[Use of flexible transnasal esophagogastroscopy in patients with unclear globus sensation]. / Einsatz der flexiblen transnasalen Ösophagogastroskopie bei Patienten mit unklarem Globus pharyngeus.

BACKGROUND: Globus pharyngeus is a common symptom with considerable suffering. Globus sensation can be caused by reflux. In many places, endoscopy of the esophagus is recommended for clarification, especially when there is a question about the presence of a hiatal hernia as the cause of reflux. Transnasal esophagogastroscopy (TNE) represents an alternative to conventional gastroesophagoscopy. It enables a quick low-complication examination of the upper aerodigestive tract in the sitting, non-sedated patient. OBJECTIVE: The aim of this work was to assess the feasibility of outpatient TNE in patients with globus sensation. Furthermore, the results of dual-probe pH monitoring were compared with the results of TNE in order to assess the value of TNE in the clarification of globus sensation and reflux. MATERIALS AND METHODS: In 30 patients with globus symptoms, 24-hour dual-probe pH monitoring and TNE were performed. In pH monitoring, reflux number, fraction time, reflux surface area index, and DeMeester score were evaluated as indicators of laryngopharyngeal reflux (LPR) and gastroesophageal reflux (GERD). Abnormalities of the esophageal mucosa and the gastroesophageal junction were recorded in TNE. The results were compared. RESULTS: The TNE could be performed without any complications. Mean examination time was 5.34 ± 0.12 min. Reflux was measured in 80% of the patients (24/30) with pH monitoring. In almost half of these patients (46%), abnormalities were detected in TNE as indirect evidence of reflux. In addition to an axial hiatal hernia, these included mucosal changes such as erosive esophagitis and Barrett's metaplasia. Patients with a hiatal hernia also suffered significantly more often from LPR than patients without a hernia (9:1). CONCLUSION: TNE is a quick and safe examination method for diagnosing patients with an unclear globus sensation. Detection of a hiatal hernia can be seen as an indication of reflux disease. Lack of evidence of a hernia does not rule out reflux. Thus, TNE is a useful addition to pH monitoring in patients with globus sensation, because reflux-related changes in the mucosa can be recognized early and adequately treated.

[Oxycodone, piritramide and tramadol for the management of postoperative pain : A registry study on use and effectiveness in clinical routine]. / Oxycodon, Piritramid und Tramadol zur postoperativen Schmerztherapie : Eine Registerstudie zur Verwendung und Wirksamkeit.

BACKGROUND: In the context of improving perioperative pain management and shortening hospital stays, potent oral analgesics, such as slow release opioids, are gaining increasingly in importance. OBJECTIVE: The aim of this study was to compare the use and effectiveness of different opioids in postoperative pain treatment in Germany. MATERIALS AND METHODS: Using data from the QUIPS database, the records of 5249 patients were evaluated. The total study population was divided into four groups: group 1 (10 mg oxycodone with or without naloxone 5 mg), group 2 (20 mg oxycodone with or without naloxone 10 mg), group 3 (piritramide) and group 4 (tramadol). Maximum pain intensity, pain-related interference with sleep and respiration, vomiting, postoperative fatigue, desire for more pain treatment and satisfaction with pain management were evaluated. RESULTS AND DISCUSSION: The differences in pain intensity were statistically significant between groups. Patients with piritramide reported more pain, more interference with sleep and respiration and more fatigue compared to those from the other groups. In the group with 10 mg oxycodone, the desire for additional pain medication was the lowest. Postoperative vomiting and satisfaction with pain management differed significantly between the four groups. Procedure-specific analysis has shown that differences between sub-groups were also significant following cholecystectomy and total knee arthroplasty. CONCLUSIONS: In summary, our findings suggest that postoperative pain treatment with slow release oral oxycodone does not show disadvantages compared to tramadol or piritramide with regard to pain-related impairments and opioid-induced side effects. This hypothesis needs to be further analyzed in controlled studies.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Psychological distress and need for psycho-oncological support in spouses of total laryngectomised cancer patients-results for the first 3 years after surgery.

PURPOSE: A total laryngectomy (TLE) leads to a variety of functional restrictions, which reduce the quality of life of cancer patients as well as their spouses. However, to date, there is little research focusing on the psychological distress of spouses of total laryngectomised cancer patients. The current study assesses psychological distress, need for psycho-oncological treatment and use of professional psychological care among spouses of total laryngectomised cancer patients. METHODS: A prospective multi-centre cohort study was conducted. Participants were interviewed in person 1, 2 and 3 years subsequent to their spouses' TLE with standardised questionnaires (HADS, Hornheide Screening) and self-designed items. RESULTS: One year after their partners' TLE, 154 spouses were interviewed. Over half of spouses (57 %) reported a high level of psychological distress and 33 % reported restlessness. Majority of spouses (21 %) reported wanting to learn relaxation methods and eight (5 %) had received psychological treatment in the past. Sixty-two spouses took part in the complete study. Over all three time points, psychological distress, the need for psycho-oncological support and the use of professional support among spouses remained stable. The need for additional professional counselling was low. CONCLUSIONS: In view of the stability of psychological distress among half of the spouses within 3 years after TLE and their refusal of professional support, there is a need for the development and evaluation of new treatment strategies to help spouses cope with psychological distress. Our results indicated the most common additional professional need was learning relaxation methods, which may be used as a starting point for the investigation of new coping strategies in future studies.

Low skeletal muscle is associated with toxicity in patients included in phase I trials.

BACKGROUND: Low muscle mass has been associated with chemotherapy toxicity. We conducted this prospective study to evaluate the effects of body composition on the occurrence of toxicity in phase I trials. PATIENTS AND METHODS: Patients were consecutively enrolled irrespective of the type of tumor or the type of drug. The Skeletal Muscle Index (SMIndex) and visceral and subcutaneous adipose tissue were assessed with computed tomography imaging by measuring cross-sectional areas of the tissues (cm(2)/m(2)). Dose-limiting toxicity (DLT) corresponded to toxicities occurring during the 1(st) cycle that necessitated dose reduction, postponement or interruption of drug administration and severe toxicity events (STE) corresponded to DLT or permanent treatment withdrawal due to toxicity. RESULTS: 93 patients were evaluated. Ten percent of patients experienced DLT and had a lower SMIndex: 40.8 ± 4.6 vs. 48.1 ± 9.6 cm(2)/m(2) (p = 0.01). STE occurred in 14 % of the patients. The only factor associated with STE was a low SMIndex: 42.4 ± 5.8 vs. 48.4 ± 9.7 cm(2)/m(2) (p = 0.02). STE were observed in 25.5 % of the patients when the SMIndex was below the median value compared to 6.5 % of patients with a high SMIndex (p = 0.02). CONCLUSION: Muscle mass is a critical predictor of severe toxicity events in phase I patients, suggesting that sarcopenia may be considered in assessing patients for eligibility of phase-1 studies.

[Vocational rehabilitation after total laryngectomy]. / Berufliche Rehabilitation nach Laryngektomie.

BACKGROUND: Aim of this study was to find out how many patients after a total laryngectomy (TLE) return to work successfully and what factors support vocational rehabilitation. PATIENTS AND METHODS: Laryngectomees (n=231) aged up to 60 years completed questionnaires and structured interviews before TLE (t1), before rehabilitation (t2), at the end of rehabilitation (t3), 1 year after TLE (t4), 2 years after TLE (t5), and 3 years after TLE (t6). RESULTS: Prior to TLE, 38% of all respondents were employed, 34% were unemployed, 23% received disability-related and 3% age-related pension retirement. One year after TLE, 13% were employed, 15% 2 years and 14% 3 years after TLE. Unemployed were 10% (t4), 5% (t5), and 7% (t6) of the patients. For 59% of all respondents it was very important to have a job. Predictors of successful vocational rehabilitation were employment prior to TLE, age <50 years, being self-employed or clerical employee, good physical functioning, good speech intelligibility, high motivation to go back to work, and support from colleagues. CONCLUSION: Only few laryngectomees return to work. However, even before TLE only a third of the patients was employed, another third was unemployed. Most of the patients receive pension retirement after TLE. As return to work is important for many patients, patient consultations should consider possibilities to support vocational rehabilitation before offering to apply for retirement.

[Use of cancer support groups by laryngectomees in central Germany]. / Inanspruchnahme von Selbsthilfegruppen für Laryngektomierte in Mitteldeutschland.

BACKGROUND: Cancer support groups provide information and coping resources as well as represent patients' interests. To date it is unknown how often cancer patients post-laryngectomy use support groups and in which parameters users of support groups differ from non-users. MATERIAL AND METHODS: In a multicentre study, 224 laryngectomees were asked about their support group membership. Further, possible predictors for membership one year post-surgery were assessed. Data were collected with a semi-structured interview and standardized instruments. RESULTS: Overall, 23% of the laryngectomized patients are actively involved in cancer support groups. The probability of a membership increases if patients are well-educated, are living in good economic conditions and in a partnership, if they perceive low family support and wish additional counselling with a physician. CONCLUSION: A cancer support group seems to "buffer" family support perceived to be insufficient. However, support group users are living more frequently in a partnership and in good economic conditions compared to non-users. Physicians and speech therapists are important mediators to cancer support groups. They particularly should inform laryngectomees who are living in bad economic conditions and who are not living in a partnership about the availability of cancer support groups.

Sequential research-related biopsies in phase I trials: acceptance, feasibility and safety.

BACKGROUND: Sequential tumour biopsies are of potential interest for the rational development of molecular targeted therapies. PATIENTS AND METHODS: From June 2004 to July 2009, 186 patients participated in 14 phase I clinical trials in which sequential tumour biopsies (13 trials) and/or sequential normal skin biopsies (6 trials) were optional. All patients had to sign an independent informed consent for the biopsies. RESULTS: Tumour biopsies were proposed to 155 patients and 130 (84%) signed the consent while normal skin biopsies were proposed to 70 patients and 57 (81%) signed the consent. Tumour biopsies could not be carried out in 41 (31%) of the 130 consenting patients. Tumour biopsies were collected at baseline in 33 patients, at baseline and under treatment in 56 patients. Tumour biopsies were obtained using an 18-gauge needle, under ultrasound or computed tomography guidance. Only nine minor complications were recorded. Most tumour biopsy samples collected were intended for ancillary molecular studies including protein or gene expression analysis, comparative genomic hybridization array or DNA sequencing. According to the results available, 70% of the biopsy samples met the quality criteria of each study and were suitable for ancillary studies. CONCLUSIONS: In our experience, the majority of the patients accepted skin biopsies as well as tumour biopsies. Sequential tumour and skin biopsies are feasible and safe during early-phase clinical trials, even when patients are exposed to anti-angiogenic agents. The real scientific value of such biopsies for dose selection in phase I trials has yet to be established.

Early PSA decrease is an independent predictive factor of clinical failure and specific survival in patients with localized prostate cancer treated by radiotherapy with or without androgen deprivation therapy.

BACKGROUND: The aim was to identify predictors of outcome in patients with localized prostate cancer treated with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 448 patients with prostate cancer received EBRT alone (n = 361, group 1) or ADT followed by EBRT (n = 87, group 2). In group 2, ADT was initiated 3 months before EBRT. After baseline prostate-specific antigen (PSA) determination (PSA(preRT)), PSA was assessed during the 6th week of the EBRT course (PSA(6wRT)) in group 1. In group 2, PSA was measured again 3 months after the start of ADT, before EBRT (PSA(ADT-preRT)). RESULTS: In group 1, median PSA(6wRT)/PSA(preRT) was 0.72 and median prostate-specific antigen velocity (PSAV) was -1.5 ng/ml/month. In the multivariate analysis, prognostic groups and PSA(6wRT)/PSA(preRT) (or PSAV) independently predicted biochemical failure (BF), clinical failure (CF), and prostate cancer-specific survival. In group 2, the median PSA(ADT-preRT) was 1.3 ng/ml. In the high-risk group, an undetectable PSA(ADT-preRT) (< or =0.2 ng/ml) predicted BF (P < 0.01) and CF (P = 0.007). CONCLUSION: A PSA decline 6 weeks after the start of EBRT when used as monotherapy and 3 months after the start of ADT in patients treated with combined ADT and EBRT is predictive of progression and specific survival.

JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome.

BACKGROUND: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. PATIENTS AND METHODS: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. RESULTS: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number--associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'--increased from 15% before treatment to 52% (P < 10(-5)) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). CONCLUSION: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+.

[Bilateral deafness and unilateral facial nerve palsy as presenting features of Wegener's granulomatosis : a case report]. / Bilaterale Ertaubung und einseitige Fazialisparese als Erstmanifestation eines M. Wegener : Ein Fallbericht.

A 72-year-old female patient presented with otitis of her left ear with inner ear depletion. Despite administration of intravenous antibiotics according to the resistogram and mastoidectomy the patient developed a similar pathological condition in the right ear and facial nerve palsy on the left side. Treatment with trimethoprim/sulfamethoxazole under the working diagnosis of a localised seronegative Wegener's granulomatosis was initiated without achieving remission. Cyclophosphamide pulse therapy in combination with high-dose methylprednisolone was initiated with rapid cure of the bilateral otitis. Sensorineural hearing loss and facial nerve palsy remained irreversible.

Impact of tumour size on axillary involvement and distant dissemination in breast cancer.

BACKGROUND: Tumour size and nodal involvement are the two main prognostic factors in breast cancer (BC). Their impact on the natural history of BC is not fully captured by analyses that ignore their quantitative nature. METHOD: Data pertaining to 18 159 patients treated with primary surgery: 3661 at the Institut Gustave-Roussy (IGR, France) between 1954 and 1983, and 14 498 in the breast cancer registry in the Stockholm-Gotland Health Care region (SG, Sweden) between 1976 and 1999, were collected. The risks of distant metastases (DMs) and of nodal involvement were analysed according to tumour size with parametric models. RESULTS: Using SG 1976-1990 as the reference group, relative risks (RRs) for DM were equal to 1.42 (95% CI: 1.29-1.56; P<10(-10)) in IGR and 0.61 (95% CI: 0.55-0.67; P<10(-10)) in SG 1991-1999. Differences in tumour size explained the increased risk in IGR (RR adjusted for tumour size 1.09; 95% CI: 0.99-1.20; P=0.07), but not the decreased risk in SG 1991-1999 (adjusted RR: 0.63; 95% CI: 0.57-0.69; P<10(-10)). The relationship between tumour size and DM risk changed significantly during the 1990s. CONCLUSION: Early diagnosis is sufficient to explain differences in the prognosis before 1990. After 1990, the use of adjuvant systemic therapies is the main reason for the reduction in DM.

[Dilatation tracheotomy update : indications, limitations and management of complications]. / Update zur perkutanen Dilatationstracheotomie : Indikation, Grenzen und Komplikationsmanagement.

Percutaneous dilatational tracheotomy is a standard procedure today for transient airway management in intensive care units. When correctly indicated and applied, preferably following interdisciplinary case discussion with the otolaryngologist, PDT seems to be as safe as classical surgical tracheotomy. The latter is the alternative when PDT is contraindicated. There is currently a trend towards one-step PDT procedures. In addition to the permanent necessity for an alternative airway, there is a series of clearly defined contraindications to PDT. In such cases, only surgical tracheotomy is viable. In contrast to surgical tracheotomy, PDT presents more challenges to the physicians and nursing staff in order to avoid specific complications such as re-cannulation into a via falsa followed by acute dyspnea. The otolaryngologist is an important partner in the management of PDT-related complications due to his discipline-specific experience. Further prospective trials, especially concerning long-term complications, are needed to answer the question of whether PDT or surgical tracheotomy is the best method in situations with overlapping indications.

Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients.

BACKGROUND: Serum thyroglobulin (Tg) is the marker of differentiated thyroid cancer after initial treatment and TSH stimulation increases its sensitivity for the diagnosis of recurrent disease. AIM: The goal of the study is to compare the diagnostic values of seven methods for serum Tg measurement for detecting recurrent disease both during L-T4 treatment and after TSH stimulation. METHODS: Thyroid cancer patients who had no evidence of persistent disease after initial treatment (total thyroidectomy and radioiodine ablation) were studied at 3 months on L-T4 treatment (Tg1) and then at 9-12 months after withdrawal or recombinant human TSH stimulation (Tg2). Sera with anti-Tg antibodies or with an abnormal recovery test result were excluded from Tg analysis with the corresponding assay. The results of serum Tg determination were compared to the clinical status of the patient at the end of follow-up. RESULTS: Thirty recurrences were detected among 944 patients. A control 131I total body scan had a low sensitivity, a low specificity, and a low clinical impact. Assuming a common cutoff for all Tg assays at 0.9 ng/ml, sensitivity ranged from 19-40% and 68-76% and specificity ranged from 92-97% and 81-91% for Tg 1 and Tg2, respectively. Using assays with a functional sensitivity at 0.2-0.3 ng/ml, sensitivity was 54-63% and specificity was 89% for Tg1. Using the two methods with a lowest functional sensitivity at 0.02 and 0.11 ng/ml resulted in a higher sensitivity for Tg1 (81% and 78%), but at the expense of a loss of specificity (42% and 63%); finally, for these two methods, using an optimized functional sensitivity according to receiver operating characteristic curves at 0.22 and 0.27 ng/ml resulted in a sensitivity at 65% and specificity at 85-87% for Tg1. CONCLUSION: Using an assay with a lower functional sensitivity may give an earlier indication of the presence of Tg in the serum on L-T4 treatment and may be used to study the trend in serum Tg without performing any TSH stimulation. Serum Tg determination obtained after TSH stimulation still permits a more reliable assessment of cure and patient's reassurance.

High survival rate with the LMT-89 regimen in lymphoblastic lymphoma (LL), but not in T-cell acute lymphoblastic leukemia (T-ALL).

The most appropriate treatment for lymphoblastic lymphomas (LL) remains uncertain. We treated 27 patients with newly diagnosed LL according to an LMT-89 protocol, which is a modified version of the LMT-81 protocol previously reported in pediatric patients. The median age was 31 years. Mediastinal enlargement was present in 25/27 patients, with pleural effusion in 12. Four patients had central nervous system involvement and 12 had bone marrow involvement and 24/27 (89%) had advanced Ann Arbor stage III-IV disease. Complete remission (CR) was achieved in 20/27 patients, unconfirmed complete remission in three patients (residual mediastinal lesion on computed tomography scan) and four failed induction therapy (ORR: 85%). Twelve patients (44%) remained in continuous CR with a median follow-up of 95 months. Survival at 3 years (when all the events occurred in our series) was 63%. Bone marrow involvement was associated with a poor outcome. Overall survival was 85+/-20% in patients without bone marrow involvement compared to 37+/-30% in patients with bone marrow involvement. The Ann Arbor stage, age and serum lactate dehydrogenase level did not influence outcomes. This LMT-89 protocol is a safe regimen and is highly effective in advanced LL without bone marrow involvement.

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma.

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.