Usage characteristics and adverse event rates ​of the direct puncture and pull techniques for percutaneous endoscopic gastrostomy in patients with malignant tumors of the upper aerodigestive tract.

BACKGROUND AND STUDY AIMS: Patients with malignant tumors of the upper gastrointestinal tract are at risk of weight loss. Early supportive nutrition therapy is therefore recommended and usually requires placement of a percutaneous endoscopic gastrostomy (PEG). The aim of this study was to compare adverse events and usage characteristics of the direct puncture technique with those of the traditional pull technique when used in patients with endoscopically passable tumors. The primary endpoint was the rate of inflammatory adverse events (AEs) at the gastrostomy fistula. The secondary endpoint was the long-term rate of puncture-site metastases. PATIENTS AND METHODS: One hundred twenty patients (median age 56; IQR 36, 86 years) were randomized and treated per protocol in this prospective open randomized single-center study. Follow-ups were conducted on the third and seventh post-interventional days, after 1, 3 and 6 months and the last follow-up 5 years after intervention. RESULTS: Within the short-term follow-up period of 6 months after PEG placement, AEs were noted in 47 patients (39.2 %). These included 22 inflammations and 16 device dislocations and were mainly found in the puncture group (33 vs. 14 in the pull group) with a significantly increased incidence in the first month after PEG insertion ( P  = 0.001). Evaluation of the 5-year data did not reveal any significant differences. The gastrostomy tube was used in 101 patients (84.2 %) (range 18 days to 5 years). CONCLUSIONS: Our results favor the pull technique for patients with endoscopically passable tumors of the upper gastrointestinal tract due to less short-term adverse events. Both systems contributed equally to secure long-term use.

The effects of multi-disciplinary psycho-social care on socio-economic problems in cancer patients: a cluster-randomized trial.

PURPOSE: We examined whether multi-disciplinary stepped psycho-social care decreases financial problems and improves return-to-work in cancer patients. METHODS: In a university hospital, wards were randomly allocated to either stepped or standard care. Stepped care comprised screening for financial problems, consultation between doctor and patient, and the provision of social service. Outcomes were financial problems at the time of discharge and return-to-work in patients < 65 years old half a year after baseline. The analysis employed mixed-effect multivariate regression modeling. RESULTS: Thirteen wards were randomized and 1012 patients participated (n = 570 in stepped care and n = 442 in standard care). Those who reported financial problems at baseline were less likely to have financial problems at discharge when they had received stepped care (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1, 0.7; p = 0.01). There was no evidence for an effect of stepped care on financial problems in patients without such problems at baseline (OR 1.1, CI 0.5, 2.6; p = 0.82). There were 399 patients < 65 years old who were not retired at baseline. In this group, there was no evidence for an effect of stepped care on being employed half a year after baseline (OR 0.7, CI 0.3, 2.0; p = 0.52). TRIAL REGISTRATION: NCT01859429 CONCLUSIONS: Financial problems can be avoided more effectively with multi-disciplinary stepped psycho-social care than with standard care in patients who have such problems.

Effects of stepped psychooncological care on referral to psychosocial services and emotional well-being in cancer patients: A cluster-randomized phase III trial.

OBJECTIVE: Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. METHODS: In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. RESULTS: Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P < .001). Well-being 6 months after baseline was 9.5 after stepped care (N = 341) and 9.4 after standard care (N = 234, ß -0.3; P = .71). After stepped care, patients with psychiatric comorbidity went more often to psychotherapists (OR 4.0, P = .05) and to psychiatrists (OR 2.3, P = .12), whereas patients without comorbidity used psychiatrists less often (OR 0.4, P = .04) than in standard care. CONCLUSIONS: Stepped care resulted in better referral to CL services. The patients' emotional well-being was not improved, but uptake of outpatient psychiatric help was increased in patients with psychiatric comorbidity and decreased in patients without.

Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany.

We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late-stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0-2.8), disability pension (OR 1.8, CI 1.0-3.2) and very low income (OR 2.6, CI 1.1-6.1) on the likelihood of advanced disease stage. It is of great concern that these socio-economic gradients occur even in systems with equal access to health care.

No association of oral lichen planus and hepatitis C virus infection in central Germany.

OBJECTIVES: Co-occurrence of oral lichen planus (OLP) and chronic hepatitis C virus (HCV) infection suggests a strong association, but the relation between mucocutaneus, autoimmune lichen planus and HCV infection remains unclear. In areas with higher prevalence of HCV infection in general population, like Japan and southern Europe, 20 to 40 % of patients with OLP test positive for anti-HCV antibodies, whereas in German populations, a co-occurrence of 4.2 to 16 % was reported. MATERIAL AND METHODS: We screened 143 patients with histopathologically proven OLP for prevalence of anti-HCV antibodies. Additionally, we examined 51 anti-HCV-positive subjects with current or past HCV infection for clinical symptoms of OLP. In all patients, confirmatory diagnosis was made by the detection of HCV RNA via reverse transcription-polymerase chain reaction (RT-PCR). A randomized control group comprised 109 blood sera samples of patients without any characteristics of OLP. RESULTS: The results of all patients showed no co-occurrence in either cohort. CONCLUSION: In conclusion, no association between oral lichen planus and chronic HCV infection in our study population was found. CLINICAL RELEVANCE: Anti-HCV antibody screening in patients with confirmed oral lichen planus is not indicated routinely in central Germany.

Effect of a structured psycho-oncological screening and treatment model on mental health in cancer patients (STEPPED CARE): study protocol for a cluster randomized controlled trial.

BACKGROUND: High levels of emotional distress in cancer patients often goes unnoticed in daily clinical routine, resulting in severe undertreatment of mental health problems in this patient group. Screening tools can be used to increase case identification, however, screening alone does not necessarily translate into better mental health for the patient. Doctors play a key role in providing basic emotional support and transferring the patients in need of such specific support to mental health professionals. This study investigates whether a stepped care model, combining screening, doctor consultation and professional psycho-oncological service in a structured way, improves the emotional wellbeing of cancer patients. METHODS/DESIGN: This study is a cluster randomized trial with two parallel groups (intervention vs. care as usual), set in an academic hospital. Participants are cancer patients, a total of 1,000 at baseline. The intervention consists of stepped psychosocial care. Step one: screening for distress, step two: feedback of screening results to the doctor in charge of the patient and consultation with the patient, and step three: based on a shared patient-doctor decision, either transferal to the consultation liaison (CL) service or not. The outcome will be emotional well-being half a year after baseline, ascertained with the Hospital Anxiety and Depression Scale. Randomization will be done by the cluster randomization of wards. DISCUSSION: Mental health problems not only cause emotional suffering but also direct and indirect costs. This calls for timely and adequate psychosocial support, especially as we know that such support is effective. However, not every cancer patient can and must be treated by a mental health professional. Allocating limited resources most sensibly and economically is of crucial importance for our healthcare system to ensure the best quality of care to as many patients as possible. It is the hope of the STEPPED CARE trial that this model is both effective and efficient, and that it can be implemented in other hospitals as well, if proven to be effective. TRIAL REGISTRATION: Clinical Trials Register (Clinicaltrials.gov) identifier: NCT01859429 registration date 17 May 2013.

Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin.

Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome-wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome-wide linkage analyses, we searched for sex-specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21-q26 and 1p31-p21, with the chromosome 1 locus showing a male-specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC-associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex-specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO.

Transforming growth factor-beta receptor type 1 (TGFBR1) is not associated with non-syndromic cleft lip with or without cleft palate in patients of Central European descent.

OBJECTIVE: Transforming growth factor-beta (TGF-ß) type 1 receptor (also known as activin receptor-like kinase 5, ALK5) is expressed in palatal tissue during embryogenesis. Experimental studies in transgenic mice with a genetic deletion of Alk5 showed that TGF-ß type 1 receptor is required for upper lip and midline fusion of the hard and soft palate. In humans, association of TGF-ß type 1 receptor gene (TGFBR1) and the development of non-syndromic cleft lip with or without cleft palate (NSCL/P) had been observed in a multiethnic sample of Chinese, Philippine, Indian and Turkish families. In order to re-evaluate the relevance of these findings, we carried out a family-based association study among 218 NSCL/P families of Central European descent. METHODS: Genomic DNA was obtained from peripheral blood of 218 complete parent-offspring triads with NSCL/P. The sample comprised 14 patients with cleft lip only (CLO) and 204 patients with cleft lip and palate (CLP). Genotyping and transmission disequilibrium test (TDT) were performed on all 218 triads with a total of 17 tagging single-nucleotide polymorphisms (SNPs). We also performed testing for extended haplotypes and a log-linear model by Weinberg was used to screen parent-of-origin effects. Furthermore the use of estimates for the relative risks (RR) of Weinberg's model was obtained. RESULTS: TDT analysis revealed no significant transmission distortion, neither at the level of individual markers nor at the level of haplotypes. Similarly negative results were obtained when we restricted our analysis to the subgroup of patients with CLP (n=204). Relative risk calculations (RR) of the children's and mothers' genotypes obtained negative results, after correction of p-values for multiple testing. Likewise application of Weinberg's log-linear model did not find any evidence for parent-of-origin effects in our sample. CONCLUSION: Despite the ample evidence supporting the role of TGF-ß type 1 receptor as a critically important and widespread morphogenetic regulator of craniofacial development in murine models, our results do not support TGFBR1 as major risk factor for NSCL/P in patients of Central European descent.

Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.

We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

Function, postoperative morbidity, and quality of life after cervical sentinel node biopsy and after selective neck dissection.

BACKGROUND: Sentinel node biopsy (SNB) has been proposed for staging of N0 neck in oral/oropharyngeal carcinomas. It is claimed that SNB may be superior to selective neck dissection (SND) with respect to quality of life (QOL) and postoperative morbidity. METHODS: Twenty-four patients after SNB and 25 patients after SND (levels I-III) were enrolled. QOL and psychosocial variables were assessed by the health-related EORTC QLQ-C30 questionnaire, the disease-specific EORTC QLQ-H&N35 module, the Hospital Anxiety and Depression Scale, and a fear of progression questionnaire. The functional status was evaluated by scores for cervical scar, extent of lymphedema (Miller score), sensory function, function of facial and hypoglossal nerve, cervical spine, and shoulder (Constant score). RESULTS: Health-related QOL measurement revealed no differences between the 2 groups. Disease-specific QOL scores showed fewer swallowing problems in SNB patients (p = .043). SNB patients felt less fear of progression, experienced significantly less impairment from cervical scars, and had less sensory dysfunction and better shoulder function. CONCLUSION: Functional outcome after SNB is significantly better than after SND; however, this is not reflected in the scores of QOL questionnaires.

IRF6 gene variants in Central European patients with non-syndromic cleft lip with or without cleft palate.

Variants in the interferon regulatory factor 6 (IRF6) gene have repeatedly been associated with non-syndromic cleft lip with or without cleft palate (NSCL/P). A recent study has suggested that the functionally relevant variant rs642961 is the underlying cause of the observed associations. We genotyped rs642961 in our Central European case-control sample of 460 NSCL/P patients and 952 controls. In order to investigate whether other IRF6 variants contribute independently to the etiology of NSCL/P, we also genotyped the non-synonymous coding variant V274I (rs2235371) and five IRF6-haplotype tagging single nucleotide polymorphisms (SNPs). A highly significant result was observed for rs642961 (P = 1.44 x 10(-6)) in our sample. The odds ratio was 1.75 [95% confidence interval (CI): 1.38-2.22] for the heterozygous genotype and 1.94 (95% CI: 1.21-3.10) for the homozygous genotype, values that are similar to those reported in a previously published family-based study. Our results thus confirm the involvement of the IRF6 variant, rs642961, in the etiology of NSCL/P in the Central European population. We also found evidence suggestive of an independent protective effect of the coding variant V274I. In order to understand fully the genetic architecture of the IRF6 locus, it will be necessary to conduct additional SNP-based and resequencing studies using large samples of patients.

TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate.

Mice with a deletion of Tgf-beta3 (-/-) and association studies in humans of different ethnicities support the involvement of TGFB3 in the etiology of orofacial clefts. In this study, we investigated the relevance of TGFB3 in the development of cleft lip and palate (CL/P) among 204 triads of central European origin. Transmission-disequilibrium test (TDT) analysis revealed no significant transmission distortions for each marker alone, and none for any possible haplotypes. However, we found strong evidence for parent-of-origin effects, with lower risk of maternal transmission compared with paternal transmission [I (M) = 0.38; confidence interval (CI): 0.17-0.86] of the risk allele T to an affected offspring at marker rs2300607. This is also expressed in an increased risk of heterozygous children having the T allele inherited from the father (R (P) = 3.47; CI: 1.32-9.11). Our data support the involvement of TGFB3 in the development of oral clefts in patients of central European origin.

Family-based association study of the MTHFR polymorphism C677T in patients with nonsyndromic cleft lip and palate from central Europe.

OBJECTIVE: The 677C-->T allele in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the etiology of nonsyndromic cleft lip and palate (CL/P). This study involved a family-based association study of the MTHFR polymorphism. PATIENTS/PARTICIPANTS: We examined 181 patients with CL/P of central European descent and their parents for this variant. RESULTS: The transmission disequilibrium test (TDT) did not confirm an association between the MTHFR 677C-->T polymorphism and nonsyndromic CL/P as previously suggested (p = .36). When comparing the offspring of mothers with periconceptional use of folate to those without, no statistically significant differences were found (p = .708). CONCLUSION: Our data suggest that the MTHFR 677C-->T polymorphism does not make a major contribution to the occurrence of CL/P among central Europeans.

Combination of surgical resection and HDR-brachytherapy in patients with recurrent or advanced head and neck carcinomas.

AIM: Due to the limited therapeutic options, the management of previously pre-treated recurrent head and neck carcinomas remains a challenging problem. The use of hyper-fractionated-accelerated interstitial high-dose-rate brachytherapy (HDR-BT) might be able to improve safety and survival after surgical resection. MATERIAL AND METHODS: From 2000 to 2006, 13 patients with pre-treated, recurrent head and neck cancer (oral, maxillary sinus, lips) were treated in a curative approach by resection the recurrent tumour and HDR-BT. The concept included coverage of the surgical defect and sealing of the brachytherapy applicators with free microvascular or myocutaneous flaps. Conventional radiotherapy and chemotherapy were added as required. The patient group was re-examined with respect to survival and outcome. Additionally 5 patients, who received this combination therapy for primary carcinomas were included in this report observation in order to evaluate the rate of complications and adverse effects. RESULTS: Kaplan-Meier-curves revealed a 2-year overall survival of 65.3%. The mean survival for recurrent carcinomas was 22.8 months. Patients treated for primary carcinoma had a mean survival of 34.5 months. Four out of five (80%) patients with primary head and neck cancer were alive and without evidence of disease 2 years after treatment. The acute and chronic adverse side effects were manageable. There were no relevant complications concerning tissue transfer. CONCLUSIONS: Surgical resection combined with HDR-BT can lead to long-lasting remissions. A simultaneous microvascular defect reconstruction provides tissue cover for brachytherapy.

Sentinel lymph node biopsy in squamous cell carcinomas of the lips and the oral cavity - a single center experience.

BACKGROUND AND OBJECTIVES: Despite the availability of initial data on sentinel lymph node biopsy (SLNB) in OSCC, its value in clinical practice remains unclear. The aim of this study is to evaluate the feasibility and potential of SLNB as a reliable staging procedure in early stage SCC of the lips and the oral mucosa. METHODS: From 2001 to 2004, 40 patients with early stage SCC of the lips and oral cavity were enrolled. The main inclusion criteria were: cN0 category by MRI and ultrasound, tumor category T1-T2, for certain sites also T3. Patients with positive SLN underwent MRND and/or radiation. Patients with negative SLN were monitored monthly. RESULTS: In eight patients, the SLN were positive. Two patients with negative SLN subsequently developed nodal disease (5% false negatives). Twenty-one patients have a follow-up longer than 24 months. Five patients died (one from nodal disease, one from local recurrence, and three from unrelated causes). One patient developed a second primary tumor, the remaining patients are free of disease. CONCLUSIONS: SLNB may contribute to more targeted lymph node dissection strategies. Further studies will have to ensure the safety of this procedure in comparison to selective neck dissection.