"What if I do nothing?" The natural history of operable cancer of the alimentary tract.

INTRODUCTION: "Natural history", or anticipated survival without treatment, is critical for patients weighing risks and benefits of cancer surgery. Current estimates concerning the natural history of cancer includes patients whose poor health precludes treatment; a cohort whose fate is likely distinctly worse than those eligible for surgery ("operable"). The study objective was to evaluate survival among patients recommended for cancer surgery but went untreated, to determine the natural history of "operable" alimentary tract cancer. METHODS: The NCDB was queried for untreated patients with clinical stage I-III esophageal, gastric, colon, and rectal cancer diagnosed between 2003 and 2009. Untreated patients who were recommended for surgery were considered "operable," while patients coded as surgically ineligible for health reasons were "inoperable." RESULTS: 5-year survival of untreated, "operable" alimentary tract cancers varied by clinical stage: esophageal cI = 10.0%, cII = 9.8%, cIII = 4.6%; gastric cI = 9.2%, cII = 5.8%, cIII = 4.3%; colon cI = 18.4%, cII = 5.0%, cIII = 10.4; and rectal cI = 17.1%, cII = 14.0%, cIII = 19.9%. At every timepoint, stage-specific survival of "operable" patients was superior to inoperable patients (p < 0.05). Additionally, median survival among "operable" patients at least doubled "inoperable" patients for each tumor. CONCLUSION: Natural history of patients with "operable" alimentary tract cancer is superior to that of "inoperable" patients. Preoperative counseling should be refined to reflect this distinction.

Safety and efficacy of retreatment with a bioengineered hyaluronate for painful osteoarthritis of the knee: results of the open-label Extension Study of the FLEXX Trial.

OBJECTIVE: To evaluate the safety of repeated intra-articular (IA) injections of Euflexxa® (1% sodium hyaluronate; IA--BioHA) for painful knee osteoarthritis (OA). DESIGN: Participants who completed the randomized, double-blind, 26-week FLEXX Trial comparing IA-BioHA to IA saline (IA-SA) for knee OA(1) received three weekly IA-BioHA injections in a 26-week Extension Study. Adverse events (AEs) were recorded and the effect of treatment on knee pain was measured immediately following a 50-foot walk test using a 100 mm visual analog scale (VAS). Responder rate, Medical Outcomes Study Short Form 36 scores, Patient's Global Assessment, and intake of rescue medication were also evaluated. RESULTS: The Extension Study included 433 subjects, 219 who received IA-BioHA and 214 who received IA-SA during the FLEXX Trial. Safety results from the Extension Study indicated that 43.4% (188/433) of subjects had AEs, of which 4.8% (21/433) were deemed treatment-related AEs. Two AEs in the Extension Study led to discontinuation, and no joint effusion was reported. Patients who continued with IA-BioHA in the Extension Study maintained their improvement from baseline, with an average reduction in pain in the VAS score of -3.5 mm. Patients initially treated with IA-SA in the FLEXX Trial also had a reduction in VAS score of -9.0 mm. Secondary efficacy variables also improved during the Extension Study. CONCLUSIONS: Repeat injections of IA-BioHA were effective, safe, well tolerated, and not associated with an increase in AEs, such as synovial effusions. Additional symptom improvements were noted for subjects who received either IA-BioHA or IA-SA in the FLEXX Trial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00379236.

Efficacy of preoperative skin traction in hip fracture patients: a prospective, randomized study.

OBJECTIVE: To compare the analgesic benefit of preoperative skin traction with the placement of a pillow under the injured extremity in patients with hip fractures. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated teaching institution. PATIENTS AND PARTICIPANTS: One hundred consecutive patients with hip fractures admitted to the authors' institution who met inclusion criteria were enrolled. Fifty-five patients had femoral neck fractures, and forty-five patients had intertrochanteric fractures. The average patient age was seventy-eight years. INTERVENTION: All patients were preoperatively randomized into two intervention groups. One group underwent placement of five pounds of skin traction on the injured extremity, whereas the second underwent placement of a pillow under the injured extremity. Fifty patients were enrolled in each intervention group. RESULTS: With respect to immediate postintervention pain levels, patients treated with a pillow showed a trend toward better pain relief, as compared with patients treated with skin traction; however, this was not statistically significant. On the morning after admission, patients treated with a pillow had a statistically significant greater reduction in pain (p = 0.04). These patients also requested a statistically significant lower amount of pain medication (p < 0.01). CONCLUSIONS: The authors think that preoperative skin traction in patients with hip fractures does not provide significant pain relief, as compared with pillow placement under the injured extremity, and thus should not be routinely performed in this patient population for analgesia.

Arthroscopic stabilization of anterior shoulder instability: a historical perspective.

The role of arthroscopic procedures in the management of glenohumeral instability continues to evolve and represents an effective alternative for addressing the pathology associated with this condition. Patient selection criteria, operative techniques, and implants all continue to evolve and have resulted in improved rates of success. Arthroscopic procedures benefit patients by avoiding the common morbidities associated with the disruption of the anterior soft tissues, including a loss of external rotation associated with open procedures. Arthroscopic procedures remain technically demanding and require skills to address all of the existing pathology. The surgeon must be prepared to address many conditions beyond the Bankart lesions including glenoid bone lesions. capsular laxity, rotator interval lesions, and SLAP lesions. In addition to the documentation of recurrence, the success of this procedure must be evaluated within the context of retained ranges of motion, recovery time, proprioceptive control, and the return to prior levels of activity. Further studies are necessary to continue to validate the efficacy of arthroscopic stabilization.

Cervical spine injuries in football.

The game of football, as it is played today, poses serious risk of injury for players of all ages. Injury may occur to any structure of the spinal column, including its bony, ligamentous and soft tissue components. The majority of cervical spine injuries occurring in football are self limited, and a full recovery can be expected. While these injuries are relatively uncommon, cervical spine injuries represent a significant proportion of athletic injuries that can produce permanent disability. The low incidence of cervical spine injuries has lead to a lack of emergency management experience of on-site medical staff. This paper will review the numerous injuries sustained by the cervical spine in football players and provide insights into prevention and guidelines for return to play.

ACL injuries in the skeletally immature patient.

Anterior cruciate ligament injuries are becoming increasingly prevalent in a younger, more athletic population. These injuries require aggressive management given the poor natural history with regard to progressive meniscal damage and advanced degenerative changes. In general, strict nonoperative management has been associated with failure in the individual committed to return to an active lifestyle. As a result a general algorithm can be expressed as follows: 1. Activity limitations and bracing are initially used for the asymptomatic skeletally immature patient with a complete ACL tear. 2. If the patient remains asymptomatic, formal reconstruction can be delayed until skeletal maturity. 3. For the symptomatic patient a precise delineation of their physical development or skeletal age is important. 4. In patients who have reached Tanner IV secondary sexual development or a skeletal age of 13-14 (F/M), a traditional transphyseal reconstruction with hamstring autografts is appropriate. 5. In the skeletally immature patient who has significant skeletal development ahead of them, the judicious use of physeal sparing procedures is an option for the surgeon comfortable with these techniques. In this case the goal is temporization until formal transphyseal reconstruction can be performed after the peak of skeletal growth.

Examination of the lateral antebrachial cutaneous nerve: an anatomic study in human cadavers.

Variations in the anatomic course of the cutaneous nerves about the lateral aspect of the elbow are important when surgical exposures and the establishment of arthroscopic portals are considered. The specific anatomic course taken by the lateral antebrachial cutaneous nerve and its relationship to the lateral epicondyle were determined by studying 33 upper extremities in 22 preserved adult cadavers. Considerable anatomic variation was found regarding the location of the lateral antebrachial cutaneous nerve as it crossed the elbow. The nerve pierced the brachial fascia an average of 3.2 cm proximal to the lateral epicondyle and was located an average of 4.5 cm medial to the lateral epicondyle as it crossed the interepicondylar line. In two instances, the nerve passed through the biceps muscle directly, prior to piercing the brachial fascia.

Proposed mechanism for the photodynamic generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine produced in cultured cells by exposure to lomefloxacin.

In this study, lomefloxacin (LMX), a widely used quinolone antibiotic with a high frequency of clinical phototoxicity, was investigated by measuring the effects of several antioxidants on its ability to form of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in cultured adult rat liver cells after exposure to UVA. In the current study the observed DNA damage, reflected by the formation of 8-oxo-dG, was almost completely inhibited by co-incubation of LMX and cultured cells with sodium azide (NaN3) that specifically quenches singlet oxygen. Vitamin E (alpha-tocopherol), known to quench both superoxide and singlet oxygen, inhibited 8-oxo-dG formation by approximately 54%. Mannitol, a hydroxyl radical scavenger, inhibited 8-oxo-dG formation by 64%. Butylated hydroxyanisole (BHA), a scavenger of hydroxyl, peroxy and alkoxy radicals, showed no inhibition of 8-oxo-dG formation but in fact enhanced levels of 8-oxo-dG by 169%. The results of this study suggest that the mechanism for the photodynamic generation of 8-oxo-dG by LMX is mediated, at least in part, by both singlet oxygen and hydroxyl radical and involves both type I and type II photosensitization.

A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation.

We have previously reported that two fluoroquinolone antibiotics gave rise to 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA of cells concurrently exposed to UV-A and that this correlated with clinical phototoxicity. To determine the structural basis for generation of oxidative damage, the ability of two synthetic fluoroquinolone candidate antibiotics, Bayer 12-8039 (12-8039) and Bayer Y3118 (Y3118), to give rise to 8-oxo-dG in cultured liver epithelial cells was compared. 12-8039 contains a methoxy group at the 8 position of the quinolone nucleus, whereas Y3118 contains a chlorine group at the same position. Y3118 produced dose-dependent increases in 8-oxo-dG formation in cultured cells after UVA irradiation, whereas the 8-OCH3-substituted 12-8039 produced no increase. Also, after exposure to 20 J/cm2 UVA, UV spectral scans of both compounds revealed that Y3118 underwent photodegradation whereas 12-8039 was stable. These results demonstrate that the presence of an 8-OCH3 group on the quinolone nucleus is important for the reduction of photogeneration of oxidative DNA damage and photodegradation in the presence of UVA irradiation. From this, we suggest that 12-8039 has little phototoxic potential.

Quinolone antibiotic photodynamic production of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in cultured liver epithelial cells.

To study the basis for the phototoxicity of quinolones, a class of synthetic antibacterials, the photodynamic ability to mediate 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) formation in cultured cells was measured for lomefloxacin (LMX), which is strongly associated with clinical phototoxicity in humans, and ciprofloxacin (CFX), which has few reports of phototoxicity. Adult rat liver (ARL-18) cells were exposed to the quinolones in the presence of UVA and DNA was extracted and analyzed by HPLC with electrochemical detection. Low levels of 8-oxo-dG were found in the DNA of nonirradiated ARL-18 cells and this was increased up to 6-fold in the presence of either LMX (50-400 microM) or up to 3.6-fold in the presence of CFX (50-400 microM) and UVA (20 J/cm2) when compared to the UVA control. Comparing separate experiments with LMX and CFX, LMX produced greater levels of 8-oxo-dG either after dark exposure or after UVA exposure at 20 J/cm2. Also, LMX and CFX were both shown to photodegrade in the presence of UVA, and it was determined that UVA photoinstability alone does not reflect phototoxic potential. These data suggest that the photodynamic potential of LMX and CFX to produce 8-oxo-dG may relate to their human clinical phototoxicity profile. We suggest that the observed clinical phototoxicity is mediated through a UVA photodynamic effect on the quinolone to form reactive oxygen species in the presence of molecular oxygen. The findings indicate that 8-oxo-dG formation can serve as a marker for the potential phototoxicity of new quinolones.

Lack of effects of ciprofloxacin and the topoisomerase II inhibitors, m-AMSA and nalidixic acid, on DNA repair in cultured rat liver cells.

Several quinolone antibiotics, including ciprofloxacin, have been reported to elicit autoradiographic unscheduled DNA synthesis (UDS) in cultured rat hepatocytes. In the present investigation, ciprofloxacin (CF), at 250-1500 microM, produced autoradiographic UDS in cultured rat hepatocytes, whereas neither the quinolone nalidixic acid nor m-AMSA, both topoisomerase II inhibitors, produced autoradiographic UDS. CF also reduced cytoplasmic [3H]thymidine levels ([3H]TdR) relative to control at 250-1500 microM and concomitantly increased nuclear grain counts accounting for most of the net increase yielding positive UDS values. To obtain definitive information on whether the positive UDS observed with CF was due to DNA repair, DNA repair synthesis was measured in parental DNA separated from newly replicated DNA using a bromodeoxyuridine incorporation density gradient method. This method was used to measure DNA repair synthesis in parental DNA of both replicating rat liver epithelial cells (ARL-18) and nonproliferating rat hepatocytes in primary culture. Primary hepatocytes exposed to CF from 250 to 1500 microM did not express DNA repair synthesis in parental DNA isolated by density gradient centrifugation but rather exhibited a concentration-related decrease in the level of [3H]TdR associated with DNA. In rat liver epithelial (ARL-18) cells, CF from 250 to 500 microM likewise did not elicit DNA repair synthesis and also caused a concentration-related decrease in the level of [3H]TdR associated with parental DNA. In contrast, in both cell types a substantial level of repair synthesis occurred in parental DNA as a result of exposure to 2-acetylaminofluorene, a DNA-reactive carcinogen, and in hepatocytes a similar finding was made for the drug hydralazine. Also, after induction of DNA repair in hepatocytes by ultraviolet light, the DNA polymerase alpha inhibitor aphidicolin almost completely abolished repair synthesis, whereas CF had a negligible effect on the inhibition of repair relative to control. These results indicate that CF did not elicit authentic DNA repair and also did not inhibit DNA repair synthesis. The fact that CF elicited autoradiographic UDS and that the topoisomerase II inhibitors m-AMSA and nalidixic acid did not indicates that effects on topoisomerase II are not the basis for the positive UDS result with CF as has been hypothesized in the past.

8-Oxodeoxyguanosine formation in the DNA of cultured cells after exposure to H2O2 alone or with UVB or UVA irradiation.

The objective of the present study was to establish whether H2O2 alone or in the presence of UVA or UVB would give rise to formation of the oxidatively damaged DNA base 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in cultured adult rat liver (ARL-18) epithelial cells. Hydrogen peroxide alone at 5 mM increased 8-oxo-dG levels by 42% of that of culture control. Compared to culture control, UVB exposure at a dose of 0.63 J/cm2 elevated 8-oxo-dG levels only 8.4%. In the presence of 5 mM H2O2 + UVB (0.63 J/cm2), 8-oxo-dG levels were elevated 155% above culture control suggesting a synergistic effect. A UVA dose of 10 J/cm2 did not elevate 8-oxo-dG levels above culture control. In the presence of 5 mM H2O2 plus UVA (12 J/cm2), 8-oxo-dG levels were elevated 310% above controls compared with an increase of 75.8% above control levels at the same dose in the absence of H2O2. These results reveal that both UVA or UVB can promote H2O2 generation of reactive oxygen species (ROS) in whole cells resulting in an increase in the formation of 8-oxo-dG, although the photodynamic generation of ROS from H2O2 occurs with a much higher efficiency in the presence of UVB. Our study also demonstrates that 8-oxo-dG can be generated in cellular DNA of whole cells exposed to H2O2 and UVA or UVB, indicating that the ROS generated in whole cell systems are long enough lived to migrate to the nucleus and cause DNA damage.

Current concepts in intramedullary nailing.

The past decade has seen a dramatic increase in the use of intramedullary nailing for fracture manage- ment. Increased availability of new techniques and instrumentation have contributed to the continuing expansion of applications for intramedullary nailing. The introduction and availability of image intensi- fiers into American hospitals has also led to the popularization of closed intramedullary nailing techniques, and locking nails have expanded the indications of closed intramedullary nailing to unstable long bone frac- tures of the femur, tibia, and humerus. New classes of nails such as the second generation Reconstruction Nail have expanded the use of intramedullary nailing for more proximal femoral fractures. In addition, advances in biomechanical and locking designs have recently led to the use of intramedullary nailing in distal femur fractures and forearm fractures. There is continuing evolution of specialized nails including a self-guiding nail, nails for use in femoral lengthening, and nails used in conjunction with intramedullary osteotomies.

Occurrence of infection in anterior cervical fusion for spinal cord injury after tracheostomy.

STUDY DESIGN: This study retrospectively reviewed the outcomes of 11 patients treated for a cervical spine injury with a tracheostomy placed before anterior cervical spine surgery. OBJECTIVES: The primary goal was to show that anterior cervical spine surgery in the setting of spinal cord injury is a viable option in patients with previous tracheostomy. SUMMARY OF BACKGROUND DATA: Respiratory failure after cervical cord injury commonly requires tracheostomy, possibly increasing the risk of soft tissue or bony infection in patients at high risk for morbidity after surgery. Although numerous studies have explored the risk of infection after tracheostomy or anterior cervical spine surgery, no study has been performed to explore the risk of infection in patients with previous tracheostomy at the time of anterior cervical spine surgery. METHODS: A retrospective review of the clinical data of 1800 spinal cord injury patients seen from 1979 to the present at the Regional Spinal Cord Injury Center of the Delaware Valley of Thomas Jefferson University with affiliated institutions of Thomas Jefferson University Hospital and Magee Rehabilitation Hospital was performed. Eleven patients were found who had existing tracheostomy at the time of anterior cervical spine surgery. Clinical follow-up period averaged 28 months with a range of 6-51 months, and radiographic analysis averaged 7 months with a range of 1-51 months. Autogenous iliac crest graft was used in all patients, consisting of an intervertebral graft after a discectomy or a strut graft after a complete corpectomy. Anterior instrumentation was used in more than 50% of the patients. RESULTS: After all patient interviews and review of all radiographs for evidence of infection, no patient was noted to have evidence of a cervical soft tissue or bony infection after surgery. The tracheostomy complications were minor and resolved quickly. CONCLUSIONS: The authors concluded that in patients with cervical cord damage resulting from nonpenetrating trauma, tracheostomy was not found to increase the risk of infection in subsequent anterior cervical surgery. Careful preparation of the skin and placement of the second surgical incision lateral to the tracheostomy site is recommended. Anterior cervical spine surgery remains a viable treatment option in this severely injured patient population.

Self psychology: contributions and limitations.

This paper describes some contributions as well as criticisms of self-psychology. It uses clinical examples to describe some limitations to using self-psychology as the sole frame of reference.

The impact of service delivery frequency on family planning program output and efficiency.

Operations research is the study of factors that can be controlled by program administrators. Among such factors is the frequency of performing program activities. The present experiment, conducted in Lima, Peru during 1985-86, tested the impact of holding family planning post sessions once per month, twice per month, and weekly. Frequency was shown to have a major impact on program outputs, costs, and cost-effectiveness. Depending on the indicator, sessions held twice per month produced between 1.5 and 2.1 times the output of those conducted once per month. Weekly sessions produced between 1.3 and 1.6 times the output of those held twice per month. At an output level of nearly 11,200 visits per year, twice-per-month sessions were estimated to be 7-38 percent more cost-effective, depending on the indicator, than once-per-month sessions, and 6-28 percent more cost-effective than weekly sessions.

PIP: Operations research is the study of factors that can be controlled by program administrators. One of these factors is the frequency of performing program activities. The operational variable is the frequency of having clinical sessions in medical back-up posts in a community-based distribution (CBD) program in Lima, Peru. The study covered 42 posts in urban marginal areas of Lima. 3 performing frequencies were compared: 1) once a month; 2) twice a month; and 3) weekly. A randomized block design was used. The study lasted 12 months--from August, 1985-July, 1986. 3 output indicators were chosen: 1) effectiveness; 2) efficiency; and 3) cost-effectiveness. Outputs include program acceptors, total visits, IUD insertions, sessions and family planning (FP) visits. The once-per-month posts finished 98% of scheduled sessions while the twice-a-month and weekly sessions finished 97% and 96%, respectively. Mean duration of the clinic sessions held by the monthly and twice-monthly posts was 2.9 hours (s.d.=.84 and .73, respectively). Mean duration for the weekly group was 2.8 hours (s.d.=.67). About 73% of the FP talks scheduled for the monthly post were really accomplished compared to 66% for the twice-monthly and weekly groups. The 42 posts held 1136 clinic sessions during the year and had 11,196 visits, including 5371 FP visits. 1705 women accepted a FP method at the posts. 77% were IUD takers; 15% chose pills; and 8% accepted barrier methods. There were 4768 IUD visits. There were 414 pill visits and 18% barrier method visits. About 89% of all FP visits were IUD-related. 87% of all IUD insertions were referred by CBD workers and 5% by supervisors. There were 2954 total visits in monthly posts; 3501 in twice-monthly; and 5641 in weekly posts. Output went up linearly with session frequency, but in lesser proportion than the rise in the number of sessions held. Differences are statistically significant for all outputs. Twice-a-month posts had 1.5-2.1 times the output of once-a-month posts; weekly posts had about 1.3-1.6 times the output as twice-a-month posts, depending on the variable chosen. With output level of nearly 11,200 visits per year, twice-a-month sessions were estimated to be 7-38% more cost-effective than once-a-month sessions; 6-28% more cost-effective than weekly sessions.

Synthesis of tritium labeled cortoic acids.

A procedure is described for the microsynthesis and purification of the high specific activity tritium labeled cortisol metabolites, 20 alpha- and 20 beta-cortolic acids and 20 alpha- and 20 beta-cortolonic acids.