Vacuum Application Increases Therapeutic Safety and Allows Intensified Local Radiation Treatment of Malignant Soft-Tissue Tumors

Purpose: In order to simplify and improve outcome of radiation therapy and final defect coverage in patients suffering from invasive soft-tissue tumors, brachytherapy and application of V.A.C.uum-assisted closure (V.A.C.^®) were combined with delaying flap incision. Patients and Methods: Two patients were excised as radically as possible and brachytherapy tubes were implanted directly on the tumor bed. At the same time, flaps for later defect coverage were preconditioned by circumcision. Brachytherapy and external- beam irradiation were performed directly on the vacuum sponge followed by subsequent defect coverage with the preconditioned flaps. Results: Excision significantly reduced tumor masses in both patients; in one case sensible and motor function of the involved extremity was clearly improved. V.A.C.^® coverage allowed repeated brachytherapy and external-beam applications following exact placing of plastic tubes and FLABs on the tumor bed. Sequential irradiation had no effect on neighboring flap tissues, which healed without impairment following transposition. Conclusion: Combination of V.A.C.^® and brachytherapy can effectively replace circumstantial and laborious IORT (intraoperative radiotherapy) procedures. Exact placement of tubes on the tumor bed without subsequent tissue coverage is conserving preconditioned flap tissues, which are transposed for final defect coverage at the end of radiotherapy. However, by circumventing radiation exposure of these tissues, a possible later irradiation sequence can be performed without endangering defect-covering flaps.     

Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines

BACKGROUND: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. METHODS: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. RESULTS: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 +/- 0.4 to 2.4 +/- 0.6 L*min-1*m-2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 +/- 430 to 1109 +/- 202 dyn*s*cm-5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. CONCLUSION: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.     

Detection of pulmonary embolism using 16-slice multidetector-row computed tomography: evaluation of different image reconstruction parameters

OBJECTIVE: To compare different image reconstruction parameters for detecting emboli of the pulmonary arteries according to anatomic levels using 16-slice multidetector-row computed tomography in patients suspected of having an acute pulmonary embolism (PE). METHODS: Sixty-two patients (33 male and 29 female) with a clinically suspected acute PE were included in the present study. Multidetector-row computed tomography scans were performed using 16-mmx0.75-mm collimation. Based on the computed tomography data set, different image reconstruction parameters were used for each patient: axial slice thicknesses (STs) of 0.75, 2, 4, and 6 mm; axial maximum intensity projection (MIP) STs of 4 mm; and coronal STs of 2 and 4 mm. In joint reading fashion, 2 experienced radiologists reviewed examination findings regarding the presence and/or absence of a PE. The reference standard for visualization and detection of PEs was defined using the axial images with a 0.75-mm ST. RESULTS: In 23 of 62 patients, a PE was diagnosed. For main and lobar pulmonary arteries, the sensitivities and specificities were as follows: axial 2-mm images, 1.0/1.0; axial 4-mm images, 1.0/1.0; axial 6-mm images, 0.97/0.99; MIP 4-mm images, 0.95/0.99; coronal 2-mm images, 1.0/1.0; and coronal 4-mm images, 1.0/1.0. Regarding segmental and subsegmental pulmonary arteries, sensitivity and specificity varied: axial 2-mm images, 0.97/1.0; axial 4-mm images, 0.81/0.99; axial 6-mm images, 0.65/0.99; axial MIP 4-mm images, 0.63/0.99; coronal 2-mm images, 0.91/0.99; and coronal 4-mm images, 0.74/0.99. CONCLUSIONS: In detecting segmental and subsegmental PEs, only the axial images with an ST of 2 mm proved to have results comparable with the axial 0.75-mm images. Therefore, thin-slice collimation and ST are mandatory for visualization of segmental and subsegmental PEs in patients suspected of having an acute PE.     

Impact of fesoterodine on quality of life: pooled data from two randomized trials

OBJECTIVE

To evaluate the effect of fesoterodine on health‐related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome.

PATIENTS AND METHODS

Pooled data from two randomized placebo‐controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine‐ER) 4 mg. HRQoL was assessed using the King’s Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire–Short Form (ICIQ‐SF), a six‐point Likert scale measuring the severity of bladder‐related problems, and treatment response.

RESULTS

By the end of treatment, all active‐treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ‐SF scores, treatment response rate, and a major improvement in self‐reported bladder‐related problems. The fesoterodine 8‐mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine‐ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (≥2 points) in bladder‐related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine‐ER, vs 21% on placebo (P < 0.001).

CONCLUSIONS

Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ‐SF, treatment response rate, and a Likert scale measuring bladder‐related problems.     

Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections?

Background Laparoscopic or endoscopic limited resection is intended to be an additional therapeutic option for the treatment of early gastric cancer. However, tumorbiologic markers to predict the outcome for patients after limited resections are missing. This study therefore investigated the prognostic relevance of p53 and bcl-2 immunoreactivity as well as the percentage of apoptotic tumor cells in early invasive pT1/pT2 tumors managed with standard operations for gastric adenocarcinoma. Methods Histologic slides of 65 pT1/pT2 gastric carcinomas were investigated for bcl-2 and p53 immunoreactivity. For 35 patients, DNA fragmentation of tumor cell nuclei was determined by the terminal uridine 5′-triphosphate (UTP) nick end-labeling (TUNEL) method. Follow-up evaluation of the patients was prospectively documented for 53.4 ± 4.1 months. Results Findings showed that bcl-2 immunoreactivity was associated with tumors of the intestinal type according to Lauren′s classification (p = 0.042), and that p53 immunoreactivity was increased in more invasive tumors (pT1 vs pT2 tumors; p = 0.047). Mean survival time was significantly longer for patients with bcl-2-negative tumors (74.3 ± 6.8 months) than for patients with bcl-2-positive tumors (50.8 ± 7.6 months; p = 0.024). The percentage of apoptotic tumor cell nuclei did not have prognostic relevance in the population studied and was not associated with several histopathologic parameters or bcl-2 and p53 immunoreactivity. Subgroup analysis indicated that the survival of patients with differentiated G2 and bcl-2-negative/p53-negative tumors was significantly longer (82 ± 6 months) than the survival of patients with G2 bcl-2- and/or p53-positive tumors (41.8 ± 12.5 months; p = 0.005), with independent prognostic relevance determined by multivariate analysis (p = 0.024). Conclusion The data reported indicate that the analysis of bcl-2 and p53 immunoreactivity seems to have prognostic implications for early invasive (pT1/pT2) gastric adenocarcinomas and may subclassify patients for minimally invasive laparoscopic or endoscopic gastric resections.     

Diagnosis and treatment of colorectal liver metastases - workflow

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.     

Preoperative Glucose and Protein Metabolism: The Influence of Diabetes Mellitus Type 2 in Patients With Colorectal Tumors

Hypermetabolism, abnormal plasma amino acid profiles, increased gluconeogenesis, and changes in liver and muscle protein turnover are well-described undesirable effects in patients with cancer and diabetes mellitus type 2 (DM2) The aim of the present study was to analyze the specific impact and interaction of these 2 disease patterns on patients’ preoperative glucose and protein metabolism. Eight nondiabetic and 8 diabetic patients devoid of cachexia underwent a stable isotope infusion study on the day before surgery for colorectal cancer or adenoma with high-grade dysplasia. Protein and glucose kinetics were assessed in a fasted state by L-[1-¹³C]leucine and [6,6²H₂]glucose. In diabetic patients, glucose metabolism was found to be elevated as the plasma glucose level increased (P = 0.013) and endogenous rate of appearance of glucose tended to be higher compared to nondiabetic patients (P = 0.083). Protein metabolism was not affected by the metabolic state of the 2 groups. Resting energy expenditure was higher in diabetic patients (P = 0.028). Under postabsorptive conditions, noncachectic patients with DM2 suffering from colorectal tumors showed an elevated turnover in glucose metabolism whereas the nondiabetic counterparts failed to demonstrate any metabolic changes due solely to malignancy.     

Relationships between unfavourable health status and smoking cessation attempts in Hungary

Summary. Objectives: The study examines associations between intentions to quit smoking and health status in three age groups of Hungarian smokers, along with social-demographic background variables. Methods: In 2002, a cross-sectional representative health survey of the sample of 12 668 adults was conducted in Hungary. The associations between health status and intentions to quit smoking were analysed with logistic regression among current smokers (N = 3 408). The influence of health-related and social predictor variables was tested separately in different age groups (18–34, 35–49, 50–64, >65). Results: Experiences of chest pain principally motivate young adults to quit smoking. Middle-aged smokers consider quitting because of suffering from cardio-vascular disease. Among the oldest, only respiratory disease influenced quitting attempts. Among social background variables only the fact of living with a spouse had an influence, gender and socio-economic status did not. Conclusions: Connections between health status and quitting intentions are weakening as age is increasing. The population seems to become gradually conscious of the connections between circulatory problems and smoking. Quitting attempts are restrained by the general attitude that ill health is a normal part of the ageing process.

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Zusammenfassung. Zusammenh?nge zwischen ungünstigem Gesundheitsstatus und Versuchen, mit dem Rauchen aufzuh?ren, in Ungarn Fragestellung: Die Studie untersucht die Zusammenh?nge zwischen der Absicht, mit dem Rauchen aufzuh?ren, und dem Gesundheitsstatus in Altersgruppen (18–34, 35–49, 50–64, >65) von ungarischen Rauchern, zusammen mit soziodemographischen Drittvariablen. Methoden: In 2002 wurde eine repr?sentative Querschnittstudie bei 12 668 Erwachsenen in Ungarn durchgeführt. Die Zusammenh?nge zwischen Gesundheitsstatus und den Versuchen, mit dem Rauchen aufzuh?ren, wurden mittels logistischer Regression bei aktuellen Rauchern (N = 3 408) analysiert. Der Einfluss von gesundheitsrelevanten und sozialen Pr?diktorvariablen wurde separat für die Altersgruppen getestet. Ergebnisse: Erfahrungen mit Brustschmerzen motiviert junge Erwachsene haupts?chlich, mit dem Rauchen aufzuh?ren. Erwachsene im mittleren Alter erw?gen einen Rauchstopp bei kardio-vaskul?ren Erkrankungen. Bei den ?ltesten Erwachsenen sind es nur Atembeschwerden, die Rauchstopp-Versuche beeinflussen. Bei den sozialen Drittvariablen hat nur die Tatsache, mit einem Ehepartner zu leben, einen Einfluss, Gender und sozio?konomischer Status hingegen nicht. Schlussfolgerungen: Zusammenh?nge zwischen Gesundheitsstatus und den Versuchen, mit dem Rauchen aufzuh?ren, werden mit zunehmenden Alter schw?cher. Die Bev?lkerung scheint sich der Verbindungen zwischen Kreislaufproblemen und Rauchen allm?hlich bewusst zu werden. Rauchstopp-Versuche werden durch die allgemeine Haltung eingeschr?nkt, dass Krankheit ein normaler Teil vom Altersprozess ist.

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Résumé. Association entre l’état de santé et l’intention d’arrêter de fumer : le cas de la Hongrie Objectifs : Identifier les liens existant entre le désir d’arrêter de fumer et l’état de santé dans quatre groupes d’age de fumeurs en Hongrie, selon plusieurs variables sociodémographiques. Méthodes : Une étude transversale a été menée en 2002 auprès d’un échantillon de 12 668 adultes hongrois. Les associations possibles entre l’état de santé et l’intention d’arrêter de fumer ont été analysées au moyen de la régression logistique parmi les actuels fumeurs (N = 3 408). L’influence des variables prédictrices liées à la santé et au statut social a été testée séparément selon le groupe d’age (18–34, 35–49, 50–64, >65 ans). Résultats : Le fait de souffrir de douleurs thoraciques pousse principalement les jeunes adultes à cesser de fumer. Les fumeurs d’age moyen envisagent de cesser de fumer lorsqu’ils souffrent de maladie cardiovasculaire. Pour les plus agés, seule une maladie respiratoire a un effet sur les tentatives de cesser de fumer. Parmi les variables sociodémographiques, seul le fait de vivre maritalement exerce une influence, mais ni le sexe ni le statut socioéconomique. Conclusions : L’association entre l’état de santé et l’intention d’arrêter de fumer diminue avec l’age. La population ne semble prendre que graduellement conscience des liens existant entre les problèmes cardiovasculaires et le tabagisme. Les tentatives d’arrêter de fumer sont limitées par la croyance générale selon laquelle un état de santé précaire fait partie du processus de vieillissement normal.

     

Taming the Fire of Nephrotoxic Botanicals

Criteria for diagnosing nephropathy and urothelial neoplasms induced by botanicals containing aristolochic acids(AAs) are well established. Highlights of recent research on AAs include mechanisms of AA intrarenal transport and metabolism and vigorous debate on whether AAs may also cause liver cancers. Many other botanicals may also cause renal injury, but a generalized framework for diagnosing botanical-induced kidney injury(BIKI) is lacking. Based on what we have learnt about the wide spectrum of phenotypes of BIKI attributed to AAs and a recently published standardized phenotypic framework of drug-induced kidney disease, we propose that BIKI may be categorized into six phenotypes(acute kidney injury, tubular dysfunction, glomerular disorders, nephrolithiasis, chronic kidney disease, and neoplasms) and four mechanistic types(A, predictable; B, idiosyncratic; C, chronic; and D, delayed). We call for international cooperation assembling a task force to develop, refine, and regularly appraise an online BIKI database, documenting botanical use, phenotypes, mechanisms, and levels of evidence. Once established, such a database may be linked with electronic patient records and pharmacovigilance channels to generate alerts, guide clinical decision-making, direct future research, and support evidence-based regulation of herbal medicines and education of healthcare professionals and the public. Finally, to prevent BIKI, we propose that a proactive approach integrating the triad of botanicals, users, and stakeholders will be needed.