The importance of topical steroids after adhesiolysis in erosive lichen planus and graft versus host disease.

The aim of this study was to assess the efficacy of a postoperative steroid regimen in maintaining vulvovaginal architecture and vaginal patency following surgical adhesiolysis in severe erosive lichen planus (ELP) and genital graft versus host disease (GVHD). Sixteen women applied potent topical steroids to the vulva and vagina from 48 hours after surgery. Sexual and urinary function and vulvovaginal anatomy were assessed at 6 weeks, 6, 12 and 24 months. All of the patients had failed sexual function due to vaginal stenosis. Eleven patients were unable to have cervical smears and three had associated haematocolpos. Vaginal adhesiolysis achieving complete patency occurred in all patients with stenosis. Fifteen (93.7%) patients were compliant with the regimen. After two years, 12 (75%) patients had maintained complete vaginal patency. Four patients (25%) developed vaginal restenosis. This study demonstrates that the potent topical steroids used post-operatively are very effective in maintaining vaginal patency and function. Impact statement What is already known on this subject? Potent topical steroids are the first line treatment for ELP and GVHD and have been reported to be helpful after surgery to release adhesions. What do the results of this study add? Topical steroids used immediately after surgical adhesiolysis in patients with vulvo-vaginal lichen planus and graft-versus-host disease improves the outcomes and maintains function, which can give a prolonged benefit. What are the implications of these findings for clinical practice and/or further research? The use of potent topical steroids should be considered as routine practice after surgery in erosive inflammatory disease to control inflammation and improve the long term outcomes for these patients.

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy.

BACKGROUND: Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear. PATIENTS AND METHODS: We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses. RESULTS: PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission. CONCLUSIONS: This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.

Probing the highly efficient room temperature ammonia gas sensing properties of a luminescent ZnO nanowire array prepared via an AAO-assisted template route.

Here, we report the facile synthesis of a highly ordered luminescent ZnO nanowire array using a low temperature anodic aluminium oxide (AAO) template route which can be economically produced in large scale quantity. The as-synthesized nanowires have diameters ranging from 60 to 70 nm and length ∼11 µm. The photoluminescence spectrum reveals that the AAO/ZnO assembly has a strong green emission peak at 490 nm upon excitation at a wavelength of 406 nm. Furthermore, the ZnO nanowire array-based gas sensor has been fabricated by a simple micromechanical technique and its NH3 gas sensing properties have been explored thoroughly. The fabricated gas sensor exhibits excellent sensitivity and fast response to NH3 gas at room temperature. Moreover, for 50 ppm NH3 concentration, the observed value of sensitivity is around 68%, while the response and recovery times are 28 and 29 seconds, respectively. The present synthesis technique to produce a highly ordered ZnO nanowire array and a fabricated gas sensor has great potential to push the low cost gas sensing nanotechnology.

Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research.

There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n=97) or allogeneic (n=50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit.

TU-E-BRA-04: Real-Time Automatic Fiducial Marker Detection in Low Contrast Cine-MV Images.

PURPOSE: Intrafraction motion tracking using beam-line MV images have gained much attention because no additional imaging dose is introduced. Since MV images have much lower contrast than kV images, a robust marker detection algorithm is a pre-requisite. In this work, we develop a novel, fast, and robust method to detect implanted markers in low-contrast cine-MV patient images. METHODS: Several marker detection methods have been proposed in the recent years. These methods are all based on template matching or its derivatives. Template matching needs to match object shape that changes significantly for different implantation and projection angle. While these methods require a large number of templates to cover the different situations, they are often forced to use a smaller number of templates to reduce the computation load because their methods all require exhaustive search in the ROI. We solve this problem by synergetic use of modern but well-tested computer vision and AI techniques - detect implanted markers utilizing discriminant analysis for initialization and mean-shift feature space analysis for sequential tracking. This novel approach avoids exhaustive search by exploiting the temporal correlation between consecutive frames and makes it possible to perform more sophisticated detection at the beginning to improve the accuracy, followed by ultrafast sequential tracking after the initialization. The method was evaluated using 1149 cine-MV images from 2 prostate IMRT patients and compared with manual marker detection results from 6 researchers. The average of the manual detection results is considered as the ground truth. RESULTS: The average RMS errors of the automatic tracking from the ground truth are 1.9 and 2.1 pixels for the 2 patients (0.26mm/pixel). The standard deviations of the results from the 6 researchers are 2.3 and 2.6 pixels. CONCLUSION: The proposed method can achieve similar marker detection accuracy to manual detection in low-contract cine-MV images.

SU-E-T-92: on the Use of High-Sensitivity Thermoluminescent Dosimeters (TLDs) for Dosimetric Characterization of Low-Energy Brachytherapy Sources.

PURPOSE: To investigate the utility and accuracy of high-sensitivity TLD for dosimetric characterization of low-energy brachytherapy sources. METHODS: One hundred high-sensitivity (TLD-100H) and 100 normal-sensitivity (TLD-100) TLDs were used in this study. The TLD-100s were annealed at 400°C for one hour and then kept at room temperature for 45 minutes followed by 80°C heating for 24 hours. To prevent temperature overshot from reducing the sensitivity of TLD-100Hs, a novel thermal reservoir was built, tested, and used to anneal TLD-100H at 240 0C for 15 minutes and then kept at room temperature for 45 minutes followed by 100 0C heating for one hour. These TLDs were then irradiated uniformly in a large cavity Cs-137 irradiator for biomedical research (Shepherd, Mark III) to test their reproducibility and to establish their relative sensitivities. The radial dose function of a Model AgX100 125I source was measured using both types of TLDs in water-equivalent solid phantoms as a test case. The radial dose function measured by the TLD-100H was compared with that measured by TLD-100 to determine its utility in brachytherapy dosimetry characterization. RESULTS: Consistent and accurate annealing of high-sensitivity TLDs was achieved by using a custom-built thermal reservoir system. TLD-100H was found to be about 18 times more sensitive than TLD-100. For a 125I source with a source-strength of 2.7U, the irradiation time for radial dose function characterization up to 7 cm can be cut down from 38 days to 3 days. The radial dose function measured by TLD-100H agreed well (within ±6%) with that measured by TLD-100. CONCLUSIONS: A novel thermal reservoir was used for consistent annealing of high-sensitivity TLDs. TLD-100H can significantly shorten the irradiation time needed for a complete characterization of radial dose function. Investigation of TLD-100H for complete brachytherapy source characterization is in progress. Supported in part by NIH grant R01-CA134627.

Nerve reconstruction in patients with obstetric brachial plexus injury results in worsening of glenohumeral deformity: a case-control study of 75 patients.

Whereas a general trend in the management of obstetric brachial plexus injuries has been nerve reconstruction in patients without spontaneous recovery of biceps function by three to six months of age, many recent studies suggest this may be unnecessary. In this study, the severity of glenohumeral dysplasia and shoulder function and strength in two groups of matched patients with a C5-6 lesion at a mean age of seven years (2.7 to 13.3) were investigated. One group (23 patients) underwent nerve reconstruction and secondary operations, and the other (52 patients) underwent only secondary operations for similar initial clinical presentations. In the patients with nerve reconstruction shoulder function did not improve and they developed more severe shoulder deformities (posterior subluxation, glenoid version and scapular elevation) and required a mean of 2.4 times as many operations as patients without nerve reconstruction. This study suggests that less invasive management, addressing the muscle and bone complications, is a more effective approach. Nerve reconstruction should be reserved for those less common cases where the C5 and C6 nerve roots will not recover.

Surgical correction of the medial rotation contracture in obstetric brachial plexus palsy.

The medial rotation contracture caused by weak external rotation secondary to obstetric brachial plexus injury leads to deformation of the bones of the shoulder. Scapular hypoplasia, elevation and rotation deformity are accompanied by progressive dislocation of the humeral head. Between February and August 2005, 44 children underwent a new surgical procedure called the 'triangle tilt' operation to correct this bony shoulder deformity. Surgical levelling of the distal acromioclavicular triangle combined with tightening of the posterior glenohumeral capsule (capsulorrhaphy) improved shoulder function and corrected the glenohumeral axis in these patients. The posture of the arm at rest was improved and active external rotation increased by a mean of 53 degrees (0 degrees to 115 degrees ) in the 40 children who were followed up for more than one year. There was a mean improvement of 4.9 points (1.7 to 8.3) of the Mallet shoulder function score after surgical correction of the bony deformity.

Improvement in abduction of the shoulder after reconstructive soft-tissue procedures in obstetric brachial plexus palsy.

Residual muscle weakness in obstetric brachial plexus palsy results in soft-tissue contractures which limit the functional range of movement and lead to progressive glenoid dysplasia and joint instability. We describe the results of surgical treatment in 98 patients (mean age 2.5 years, 0.5 to 9.0) for the correction of active abduction of the shoulder. The patients underwent transfer of the latissimus dorsi and teres major muscles, release of contractures of subscapularis pectoralis major and minor, and axillary nerve decompression and neurolysis (the modified Quad procedure). The transferred muscles were sutured to the teres minor muscle, not to a point of bony insertion. The mean pre-operative active abduction was 45 degrees (20 degrees to 90 degrees ). At a mean follow-up of 4.8 years (2.0 to 8.7), the mean active abduction was 162 degrees (100 degrees to 180 degrees ) while 77 (78.6%) of the patients had active abduction of 160 degrees or more. No decline in abduction was noted among the 29 patients (29.6%) followed up for six years or more. This procedure involving release of the contracted internal rotators of the shoulder combined with decompression and neurolysis of the axillary nerve greatly improves active abduction in young patients with muscle imbalance secondary to obstetric brachial plexus palsy.

Macular hole surgery without prone positioning.

PURPOSE: To investigate the role of vitrectomy without prone posturing in the anatomic and functional outcome of macular hole surgery (MHS). METHODS: Forty-one consecutive eyes of 41 patients with stage II-IV full-thickness macular holes underwent pars plana vitrectomy and 16% C3F8 tamponade. In 25 cases posturing group (P), subjects were instructed to assume prone positioning for 10 days postoperatively, whereas in 16 cases non-posturing group (NP) patients were advised to avoid lying supine but no other posturing instructions were given. Preoperative, intraoperative and postoperative clinical data were collected, with macular hole closure rate and change in LogMAR visual acuity, contrast sensitivity, metamorphopsia, and 25-Visual Function Questionnaire (VFQ-25) being the primary outcome measures. RESULTS: Over a mean follow-up of 4.21.2 months, anatomical hole closure was noted in 22/25 (88%) and 14/16 (87.5%) in groups P and NP respectively. Visual acuity improved by a mean of eight letters and there was no significant difference in the two groups (P=0.724). Similarly, postoperative prone posturing did not have an effect on the final contrast sensitivity, metamorphopsia, and VFQ-25 composite scores (P=0.238, P=0.472, and P=0.87, respectively). However, eyes in group NP developed significantly more severe cataract in the early postoperative period (P=0.02). CONCLUSIONS: Prone posturing following MHS provides no functional or anatomic benefit but it is associated with slower progression of cataract. Combined phacovitrectomy without face down positioning may be considered for all phakic patients undergoing MHS.

Giant cell tumor of bone: Multimodal approach.

BACKGROUND: The clinical behavior and treatment of giant cell tumor of bone is still perplexing. The aim of this study is to clarify the clinico-pathological correlation of tumor and its relevance in treatment and prognosis. MATERIALS AND METHODS: Ninety -three cases of giant cell tumor were treated during 1980-1990 by different methods. The age of the patients varied from 18-58 yrs with male and female ratio as 5:4. The upper end of the tibia was most commonly involved (n=31), followed by the lower end of the femur(n=21), distal end of radius(n=14), upper end of fibula (n=9), proximal end of femur(n=5), upper end of the humerus(n=3), iliac bone(n=2), phalanx (n=2) and spine(n=1). The tumors were also encountered on uncommon sites like metacarpals (n=4) and metatarsal(n=1). Fifty four cases were treated by curettage and bone grafting. Wide excision and reconstruction was performed in twenty two cases. Nine cases were treated by wide excision while primary amputation was performed in four cases. One case required only curettage. Three inaccessible lesions of ilium and spine were treated by radiotherapy. RESULTS: 19 of 54 treated by curettage and bone grafting showed a recurrence. The repeat curettage and bone grafting was performed in 18 cases while amputation was done in one. One each out of the cases treated by wide excision and reconstruction and wide excision alone recurred. In this study we observed that though curettage and bone grafting is still the most commonly adopted treatment, wide excision of tumor with reconstruction has shown lesser recurrence. CONCLUSION: For radiologically well-contained and histologically typical tumor, curettage and autogenous bone grafting is the treatment of choice. The typical tumors with radiologically deficient cortex, clinically aggressive tumors and tumors with histological Grade III should be treated by wide excision and reconstruction.

Dose rate constant of a cesium-131 interstitial brachytherapy seed measured by thermoluminescent dosimetry and gamma-ray spectrometry.

The aim of this work was to conduct an independent determination of the dose rate constant of the newly introduced Model CS-1 131Cs seed. A total of eight 131Cs seeds were obtained from the seed manufacturer. The air-kerma strength of each seed was measured by the manufacturer whose calibration is traceable to the air-kerma strength standard established for the 131Cs seeds at the National Institute of Standards and Technology (1 sigma uncertainty < 1%). The dose rate constant of each seed was measured by two independent methods: One based on the actual photon energy spectrum emitted by the seed using gamma-ray spectrometry and the other based on the dose-rate measured by thermoluminescent dosimeter (TLD) in a Solid Water phantom. The dose rate constant in water determined by the gamma-ray spectrometry technique and by the TLD dosimetry are 1.066 +/- 0.064 cGyh(-1)U(-1) and 1.058 +/- 0.106 cGyh(-1)U(-1), respectively, showing excellent agreement with each other. These values, however, are approximately 15% greater than a previously reported value of 0.915 cGyh(-1)U(-1) [Med. Phys. 31, 1529-1538 (2004)]. Although low-energy fluorescent x rays at 16.6 and 18.7 keV, originating from niobium present in the seed construction, were measured in the energy spectrum of the 131Cs seeds, their yields were not sufficient to lower the dose rate constant to the value of 0.915 cGyh(-1)U(-1). Additional determinations of the dose rate constant may be needed to establish an AAPM recommended consensus value for routine clinical use of the 131Cs seed.

Amifostine and autologous hematopoietic stem cell support of escalating-dose melphalan: a phase I study.

This study was conducted to define a new maximum tolerated dose and the dose-limiting toxicity (DLT) of melphalan and autologous hematopoietic stem cell transplantation (AHSCT) when used with the cytoprotective agent amifostine. Fifty-eight patients with various types of malignancy who were ineligible for higher-priority AHSCT protocols were entered on a phase I study of escalating doses of melphalan beginning at 220 mg/m(2) and advancing by 20 mg/m(2) increments in planned cohorts of 4 to 8 patients until severe regimen-related toxicity (RRT) was encountered. In all patients, amifostine 740 mg/m(2) was given on 2 occasions before the first melphalan dose (ie, 24 hours before and again 15 minutes before). AHSCT was given 24 hours after the first melphalan dose. Melphalan was given in doses up to and including 300 mg/m(2). Hematologic depression was profound, although it was rapidly and equally reversible at all melphalan doses. Although mucosal RRT was substantial, it was not the DLT, and some patients given the highest melphalan doses (ie, 300 mg/m(2)) did not develop mucosal RRT. The DLT was not clearly defined. Cardiac toxicity in the form of atrial fibrillation occurred in 3 of 36 patients treated with melphalan doses >/=280 mg/m(2) and was deemed fatal in 1 patient given melphalan 300 mg/m(2). (Another patient with a known cardiomyopathy was given melphalan 220 mg/m(2) and died as a result of heart failure but did not have atrial fibrillation.) Another patient given melphalan 300 mg/m(2) died of hepatic necrosis. The maximum tolerated dose of melphalan in this setting was thus considered to be 280 mg/m(2), and 27 patients were given this dose without severe RRT. Moreover, 38 patients were evaluable for delayed toxicity related to RRT; none was noted. Tumor responses have been noted at all melphalan doses and in all diagnostic groups, and 21 patients are alive at median day +1121 (range, day +136 to day +1923), including 16 without evidence of disease progression at median day +1075 (range, day +509 to day +1638). Amifostine and AHSCT permit the safe use of melphalan 280 mg/m(2), an apparent increase over the dose of melphalan that can be safely administered with AHSCT but without amifostine. Further studies are needed not only to confirm these findings, but also to define the antitumor efficacy of this regimen. Finally, it may be possible to evaluate additional methods of further dose escalation of melphalan in this setting.

Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma.

High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m(2) plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D +100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL+AF+AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D +1163 (range D +824 to D +1630); one of these patients had a nonmyeloablative allograft as consolidation on D +106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL+AF+AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.

Low plasma zinc and iron in pica.

OBJECTIVE: To determine role of trace elements in causation of pica with specific reference to zinc and iron we studied plasma levels of iron (Fe), Zinc (Zn), calcium (Ca) and magnesium (Mg) and blood lead (Pb) levels by atomic absorption spectrophotometer in 31 children with pica (Pica Group) and 60 controls matched for age, sex and nutrition (Control Group) in an observational case and control study in the settings of outpatient clinic of a tertiary care, teaching hospital. METHODS: Data from each group were further stratified by hemoglobin level <9 and >9 g/dl into two subgroups pica-1 and pica-2, and control-1 and control-2 respectively, to control for confounding effect of iron deficiency anemia. RESULTS: The plasma Fe level (mean +/- SD) in children with pica (42.7 +/- 9.2) mg/dl) was about 20% lower than that in controls (51.5 +/- 10.0 mg/dl, p < 0.001). Plasma Zn levels in the pica group (60 +/- 4.4 mg/dl) was about 45% lower than those in controls (110.2 +/- 8.5 mg/dl, p<0.001). Correlation of Zn and Fe levels with pica-related variables such as age at onset, duration and frequency and number of inedible objects ingested was not significant. CONCLUSION: These findings suggest that hypozincemia with low iron levels may be the possible cause of pica and contradict the contention that low levels of plasma Zn and Fe could be an effect of pica.

Efficacy of plant-produced recombinant antibodies against HCG.

BACKGROUND: Antibody engineering facilitates the construction of different antibody formats [single chain variable fragment (scFv), diabody, full-size chimeric monoclonal antibody] with ease. METHODS: We constructed recombinant antibodies against HCG, which is widely used in pregnancy testing and is also produced by a number of cancers. RESULTS: The recombinant antibodies were transiently expressed in tobacco leaves to levels of up to 40 mg of pure protein per kg fresh leaf weight. Enzyme linked immunosorbent assay (ELISA) and electrophoretic mobility assay (EMSA) confirmed antibody specificity for the beta subunit of beta-HCG. The efficacy was confirmed by inhibiting HCG induced testosterone production by Leydig cells in vitro and by blocking the HCG induced increase in mouse uterine weight in vivo. CONCLUSIONS: Passive immunization with recombinant HCG-specific antibodies may have clinical utility as (i) diagnostic and therapeutic tools for HCG-expressing cancers and (ii) contraceptive measures.