the rate correlated with the severity of ligament laxity, the duration from injury to surgery and the length of follow-up time. CONCLUSION: Despite the functional improvement, the currently devised surgical techniques only have modest success in restoration of ligament stability in knees with combined PCL and posterolateral instabilities. Further improvement in surgical technique including a dynamic reconstruction of the popliteus tendon complex seems necessary. The rate of degenerative changes of the affected knee appeared proportional to the duration of injury, the severity of ligament laxity and the length of follow-up time. The results of this study led us to recommend early surgical reconstruction for knees with combined posterior cruciate and posterolateral instabilities.

Circulating soluble Fas in patients with breast cancer.

It has been suggested that circulating soluble Fas (sFas) contributes to tumor progression. However, little is known about the role of sFas in breast cancer. This study was designed with the aim of elucidating the possible relation between sFas and breast cancer. A series of 57 consecutive patients with invasive breast cancer undergoing surgery were prospectively included in the study and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumors (6 with fibrocystic disease, 6 with fibroadenoma). Serum concentrations of sFas were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor status, lymph node status, tumor grading, and TNM staging were reviewed and recorded. The mean value of circulating sFas in patients with invasive breast cancer was 794.2 +/- 183.0 pg/ml and that of the control group 582.1 +/- 62.8 pg/ml; the difference was significant (p < 0.001). Furthermore, there were significantly higher serum levels of sFas in the older patients (age > or = 50) (p = 0.020) and in those with a more advanced TNM stage (p = 0.021). In the multivariate analysis, TNM stage (p = 0.005) appeared to be an independent factor for significantly higher circulating sFas in patients with invasive breast cancer. Thus circulating sFas levels may reflect the severity of invasive breast cancer. Hence the possible prognostic value of sFas for breast cancer deserves further elucidation and evaluation with long-term patient follow-up.

The often poor clinical outcome of infected total knee arthroplasty.

The clinical outcomes of various options of treatment in 26 infected total knee arthroplasties (TKAs) with successful eradication and no recurrence of infection for at least 2 years were compared. There were 20 women and 6 men with an average age of 67.7 years. The average follow-up time was 48 months (range, 24-83 months). The evaluation parameters included pain score, knee score, functional score, and radiograph of the knee. The TKAs with acute infection showed significantly better outcome and clinical results when compared with noninfected TKAs. The clinical outcome of chronic infection was less favorable. Arthrodesis achieved better pain relief, whereas reimplantation TKA showed better function. No significant difference in knee scores was observed, however, between reimplantation TKA and arthrodesis. Approximately 50% of reimplantation TKAs had mild-to-moderate knee pain.

DNA index and S-phase fraction in curative resection of colorectal adenocarcinoma: analysis of prognosis and current trends.

The DNA index (DI) and S-phase fraction (SPF) have been said to be independent factors in colorectal adenocarcinoma and have a different distribution from the clinicohistologic parameters. This study assesses the real efficacy of DI and SPF for curative resection of colorectal adenocarcinomas with respect to the prognosis and the clinicohistologic parameters. From July 1991 to October 1994 a total of 666 patients underwent curative resection of colorectal adenocarcinoma and DNA flow cytometry in Kaohsiung Chang Gung Memorial Medical Center Hospital, Taiwan. We defined diploid tumors as having a DI of ? 0.9 but <1.1 and a nondiploid tumor as having a DI of <0.9 OR > 1.1. A high SPF was defined as being more than the median value for the total SPF. Altogether, 495 cases (74.32%) had a 5-year cancer-free survival. Tumor stage, DI, tumor location, and tumor morphology were associated with significant cancer-free survival in the univariate analysis (p = 0.0295, <0.001, 0.0357, and <0.001, respectively). After all factors were entered into the multivariate analysis, the independent factors for cancer-free survival were found to be stage, tumor location, and morphology (p < 0.001, 0.012, and 0.044, respectively). In cases distinguished by the DI, diploid tumors had significantly more frequent right colon locations (p <0.001). After cases were separated by the SPF (median value 18.4%), better histology (well differentiated adenocarcinoma) was noted with a low SPF (p = 0.017). No other clinicohistologic parameters had significant differences shown by the DI or SPF. Thus DI and SPF failed to appear as independent factors for 5-year cancer-free survival. The independent factors for curative colorectal adenocarcinoma were tumor stage, location, and morphology. Diploid tumors were located at the right colon more often, and low SPF indicated better histology in the univariate analysis.

Comparison of autogenous and allogenous posterior cruciate ligament reconstructions of the knee.

This prospective clinical study was performed to compare the functional results and clinical outcomes of 32 autogenous and 23 allogenous posterior cruciate ligament (PCL) reconstructions with an average follow-up of 34 months. Both groups showed similar age, gender and follow-up time. The indications for surgery included knees with functional disability due to pain and instability from high-energy PCL injury with failure of conservative treatments. Arthroscopic single-bundle PCL reconstruction was performed with a similar technique in both groups with the exception of graft selection. All patients received the same postoperative rehabilitation. The evaluation parameters included functional assessment, ligament laxity, functional score, kinematics evaluation and radiographic examination. Autogenous and allogenous PCL reconstructions showed comparable functional results and clinical outcomes. No statistically significant difference was noted in ligament laxity and radiographic changes between the two groups. Complications were more prevalent with autogenous grafts. In conclusion, autogenous and allogenous tendon grafts are equally effective in PCL reconstruction.

Systemic immune response after laparoscopic and open cholecystectomy.

The laparoscopic approach is thought to reduce the postoperative immunologic and metabolic effects of an open operation. This study was designed with the aim of comparing the systemic immune response after laparoscopic and open cholecystectomy. Seventeen patients with gallbladder stones were assigned to undergo either a laparoscopic (n = 9) or open (n = 8) approach. The postoperative immune response was assessed by measuring the serum levels of soluble Fas (sFas), soluble L-selectin (sL-selectin), and transforming growth factor-beta1 (TGFbeta1) preoperatively and 2 hours, 1 day, and 2 days postoperatively. Both approaches resulted in a significant decrease in sFas levels 1 and 2 days postoperatively. The open approach evoked a transient increase in sL-selectin levels 2 hours postoperatively. Moreover, the open approach resulted in a persistent, significant increase in TGFbeta1 levels postoperatively. Comparison of open versus laparoscopic cholecystectomy has shown no significant difference in sFas level and a statistically significant increase of sL-selectin (within 2 hours) and TGFbeta levels after open surgery. Although both laparoscopic and open cholecystectomy evoked an alteration of the systemic immune response, our data showed that such immune response may be less after the laparoscopic approach.

Obstructive jaundice alters LFA-1alpha expression in rat small intestine.

Translocation of bacteria and endotoxtin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. The regulation of gastrointestinal mucosal response to injury is thus of important clinical as well as biological relevance. Integrins play a critical role in enterocyte migration, which is essential to mucosal healing. This study is designed to evaluate the integrins status in obstructive jaundice. Male Sprague-Dawley rats (N = 37) were randomized to three groups. Group 1 (N = 12) underwent common bile duct ligation (CBDL), group 2 (N = 12) underwent common bile duct ligation with oral glutamine administration (CBDL + G), and group 3 (N = 13) underwent a sham operation (sham control). After seven days, segments of proximal jejunum and distal ileum were harvested, and cell surface immunohistochemical expression of LFA-1alpha and VLA-6 were evaluated and recorded. The staining intensities were graded on a scale of 0-4. Comparisons among the three groups were performed. There was no significant difference in VLA-6 staining on small intestine among the three groups (P > 0.05). There was also no significant difference in LFA-1alpha staining the on jejunum between group 1 (CBDL) and group 3 (sham control) (P > 0.05). However, the LFA-1alpha staining on the ileum in group 1 (CBDL) significantly decreased when compared with group 3 (sham control) (P = 0.008). With oral glutamine administration (0.2 g/kg body weight, once daily), LFA-1alpha staining on the ileum was significantly restored in group 2 (CBDL + G). In conclusion, obstructive jaundice for one week down-regulates LFA-1alpha expression on rat ileum. With oral glutamine administration, such down-regulation of LFA-1alpha expression on rat ileum can be restored. Such a phenomenon is intriguing and deserves further evaluation and elucidation.

Effect of bile acid replacement on endotoxin-induced tumor necrosis factor-alpha production in obstructive jaundice.

There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-alpha) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-alpha levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-alpha levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and intestinal bile acid replacement can inhibit this phenomenon.