Long-term outcomes of patients with soft tissue sarcoma of the chest wall: Analysis of the prognostic significance of microscopic margins.

Data on prognostic factors and treatment outcomes for chest wall soft tissue sarcomas (STS) are sparse. Wide resections with negative margins are the mainstay of therapy, but the prognostic impact of surgical margins remains controversial. The purpose of the present study was to determine the significance of microscopic margins through a long-term follow-up. The associations between local recurrence-free survival (LRFS), overall survival (OS) and potential prognostic factors were retrospectively assessed in a consecutive series of 110 patients who were suitable for surgical treatment with curative intent. Potential prognostic factors were assessed using univariate and multivariate analyses. The median follow-up time following primary diagnosis was 9.6 years [95% confidence interval (CI), 7.2-10.5]. In the entire cohort, the 5-year estimates of the OS and LRFS rates were 66.0% (95% CI, 55.9-74.3) and 60.6% (95% CI, 50.3-69.4), respectively. A total of 27 patients (24.5%) developed distant metastases with a median survival time of 0.9 years following the diagnosis of metastasis. Surgical margins attained at the initial resection and eventual re-excisions significantly influenced OS in univariate analysis (5-year OS, R0 69.9% vs. R1/R2 38.5%; P=0.046), but this failed to reach statistical significance in the multivariate analysis. In the multivariate analysis, significant adverse prognostic features of LRFS included angiosarcoma subtype, G2 and G3 histology. For OS, the only independent significant predictors were age >50 years, tumor size >5 cm, angiosarcoma subtype and G3 histology. The results of the present study suggest that tumor biology, as reflected by the histological grade, influences the final outcome in patients with chest wall STS. Surgical margins failed to reach statistical significance in multivariate analysis as they demonstrated a dependency towards the independent predictors of OS. Subsequently, a positive margin status may be a result rather than a cause of biological aggressiveness, and it may not influence the outcome directly.

Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as the Resected Tumor Has No Ink on It.

BACKGROUND: Soft tissue sarcomas (STS) arising in the extremities pose a therapeutic challenge due to concerns of functional morbidity. Resections with negative margins are the mainstay of therapy, but the prognostic significance of surgical margins remains controversial. The purpose of this study was to determine the prognostic impact of surgical margins and clear margin widths in patients with STS of the extremities. MATERIALS AND METHODS: We assessed the relationship between local recurrence-free (LRFS), disease-specific (DSS), and metastasis-free survival (MFS) and potential prognostic factors retrospectively in a consecutive series of 643 patients treated at our institution between 1996 and 2016. Potential prognostic factors were assessed using univariate and multivariate analyses. RESULTS: The median follow-up time after primary diagnosis was 5.4 years (95% confidence interval [CI]: 4.8-6.0). The five-year estimates of the DSS, LRFS, and MFS rates in the entire cohort were 85.3% (95% CI: 81.6-88.3), 65.3% (95% CI: 60.8-69.5) and 78.0% (95% CI: 74.1-81.4), respectively. Histological grade and the quality of surgical margins were independent prognostic factors of all three survival endpoints (LRFS, DSS, MFS) in multivariate analyses. Within the R0 subgroup, univariate and multivariate analyses of categorized (≤1 mm vs. 1-5 mm vs. >5 mm) and non-categorized margin widths revealed that close and wide negative margins led to similar outcomes. Adjuvant radiation improved local control independently, but not DSS and MFS. CONCLUSION: Microscopically negative margins were associated with better LRFS, DSS, and MFS regardless of whether adjuvant radiation was applied. Here, surgical margins can be close as long as the resected tumor has no ink on it. IMPLICATIONS FOR PRACTICE: In the present retrospective analysis of 643 patients with primary soft issue sarcomas of the extremities, surgical margins could be identified as independent predictors of local recurrence-free, disease-specific, and metastasis-free survival. Given the diminished outcome of patients left with positive margins, surgical efforts should aim to achieve microscopically negative margins whenever feasible. It is noteworthy that only the quality of surgical margins, but not the negative margin width attained, had an influence on the prognosis. Our findings suggest that surgical margins can be close as long as the resected tumor has no ink on it.

Somatic Leiomyosarcoma of the Soft Tissues: A Single-Institutional Analysis of Factors Predictive of Survival in 164 Patients.

BACKGROUND: Somatic leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma entity with a high metastatic potential. The purpose of this study was to identify prognostic indicators of survival in patients with somatic LMS of the soft tissues. METHODS: We retrospectively assessed the relationship between local recurrence-free survival (LRFS), disease-specific survival (DSS), overall survival (OS) and potential prognostic factors in 164 patients who were suitable for surgical treatment in curative intent. Patients with soft tissue LMS of the extremities, the truncal wall and the head and neck area were included. The median follow-up time was 4.9 years. RESULTS: In the entire cohort, the 5-year estimate of the DSS, OS and LRFS rate were 74.5% (95% confidence interval [CI] 65.0-81.8), 70.6% (95% CI: 60.9-78.3) and 63.4% (95% CI 53.4-71.9), respectively. Thirty-eight patients (23.2%) developed distant metastases with a median survival time of 1.5 years after diagnosis of metastasis. Surgical margins attained at the initial oncologic resection and eventual re-excisions did not influence DSS, OS and LRFS significantly. Within the R0 subgroup, close and wide negative margins led to similar outcomes. High histologic grade (P < 0.001), size >5 cm (P = 0.002) and subfascial localisation (P = 0.002) were associated with significantly diminished DSS in univariate analysis. In multivariate analysis, only histologic grade was found to be an independent prognostic factor of DSS. CONCLUSIONS: The data from this study could not determine a prognostic significance of surgical margins suggesting that tumour characteristics other than margin status are important. Tumour biology reflected by the histologic grade dictates the final outcome.

Review of the literature and individual patients' data meta-analysis on efficacy and tolerance of nitroxoline in the treatment of uncomplicated urinary tract infections.

BACKGROUND: Nitroxoline, a hydroxychinoline derivate, has been used for many years to treat urinary tract infections (UTI). Many uncontrolled, but only few controlled clinical studies have been published. Four so far unpublished, controlled clinical studies were meta-analysed. METHODS: A narrative literature review was performed. In addition the individual patient data (IPD) of 466 females with uncomplicated UTI of four prospective, single blind, randomized, clinical studies with similar protocols using nitroxoline (250 mg tid) versus cotrimoxazole (960 mg bid) or norfloxacin (400 mg bid) as controls for 5 days (sporadic UTI) or 10 days (recurrent UTI) were meta-analysed. The primary aim was eradication of bacteriuria 7-13 days after end of therapy (test of cure). Clinical efficacy was determined by elimination of symptoms and safety by adverse events and laboratory tests. RESULTS: Reviewing a total of 26 uncontrolled, 2 controlled and one postmarketing studies including more than 11,000 patients, good efficacy and safety of nitroxoline could be confirmed. In the four unpublished controlled studies a total of 234 patients were treated orally with nitroxoline and 232 with controls. The safety of nitroxoline was very good and comparable to the controls (adverse events 9.4% vs 7.8%; p = 0.360). In the mMITT set (at least one outcome result), in the PP set (test of cure outcome) and in the modified PP set (missing test of cure rated failure) more than 90% of the patients showed eradication of bacteriuria with nitroxoline, which also met statistical non-inferiority compared to the controls (10% non-inferiority margin) in all three evaluation sets. The clinical efficacy was similar between the two treatment groups. CONCLUSION: The IPD meta-analysis using objective parameters (elimination of bacteriuria) demonstrated equivalent efficacy (non-inferiority) of nitroxoline with the controls tested (cotrimoxazole, norfloxacin) in the treatment of uncomplicated UTI. Considering the good safety and efficacy of nitroxoline as also shown in many uncontrolled and observational studies and the world wide increase of resistance of uropathogens against cotrimoxazole and fluoroquinolones, but not against nitroxoline within the last 20 years, nitroxoline should be reconsidered as one of the first line antibiotics for the treatment of uncomplicated UTI.

Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?

UNLABELLED: Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the "cardiac fatigue" caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. METHODS: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. RESULTS: When comparing triathletes with LVM <220g  and athletes with LVM >220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. CONCLUSION: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.

Sequence variations in subjects with self-reported multiple chemical sensitivity (sMCS): a case-control study.

Polymorphisms in several genes contribute to interindividual differences in the metabolism of xenobiotics, and may lead to toxicity and disease. The balance between activation and/or detoxification processes may influence an individual's susceptibility to disease. One postulated mechanism underlying multiple chemical sensitivity (MCS) is based on increased metabolism of xenobiotics. The aim of the present study was to determine such polymorphisms in cases with self-reported MCS (sMCS) and controls. sMCS cases (14 men, 45 women, mean age: 48 yr) and controls (14 men, 26 women, mean age: 44 yr) of the same anthroposphere were characterized using the MCS-questionnaire from Huppe and coworkers (2000) and a standardized questionnaire for living conditions and living factors. Allelic frequencies of genomic variations for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were determined. The MCS questionnaire from Huppe et al. (2000) differentiated between cases and controls with 87.5% sensitivity and 90% specificity. Compared to controls the sMCS cases had lower exposures, especially to odorous factors, and worse social conditions. No significant differences of the allelic distribution of genetic polymorphisms in the genes for 5HTT, NAT1, NAT2, PON1, PON2, and SOD2 were found between cases and controls. The results are in contrast to the study of McKeown-Eyssen and coworkers (2004) but in accordance with the German MCS multicenter study. Although the MCS questionnaire from Huppe et al. (2000) allowed us to differentiate sMCS cases and controls, it was not strong enough for a discrimination based on sequence variations in genes for enzymes involved in xenobiotic metabolism. Therefore, further research needs to focus on a unique phenomenological characterization of MCS.