Laparoscopic surgery for rectal cancer reveals comparable oncological outcome even in context of worse short-term results-long-term analysis of nearly 500 patients from two high-volume centers.

PURPOSE: Large randomized controlled trials have investigated the oncological value of the laparoscopic approach to colorectal cancer. Mainly, non-inferiority for the laparoscopic approach regarding long-term survival could be shown. Nevertheless, some recent trials revealed inferiority especially due to histopathological quality of specimen or location of the tumor in the rectum. The main objective of this study was to compare two historical patient collectives of specialized centers for either the laparoscopic or the open resection approach, regarding long-term survival and disease progression of rectal cancer according to tumor localization in a retrospective propensity score-matched analysis. METHODS: A retrospective analysis, based on two prospectively maintained institutional colorectal cancer databases, was performed. The database of the reference center in Erlangen maintained almost exclusively open operations whereas the database in Lübeck maintained to a vast majority laparoscopic operations. To adjust risk profiles, a 1:1 propensity score matching was performed. RESULTS: Seven hundred fifty-five patients of both centers (Erlangen, n = 507, Lübeck n = 248) were included. Propensity score matching resulted in two equalized groups with 248 patients. Regarding the postoperative complications, advantages for the open approach were seen. Analyzing the survival data, no differences in disease-free as well as overall survival were shown. Also, no differences in the overall loco-regional recurrence and distant metastasis rate were detected. CONCLUSION: In centers with adequate expertise, open and laparoscopic procedures result in equivalent oncologic long-term outcomes. Advantages for the open resected group concerning short-term results and complications were detected, due to remarkably low rates of anastomotic leakage.

Correction to: The proliferation marker pKi-67 becomes masked to MIB-1 staining after expression of its tandem repeats.

In the PubMed citation records, the author's name shows.

Radical Resection of Locally Recurrent Colorectal Cancer Significantly Improves Overall Survival: A Single-Center Cohort Study.

BACKGROUND: Despite multimodal treatment strategies, locoregional recurrence rates are still significant in colorectal carcinoma (CRC). METHODS: Clinical, pathological, perioperative, and survival data of 203 patients with recurrent CRC enlisted in a prospective database from 1990 to 2011 were analyzed. RESULTS: Median disease-free survival in our cohort of 203 patients was 23 months after resection of the primary tumor. In total, 113 of these patients had surgical therapy with resection of the recurrent tumor. The primary tumor was localized in the rectum in 63 (56%) patients and in the colon in 50 (44%) patients. A complete resection of the recurrent tumor (R0) was achieved in 69 (61%) patients. Postoperative complications occurred in 42 (37%) patients. Postoperative mortality was 2.7%. The median overall survival for R0-resected patients without distant metastasis was 91 months. Those patients had better overall survival compared to patients in whom no complete resection of the recurrent tumor was possible (p < 0.001). There was no statistically significant difference (overall survival) between patients that had R0-resection with systemic metastasis and R1 (p = 0.794) or R2 (p = 0.422) resection. CONCLUSION: Surgical resection of a locally recurrent CRC leads to a substantial long-term survival rate for R0-resected patients.

Influence of Anastomotic Leak After Elective Colorectal Cancer Resection on Survival and Local Recurrence: A Propensity Score Analysis.

BACKGROUND: The occurrence of anastomotic leakage is still a life-threatening complication for patients after colorectal surgery. In literature not only an impact on the short-term outcome but also on long-term survival and local recurrence of colorectal cancer patients is discussed. OBJECTIVE: This study aimed to investigate the impact of anastomotic leakage on long-term survival and local recurrence. DESIGN: A total of 1122 patients with resections for colorectal cancer were analyzed. In 94 patients (8.4%) there was clinical proof of anastomotic leakage. A reference group was defined as the 1028 patients without anastomotic leakage using 1:1 propensity score-matching according to the following criteria: age, sex, International Union Against Cancer stage, Karnofsky index, tumor site, and grading, as well as adjuvant chemotherapy. A calculation of overall survival, disease-free survival, and local recurrence rate was performed for both groups. SETTINGS: The study was conducted using a retrospective matched-pairs analysis, based on a prospectively maintained institutional colorectal cancer database. PATIENTS: Ninety-four patients with anastomotic leakage and 94 matched control subjects from a total of 1122 patients with resections for colorectal cancer were studied. MAIN OUTCOME MEASURES: Overall survival, disease-free survival, and local recurrence rate for patients with colorectal cancer with and without anastomotic leakage were measured. RESULTS: The propensity score matching successfully created 2 groups with no significant differences in the matching criteria. Survival analysis disclosed no significant differences between the groups in terms of overall survival, disease-free survival, and local recurrence rate. Univariate analysis identified age, Karnofsky index, International Union Against Cancer stage, and lymph node metastasis as significant prognostic factors. Multivariable analysis of these variates revealed age and positive lymph nodes as independent predictors of overall survival and disease-free survival. LIMITATIONS: The study was limited by nature of being a retrospective analysis and monocentric study. CONCLUSIONS: This matched-pairs analysis, comparing patients with colorectal cancer with and without anastomotic leakage, revealed no significant differences in overall survival, disease-free survival, and local recurrence rate. Contrary results in the literature might be caused by nonbalanced settings in nonmatched collectives. See Video Abstract at http://links.lww.com/DCR/A811.

Protein levels of clusterin and glutathione synthetase in platelets allow for early detection of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent malignancies in the Western world. Early tumor detection and intervention are important determinants on CRC patient survival. During early tumor proliferation, dissemination and angiogenesis, platelets store and segregate proteins actively and selectively. Hence, the platelet proteome is a potential source of biomarkers denoting early malignancy. By comparing protein profiles of platelets between healthy volunteers (n = 12) and patients with early- (n = 7) and late-stage (n = 5) CRCs using multiplex fluorescence two-dimensional gel electrophoresis (2D-DIGE), we aimed at identifying differentially regulated proteins within platelets. By inter-group comparisons, 94 differentially expressed protein spots were detected (p < 0.05) between healthy controls and patients with early- and late-stage CRCs and revealed distinct separations between all three groups in principal component analyses. 54 proteins of interest were identified by mass spectrometry and resulted in high-ranked Ingenuity Pathway Analysis networks associated with Cellular function and maintenance, Cellular assembly and organization, Developmental disorder and Organismal injury and abnormalities (p < 0.0001 to p = 0.0495). Target proteins were validated by multiplex fluorescence-based Western blot analyses using an additional, independent cohort of platelet protein samples [healthy controls (n = 15), early-stage CRCs (n = 15), late-stage CRCs (n = 15)]. Two proteins-clusterin and glutathione synthetase (GSH-S)-featured high impact and were subsequently validated in this independent clinical cohort distinguishing healthy controls from patients with early- and late-stage CRCs. Thus, the potential of clusterin and GSH-S as platelet biomarkers for early detection of CRC could improve existing screening modalities in clinical application and should be confirmed in a prospective multicenter trial.

Conception of the Lübeck Toolbox curriculum for basic minimally invasive surgery skills.

PURPOSE: Difficulties at the beginning of the learning curve in minimally invasive surgery (MIS) can well be overcome by simulation outside the operating room. Despite a great number of available devices, standardized, structured, and validated training curricula for video simulators are scarce. METHODS: The Lübeck Toolbox (LTB) video trainer provides six training modules and online video tutorials. Proficiency levels for the tasks were defined by performance analysis of MIS experts (n = 15). Mean values of the best performed repetitions were set as benchmarks for a validation study with n = 30 MIS novices and the learning curves calculated. The novices performed a cholecystectomy on a pig organ model before and after the curriculum which were analyzed using the GOALS score. RESULTS: Benchmarks defined by expert performance for the task Nos. 1 to 6 were 72 s (± 8) (Pack Your Luggage), 49 s (± 9) (Weaving), 66 s (± 10) (Chinese Jump Rope), 89 s (± 28) (Triangle Cut), 138 s (± 44) (Hammer Cut), and 98 (± 22) (Suturing). The median numbers of required repetitions by the novices to reach the proficiency level were n = 42 (7-80), n = 26 (9-55), n = 32 (14-77), n = 44 (15-59), n = 19 (6-68), and n = 26 (15-60). These values were all located at the beginning of the plateau phase of the learning curves. GOALS score improved significantly after completion of the curriculum (18.0 (± 2.6) vs. 10.9 (± 1.6), p < 0.0001). CONCLUSION: The LTB curriculum constitutes a new highly standardized and proficiency level-based training program for basic skills in MIS. Transferability of the task content to a (sub)-realistic environment could be demonstrated. Still, future trials will have to further validate the effectiveness of the LTB curriculum.

Cold-Plasma Coagulation on the Surface of the Small Bowel Is Safe in Pigs.

INTRODUCTION: Surgical treatment in patients with peritoneal carcinomatosis is often limited by the extent of small bowel involvement. We investigated the results of the application of cold-plasma coagulation on the surface of the small bowel. METHODS: After permission by the federal government of Schleswig-Holstein, 8 female pigs underwent a laparoscopy and cold-plasma coagulation on the small bowel with different energy levels. Cold plasma is generated by high-frequency energy that is directed through helium gas. After 12 to 18 days a laparotomy was done and the abdomen was inspected for peritonitis, fistula, or other pathology. RESULTS: Perioperative morbidity was low with transient diarrhea in 1 pig and loss of appetite for 1 day in another pig. We saw 1 interenteric fistula that was clinically not apparent after accidently prolonged application of cold-plasma coagulation (6 seconds instead of 2 seconds) with the highest energy level of 100 W. We did not observe any mortality. The depth of necrosis after application of different energy levels was dependent on the generator energy. We observed statistically significant differences between the different energy levels (20 W vs 10 W [P = .014], 75 W vs 50 W [P = .011]). The comparison of the necrosis depths after the application of 100 W and 75 W almost reached statistical significance (P = .059). We observed distinct interenteric adhesions as a result of the coagulation. DISCUSSION: The application of cold-plasma coagulation on the surface of vital bowel in pigs is safe. We would recommend against the use of the highest energy level of 100 W before more clinical data are available.

Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies.

Cancer proteomics provide a powerful approach to identify biomarkers for personalized medicine. Particularly, biomarkers for early detection, prognosis and therapeutic intervention of bone cancers, especially osteosarcomas, are missing. Initially, we compared two-dimensional gel electrophoresis (2-DE)-based protein expression pattern between cell lines of fetal osteoblasts, osteosarcoma and pulmonary metastasis derived from osteosarcoma. Two independent statistical analyses by means of PDQuest® and SameSpot® software revealed a common set of 34 differentially expressed protein spots (p < 0.05). 17 Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in one high-ranked network associated with Gene Expression, Cell Death and Cell-To-Cell Signaling and Interaction. Ran/TC4-binding protein (RANBP1) and Cathepsin D (CTSD) were further validated by Western Blot in cell lines while the latter one showed higher expression differences also in cytospins and in clinical samples using tissue microarrays comprising osteosarcomas, metastases, other bone malignancies, and control tissues. The results show that protein expression patterns distinguish fetal osteoblasts from osteosarcomas, pulmonary metastases, and other bone diseases with relevant sensitivities between 55.56% and 100% at ≥87.50% specificity. Particularly, CTSD was validated in clinical material and could thus serve as a new biomarker for bone malignancies and potentially guide individualized treatment regimes.

Assessing quality and functionality of DNA isolated from FFPE tissues through external quality assessment in tissue banks.

BACKGROUND: Biobanks are becoming increasingly important for assessment of disease risk as well as identification and validation of new diagnostic biomarkers and druggable targets. The validity of data obtained from biobanks is critically limited by the biomaterial quality of the biological samples. External quality assessment (EQA) programs suitable to comprehensively measure the biomaterial quality in archived materials are currently lacking. We report on quantitative assay designs for the analysis of both structural and functional integrity of DNAs that were applied in a first pilot EQA within the priority program on tumor tissue biobanking funded by the German Cancer Aid. METHODS: Participating biobanks isolated DNAs from a standardized set of 10 samples comprising sections of four different formalin-fixed paraffin-embedded tissues using their standard operating procedures. Isolated DNAs and analytical results were returned and analyzed centrally for nucleic acids yield, purity, fragmentation and amplificability at a quantitative level using dedicated assay designs. RESULTS: The amount of extracted DNA varied in isolates ranging between 1.5 µg and 25.8 µg. Quantification of DNA fragmentation and amplificability allowed to highlight considerable discrepancies in DNA quality. Amplicons yielded from the isolates of these identical EQA samples ranged from 105 to 411 bp suggesting differences between residual inhibitors of downstream enzymatic reactions. CONCLUSIONS: The quality of extraction of bioanalytes from biomaterial archives is heterogeneous even for stable biomolecules like DNA isolated with highly standardized methods. EQAs are appropriate tools to uncover strengths and weaknesses in biobanks in a systematic fashion. Biomaterial integrity is insufficiently reflected by standard methods, but needs to be assessed to improve biobank interoperability. Finally, our results also point towards the problem of measuring the quality of more delicate biomolecules like proteins or metabolites.

Is laparoscopic treatment of incisional and recurrent hernias associated with an increased risk for complications?

INTRODUCTION: Hernias of the ventral abdominal wall can be treated with an intraperitoneal onlay mesh (IPOM). The aim of this cohort study was to analyze the complications and recurrence rates after laparoscopic ventral hernia repair focusing especially on incisional and recurrent hernias. METHODS: The study population comprised 149 patients with a hernia of the abdominal wall, which was treated with an IPOM between January 2006 and January 2011. RESULTS: Fifty-one patients had a primary hernia (group I) and 98 patients had preceding abdominal surgery (group II). In group II 64 patients had an incisional hernia and 34 patients had a recurrent hernia. The median body mass index was 30.3 kg/m(2) (14.8-69.1) without any significance in sub-group comparison. The mean duration of surgery and the length of stay were significantly longer in group II (p < 0.05). The overall rate of minor complications was 18.1%. There were significantly more minor complications in group II (7.8% vs. 23.5%, p = 0.02). Notably, there were also significantly more major complications in group II (14.3% vs. 2.0%; p = 0.02). The recurrence rate was significantly higher in group II (group I: 3.9% vs. group II: 16.3%, p < 0.05). There were no early recurrences in group I, but 5 early recurrences in group II. CONCLUSION: Laparoscopic treatment of complex hernias as incisional hernias, recurrent hernias and hernias with interenteric and enteroperitoneal adhesions is associated with high rates of minor and major complications. A high level of expertise of the surgeon and the camera-guiding assistant is therefore needed.

Colorectal neoplasia in IBD--a single-center analysis of patients undergoing proctocolectomy.

PURPOSE: The risk, prevention, and treatment of colorectal neoplasia in inflammatory bowel disease (IBD) are still a matter of debate. The aim of this study was to analyze the occurrence of colorectal neoplasia in IBD patients who underwent proctocolectomy. METHODS: The study population comprised of 123 IBD patients who underwent proctocolectomy because of neoplasia, therapy refractivity, or complications between January 2000 and July 2011. RESULTS: One hundred fourteen (92.7%) patients were pre-operatively diagnosed with ulcerative colitis, 5 (4.1%) with colitis indeterminata, and 4 (3.3%) with colonic Crohn's disease. Colectomy was indicated in 39 (31.7%) patients because of a neoplasia, in 68 (55.3%) because of a refractory course of the disease, and in 16 (13.0%) because of complications. Neoplasia was found in 36 patients on a histopathologic evaluation of the colectomy specimens. Ten (8.1%) patients post-operatively showed a pre-operatively not described advanced neoplasia. In three (2.4%) of these patients, the detection of advanced neoplasia (two high-grade intraepithelial neoplasias (IENs), one carcinoma) was a complete de novo finding. Carcinoma had not been diagnosed pre-operatively in six (4.9%) patients. A multifocal distribution of neoplasia was seen in 66.7% of patients with neoplasia. The median duration of disease was 15.5 years in case of neoplasia opposed to 6.0 years in those without neoplasia detection. CONCLUSION: Our data demonstrate a high rate of pre-operatively undetected high-grade IENs and carcinoma and a frequent multifocal occurrence in IBD patients with long-standing inflammation of the colon. This should be kept in mind for treatment decisions particularly in patients with a chronic refractory course of the disease.

Conversion of laparoscopic surgery for perforated peptic ulcer: a single-center study.

PURPOSE: A perforated peptic ulcer can be managed laparoscopically in selected patients. The purpose of this study was to evaluate whether conversion of emergency laparoscopy is inferior to primary median laparotomy in terms of postoperative morbidity and mortality. METHODS: We analyzed patients who underwent laparoscopic or open surgery for a perforated peptic ulcer at the Department of Surgery, University of Schleswig-Holstein, Campus Luebeck between January, 1996 and December, 2010. Perforations were graded according to the Boey classification, a preoperative risk-scoring system. RESULTS: Conversion to laparotomy was necessary in 20 of the 45 patients who underwent laparoscopic surgery (CG); therefore, laparoscopic operations were completed in 25 patients (LG). The third patient cohort comprised 139 patients who underwent primary laparotomy (OG). Overall minor morbidity was significantly lower (p = 0.048) in the LG patients than in the OG patients, whereas no significant differences were found in major morbidity and mortality, particularly between the OG and CG. CONCLUSION: Patients' suitability for laparoscopic management should be decided on according to Boey's clinical scoring system. Our findings demonstrated that conversion from laparoscopy to laparotomy was not associated with elevated postoperative morbidity or mortality versus initial laparotomy. Therefore, emergency operations may be commenced laparoscopically in selected patients, especially considering the postoperative advantages of this approach.

Laparoscopic versus open reversal of a Hartmann procedure: a single-center study.

PURPOSE: Re-anastomosis after a Hartmann procedure is associated with a higher morbidity and mortality than other elective colorectal operations. The goal of this comparative study was to evaluate whether laparoscopic reversal is a justified operative approach, although the initial operation is most often an emergency laparotomy. METHODS: A retrospective analysis was conducted on data collected on all 70 patients who underwent laparoscopic and open reversal of a Hartmann procedure at the Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, between January 1999 and December 2011. Together with general demographic data, the analysis included the indication for the initial Hartmann procedure, time to reversal, intraoperative findings, the choice of operative method, operating time, postoperative pain control, return of normal bowel function, length of hospital stay, and peri- and postoperative morbidity and mortality. RESULTS: In most patients, the Hartmann procedure was performed after a perforated sigmoid diverticulitis. We were not able to find any statistically significant differences with respect to gender, body mass index (BMI) and American Society of Anesthesiologists classification between the laparoscopic group (LG) (N = 24 patients) and the open group (OG) (N = 46). In the LG, patients were significantly younger (p = 0.019). The median operating time was 210 min (75-245) in the LG, which was significantly longer than in the OG (166 min; 66-230). The statistical analysis of the duration of postoperative analgesic therapy (LG 7 days; OG 12 days), return to normal diet (LG 3 days; OG 4 days), return of normal bowel function (LG 3 days; OG 4 days) and length of hospital stay (LOS) (LG 10 days; OG 15 days) detected significant differences in advantage for the LG. Unplanned return to theatre during index admission was only necessary in the OG (N = 7, 15.2 %). With a median follow-up of 8 months (range 1-20), we observed a comparable number of minor complications in both groups but a significantly higher number of major complications in the OG (N = 27, 58.7%) (p = 0.001). Conversion occurred in three cases (12.5%). There was no mortality in either of the two groups. CONCLUSIONS: This study was able to demonstrate the feasibility of the laparoscopic approach. In terms of postoperative results it should be seen as equivalent to the open procedure. However, the laparoscopic approach requires profound surgical expertise. The indication should be made after a careful risk/benefit analysis for each individual patient.

Prospective Analysis of More than 1,000 Patients with Rectal Carcinoma: Are There Gender-Related Differences?

BACKGROUND: Since the beginning of the new millennium gender medicine has become more and more relevant. The goal has been to unveil differences in presentation, treatment response, and prognosis of men and women with regard to various diseases. METHODS: This study encompassed 1,061 patients who underwent surgery for rectal cancer at the Department of Surgery, University Medical Center Schleswig-Holstein Campus Lübeck, Germany, between January 1990 and December 2011. Prospectively documented demographic, clinical, pathological, and follow-up data were obtained. Analysis encompassed the comparison of clinical, histopathological, and oncological parameters with regard to the subcohorts of male and female patients. RESULTS: No statistically significant differences could be found for clinical and histopathological parameters, location of tumor, resection with or without anastomosis, palliative or curative treatment, conversion rates, duration of surgery, and long-term survival. For the entire cohort, gender-related statistically significant differences in complications encompassed anastomotic leakage, burst abdomen, pneumonia, and urinary tract complications all of which occurred more often in men. CONCLUSION: Data obtained in this study suggest that there are no gender-related differences in the oncologic surgical treatment of patients with rectal carcinoma. However, male sex seems to be a risk factor for increased early postoperative morbidity.

Aneuploidy characterizes adjacent non-malignant mucosa of ulcerative colitis-associated but not sporadic colorectal carcinomas: a matched-pair analysis.

INTRODUCTION: Aneuploidy has been suggested as independent prognostic marker in ulcerative colitis (UC) patients for developing UC-associated colorectal carcinomas (UCCs). UCCs are associated with a poorer prognosis and more frequently present with synchronous carcinomas when compared with sporadic colorectal carcinomas (SCCs). The authors therefore investigated if the adjacent non-malignant mucosa of aneuploid UCCs and aneuploid SCCs shows differences regarding the frequency of aneuploidy and if this aneuploidy is associated with histomorphological alterations. METHODS: Primary tumors of 25 UCCs and 20 SCCs were selected showing exclusively aneuploid DNA patterns and matching DNA stemlines. The UCCs' (n = 82) and SCCs' (n = 40) adjacent non-malignant mucosa were evaluated for histopathology and assessed for DNA ploidy status by image cytometry. RESULTS: UCCs' non-malignant mucosa showed dysplasia in 31.7% and aneuploidy in 89%. In contrast, SCCs' non-malignant mucosa revealed no dysplasia and aneuploidy in only 5%. Irrespective of dysplastic lesions, aneuploidy was observed more frequently in adjacent non-malignant mucosa of UCCs than of SCCs (p < 0.001). Neither a correlation between aneuploidy and inflammation (p = 0.916) nor between aneuploidy and dysplastic lesions (p = 0.159) could be observed. CONCLUSION: Aneuploidy is more frequent in adjacent non-malignant mucosa of aneuploid UCCs than in adjacent non-malignant mucosa of aneuploid SCCs. Furthermore, aneuploidy seems to be irrespective of inflammation or dysplasia. The results therefore emphasize the importance of aneuploidy for UC-associated carcinogenesis and its potential as new diagnostic target.

Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis.

BACKGROUND: Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences. METHODS: Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR. RESULTS: Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development. CONCLUSIONS: The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.

The "North German Tumor Bank of Colorectal Cancer": status report after the first 2 years of support by the German Cancer Aid Foundation.

PURPOSE: Research projects and clinical trials strongly rely on high-quality biospecimens which are provided by biobanks. Since differences in sample processing and storage can strongly affect the outcome of such studies, standardization between biobanks is necessary to guarantee reliable results of large, multicenter studies. The German Cancer Aid Foundation (Deutsche Krebshilfe e.V.) has therefore initiated the priority program "tumor tissue banks" in 2010 by funding four biobank networks focusing on central nervous system tumors, melanomas, breast carcinomas, and colorectal carcinomas. The latter one, the North German Tumor Bank of Colorectal Cancer (ColoNet) is managed by surgeons, pathologists, gastroenterologists, oncologists, scientists, and medical computer scientists. METHODS AND RESULTS: The ColoNet consortium has developed and harmonized standard operating procedures concerning all biobanking aspects. Crucial steps for quality assurance have been implemented and resulted in certification according to DIN EN ISO 9001. A further achievement is the construction of a web-based database for exploring available samples. In addition, common scientific projects have been initiated. Thus, ColoNet's repository will be used for research projects in order to improve early diagnosis, therapy, follow-up, and prognosis of colorectal cancer patients. Apart from the routine sample storage at -170 °C, the tumor banks' unique characteristic is the participation of outpatient clinics and private practices to further expand the sample and clinical data collection. CONCLUSION: The first 2 years of funding by the German Cancer Aid Foundation have already led to a closer scientific connection between the participating institutions and to a substantial collection of biospecimens obtained under highly standardized conditions.

Aneuploidy and elevated CEA indicate an increased risk for metachronous metastasis in colorectal cancer.

PURPOSE: Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear. METHODS: Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM-). In addition, an enlarged collective (n = 217; n TM+ = 85, n TM- = 132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry. RESULTS: The matched-pair collective showed aneuploidy in 71.1 % (TM-) and 85.0 % (TM+; p = 0.076), and elevated CEA in 24.5 % (TM-) and 52.2 % [TM+; odds ratio (OR), 3.414; p = 0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM-) and 83.5 % (TM+; OR 2.050, p = 0.038), and elevated CEA in 28.6 % (TM-) and 48.9 % (TM+; OR 2.391, p = 0.020). Elevated CEA and aneuploidy did not show any association (p = 0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p = 0.019), both elevated CEA level (OR 2.633, p = 0.015) and aneuploidy (OR 1.929, p = 0.058) were independent predictive markers for metachronous metastasis. CONCLUSIONS: Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.

Outcome and management of invasive candidiasis following oesophageal perforation.

The regular colonisation of the oesophagus with a Candida species can, after oesophageal perforation, result in a contamination of the mediastinum and the pleura with a Candida species. A patient cohort of 80 patients with oesophageal perforation between 1986 and 2010 was analysed retrospectively. The most common sources with positive results for Candida were mediastinal biopsies and broncho-alveolar secretions. Candida species were detected in 30% of the patients. The mortality rate was 41% in patients with positive microbiology results for Candida, whereas it was 23% in the remaining patient cohort. This difference did not reach statistical significance (P = 0.124). Mortality associated with oesophageal perforation was attributed mainly to septic complications, such as mediastinitis and severe pneumonia. During the study period we observed a shift towards non-albicans species that were less susceptible or resistant to fluconazole. In selected patients with risk factors as immunosuppression, granulocytopenia and long-term intensive-care treatment together with the finding of Candida, an antimycotic therapy should be started. A surgical approach offers the possibility to obtain deep tissue biopsies. The antimycotic therapy should start with an echinocandin, as the resistance to fluconazole is growing and to cover non-albicans Candida species, too.

Complications after end-to-end vs. side-to-side anastomosis in ileocecal Crohn's disease--early postoperative results from a randomized controlled multi-center trial (ISRCTN-45665492).

BACKGROUND: Recurrent Crohn's disease activity at the site of anastomosis after ileocecal resection is of great surgical importance. This prospective randomized multi-center trial with an estimated case number of 224 patients was initially planned to investigate whether stapled side-to-side anastomosis, compared to hand-sewn end-to-end anastomosis, results in a decreased recurrence of Crohn's disease following ileocolic resection (primary endpoint). The secondary endpoint was to focus on the early postoperative results comparing both surgical methods. The study was terminated early due to insufficient patient recruitment and because another large study investigated the same question, while our trial was ongoing. METHODS AND STUDY DESIGN: Patients with stenosing ileitis terminalis in Crohn's disease who underwent an ileocolic resection were randomized to side-to-side or end-to-end anastomosis. Due to its early discontinuation, our study only investigated the secondary endpoints, the early postoperative results (complications: bleeding, wound infection, anastomotic leakage, first postoperative stool, duration of hospital stay). RESULTS: From February 2006 until June 2010, 67 patients were enrolled in nine participating centers. The two treatment groups were comparable to their demographic and pre-operative data. BMI and Crohn's Disease Activity Index were 22.2 (± 4.47) and 200.5 (± 73.66), respectively, in the side-to-side group compared with 23.3 (± 4.99) and 219.6 (± 89.03) in the end-to-end group. The duration of surgery was 126.7 (± 42.8) min in the side-to-side anastomosis group and 137.4 (± 51.9) min in the end-to-end anastomosis group. Two patients in the end-to-end anastomosis group developed an anastomotic leakage (6.5%). Impaired wound healing was found in 13.9% of the side-to-side anastomosis group, while 6.5% of the end-to-end anastomosis group developed this complication. The duration of hospital stay was comparable in both groups with 9.9 (± 3.93) and 10.4 (± 3.26) days, respectively. CONCLUSIONS: Because of the early discontinuation of the study, it is not possible to provide a statement about the perianastomotic recurrence rates regarding the primary endpoint. With regard to the early postoperative outcome, we observed no difference between the two types of anastomosis.