Bertram Reingruber

Pectus excavatum and pectus carinatum patients suffer from lower quality of life and impaired body image: a control group comparison of psychological characteristics prior to surgical correction.

OBJECTIVE The aim of this study was to evaluate the effects of anterior chest-wall deformities on disease-specific and health-related quality of life, body image, and psychiatric comorbidity prior to surgical correction. METHODS A total of 90 patients (71 with pectus excavatum, 19 with pectus carinatum) presenting themselves for pectus repair and 82 control subjects were recruited for this study. The objective severity of the deformity was determined through the funnel-chest index by Hümmer and the Haller index. Disease-specific quality of life was measured with the Nuss Questionnaire modified for Adults (NQ-mA) and health-related quality of life was determined by the Short-Form-36 Health Survey (SF-36). Body image was assessed via the Body Image Questionnaire (FKB-20), the Dysmorphic Concern Questionnaire (DCQ), and a self-evaluation of the subjective impairment of the appearance. The Diagnostic Interview for Mental Disorders - Short Version (Mini-DIPS), the General Depression Scale (Allgemeine Depressionsskala, ADS), and a self-rating of self-esteem were used to evaluate general psychological impairment. RESULTS Compared with control group results, physical quality of life was reduced in patients with pectus excavatum, while mental quality of life was decreased in patients with pectus carinatum (p<0.05). Body image was highly disturbed in all the patients and differed significantly from the control group (p<0.01). Patients with pectus carinatum appeared to be less satisfied with their appearance than those with pectus excavatum (p=0.07). Body image distress was multivariately associated with both reduced mental quality of life and low self-esteem (p<0.001). Body image did not influence physical quality of life. Patients displayed no elevated rates of mental disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. CONCLUSION Since self-perception is a major contributor to therapeutic decision making, a systematic evaluation of body image should be included in the assessment of patients with chest deformities. Body image concerns may be even more relevant to the decision-making process than physical restrictions. Exaggerated dysmorphic concerns should be prospectively investigated in their ability to influence the extent of satisfaction with the surgical outcome.

Common denominator genes that distinguish colorectal carcinoma from normal mucosa

PurposeMicroarray technology has been used by a growing number of investigators and several studies have been published that list hundreds of genes differentially expressed by colorectal carcinoma (CRC) and normal mucosa (MC). On the basis of our own and other investigators’ microarray data, our goal was to identify a common denominator gene cluster distinguishing CRC from MC.MethodsThirty GeneChips (HG-U133A, Affymetrix) were hybridized, 20 with RNA of CRC stages I–IV (UICC) and 10 with MC. Expression signals showing at least a 4-fold difference between CRC and MC (p<0.01) were identified as differentially expressed. In addition, in our integrative data analysis approach only those genes whose expression was altered simultaneously in at least 2 of 5 recently published studies were subjected to an unsupervised hierarchical cluster analysis.ResultsWe detected 168 up- and 283 down-regulated genes in CRC relative to MC. Twenty-three genes were filtered from the five articles reviewed. An unsupervised hierarchical cluster analysis of these 23 genes confirmed the high specificity of these genes to differentiate between CRC and MC in our microarray data.ConclusionsColorectal cancer and mucosa could be clearly separated by 23 genes selected for being differentially expressed more than once in a recent literature review. These genes represent a common denominator gene cluster that can be used to distinguish colorectal MC from CRC.

Age and manifestation related symptoms in familial adenomatous polyposis

BackgroundTo identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis.MethodsWe undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups.ResultsFAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40.ConclusionThe commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

Is local excision of pT1-ampullary carcinomas justified?

We propose that local excision of carcinomas of the ampulla of Vater is justifiable under the following conditions: when the tumour is limited to the ampulla of Vater as diagnosed by pre-operative endoluminal sonography (uT1) and UICC-staging (pT1); and when it is graded G1 or G2 and there is no lymphatic infiltration and the tumour is completely resected (R0). Under these conditions peri-operative morbidity and mortality were significantly reduced compared with more extensive surgery. There was no local recurrence of tumour in our study and long-term survival rates were comparable with Whipples procedure. This implies that lymphatic spread is limited in localized disease and the feasibility of the proposed procedure may therefore be analogous to localized resections in other malignant tumours, e.g. carcinoma of the rectum.

DNA microarrays: a new diagnostic tool and its implications in colorectal cancer

Effective treatment of colorectal cancer requires early detection and diagnostic and prognostic accuracy in characterizing patients of various risk groups. The development of DNA microarray makes it possible to analyze thousands of genes in a single tissue sample in one experiment and to characterize the biological behavior of colorectal cancer cells. Different cluster algorithms have been used to analyze large datasets on gene expression data, and initial results show significant differences between colorectal cancer and normal colon tissue. Although more than 6000 genes have been analyzed between colorectal cancer and normal tissue, different expression levels have been found in only 100–500 transcripts depending on the cluster algorithm. Most transcripts belong to genes involved in cell growth regulation, differentiation of cells, ribosomal proteins or metalloproteinase. A future goal in microarray technology will be the development of clustered gene chips which characterize each tumor type specifically and focus on gene expression that specifies cell identity.

Transcription of Cytokeratins 8, 18, and 19 in Bone Marrow and Limited Expression of Cytokeratins 7 and 20 by Carcinoma Cells: Inherent Limitations for RT-PCR in the Detection of Isolated Tumor Cells

The suitability of “real-time” quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8, CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone marrow specimens from noncancer patients, and 30 bone marrow specimens from patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow specimens from noncancer patients demonstrated background transcription of CK8 (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1 copies/103 copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly lower. When maximal background values were used as a threshold value to define positivity in tumor cell dilution experiments, sensitivity levels of one tumor cell in 104 bone marrow cells were determined for CK7 and CK20 RT-PCR assays. Maximal background expression values of the different CKs as obtained in the control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times (CK7) in bone marrow specimens from cancer patients, with none of these specimens exceeding the maximal background expression value of CK8. We conclude that RT-PCR for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor cells in bone marrow of cancer patients. On the other side, the limited number of gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that assay sensitivity for these CKs might be limited because of their selective expression by carcinoma cells.

Aesthetic and functional correction of female, asymmetric funnel chest - a combined approach.

There is still sparse information published about the surgical correction of female funnel chest deformity. Women with severe asymmetric funnel chest deformity often present with asymmetric, hypoplastic breasts. These patients frequently complain of physiological limitations in connection with gross aesthetic impairment. To correct these two features a combined approach is presented in this study. 10 women were operated with correction of the thoracic wall deformity by open retrosternal mobilisation and metal plate fixation. Either during the same procedure or in a secondary operation, submuscular breast augmentation was performed to correct breast hypoplasia and asymmetry. All patients tolerated the operation very well without any complications. Aesthetic outcome was rated good to excellent in secondary breast augmentation, whereas simultaneous implant positioning was prone to cause symmastia. In conclusion we recommend correction of female asymmetric funnel chest by primary sternal reduction with secondary breast augmentation during metal plate removal 1 year after.

Incisional hernia repair: tensiometry for the selection of the appropriate procedure.

OBJECTIVE To audit the early and late results of repairs of incisional hernias before and after the introduction of peroperative tensiometry. DESIGN Retrospective study. SETTING University hospital, Germany. PATIENTS 675 operations on 553 patients in 18 years. INTERVENTIONS Before we introduced tensiometry we closed 560 incisional hernias by direct suture and 63 by the inlay-onlay technique. Since we took up tensiometry the numbers were 9 and 43, respectively. MAIN OUTCOME MEASURES Postoperative complications including recurrences. RESULTS Recurrences developed in 246/560 (44%) after direct suture in the early series, compared with 2/9 (22%) after adoption of tensiometry. After inlay-onlay operations there were 4/63 (6%) recurrences before, and 1/43 (2%) after adoption of tensiometry. CONCLUSIONS Tensiometry allows the surgeon to tailor his operation to the conditions that he finds during the operation.

Characterization of gene expression profiles of T cells during anti-tumor response

Background and aimsT cells of tumor-bearing mice or cancer patients exhibit an immune dysfunction, enabling the tumor to escape immune surveillance.MethodsThe experiments are based on EL4 thymoma cells that were transfected with costimulatory ligands B7-1, B7-2, or both at the same time. We used oligonucleotide-based DNA chip microarrays to characterize the genomic expression profile of peripheral T cells according to their anti-tumor immune response in vivo. These murine T cells were also characterized by ELISA, FACS analysis, and co-stimulatory assays.ResultsUsing commonly established methods, such as FACS analysis or the analysis of the cytokine profile by ELISA, it was not possible to determine functional differences in the in vivo activity of T lymphocytes against tumor cells. EL4 tumor cells induced multiple anti-tumor immune responses in vivo depending on their B7 expression.We successfully used microarray analysis to identify genes that were differentially expressed in the dysfunctional T cells, which were unable to reject tumors in vivo. Although Th1 and Th2 cytokine expression was not affected, we observed differential expression of genes involved in the regulation of an innate immune response.ConclusionOur results provide evidence that the anti-tumor response can be identified by the “gene profile” of T cells. Genomic scale analysis offers the opportunity to identify subtle changes in gene expression in T cells reflecting a distinct biological behavior in vivo.

Abstimmung der präoperativen Routinediagnostik zwischen niedergelassener Praxis und Chirurgischer Universitätsklinik

In an attempt to shorten the preoperative in-patient period and to avoid unnecessary investigations, a cooperative patient management model was established for a number of surgical operations at the University Departments of Surgery, Anaesthesiology and their referring Specialist and General Practitioners. The latter were requested to carry out the previously defined preoperative routine investigations, which allowed for a marked reduction in hospital diagnostics. Ambulatory preoperative patient management and a new admission routine resulted in a 57% decrease of the average preoperative in-patient stay for the observed procedures.