Assessment of non-small cell lung cancer viability and necrosis with three radiopharmaceuticals

Assessment of tumor viability and necrosis of non-small cell lung cancer and detection of distant metastases are important for diagnosis, staging, monitoring the response to treatment and planning long-term management. We performed scintigraphy on patients with non-small cell lung cancer to determine the utility of three tumor targeting tracers for diagnosing primary lung cancer, for differentiating viable from necrotic tumor tissue and for detecting distant bone and soft tissue metastases. Our patients were divided into groups. Group A consisted of 27 patients, 25 male and 2 female, mean age 59 years, range from 35 to 72 years. These patients underwent radioimmunoscintigraphy (RIS) using monoclonal antibody against human milk fat globule labeled with technetium-99m ((99m)Tc). Group B consisted of 23 patients, 21 male and 2 female, mean age 56 years, range: 37 to 70 years. Group C consisted of 24 patients, 20 male and 4 female, mean age 58 years, range: 35 to 74 years. Both Groups B and C underwent chest and whole-body scintigraphy with 555 MBq of (99m)Tc-sestamibi ((99m)Tc-S) and 111 MBq of thallium-201 chloride ((201)TlCl), respectively. Tumor to non-tumor ratio was calculated. Our findings show that RIS had 52% sensitivity in detecting primary non-small cell lung cancer. In contrast, the sensitivity of (99m)Tc-S and of (201)Tl scintigraphy was 87% and 88%, respectively. High uptake of all three radiopharmaceuticals was found in 6 patients with distant soft tissue and bone tissue metastases and in 1 patient with brain metastasis. Mean tumor to non-tumor ratios were similar: for RIS 1.7+/-0.4, for (99m)Tc-S 1.6+/-0.3 and for (201)Tl 1.6+/-0.2. In conclusion: (99m)Tc-S and (201)Tl scintigraphy are superior to RIS for detecting non-small primary lung cancers and potentially clinically useful methods for detecting primary lung cancer as above, as well as bone and soft tissue metastases.     

Indications, results and techniques of permanent prostate brachytherapy for localized prostate cancer

Introduction and objectiveProstate brachytherapy is a first-line therapeutic approach for localized prostate cancer in selected patients. We present our experience in brachytherapy and a thorough review of the literature.Materials and MethodsA review of the literature and evaluation of patient’s selection was done. Furthermore the implantation technique, oncological results according to the different risk groups and acute and chronic complications were also analyzed.ResultsThe biochemical relapse-free 10 year survival rate was 87-96% in low risk tumours and 63-86% in intermediate risk tumours. A total of 3-24% underwent urinary retention that required TURP in 0-8,7%. Other complications were urinary incontinence in 0-6,7%, proctitis in 0-15,5%, erectile dysfunction in 6,3-30%, rectal ulcer/fistula in 0-5,4%.ConclusionsProstate brachytherapy is a safe and effective treatment in low and intermediate risk patients with prostate cancer.     

Evaluation of elbow and shoulder problems in professional baseball pitchers

When a professional athlete injures an elbow or shoulder, the uninjured joint must receive as much attention as the injured joint. Is there a relationship between injury of one joint and subsequent injury of the other joint? In the prospective study reported here, we created a database (a) to determine whether injury to one joint was more likely to result in a problem with the other joint and (b) to analyze for trends and correlations. A survey was administered to all pitchers on a professional baseball team to collect data about shoulder and elbow problems during their careers. Eighty-four pitchers (737 seasons of experience, 52 index injuries) were evaluated. Of the injured players, 27 were treated surgically. Risk for later injury was 4.6 times larger for players who had an index surgery than for those who had not. Of the players who had ulnar collateral ligament (UCL) reconstruction, 42% later sustained a shoulder injury. No player with rotator cuff surgery sustained a subsequent elbow or shoulder injury. There were significantly more upper extremity injuries with right-handed throwers. An elbow injury was more likely to result in shoulder problems, specifically after UCL reconstruction. Players who required surgery were almost 5 times more likely to have a later injury or surgery than players who did not require surgery.     

A biomechanical comparison of scaphoid fixation with bone grafting using iliac bone or distal radius bone

PURPOSE: Although many scaphoid fractures may be treated by immobilization, complex scaphoid fractures generally require bone grafting with internal fixation. A preferred source of bone graft for scaphoid grafting is the iliac crest. Donor site morbidity from iliac crest harvest, however, is a known complication, and the comparable strength and osteogenic properties of bone harvested from other sites are unclear. To this end, we have conducted a cadaveric comparative investigation of the strength of scaphoid nonunions with bone graft and internal fixation using either iliac crest bone or distal radius bone. METHODS: Ten paired, human, fresh-frozen cadaveric wrists were used to create a standard midwaist wedge osteotomy into which identically shaped distal radius or iliac crest bone wedges were internally fixed using headless compression screws. After bone density and computed tomography assessment of the bones, benchtop biomechanical testing was conducted to compare the strength of the scaphoids after iliac and distal radius grafting, at 2-mm displacement, and at failure. RESULTS: Analysis of scaphoid length, width, height, weight, density, and screw placement revealed no statistical differences between both bone graft groups. Although not significant, scaphoid nonunions grafted with distal radius bone evidenced a reduced load (3.23 +/- 0.26 Nm) to 2-mm displacement compared with iliac crest bone (5.97 +/- 0.68 Nm). Similarly, though not significant, scaphoids grafted with distal radius bone showed a reduced load (4.18 +/- 0.30 Nm) to failure compared with iliac crest bone grafting (6.42 +/- 0.66 Nm). Although no significance was found between the 2 grafting methods, a trend toward greater strength in the iliac crest graft group was observed. CONCLUSIONS: Given the comparable biomechanical strength shown between iliac and distal radius bone in this study and the simplified surgical technique of distal radius harvesting, the data justify use of distal radius bone as a viable alternative donor source in scaphoid fracture treatment.     

Long-term results after closed reduction of latedetected hip dislocation: 60 patients followed up to skeletal maturity

Background This retrospective study was undertaken because there is limited knowledge about the long-term results after closed reduction of late-detected hip dislocation. The aims were to evaluate the outcome after skeletal maturity and to find predictive factors for good and poor results.

Patients and methods The material included 60 patients (78 hips, 53 girls) treated during the period 1958-62. The primary treatment was skin traction for 36 (16-76) days. Closed reduction was performed in all hips except 4 that needed open reduction. The mean age at reduction was 20 (4-65) months. Hip spica plaster was worn for 9 (6-20) months. Within 3 years of the start of treatment, derotation femoral osteotomy was performed because of increased femoral anteversion in 35 patients. Later, 28 patients underwent additional surgery on the femur or acetabulum to improve femoral head coverage. Radiographs at the time of diagnosis and during follow-up to skeletal maturity were assessed. The average age of the patients at the most recent follow-up was 26 (15-42) years.

Results The femoral head coverage normalized during the primary treatment and then decreased somewhat during the remaining growth period. The dysplasia of the acetabulum improved markedly during the first year after reduction. It continued to improve, but to a much lesser degree, until 8-10 years of age. A satisfactory radiographic outcome at skeletal maturity (Severin grades I and II) was obtained in 63% of the hips. Early derotation osteotomy of the femur did not improve the outcome. Avascular necrosis of the femoral head occurred in 14% of the hips. Risk factors for unsatisfactory outcome at skeletal maturity were high initial dislocation, steep acetabulum 1 year after reduction, reduced femoral head coverage at age 8-10 years, and avascular necrosis.

Interpretation The specific risk factors and the radiographic outcome—with satisfactory long-term results in nearly two-thirds of the patients—would be valuable for comparison with outcome studies after more modern treatment regimes.     

Immune response to perforated and partially demineralized bone allografts

Immune responses have been shown to be involved in the pathogenesis of clinical complications of cortical bone allografts. In an attempt to reduce the immunogenicity of these allografts, we evaluated cortical bone allografts modified by laser perforation and partial demineralization transplanted orthotopically into sheep tibiae. The recipient animals were divided into three groups, of eight animals each, according to the type of cortical allograft that was transplanted: group 1, no treatment (control); group 2, demineralization only; and group 3, laser perforation and partial demineralization. All animals were tissue-typed by biochemical definition of MHC class I molecules, using unidimensional isoelectric focusing and Western blotting. Mismatches of donors and recipients were assessed by testing samples of each donor and recipient pair in parallel and by comparing their individual bands. Donor-specific alloantibodies were detected by a similar technique, using an enzyme-linked immunosorbent assay (ELISA) format. Negative controls were included in all tests. All grafts were poorly immunogenic, whether they were untreated, processed by partial demineralization, or processed by both laser perforation and partial demineralization. Only two recipient animals showed a transient, antibody-mediated donor-specific immune response. One of these animals had received a control allograft, whereas the other animal had received a laser-perforated and partially demineralized bone allograft. All of the grafts in this study, including control grafts, were stripped of soft tissues and their bone marrow was removed; cellular sources of alloantibody stimulation may have been eliminated by these processes. The results of this study suggest that immune responses to bone allografts may be reduced by removing the bone marrow and adjacent soft tissues. The processing of cortical bone allografts by laser perforation and partial demineralization appeared to have little effect on immune responses.     

Determinants of bone strength and fracture incidence in adult Finns: Cardiovascular Risk in Young Finns Study (the GENDI pQCT study)

Summary

Peripheral bone strength and fracture risk were studied in young adult Finns. Peripheral bone measures were associated with risk factors of osteoporosis in young adults and discriminated between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.

Purpose

This is a cross-sectional study of the determinants of bone strength and fracture risk in young Finns using peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS).

Methods

pQCT scans were performed in 1,884 subjects at distal and shaft sites of non-dominant radius and left tibia, and QUS measures (n?=?1,415) at the left calcaneus. Lifestyle factors and medical conditions affecting bone health were assessed with questionnaires.

Results

In men, the youngest age cohort had the lowest trabecular volumetric bone mineral density (vBMD) at radius and tibia (difference between the youngest and the oldest, 4.4% and 5.6%, respectively, P?<?0.001) and lowest speed of ultrasound at the calcaneus (difference 0.5%, P?=?0.016). In women, bone traits did not differ by age groups. When sexes were pooled, underweight (relative risk (RR)?=?2.95, P?<?0.001), excess alcohol intake (1.52, P?=?0.036), smoking (1.29, P?=?0.025), Crohn’s disease or inflammatory bowel syndrome (2.43, P?=?0.016), epilepsy (2.54, P?=?0.011), use of corticosteroids (2.01, P?<?0.001) and inactivity (1.34, P?=?0.045) increased the risk of low trabecular vBMD. RRs for low-energy fractures were excess alcohol intake (2.58, P?=?<0.001), anorexia (3.74, P?=?0.041) and hypogonadism (2.08, P?=?0.015). Same risk factors predicted BMD and fractures in both sexes. Trabecular bone mineral content, vBMD and bone strength index showed greatest differences (4–9%; P?<?0.05) between those with and without low-energy fractures.

Conclusions

Peripheral QCT traits are associated with common risk factors of osteoporosis in young Finns and discriminate between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.     

Prognostic significance of thymidylate synthase polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy

Aim There is a lack of prognostic factors of preoperative chemoradiation for locally advanced rectal cancer. Thymidylate synthase (TS) is the most important target of 5‐fluorouracil; three main genetic polymorphisms of TS have been described. We analysed the prognostic value of these in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation. Method Ninety‐nine patients treated between November 2001 and March 2009 were included. All were treated by radiotherapy (5040 cGy) and concomitant fluoropyrimidine‐based chemotherapy. Three polymorphisms were analysed: (i) a double (2R) or triple (3R) repeat of a 28 base pair (bp) tandem sequence upstream of the ATG codon initiation site in the 5′‐terminal regulatory region, (ii) a functional G > C single nucleotide polymorphism present in the second repeat of the 3R alleles and (iii) a 6 bp deletion at nucleotide 1494 in the 3′‐untranslated region. DNA was extracted from paraffin‐embedded core biopsies taken from the tumour and the genotype was analysed using polymerase chain reaction restriction fragment length polymorphism. Results The 6 bp polymorphism was significantly associated with disease‐free survival (+ 6 bp/+ 6 bp vs?6 bp/?6 bp, P = 0.032 logistic regression). No differences were found in disease‐free survival according to the other polymorphisms studied. No relationship was observed between the different TS genotypes and pathological regression. Conclusion The study suggests that the TS 6 bp polymorphism may be a predictor of disease‐free survival in patients with locally advanced rectal cancer treated with fluoropyrimidine‐based chemoradiation.     

Removal of Protein‐Bound,Hydrophobic Uremic Toxins by a Combined Fractionated Plasma Separation and Adsorption Technique

Protein‐bound uremic toxins, such as phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate, contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, based on their protein binding, these hydrophobic uremic toxins are poorly cleared during conventional dialysis and thus accumulate in CKD‐5D patients. Therefore, we investigated whether hydrophobic and cationic adsorbers are more effective for removal of protein‐bound, hydrophobic uremic toxins than conventional high‐flux hemodialyzer. Five CKD‐5D patients were treated using the fractionated plasma separation, adsorption, and dialysis (FPAD) system for 5 h. A control group of five CKD patients was treated with conventional high‐flux hemodialysis. Plasma concentrations of phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate were measured. Removal rates of FPAD treatment in comparison to conventional high‐flux hemodialysis were increased by 130% for phenylacetic acid, 187% for indoxyl sulfate, and 127% for p‐cresol. FPAD treatment was tolerated well in terms of clinically relevant biochemical parameters. However, patients suffered from mild nausea 2 h after the start of the treatment, which persisted until the end of treatment. Due to the high impact of protein‐bound, hydrophobic uremic toxins on progression of CKD and CVD in CKD‐5D patients, the use of an adsorber in combination with dialysis membranes may be a new therapeutic option to increase the removal rate of these uremic toxins. However, larger, long‐term prospective clinical trials are needed to demonstrate the impact on clinical outcome.