Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer.

Purpose: Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival. Methods and Materials: Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation. Statistical models were used to test associations between clinical characteristics and outcomes, including upper GI bleeding, radiation treatment breaks, and weight loss during therapy. Results: Between 1999 and 2012, 211 patients were treated with radiation for pancreatic cancer. All patients received concurrent chemotherapy with either gemcitabine (174) or 5-fluorouracil (27), and 67 received intensity modulated radiation therapy (IMRT). Overall, 18 patients experienced an upper GI bleed related to treatment, with 70% of bleeds occurring in the stomach or duodenum, and among those patients, 11 (61%) patients had a pancreatic head tumor and 17 (94%) patients had a metallic biliary stent. IMRT was associated with decreased risk of postradiation nausea (odds ratio, 0.27 [0.11, 0.67], P = .006) compared with 3-dimensional conformal radiation. Regarding long-term toxicities, patients with a metallic biliary stent at the time of radiation therapy were at a significantly higher risk of developing upper GI bleeding (unadjusted hazard ratio [HR], 15.41 [2.02, 117.42], P = .008), even after controlling for radiation treatment modality and prescribed radiation dose (adjusted HR, 17.38 [2.26, 133.58], P = .006). Furthermore, biliary stent placement was associated with a higher risk of death (HR, 1.99 [1.41, 2.83], P < .001) after adjusting for demographic, treatment-related, and patient-related variables. Conclusions: Metallic biliary stents may be associated with an increased risk of upper GI bleeding and mortality. Furthermore, IMRT was associated with less nausea and short-term toxicity compared with 3-dimensional conformal therapy.

Corrective Osteotomy for Symptomatic Radial Head and Neck Malunions in the Skeletally Immature.

BACKGROUND: Radial head and neck fracture malunion can lead to pain, stiffness, deformity, and functional limitations. This study analyzed the early radiographic and functional outcomes of corrective osteotomy for symptomatic radial head and/or neck malunion in skeletally immature patients. METHODS: Thirteen pediatric patients treated with corrective osteotomy for symptomatic radial head and/or neck malunion from 2004 to 2018 were identified. Radiographic union, range of motion, pain, and complications were recorded. Functional outcomes were assessed using the Broberg and Morrey Elbow Scale. RESULTS: The average age at the time of surgery was 12.3 years (range: 8.6 to 16.3). The mean time from injury to osteotomy was 7.5 months (range: 2 to 24.1 mo). Before osteotomy, mean radial head-shaft angulation was 23 degrees (range: 5 to 57 degrees), mean displacement was 76% (range: 0 to 55), average elbow flexion contracture was 18 degrees (range: 0 to 60 degrees), and average elbow flexion was 112 degrees (range: 95 to 135 degrees). After a mean follow-up of 14.3 months, 12 of 13 osteotomies (92%) healed; 1 patient had a painless nonunion. The number of patients reporting pain decreased from 9 to 2 ( P =0.012). Radiographic alignment and range of motion improved in all patients. Mean angulation and displacement improved to 8 degrees (range: 2 to 15 degrees, P =0.001) and 3% (range: 0 to 18 degrees, P =0.001), respectively. Mean elbow flexion contracture was reduced to 5 degrees (range: 0 to 30 degrees, P =0.008), and the average elbow flexion increased to 128 degrees (range: 100 to 135 degrees, P <0.001). Three patients underwent implant removal for complications, including heterotopic ossification and avascular necrosis. Physeal arrest did not lead to any adverse sequelae. The sole case of avascular necrosis had a reduced range of motion but no pain. The mean postoperative Broberg and Morrey score was 91.1; 7 patients had excellent postoperative scores, 4 good, and 2 fair. CONCLUSIONS: Corrective osteotomy for symptomatic malunion of the radial head and/or neck in skeletally immature patients can improve elbow alignment, motion, pain, and function. Preservation of the soft-tissue attachments to the proximal epiphysis and rigid internal fixation are critical components of this surgical technique. LEVEL OF EVIDENCE: Therapeutic Level IV.

Real-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment.

Ionizing radiation acoustic imaging (iRAI) allows online monitoring of radiation's interactions with tissues during radiation therapy, providing real-time, adaptive feedback for cancer treatments. We describe an iRAI volumetric imaging system that enables mapping of the three-dimensional (3D) radiation dose distribution in a complex clinical radiotherapy treatment. The method relies on a two-dimensional matrix array transducer and a matching multi-channel preamplifier board. The feasibility of imaging temporal 3D dose accumulation was first validated in a tissue-mimicking phantom. Next, semiquantitative iRAI relative dose measurements were verified in vivo in a rabbit model. Finally, real-time visualization of the 3D radiation dose delivered to a patient with liver metastases was accomplished with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the 3D radiation dose deposition during treatment, potentially improving radiotherapy treatment efficacy using real-time adaptive treatment.

A Safe and Practical Cycle for Team-Based Development and Implementation of In-House Clinical Software.

PURPOSE: Due to a gap in published guidance, we describe our robust cycle of in-house clinical software development and implementation, which has been used for years to facilitate the safe treatment of all patients in our clinics. METHODS AND MATERIALS: Our software development and implementation cycle requires clarity in communication, clearly defined roles, thorough commissioning, and regular feedback. Cycle phases include design requirements and use cases, development, physics evaluation testing, clinical evaluation testing, and full clinical release. Software requirements, release notes, test suites, and a commissioning report are created and independently reviewed before clinical use. Software deemed to be high-risk, such as those that are writable to a database, incorporate the use of a formal, team-based hazard analysis. Incident learning is used to both guide initial development and improvements as well as to monitor the safe use of the software. RESULTS: Our standard process builds in transparency and establishes high expectations in the development and use of custom software to support patient care. Since moving to a commercial planning system platform in 2013, we have applied our team-based software release process to 16 programs related to scripting in the treatment planning system for the clinic. CONCLUSIONS: The principles and methodology described here can be implemented in a range of practice settings regardless of whether or not dedicated resources are available for software development. In addition to teamwork with defined roles, documentation, and use of incident learning, we strongly recommend having a written policy on the process, using phased testing, and incorporating independent oversight and approval before use for patient care. This rigorous process ensures continuous monitoring for and mitigatation of any high risk hazards.

The Impact of Collagenase Clostridium histolyticum Introduction on Dupuytren Treatment Patterns in the United States.

PURPOSE: The U.S. Food and Drug Administration approved the use of collagenase Clostridium histolyticum (CCH) in the United States in February 2010. This study addresses the impact of that approval on the number of Dupuytren contracture (DC) encounters and treatment patterns in the United States. METHODS: Using the Intercontinental Marketing Services Health Office-Based Medical Claims database, we identified the monthly number of DC encounters and DC procedures between January 2007 and December 2013. Collagenase Clostridium histolyticum usage data from March 2010 to December 2013 was derived from the U.S. CCH manufacturer's data warehouse. Using the combined data, the yearly increasing trends in DC encounters and treatment volume were compared before and after the introduction of CCH. Time trends in the relative procedure frequencies were then examined. Finally, the presence of seasonal variation was tested for in each treatment type. RESULTS: Dupuytren contracture encounters increased on average by 19,015 per year between 2007 and 2009, whereas between 2011 and 2013, DC encounters increased on average by 34,940 per year. In terms of absolute procedure counts, the surgery trend line began decreasing in 2010 with the release of CCH. Meanwhile, CCH continuously increased between 2010 and 2013, and needle aponeurotomy (NA) remained relatively stable. By the year 2013, minimally invasive techniques (NA and CCH) comprised 39% of all treatment, compared with only 14% in 2007. Lastly, there was a statistically significant seasonal increase in the number of surgical procedures during the wintertime but no seasonal variation in NA or CCH. CONCLUSIONS: After the introduction of CCH, the number of Dupuytren encounters increased at a greater annual rate. The introduction and growth of CCH coincided with a decrease in surgery. The number of NA procedures remained steady throughout the study period. The number of open surgery cases followed a predictable seasonal variation with more procedures during the winter months, but this seasonal variation was not seen with less invasive techniques. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis II.

SafetyNet: Streamlining and Automating QA in radiotherapy.

Proper quality assurance (QA) of the radiotherapy process can be time-consuming and expensive. Many QA efforts, such as data export and import, are inefficient when done by humans. Additionally, humans can be unreliable, lose attention, and fail to complete critical steps that are required for smooth operations. In our group we have sought to break down the QA tasks into separate steps and to automate those steps that are better done by software running autonomously or at the instigation of a human. A team of medical physicists and software engineers worked together to identify opportunities to streamline and automate QA. Development efforts follow a formal cycle of writing software requirements, developing software, testing and commissioning. The clinical release process is separated into clinical evaluation testing, training, and finally clinical release. We have improved six processes related to QA and safety. Steps that were previously performed by humans have been automated or streamlined to increase first-time quality, reduce time spent by humans doing low-level tasks, and expedite QA tests. Much of the gains were had by automating data transfer, implementing computer-based checking and automation of systems with an event-driven framework. These coordinated efforts by software engineers and clinical physicists have resulted in speed improvements in expediting patient-sensitive QA tests.

Enhancing safety and quality through preplanning peer review for patients undergoing stereotactic body radiation therapy.

PURPOSE: Because of its high dose per fraction delivery, stereotactic body radiation therapy (SBRT) requires real-time process assurance to promote safe, high-quality treatments. In an effort to assure safety and first-time quality, we instituted a pilot, single-institution, SBRT peer review process before treatment planning. Here, we present a summary of the results of that process over a 26-month period. METHODS AND MATERIALS: Before planning, all patients were presented at an SBRT "rounds" that required, at a minimum, the treating attending or resident physician, an independent attending physician, a physicist, and a dosimetrist. Items reviewed included imaging, image registration, target contours, prescription, and planning goals. The results of peer review were prospectively recorded and logistic regression models were used to assess the relationship between various physician and case characteristics and the odds of a change being made. RESULTS: A total of 513 SBRT cases were peer reviewed before planning. In 22.6% of cases, at least 1 change was made because of this process. A lower change rate was observed in higher volume SBRT body sites (lung and liver). In all body sites, gross and planning target volume contours were changed 8.2% and 5.5% of the time, respectively. The prescription was changed 4.9% of the time, and organs at risk goals were changed 7.2% of the time. The odds of having a change were significantly lower when the treating oncologist had more SBRT experience. CONCLUSIONS: Preplanning peer review by an independent physician, physicist, and dosimetrist resulted in changes in nearly one-quarter of SBRT patients, potentially preventing suboptimal treatments. The odds of a change being required were decreased in higher volume body sites and when the treating oncologist was more experienced with SBRT, underscoring the potential importance of peer review in uncommon SBRT sites and at low-volume SBRT centers.

Development of a brachytherapy audit checklist tool.

PURPOSE: To develop a brachytherapy audit checklist that could be used to prepare for Nuclear Regulatory Commission or agreement state inspections, to aid in readiness for a practice accreditation visit, or to be used as an annual internal audit tool. METHODS AND MATERIALS: Six board-certified medical physicists and one radiation oncologist conducted a thorough review of brachytherapy-related literature and practice guidelines published by professional organizations and federal regulations. The team members worked at two facilities that are part of a large, academic health care center. Checklist items were given a score based on their judged importance. Four clinical sites performed an audit of their program using the checklist. The sites were asked to score each item based on a defined severity scale for their noncompliance, and final audit scores were tallied by summing the products of importance score and severity score for each item. RESULTS: The final audit checklist, which is available online, contains 83 items. The audit scores from the beta sites ranged from 17 to 71 (out of 690) and identified a total of 7-16 noncompliance items. The total time to conduct the audit ranged from 1.5 to 5 hours. CONCLUSIONS: A comprehensive audit checklist was developed which can be implemented by any facility that wishes to perform a program audit in support of their own brachytherapy program. The checklist is designed to allow users to identify areas of noncompliance and to prioritize how these items are addressed to minimize deviations from nationally-recognized standards.

Biomechanical evaluation of 5 fixation devices for proximal interphalangeal joint arthrodesis.

PURPOSE: To determine in a cadaver model which, among 5 fixation methods for proximal interphalangeal (PIP) joint arthrodesis, has the greatest stiffness. METHODS: Thirty-five cadaver digits were randomly assigned to 1 of 5 fixation groups: oblique K-wire with coronal intraosseous wiring, tension-band wire (TBW), dorsal plate, intramedullary linked screw (IMS), and 90/90 wiring (90/90W). Testing was done by applying bending moments to the PIP joint in the sagittal and frontal planes. The force/displacement curves were used to estimate the stiffness of each construct. Ultimate strength was determined by loading to failure in extension. RESULTS: The IMS had significantly higher stiffness than all wiring constructs in all planes of motion and significantly greater stiffness in extension than the dorsal plate. The IMS stiffness exceeded 10 N/mm across all bending directions and showed an ultimate strength of 21 N. The plate demonstrated higher stiffness in radial bending than the oblique K-wire with coronal intraosseous wiring and TBW. There were no differences in stiffness between the IMS and plate in all modes of testing except extension. Load-to-failure testing of the devices showed the IMS device to be significantly stronger than the TBW, 90/90W, and plating constructs. CONCLUSIONS: The IMS resisted larger bending moments than all wiring constructs and showed the greatest ultimate strength when compared with 3 of the tested arthrodesis techniques. The plate was significantly better than 2 of the wiring constructs, but only in radial bending. No differences were found between the, TBW, and 90/90W when compared with each other. CLINICAL RELEVANCE: The stiffness necessary for a successful PIP joint fusion has not been quantified, but according to this study, the IMS was the most favorable biomechanical construct for initial stability.

Primary peritoneal clear cell carcinoma treated with IMRT and interstitial HDR brachytherapy: a case report.

Primary peritoneal clear cell carcinoma (PP-CCC), which is a rare tumor with poor prognosis, is typically managed with surgery and/or chemotherapy. We present a unique treatment approach for a patient with a pelvic PP-CCC, consisting of postchemotherapy intensity-modulated radiation therapy (IMRT) followed by interstitial high-dose-rate (HDR) brachytherapy. A 54-year-old female with an inoperable pelvic-supravaginal 5.6 cm T3N0M0 PP-CCC tumor underwent treatment with 6 cycles of carboplatin and taxol chemotherapy. Postchemotherapy PET/CT scan revealed a residual 3.3 cm tumor. The patient underwent CT and MR planning simulation, and was treated with 50 Gy to the primary tumor and 45 Gy to the pelvis including the pelvic lymph nodes, using IMRT to spare bowel. Subsequently, the patient was treated with an interstitial HDR brachytherapy implant, planned using both CT and MR scans. A total dose of 15 Gy in 5 Gy fractions over two days was delivered with Ir-192 HDR brachytherapy. The total prescribed equivalent 2 Gy dose (EQD2) to the HDR planning target volume (PTV) from both the EBRT and HDR treatments ranged between 63 and 68.8 Gy2 due to differential dosing of the primary and pelvic targets. The patient tolerated radiotherapy well, except for mild diarrhea not requiring medication. There was no patient-reported acute toxicity one month following the radiotherapy course. At four months following adjuvant radiation therapy, the patient had near complete resolution of local tumor on PET/CT without any radiation-associated toxicity. However, the patient was noted to have metastatic disease outside of the radiation field, specifically lesions in the liver and bone. This case report illustrates the feasibility of the treatment of a pelvic PP-CCC with IMRT followed by interstitial HDR brachytherapy boost, which resulted in near complete local tumor response without significant morbidity.

Migration check tool: automatic plan verification following treatment management systems upgrade and database migration.

Software upgrades of the treatment management system (TMS) sometimes require that all data be migrated from one version of the database to another. It is necessary to verify that the data are correctly migrated to assure patient safety. It is impossible to verify by hand the thousands of parameters that go into each patient's radiation therapy treatment plan. Repeating pretreatment QA is costly, time-consuming, and may be inadequate in detecting errors that are introduced during the migration. In this work we investigate the use of an automatic Plan Comparison Tool to verify that plan data have been correctly migrated to a new version of a TMS database from an older version. We developed software to query and compare treatment plans between different versions of the TMS. The same plan in the two TMS systems are translated into an XML schema. A plan comparison module takes the two XML schemas as input and reports any differences in parameters between the two versions of the same plan by applying a schema mapping. A console application is used to query the database to obtain a list of active or in-preparation plans to be tested. It then runs in batch mode to compare all the plans, and a report of success or failure of the comparison is saved for review. This software tool was used as part of software upgrade and database migration from Varian's Aria 8.9 to Aria 11 TMS. Parameters were compared for 358 treatment plans in 89 minutes. This direct comparison of all plan parameters in the migrated TMS against the previous TMS surpasses current QA methods that relied on repeating pretreatment QA measurements or labor-intensive and fallible hand comparisons.

Annexin A6 interacts with p65 and stimulates NF-κB activity and catabolic events in articular chondrocytes.

OBJECTIVE: ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic (OA) articular chondrocytes but not in healthy articular chondrocytes. This study was undertaken to determine whether annexin A6 affects catabolic events in these cells. METHODS: Articular chondrocytes were isolated from Anxa6-knockout mice, wild-type (WT) mice, and human articular cartilage in which ANXA6 was overexpressed. Cells were treated with interleukin-1ß (IL-1ß) or tumor necrosis factor α (TNFα), and expression of catabolic genes and activation of NF-κB were determined by real-time polymerase chain reaction and luciferase reporter assay. Anxa6(-/-) and WT mouse knee joints were injected with IL-1ß or the medial collateral ligament was transected and partial resection of the medial meniscus was performed to determine the role of Anxa6 in IL-1ß-mediated cartilage destruction and OA progression. The mechanism by which Anxa6 stimulates NF-κB activity was determined by coimmunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of IL-1ß-treated Anxa6(-/-) and WT mouse chondrocytes for p65 and Anxa6. RESULTS: Loss of Anxa6 resulted in decreased NF-κB activation and catabolic marker messenger RNA (mRNA) levels in IL-1ß- or TNFα-treated articular chondrocytes, whereas overexpression of ANXA6 resulted in increased NF-κB activity and catabolic marker mRNA levels. Annexin A6 interacted with p65, and loss of Anxa6 caused decreased nuclear translocation and retention of the active p50/p65 NF-κB complex. Cartilage destruction in Anxa6(-/-) mouse knee joints after IL-1ß injection or partial medial meniscectomy was reduced as compared to that in WT mouse joints. CONCLUSION: Our data define a role of annexin A6 in the modulation of NF-κB activity and in the stimulation of catabolic events in articular chondrocytes.

Impact of preoperative MRSA screening and decolonization on hospital-acquired MRSA burden.

BACKGROUND: Hospital-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a source of morbidity and mortality. S. aureus is the most common pathogen in prosthetic joint infections and the incidence of MRSA is increasing. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the MRSA prevalence density rate at a specialty orthopaedic hospital before and after the implementation of a screening and decolonization protocol,(2) to compare our prevalence density to that of an affiliated university hospital, to control for changes in MRSA prevalence density that might have been independent of the decolonization protocol, and (3) to measure the admission prevalence density rate of MRSA in an elective orthopaedic surgery population and the compliance rate of 26 patients with the protocol [corrected]. METHODS: In October 2008, we implemented a MRSA screening and decolonization protocol for patients undergoing elective orthopaedic surgery. Nasal swabs were used for screening and mupirocin nasal ointment and chlorhexidine skin antisepsis where prescribed for decolonization to all patients. At the surgical visit, compliance was measured and the patients who were MRSA positive received vancomycin for antibiotic prophylaxis. Institution wide surveillance for multidrug-resistant organisms, including MRSA provided a comparison of the change in MRSA burden at the orthopaedic hospital versus the university hospital. RESULTS: Before implementation of the preoperative staphylococcal decolonization protocol there were 79 MRSA-positive cultures in 64,327 patient-days for a prevalence density rate of 1.23 per 1000 patient-days. After protocol implementation, 53 MRSA-positive cultures were identified in 63,860 patient-days for a rate of 0.83 per 1000 patient-days. Before the protocol, the MRSA prevalence density at the specialty hospital was similar to that of the university hospital; after implementation of the protocol, the prevalence density at the specialty hospital was 33% lower than that of the university hospital. The MRSA admission prevalence was 3.02%. The compliance rate was greater than 95%. CONCLUSIONS: Implementation of a staphylococcal decolonization protocol at a single specialty orthopaedic hospital decreased the prevalence density of MRSA.

Computer-assisted surgery patterns of ligamentous deformity of the knee: a clinical and cadaveric study.

Knee malalignment during total knee arthroplasty (TKA) is commonly classified as either varus or valgus on the basis of a standing anteroposterior radiograph. Computer-assisted surgery (CAS) navigation TKA provides precise dynamic evaluation of knee alignment throughout the full range of motion (FROM). The goal of this study was to classify patterns of CAS-generated knee deformity curves that match specific soft tissue contracture combinations. This can then be applied as an algorithm for soft tissue balancing on the basis of the preoperative knee deformity curve. Computer navigation-generated graphs from 65 consecutive TKA procedures performed by a single surgeon were analyzed. A stress-strain curve of the coronal alignment of the knee was recorded throughout FROM before bony resection. All graphs were classified into groups according to their pattern. Cadaveric knee models were then used to test the correlation between isolated and combined ligamentous contractures and identified CAS deformity curves. An analysis of the intraoperative knee alignment graphs revealed four distinct patterns of coronal deformity on the basis of intraoperative data: 13% diagonal, 18.5% C-shaped, 43.5% comma shaped, and 25% S-shaped. Each represents the change in varus and valgus alignment during FROM. All patterns were reproduced with cadaveric knees by recreating specific contracture constellations. A tight posterior capsule gave an S-shaped curve, a tight lateral collateral ligament gave a C-shaped curve, tight medial collateral ligament gave a diagonal curve, and a tight posterior lateral corner gave a comma-shaped curve. Release of the specific contractures resulted in correction of all patterns of deformity as measured by CAS. We propose a new classification system for coronal plane knee deformity throughout FROM. This system intends to match individual and combined soft tissue pathological contractures to specific stress-strain curves obtained through routine knee CAS preparation. This classification system may provide surgeons with a general guide for soft tissue balancing during computer-navigated TKA.

The dosimetric impact of prostate rotations during electromagnetically guided external-beam radiation therapy.

PURPOSE: To study the impact of daily rotations and translations of the prostate on dosimetric coverage during radiation therapy (RT). METHODS AND MATERIALS: Real-time tracking data for 26 patients were obtained during RT. Intensity modulated radiation therapy plans meeting RTOG 0126 dosimetric criteria were created with 0-, 2-, 3-, and 5-mm planning target volume (PTV) margins. Daily translations and rotations were used to reconstruct prostate delivered dose from the planned dose. D95 and V79 were computed from the delivered dose to evaluate target coverage and the adequacy of PTV margins. Prostate equivalent rotation is a new metric introduced in this study to quantify prostate rotations by accounting for prostate shape and length of rotational lever arm. RESULTS: Large variations in prostate delivered dose were seen among patients. Adequate target coverage was met in 39%, 65%, and 84% of the patients for plans with 2-, 3-, and 5-mm PTV margins, respectively. Although no correlations between prostate delivered dose and daily rotations were seen, the data showed a clear correlation with prostate equivalent rotation. CONCLUSIONS: Prostate rotations during RT could cause significant underdosing even if daily translations were managed. These rotations should be managed with rotational tolerances based on prostate equivalent rotations.

The effect of arthroscopic partial medial meniscectomy on tibiofemoral stability.

BACKGROUND: There is still little known regarding the effects of meniscus resection size on tibiofemoral stability. PURPOSE: To determine if partial medial meniscectomy of the posterior horn significantly alters tibiofemoral stability as measured by the anterior-posterior (AP) position and laxity of the medial femoral condyle. STUDY DESIGN: Controlled laboratory study. METHODS: Five cadaveric knees were dissected to the capsule, preserving all ligaments and the quadriceps tendon. Each specimen was first tested on a rig where the AP position and laxity of the medial femoral condyle were measured while a range of forces was applied from full extension to 90° of flexion. Magnetic resonance imaging (MRI) at 3 tesla was then performed for baseline measurements of the meniscus before partial meniscectomy. Arthroscopic partial medial meniscectomy aimed at 30% of the posterior horn was then performed, followed by repeat mechanical testing and MRI. The sequence was then repeated for arthroscopic partial meniscectomy aimed at 60% and 100% of the posterior horn of the medial meniscus. RESULTS: The MRI analysis demonstrated that 22% ± 9% of the original width of the posterior horn was removed at the first resection, 46% ± 11% was removed at the second resection, and the third resection was 100% removal of the posterior horn for all specimens. After 22% resection, no significant difference in AP laxity was observed. A statistically significant increase in AP laxity was observed with 46% resection under a 500-N compressive load compared with the intact meniscus. After full resection, significant increases in AP laxity were observed under a 50-N compressive load compared with the intact and 22% and 46% resections. The 22% resection had similar AP positions as the intact knee, whereas the 46% resection and 100% removal of the posterior horn had statistically further posterior AP positions than the intact knee. CONCLUSION: Partial medial meniscectomy with ≥46% resection of the original width of the posterior horn significantly altered the AP position of the medial femoral condyle and also increased laxity. CLINICAL RELEVANCE: These mechanical changes may lead to abnormal cartilage loading and early osteoarthritis.

Barbed sutures for arthroplasty closure--does it decrease the risk of glove perforation?

Recent resurgence in the interest of barbed suture has extended its application to wound closures in total joint surgery. Improved suture biomaterials and barb geometry has lead to consideration for its use in various orthopedic procedures including arthroplasty. The reported superior wound tensile stress distribution, no need for knots, and ability to close multiple layers with one suture make it an attractive option for deep wound closure after total joint surgery. However, inherent to the design of this suture are barbs that pose a risk of glove perforation and the potential for the transmission of blood borne pathogens. This study reports no increase in the incidence of glove perforation with use of barbed suture for deep wound closure after total joint arthroplasty.

A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer.

PURPOSE: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). METHODS AND MATERIALS: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × upper limit of normal. FDR-G (1000 mg/m(2)/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥ 3, neutropenic fever, or deterioration in performance status to ≥ 3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. RESULTS: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. CONCLUSIONS: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

Potential use of ultrasound speckle tracking for motion management during radiotherapy: preliminary report.

We prospectively evaluated real-time ultrasound speckle tracking for monitoring soft tissue motion for image-guided radiotherapy. Two human volunteers and 1 patient with a proven hepatocellular carcinoma, who was being prepared for radiation therapy treatment, were scanned using a clinical ultrasound scanner modified to acquire and store radiofrequency signals. Scans were performed of the liver in the volunteers and the patient. In the patient, the speckle-tracking results were compared to those measured on a treatment-planning 4-dimensional computed tomogram with tumors contoured manually in each phase and with estimates made by hand on gray scale ultrasound images. The surface of the right lung and the prostate were scanned in a volunteer. The liver and lung surface were scanned during respiration. To simulate prostate motion, the ultrasound probe was rocked in an anterior-posterior direction. The correlation coefficients of all motion measurements were significantly correlated at all sites (P < .00001 for all sites) with 0 time delays. Ultrasound speckle-tracking motion estimates of tumor motion were within 2 mm of estimates made by hand tracking on gray scale ultrasound images and the 4-dimensional computed tomogram. The total tumor motion was greater than 20 mm. The angular displacement of the prostate was within 0.02 radians (1.1°) with displacements measured by hand. Speckle tracking could be used to monitor organ motion during radiotherapy.

Prostate intrafraction translation margins for real-time monitoring and correction strategies.

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.