Microsatellite instability in endometrial carcinoma.

Microsatellite instability (MI), detected as electrophoretic shifts in allele sizes of microsatellite DNA sequences, has been identified in some colorectal carcinomas. Investigators have previously attributed such microsatellite instability to replication errors (RER). The colorectal carcinomas with RER have been found to arise either sporadically or in association with the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Because endometrial carcinoma is also commonly associated with HNPCC, we studied 30 cases of endometrial carcinoma to characterize the presence of MI in these neoplasms. Seven cases (23%) showed MI. Four cases showed both Type I (large shifts) and Type II (small shifts) mutation patterns and the remaining three cases showed Type I mutations only. We conclude that MI frequently occurs in endometrial cancers and that this type of genetic alteration may be an important pathogenetic feature of this tumor type.

Micropapillary serous carcinoma of the ovary. A distinctive low-grade carcinoma related to serous borderline tumors.

According to the International Federation of Gynecology and Obstetrics (FIGO) and the World Health Organization (WHO), stromal invasion, defined as destructive infiltrative growth, is the sole criterion used to distinguish serous borderline tumors from invasive serous carcinomas of the ovary. Although this criterion effectively identifies most malignant tumors, it does not permit the identification of a small subset of well-differentiated ovarian carcinomas that do not display destructive infiltrative growth but that may be associated with malignant behavior. In this study, we describe a group of such serous neoplasms that have distinctive morphologic features and that are often associated with progressive, invasive disease. We have designated these tumors micropapillary serous carcinomas (MPSC). They are characterized by a filigree pattern of highly complex micropapillae arising directly from large, bulbous papillary structures. The micropapillae are covered by round to cuboidal cells with a high nuclear-to-cytoplasmic ratio. Typical serous borderline tumors tend to display a hierarchical pattern of branching terminating in small papillae or tufts, and the cells covering the papillae tend to be more columnar and often ciliated compared with cells of MPSC. We reviewed more than 400 cases of serous ovarian borderline tumors and well-differentiated serous carcinomas and identified 26 cases of MPSC. Seventeen tumors lacked destructive infiltrative growth (noninvasive), and nine contained areas of invasion ranging from minimal to extensive. Eight of the 26 tumors were stage I, and none of the patients developed recurrence whether or not their tumors had demonstrable invasion. In contrast, of the 16 women presenting with stage II disease or higher and who had more than 1 year of follow-up, eight (50%) have either died of intra-abdominal carcinomatosis or are alive with carcinoma. Twenty-four (92%) of MPSCs contained areas of serous borderline tumor. The frequent association of MPSCs with serous borderline tumors suggests that MPSCs arise from the latter and may account for the few cases of serous borderline tumors that have been associated with progression to invasive carcinoma.

Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.

Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.

Late recurrence of clear-cell adenocarcinoma of the cervix: case report.

In the last 10 years, new observations have been made of the biologic behavior of clear-cell adenocarcinoma of the cervix and vagina arising in young women exposed to diethylstilbestrol in utero. Of particular note is the tumor's capacity to recur after an extended disease-free interval following initial therapy. We report the case of a woman who had her first recurrence 17 years after initial therapy, presenting with metastatic disease to the lungs and cerebellum. This case represents the longest reported interval between primary therapy and recurrence and supports the conclusion made by others that women who have been treated for clear-cell adenocarcinoma of the cervix and vagina may remain at risk of disease progression for many years after initial therapy. Therefore, these women should continue to be monitored. We also recommend periodic chest x-rays for two reasons: 1) The lungs are the most common site of distant spread of disease; and 2) metastatic nodules may be amenable to curative surgical intervention.

Subtle injuries of the Lisfranc joint.

In fifteen patients, a subtle injury of the Lisfranc joint (tarsometatarsal articulation) was found. The lesion was defined as a diastasis of two to five millimeters between the bases of the first and second metatarsals, as seen on anteroposterior radiographs. There often was a long delay between injury and diagnosis. Eight patients were treated with a below-the-knee cast only, three had treatment with a cast and then tarsometatarsal arthrodesis, two had no initial treatment but later had arthrodesis, and two had open reduction and internal fixation. The duration of follow-up ranged from two to thirteen years after the diagnosis. There was no correlation between the severity of the diastasis and the patient's functional result. Marked disability and pain persisted in seven patients, and six of them had flattening of the longitudinal arch. Maintenance of the longitudinal arch usually was associated with a better functional outcome. When a patient has a subtle injury of the Lisfranc joint, weight-bearing lateral radiographs of both feet are needed to identify flattening of the longitudinal arch. Such radiographs should be made routinely in the evaluation of all injuries of the foot that may involve the Lisfranc joint.

Anatomy of the lateral ankle ligaments.

The anatomy of the lateral ankle ligaments that is frequently described in articles and book chapters often lacks the precision of orientation and attachment points. We believe a knowledge of this precise anatomy is important to better reconstruct or repair lateral ligaments. We dissected cadaveric ankles free of skin and soft tissue and made the following measurements: areas of attachments of the anterior talofibular ligament, length and width of the anterior talofibular ligament, and locations of the attachments on the fibula and talus. The same measurements were made of the calcaneofibular and posterior talofibular ligaments. The distance of the calcaneofibular calcaneal attachments from the subtalar joint as well as the angle in the sagittal plane with the fibula was determined. We then used these anatomic attachments of the ligaments to make comparisons with the Watson-Jones and modified Elmslie reconstructions. Our results enable us to suggest a more anatomic placement for ligaments in a reconstruction.

Short-term effects of knee washout for osteoarthritis.

Twenty-nine knees in 23 patients with symptomatic osteoarthritis underwent washout with lactated Ringer's solution. Two arthroscopic cannulas were placed into the knee under local anesthetic. Three liters of fluid were run through the knee using varying inflow and outflow to alternately inflate and deflate the knee. We obtained Hospital for Special Surgery knee scores, Knee Society pain and function ratings, and visual analog pain scales before washout and up to 2 years after washout. At 1 year, the mean Hospital for Special Surgery score increased from 72 to 87, the Knee Society pain rating from 64 to 89, and the Knee Society function rating from 62 to 82. Twenty-five knees had a good or excellent result at 1 year. Twenty-one of these were observed at 2 years; 17 had good or excellent results. This study confirms the value of a fluid washout in an arthritic knee for some patients. This may explain some of the symptom relief seen with arthroscopic procedures in this condition.

Postoperative return of motion in anterior cruciate ligament and medial collateral ligament injuries. The effect of medial collateral ligament rupture location.

Twenty consecutive patients with combined anterior cruciate/medial collateral ligament injuries were analyzed to determine if a correlation exists between the location of medial collateral ligament disruption and postoperative return of motion. All patients were treated operatively by autogenous patellar tendon anterior cruciate ligament reconstruction and primary medial collateral ligament repair. The mean followup was 379 days. The patients (12 men and 8 women; mean age, 23 years) were divided into two groups based on the location of superficial medial collateral ligament rupture. Group P consisted of 13 patients with lesions at or proximal to the joint line; Group D consisted of 7 patients with disruptions distal to the joint line. Group D patients had a more rapid return of motion for both flexion and extension. At the conclusion of followup, patients from Group D also achieved 8 degrees more flexion and 3 degrees more extension. There were eight additional procedures performed on five patients, all from Group P, required to treat difficulty regaining motion. Among these patients with anterior cruciate/medial collateral ligament injuries there are two distinct groups, each with different prognoses related to return of motion based on the location of the medial collateral ligament disruption. We suggest that patients with double-ligament injuries, where the medial collateral ligament lesion is proximal, should be managed very aggressively to regain motion.

Biomechanical and histological observations of the dog patellar tendon after removal of its central one-third.

The use of a central one-third patellar tendon as an autograft for surgical reconstruction of a damaged cruciate ligament is common. Few complications of its use have been reported. However, recent clinical studies indicate that decreased quadriceps strength, decreased range of motion, decreased thigh circumference, and patellofemoral problems can be associated with this procedure. Some of these complications may result from alterations in the biomechanical properties of the remaining patellar tendon. The objective of this study was to examine biomechanically and histologically the fate of the remaining patellar tendon after removal of its central one-third. Three groups of dogs were used for this study. On one knee the central third of the patellar tendon was removed, while the contralateral side was used as a control. One group was immediately euthanized, while the other two groups were euthanized at 3 and 6 months. Control and operated patella-patellar tendon-tibia preparations were harvested and stretched to failure at 100% strain per second. The 3 and 6 month groups had a 10% decrease in length of the operated patellar tendon versus the contralateral control. There was a very significant increase in cross-sectional area of the patellar tendon at 3 months, and a further increase at 6 months. The failure load was 70% of the controls at 3 months and 60% of the controls at 6 months. The stiffness and modulus of the operated tendon within the physiologic range were dramatically reduced to 70% and 33% of controls at 6 months, respectively. These overall results were observed with the central one-third defect closed or left open in surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of tendon length and fit on the strength of a tendon-bone tunnel complex. A biomechanical and histologic study in the dog.

Using a dog model, we examined the influence of tendon length and fit within a bone tunnel on the pull-out strength of a tendon-bone tunnel complex at 6 weeks after fixation. Fourteen adult mongrel dogs (weight, 25 to 30 kg) underwent bilateral hindlimb surgery in which the extensor digitorum longus tendon was transplanted into an extraarticular metaphyseal bone tunnel. Our findings demonstrated that pull-out strength at 6 weeks was enhanced by increasing the length of tendon within the tunnel. The average load to failure with 1 cm of tendon within the tunnel was 153.7 +/- 78.6 N, compared with 265.5 +/- 93.3 N for the specimens with 2 cm of tendon in the tunnel. Tendon fit within the tunnel was also found to be important. The average load to failure when a tendon was placed in a 4.2-mm diameter tunnel was 301 +/- 61 N at 6 weeks. The average load to failure when the tendon was placed within a 6-mm diameter tunnel was 228 +/- 65 N. These differences were statistically different. Histologically, the interface between the tendon and bone appeared to be most mature when there was intimate bone-to-tendon contact. These data suggest that maximizing tendon length within a bone tunnel and minimizing tendon-tunnel diameter mismatch will maximize the strength of a tendon-bone tunnel complex at 6 weeks.

Analysis of athletic performance with prophylactic ankle devices.

We evaluated the effect of different ankle support devices on athletic performance. Thirty varsity college athletes were tested with both ankles supported by taping, Swede-O brace, Kallassy brace or left unsupported. The athletes performed four events: broad jump, vertical leap, 10 yard shuttle run, and 40 yard sprint. The events and appliances were randomized to prevent bias by fatigue. Compared to the results when no support was used, ankle taping resulted in a significant decreased performance in the vertical jump (4%), shuttle run (1.6%), and sprint (3.5%) (P less than 0.05). Use of the Swede-O brace decreased performance in the vertical jump (4.6%), broad jump (3.6%), and time of the sprint (3.2%). Results using the Kallassy brace showed a decrease in the vertical jump (3.4%) when compared to no support. The test results of the shuttle run with taping were slower than the Kallassy brace (P less than 0.05). Wearing the Swede-O brace caused the athletes' broad jump distance to decrease more than the Kallassy brace (P less than 0.05). Subjective questionnaires supported the Kallassy brace as the most comfortable support and the one that decreased performance the least. Taping of the ankles is universally accepted for ankle prophylaxis. This study has shown a decrease in performance when ankles are taped compared to ankles with no protection. Since the decreases in performance caused by ankle braces are minor, this should not be used as a criterion for selection of prophylactic support compared to taping.

The effect of reconstruction of the medial patellofemoral ligament on patellar tracking.

We evaluated patellar tracking in six cadaveric knees with the medial restraints intact and then sectioned to determine their contribution to lateral translation of the patella with and without a lateral force on the patella. The medial patellofemoral ligament was then reconstructed with a gracilis tendon graft and patellar tracking was again evaluated. The knees were extended using a materials testing machine, and patellar tracking was measured with a position sensing system. With no lateral force applied to the patella, patellar tracking was unaffected by the presence or absence of the medial restraints or by reconstruction of the medial patellofemoral ligament. With a lateral force applied to the patella, patellar tracking was changed significantly by the loss of the medial restraints. Normal patellar tracking was substantially restored by reconstruction of the medial patellofemoral ligament.

Soft tissue restraints to lateral patellar translation in the human knee.

The purpose of this investigation was to identify and quantify the soft tissue restraints, both medially and laterally, to lateral patellar translation. These restraints to lateral patellar translation at 20 degrees of knee flexion were tested biomechanically on a universal testing instrument in nine fresh-frozen cadaveric knees. After preconditioning the tissues, the patella of each intact knee was translated laterally to a distance at which a force of 200 N was recorded. This distance was used to translate the patella for the remaining structures to be sectioned. The contribution of each structure to the total restraining force was determined as the percent of the force to restrain the intact specimen by sectioning the restraints in a predetermined order. The contribution of each structure to the restraining force was defined as the difference between the restraining force before and after its sectioning. The medial patellofemoral ligament was found to be the primary restraint to lateral patellar translation at 20 degrees of flexion, contributing 60% of the total restraining force. The medial patellomeniscal ligament contributed 13% of the total force, and the lateral retinaculum contributed 10%. The medial patellotibial ligament and superficial fibers of the medial retinaculum were not functionally important in preventing lateral translation. The previously unrecognized contribution of the lateral retinaculum as a restraint to lateral patellar translation may shed new light on the failures of isolated lateral release for acute lateral dislocation of the patella.

A prospective evaluation of untreated acute grade III acromioclavicular separations.

We prospectively studied the natural history of untreated acute grade III acromioclavicular separations. Twenty-five patients were treated nonoperatively with a sling for comfort through progressive early range of motion as tolerated. Ten additional uninjured subjects underwent strength testing to evaluate the difference between the dominant and nondominant sides so that patient data could be standardized. The patients were examined at intervals of 6, 12, 24, 36, and 52 weeks after injury, at which time they completed a subjective questionnaire and underwent isometric dynamometer testing as well as military press and bench press strength testing. One patient underwent a surgical procedure at 2 weeks after injury because of cosmetic concerns. Twenty of the 25 patients completed the 1-year evaluation and strength-testing protocol. Subjectively, 4 of the 20 patients (20%) thought that their long-term outcome was suboptimal, although for 3 of them it was not enough to warrant surgery. Objective examination and strength testing of the 20 patients revealed no limitation of shoulder motion in the injured extremity and no difference between sides in rotational shoulder muscle strength. The bench press was the only strength test that showed a significant short-term difference, with the injured extremity being an average of 17% weaker. This study documents the natural history of patients with an untreated acute grade III acromioclavicular separation and provides a reference with which to judge all other proposed methods of treatment.

Biomechanical and histological properties of the canine patellar tendon after removal of its medial third.

Three groups of dogs were used for this study. All dogs had the medial third of the patellar tendon removed from one knee, while the contralateral knee was used as a control. The time zero group was immediately sacrificed; the other two groups were sacrificed at 3 and 6 months. Once the tissues were harvested, the patellar tendon was isolated and biomechanical and histologic analyses were conducted. Three and 6 months after surgery, there was a large amount of visible scar tissue in the tendon. The cross-sectional area of the tendons was 275% and 288% of controls at 3 and 6 months, respectively. The tensile modulus of the tendon was statistically less than controls at both 3 and 6 months. The energy to failure and stiffness of the operated tendons were not statistically different than controls at 3 or 6 months after surgery. The results of this study directly contrast with those of an earlier study of the removal of the central third of the patellar tendon. While a number of factors could explain differences observed between removal of a central or medical third, this study confirms the short-term damaging effects of surgical removal of a portion of the patellar tendon to reconstruct a torn anterior cruciate ligament.

Obtaining intra-articular bone grafts arthroscopically for intra-articular grafting.

Autogenous bone graft is frequently necessary for arthroscopic procedures and even small open procedures that involve cruciate revision, osteochondritis dissecans repair, and fracture reduction and internal fixation. Currently used sites to obtain bone graft are the iliac crest and Gerdy's tubercle. This article describes an arthroscopic technique for harvest of small amounts of bone graft from the distal femur. This avoids the morbidity of the extra-articular harvest. Tube harvesters frequently used for osteochondral autografts are the primary tool required for this technique. However, as described, the obtaining of bone graft is much less technically exacting than when procuring osteochondral bone plugs. This provides a safe, simple way to obtain extra autogenous bone at minimal additional operative morbidity.

Axillary nerve temperatures during radiofrequency capsulorrhaphy of the shoulder.

PURPOSE: The purpose of this study was to determine the temperatures along the course of the axillary nerve during radiofrequency (RF) capsulorrhaphy of the shoulder in a cadaver model. The hypothesis of this project was that temperatures capable of damaging neural tissue would be recorded during simulated RF capsulorrhaphy. TYPE OF STUDY: Basic science evaluation. METHODS: This study used 9 fresh-frozen cadaver shoulder capsules removed en bloc along with the underlying axillary nerve and soft tissue. The axillary nerve was instrumented with 4 thermocouples placed along the course of the nerve (2 thermocouples anterior and 2 posterior to the 6 o'clock position, spaced 7 mm apart). Each of the specimens underwent RF thermal capsulorrhaphy during which the temperature at each of the thermocouple positions was continuously recorded. RESULTS: The average of the maximum temperature at each of the 4 positions measured along the course of the axillary nerve were 52.2 +/- 18.0 degrees C at the most anterior place probed, 45.8 +/- 5.44 degrees C (mid anterior), 44.5 +/- 8.7 degrees C (mid posterior), and 42.8 +/- 10.1 degrees C at the most posteriorly positioned probe. Two specimens had a maximum temperature greater than the 67 degrees C set point of the device, and 7 specimens had a maximum temperature greater than 45 degrees C in at least 1 thermocouple position. CONCLUSIONS: This study shows that heating of the axillary nerve can occur during RF capsular shrinkage of the shoulder and may potentially reach levels that can damage neural tissue.

Pitfalls associated with fixation of osteochondritis dissecans fragments using bioabsorbable screws.

The purpose of this study was to evaluate 2 cases in which bioabsorbable screw fixation for an osteochondritis dissecans lesion of the femoral condyle resulted in complications necessitating the need for secondary surgery. We reviewed the case history of these patients and described the circumstances under which the bioabsorbable screws were used, the events leading to the need for secondary surgery, and the ultimate outcome. In the 2 cases presented, these implants were found to retain their mechanical stiffness for many months. This resulted in articular damage in 1 case after the treated lesion failed to heal. In the second case, screw breakage 8 months after implantation resulted in it becoming a loose body, which required removal during a second arthroscopic procedure. We conclude that these implants retain their mechanical properties for many months and cannot be relied on to degrade quickly. If a treated lesion fails to heal, these implants can cause mechanical problems due to their retained structural properties.

Lisfranc injuries in the athlete.

Injuries to the Lisfranc joint in the athlete comprise a very small proportion of tarsometatarsal injuries and are unique in several different ways. The energy involved appears to be on a much smaller order of magnitude than more commonly encountered injuries leading to obvious fracture and dislocation. Second metatarsal subluxation with diastasis between the first and second metatarsal tends to be the most commonly encountered injury; however, the true extent of injury cannot be based solely on the amount of diastasis present. Lateral weight-bearing radiographs facilitate evaluation of the normal medial cuneiform-fifth metatarsal relationship, which when disrupted indicates an injury more significant than a simple sprain and the possible need for open reduction and internal fixation. Finally, the restoration of this normal radiographic relationship between the medial cuneiform and fifth metatarsal on lateral weight-bearing views correlates well with the prognosis for achieving an asymptomatic, well-functioning foot, allowing a return to a competitive level of athletic participation.