Minimally invasive spinal decompression surgery in diabetic patients: perioperative risks, complications and clinical outcomes compared with non-diabetic patients' cohort.

BACKGROUND: Prior studies have documented an increased complication rate in diabetic patients undergoing spinal surgery. However, the impact of diabetes on the risk of postoperative complications and clinical outcome following minimally invasive spinal (MIS) decompression is not well understood. OBJECTIVES: To compare complication rates and outcomes of MIS decompression in diabetic patients with a cohort of non-diabetic patients undergoing similar procedures. METHODS: Medical records of 48 patients with diabetes and 151 control patients that underwent minimally invasive lumbar decompression between April 2009 and July 2014 at our institute were reviewed and compared. Past medical history, the American Society of Anesthesiologists score, perioperative mortality, complication and revision surgeries rates were analyzed. Patient outcomes included: the visual analog scale and the EQ-5D scores. RESULTS: The mean age was 68.58 ± 11 years in the diabetic group and 51.7 ± 17.7 years in the control group. No major postoperative complications were recorded in either group. Both groups were statistically equivalent in their postoperative length of stay, minor complications and revision rates. Both groups showed significant improvement in their outcome scores following surgery. CONCLUSIONS: Our results indicate that minimally invasive decompressive surgery is a safe and effective treatment for diabetic patients and does not pose an increased risk of complications. Future prospective studies are necessary to validate the specific advantages of the minimally invasive techniques in the diabetic population. These slides can be retrieved under Electronic Supplementary Material.

Cost-effectiveness analysis of intensity-modulated radiation therapy with normal and hypofractionated schemes for the treatment of localised prostate cancer.

The aim of our analysis was to compare the cost-effectiveness of high-dose intensity-modulated radiation therapy (IMRT) and hypofractionated intensity-modulated radiation therapy (HF-IMRT) versus conventional dose three-dimensional radiation therapy (3DCRT) for the treatment of localised prostate cancer. A Markov model was constructed to calculate the incremental quality-adjusted life years and costs. Transition probabilities, adverse events and utilities were derived from relevant systematic reviews. Microcosting in a large university hospital was applied to calculate cost vectors. The expected mean lifetime cost of patients undergoing 3DCRT, IMRT and HF-IMRT were 7,160 euros, 6,831 euros and 6,019 euros respectively. The expected quality-adjusted life years (QALYs) were 5.753 for 3DCRT, 5.956 for IMRT and 5.957 for HF-IMRT. Compared to 3DCRT, both IMRT and HF-IMRT resulted in more health gains at a lower cost. It can be concluded that high-dose IMRT is not only cost-effective compared to the conventional dose 3DCRT but, when used with a hypofractionation scheme, it has great cost-saving potential for the public payer and may improve access to radiation therapy for patients.

The effect of maternal habitus on macronutrient content of human milk colostrum.

OBJECTIVE: There is a paucity of studies on the impact of maternal body mass index (BMI) on macronutrient content of human milk colostrum (HMC). The objective of this study was to compare macronutrient content of HMC in healthy women of term infants in relation to their BMI. We hypothesized that mother habitus influences human milk colostrum content. METHOD: Colostrum was collected from 109 healthy mothers of hospitalized healthy term infants divided into four prepregnancy BMI groups: 12 underweight, 59 normal weight, 20 overweight, and 18 obese women between 24 and 72 h after birth. Macronutrient content was measured using mid-infrared spectroscopy. RESULTS: There were no significant differences in macronutrients between the BMI groups. We performed four separate stepwise backward multiple regression analyses taking into account fat, carbohydrate, protein or energy content as dependent variables and maternal BMI, parity, gestational age, infant gender, maternal age, maternal education, mode of delivery and time postdelivery. In these analyses, fat, carbohydrate and energy content were not related to maternal BMI, while protein content was significantly and positively correlated with BMI (P=0.008) and negatively correlated with gestational age (P=0.004) and time postdelivery (P<0.001). Colostrum carbohydrate content was positively correlated with parity. Colostrum fat and energy content were negatively correlated with maternal age and positively correlated with parity. CONCLUSION: Most macronutrient and energy content of colostrum are unaffected by prepregnancy maternal BMI, with the exception of protein content that is positively related to maternal BMI.

The effect of between-breast differences on human milk macronutrients content.

OBJECTIVE: Little is known about the effect of maternal handedness and preferential side of breastfeeding upon macronutrients concentration in human milk (HM). We aimed to compare macronutrients content of HM from both breasts, taking into account the self-reported preferential feeding ('dominant') breast, breast size and handedness (right versus left). We tested the null hypothesis that macronutrients content of HM is not affected by breast dominancy, breast size or maternal handedness. STUDY DESIGN: Fifty-seven lactating mothers were recruited. HM macronutrients were measured after mid manual expression using infrared transmission spectroscopy. RESULTS: Out of the 57 mothers recruited, 12 were excluded from the analyses because they brought in insufficient samples. Among the 22 who reported a size difference, 16 (73%) had a larger left breast (P<0.001). Approximately a third of women reported no breastfeeding side dominance, a third reported a right dominance and another third reported a left dominance. Breastfeeding side dominance was unaffected by either handedness or breasts size. When size asymmetry was reported (n=22) the dominant side was also the larger breast in 16 (73%) women, the smaller breast in 2 (9%) women, whereas 4 (18%) additional women with asymmetry had no preferential breastfeeding side. There were no statistically significant differences in macronutrients between the right and the left breasts. In multiple stepwise backward regression analysis, fat, carbohydrate, protein and energy contents were unaffected by maternal handedness, breast side dominance or breast size asymmetry. CONCLUSIONS: Macronutrients content of mid expression HM is unaffected by maternal handedness, breast size or breast side dominance.

Correlation between tumor-associated proteins and response to neoadjuvant treatment in patients with advanced squamous-cell esophageal cancer.

BACKGROUND: Possible predictive markers of response to neoadjuvant radiochemotherapy (NRCT) of esophageal cancer have been identified. PATIENTS AND METHODS: Patient biopsies were obtained from both tumor and normal tissue before the NRCT of locally advanced esophageal squamous cell carcinoma. Protein solutions were separated and immunoblot analysis was performed with heat shock protein (Hsp)16.2, heme-binding protein 2 (SOUL), BCL2-associated X protein (Bax), B-cell-associated leukemia protein 2 (Bcl-2) and heat shock protein 90 (Hsp90) antibodies. Following NRCT, the patients were restaged according to the Response Evaluation Criteria In Solid Tumors (RECIST). Following resections the pathological down-staging was evaluated. RESULTS: Clinical restaging revealed a response rate of 65%. Pathological examination revealed down-staging in 30% and 25% of the cases for the T and N categories respectively. Compared to the normal esophageal mucosa, a decreased expression of Hsp16.2, Hsp90 and SOUL proteins and an increased Bax/Bcl-2 ratio was found in the responding tumors. CONCLUSION: Hsp16,2, Hsp90 and SOUL expression and Bax/ Bcl-2 ratio correlates to the efficacy of NRCT and predict outcome in patients with locally advanced squamous-cell esophageal cancer.

Brachytherapy of vestibular schwannomas: report of three cases.

OBJECTIVE: Gamma knife and multileaf collimator LINAC have recently gained notoriety in the treatment of vestibular schwannomas. Without the use of gamma knife or LINAC, we have successfully pursued the 125-iodine interstitial irradiation of three vestibular schwannomas. CASE REPORT: Up to March 2004, there was a 57 and 45 month follow-up period in two cases. One patient died of heart insufficiency 15 months after the brachytherapy. At the end of the follow-up period audiometric examinations revealed slight improvements of hearing in patients 1 and 2. In patient 1, the tumor volume measured was 4.06 mL on the control CT indicating a 40 % shrinkage in comparison to the 6.74 mL target volume at the brachytherapy. In patient 2, the tumor volume measured on the control MRI was 6.64 mL, indicating a 42 % shrinkage of the 11.45 mL target volume at the time of brachytherapy. Eleven months after the brachytherapy in patient 3 we found 10 % tumor shrinkage, a post-irradiation cyst developed inside the tumor and reached up to 35 % of the tumor volume. INTERVENTION: In the treatment of three vestibular schwannomas we have used CT and image-fusion guided 125-iodine stereotactic brachytherapy. CONCLUSION: Due to financial considerations, gamma knife and LINAC are not available for many countries and neurosurgical institutes. In the absence of the above-mentioned radiosurgical methods, we have shown brachytherapy as a new alternative and solution in the treatment of the three patients studied with vestibular schwannoma.

CT densitometry of the brain: a novel method for early detection and assessment of irradiation induced brain edema.

The purpose of the study was to examine if the CT densitometric analysis during radiotherapy (RT) of brain tumors is suitable for the early detection of RT induced brain edema (BE), predicting related neurological progress, and assessing the effects of different edema therapies. Planimetric CT-densitograms were constructed by modifying the "High-Lighting" method. Three theoretical density regions were defined and color-coded on the images of the brain. These were defined as edema (10-20 HU), mild edema, and normal brain (29-38 HU). Corresponding axial CT slices were created at the mid-level of the lesion and that of the periventricular white matter to verify the changes in perifocal and diffuse BE. The monitoring was performed on 50 solitary brain tumor patients treated with RT. During RT courses weekly CT-densitometric examinations were carried out. We experienced that changes in densitograms coincided with clinical symptoms, furthermore, preceded the latter. With the use of preventive edema medication based on diuretics and along with adjunctive edema medication adopted to densitograms, the 5-7 week irradiation was completed without ultimate worsening in performance state in 49 of 50 cases and besides we succeeded in avoiding the routine usage of steroids. Based on our findings the CT-densitometry is suitable for early detection and continuous assessment of BE and preventing patient distress during RT. This simple, reproducible and non-invasive procedure could provide an additional clinical tool for new treatment strategies.

The time-course of metastases from breast cancer after mastectomy and breast-conserving surgery with and without isolated local-regional recurrence.

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local-regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.

[The effect of tumour bed boost on local control after breast conserving surgery. First results of the randomized boost trial of the National Institute of Oncology] / A tumorágy kiegészítô besugárzásának hatása a lokális daganatmentességre emlômegtartó mûtét után. First results of the randomized boost trial of the National Institute of Oncology.

PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC) after breast conserving surgery in a prospective study. METHODS: Between 1995 and 1998, 207 women with early invasive breast cancer who underwent conservative operation were treated by 50 Gy irradiation to the whole breast and then randomly assigned to receive either no further radiotherapy (n=103) or a boost to the tumour bed (n=104) with either 16 Gy electron (n=52) or 12-14.25 Gy high dose rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude rate of local recurrence was 6.7% with and 13.6% without boost. The respective rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC, relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1% (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111), respectively, in favour of the boost group. Systemic treatments had no significant impact on LTC (88.9% with and 89.6% without systemic treatment, p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free survival was improved significantly with boost. However, the influence of boost treatment on breast cancer-specific survival should be tested in further studies. In spite of the higher incidence of late radiation side effects in the boost arm, boost dose is strongly recommended for patients at high risk for local recurrence. The final results of the EORTC trial and other ongoing studies will help to clarify the indication of boost dose according to prognostic subgroups.

[CT- and MRI-guided conformal interstitial and external beam radiotherapy of primary brain tumors: prospects in Hungary]. / Elsódleges agydaganatok CT-alapú 3D konformális sugárkezelése: külsó és szövetközi besugárzási lehetóségek hazánkban.

The technical improvements gained over the last decade in neuroradiology and radiotherapy have brought significant theoretical and experimental changes in the treatment of primary glial brain tumours. The follow-up of patients with CT, MRI and isotope diagnostic examinations proves that the relapses take place in the vicinity of the primary site in most cases. Consequently, the conventional large fields or whole brain irradiation techniques have been phased out and the conformal irradiation methods focused on the tumorous targets have gained ground. The exact neuroanatomic projection, the image based 3-dimensional treatment planning methods and the conformal irradiation techniques ensure that only the tumorous or the potentially infiltrated regions become irradiated with maximal protection of the normal brain tissues. The increased protection of the normal tissues makes a dose escalation possible, which may result in the augmentation of the therapeutic benefits. In Hungary both the interstitial and the external beam conformal radiotherapies of the CNS have become accessible in practice over the recent years. In possession of manifold treatment modalities (percutaneous fractionated conformal radiotherapy, stereotactic radiosurgery, high dose rate after-loading and low dose rate interstitial irradiation), it is found necessary to overview the indicative territories, advantages, limitations and possible complications of different interventions. The authors describe the possible routes of further improvements and ways of dose escalation. Nevertheless, it is emphasised that gliomas--with reduced radiosensitivity and high potential to infiltrate the adjacent brain tissues-represent the illness in the whole CNS. It implies that in the future it will probably be necessary to initiate systemic therapeutic modalities in the course of routine treatment strategies in addition to the focused and more effective radiotherapy regimens.

CT-image-based conformal brachytherapy of breast cancer. The significance of semi-3-D and 3-D treatment planning.

PURPOSE: To compare the conventional 2-D, the simulator-guided semi-3-D and the recently developed CT-guided 3-D brachytherapy treatment planning in the interstitial radiotherapy of breast cancer. PATIENTS AND METHODS: In 103 patients with T1-2, N0-1 breast cancer the tumor bed was clipped during breast conserving surgery. Fifty-two of them received boost brachytherapy after 46 to 50 Gy teletherapy and 51 patients were treated with brachytherapy alone via flexible implant tubes. Single, double and triple plane implant was used in 6, 89 and 8 cases, respectively. The dose of boost brachytherapy and sole brachytherapy prescribed to dose reference points was 3 times 4.75 Gy and 7 times 5.2 Gy, respectively. The positions of dose reference points varied according to the level (2-D, semi-3-D and 3-D) of treatment planning performed. The treatment planning was based on the 3-D reconstruction of the surgical clips, implant tubes and skin points. In all cases the implantations were planned with a semi-3-D technique aided by simulator. In 10 cases a recently developed CT-guided 3-D planning system was used. The semi-3-D and 3-D treatment plans were compared to hypothetical 2-D plans using dose-volume histograms and dose non-uniformity ratios. The values of mean central dose, mean skin dose, minimal clip dose, proportion of underdosaged clips and mean target surface dose were evaluated. The accuracy of tumor bed localization and the conformity of planning target volume and treated volume were also analyzed in each technique. RESULTS: With the help of conformal semi-3-D and 3-D brachytherapy planning we could define reference dose points, active source positions and dwell times individually. This technique decreased the mean skin dose with 22.2% and reduced the possibility of geographical miss. We could achieve the best conformity between the planning target volume and the treated volume with the CT-image based 3-D treatment planning, at the cost of worse dose homogeneity. The mean treated volume was reduced by 25.1% with semi-3-D planning, however, it was increased by 16.2% with 3-D planning, compared to the 2-D planning. CONCLUSION: The application of clips into the tumor bed and the conformal (semi-3-D and 3-D) planning help to avoid geographical miss. CT is suitable for 3-D brachytherapy planning. Better local control with less side effects might be achieved with these new techniques. Conformal 3-D brachytherapy calls for new treatment planning concepts, taking the irregular 3-D shape of the target volume into account. The routine clinical application of image-based 3-D brachytherapy is a real aim in the very close future.

The application of image fusion in stereotactic brachytherapy of brain tumours.

BACKGROUND: The visualization of any morphological volume (i.e. CT, MRI) together with an additional second morphological volume (i.e. CT, MRI) or functional data set, which may come from SPECT or PET, is a new method for treatment planning, verification and follow-up of interstitial irradiation. METHOD: The authors present their experience on interstitial irradiation of brain tumours with stereotactically implanted I-125 seeds supported by image fusion. The image fusion was performed by the BrainLab-Target 1.13 software on Alfa 430 (Digital) workstation before, during, and after interstitial irradiation of brain tumours with Iodine125 seeds. RESULTS AND INTERPRETATION: On the basis of 20 brachytherapeutic image fusion of stereotactic CT (slices with fiducials) with additional stereotactic CT, MRI, PET and SPECT images provides more accurate and precise target volume, more exact localization of catheters and isotope seeds (verification fusion), differentiation between the localization and amount of the necrotic and proliferating parts of the tumours and shows the volume changes in consequence of interstitial irradiation. The image fusion should help to improve the accuracy and minimize the perifocal morbidity of interstitial irradiation.

Sole brachytherapy of the tumor bed after breast conserving surgery: a new radiotherapeutic strategy for patients at low risk of local relapse.

The aim of the study was to test the hypothesis, if there were subgroups of early breast cancer patients in which sole brachytherapy (BT) of the tumor bed was a feasible and safe treatment option after breast conserving surgery (BCS). Forty four prospectively selected patients with Stage I-II breast cancer were entered into a protocol of postoperative tumor bed irradiation using interstitial high dose rate (HDR) implants. The HDR fractionation schedules were calculated according to the linear quadratic model. In 8 patients 7 x 4.33 Gy, in the other 36 patients 7 x 5.2 Gy were delivered to the tumor bed with 2 cm margin. The treatment planning was based on the 3 dimensional (3D) reconstruction of the clipped excision cavity, catheters and skin points. A conformal semi-3D dose planning was used. The side effects were assessed by mammograms, MRI- and clinical examinations. At a median follow up of 20 (7-36) months 1 (2.3%) local and 1 (2.3%) regional failure was observed. Distant metastasis did not occur. The cosmetic results were judged to be excellent in each case. G2 radiation side effects were observed in 2 (4.5%) cases. Postoperative sole BT of the tumor bed with careful patient selection and adequate quality assurance seems to be a feasible alternative to whole breast radiotherapy after BCS. Sole BT shortens the time of radiotherapy from 5-6 weeks to 5 days, and reduces the costs of treatment. The skin and volume sparing effect of interstitial irradiation may decrease the side effects of radiotherapy. A randomized study is in progress to define which subgroups of patients should be candidates for BT alone after BCS.

New 5'-(CGG)n-3' repeats in the human genome.

We identified new, potentially unstable loci in the human genome containing 5'-(CGG)n-3' trinucleotide repeats by screening a human subgenomic library as well as a chromosome 16 library with a 5'-(CGG)17-3' oligodeoxyribonucleotide probe. Five different clones were isolated, two from the chromosome 16 library and three from the subgenomic library. Determinations of the nucleotide sequences have revealed that the E7 clone displayed, in addition to the 5'-(CGG)n-3' trinucleotide repeat, a 5'-(CAG)n-3' and a 5'-(CCT)n-3' trinucleotide repeat. Two clones, CL16-1 and P5-5, had homologies to known genes, the human casein kinase II alpha' subunit (chromosome 16) and the human calcium-activated potassium channel (chromosome 10), respectively. Clones E7 and P4 were assigned to chromosome 6, whereas CL16-8 mapped to chromosome 16. Their potential coding capacities were assessed by RNA transfer (Northern blotting) experiments. Four different transcripts were identified by using the E7 clones as hybridization probes, three of them being brain-specific. The P4 clone was expressed in placenta and skeletal muscle. Minor polymorphisms within the repeats were observed in normal and in fragile X individuals. Lung and colon carcinoma cell lines in which some microsatellites were shown to be unstable were also investigated. Expansions of the 5'-(CGG)n-3' repeats were not found.

Stability of transgene methylation patterns in mice: position effects, strain specificity and cellular mosaicism.

The methylation status of a transgene, which carried the adenovirus type 2 E2A late promoter linked to the chloramphenicol acetyltransferase gene, was studied in three transgenic mouse lines (5-8, 7-1 and 8-1). These lines were analysed over a large number of offspring generations beyond the founder animal. In mating experiments, the influence of the parent-of-origin and strain-specific backgrounds on the transgene methylation patterns were assessed and found to have no effect on the pre-established methylation patterns in mouse lines 5-8 and 8-1. The founder animal 7-1 carried two groups of a total of ten transgenes, which were located on two different chromosomes. These arrays of transgenes could be segregated into separate mouse lines 7-1A and 7-1B. The transgenes of 7-1A animals exhibited cellular mosaic methylation patterns that were demethylated in approximately 10% of the offspring in a mixed genetic background. Upon further transmission of these transgenes in a mixed genetic background, the grandparental methylation patterns were reestablished in most progeny. Mating to inbred DBA/2 mice resulted in maintenance of the demethylated pattern or in further demethylation of the transgenes in approximately 50% of the offspring. In contrast, an equal number of transgenic siblings from matings to C57BL/6 mice showed a return to the original methylation pattern. The mosaic methylation status of this locus was apparently controlled by mouse-strain-specific factors. The methylation patterns of the 7-1B transgenes were not cellular mosaic and remained stable in all offspring, as with lines 5-8 and 8-1. Hence, the strain-dependent and cellular mosaic transgene methylation patterns of 7-1A animals were probably a consequence of the chromosomal integration site of the transgenes (position effect).