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Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

IntroductionWith growing emphasis on surgical safety, it appears fundamental to assess the safety of colorectal resection involving primary stapled anastomosis. Surgical stapling devices can considerably foster patient safety in colorectal surgery, but their misuse or malfunction encompass a unique risk of postoperative complications. The Digital Device Briefing Tool (DDBT) is a digital cognitive aid developed to enhance safe use of the Ethicon circular stapling device during colorectal resection. The purpose of this study is to evaluate how a digital operative workflow, including DDBT, compared with routine surgical care, affects morbidity and mortality in patients undergoing left-sided colorectal resection with primary stapled colorectal anastomosis for colorectal cancer or benign disease.Methods and analysisA multicentre, prospective cohort study will be conducted at five certified academic colorectal centres in Germany. It compares a non-digital with a Johnson & Johnson digital solution (Surgical Process Institute Deutschland (SPI))-guided operative workflow in patients undergoing left hemicolectomy, sigmoidectomy, anterior rectal resection and Hartmann reversal procedure. The sample size is set at 528 cases in total, divided into 3 groups (a non-digital and two SPI-guided workflow cohorts, with and without DDBT) in a ratio of 1:1:1, with 176 patients each. The primary endpoint is a composite outcome comprising the overall rate of surgical complications, including death, during hospitalisation and within the first 30 days after colorectal resection. Secondary endpoints include operating time, length of hospital stay and 30-day hospital readmission rate.Ethics and disseminationThis study will be performed in line with the Declaration of Helsinki. The ethics committee of the Charité—University Medicine Berlin, Germany, approved the study (No: 22-0277-EA2/060/22). Study Investigators will obtain written informed consent from each patient before a patient may participate in this study. The study results will be submitted to an international peer-reviewed journal.Trial registration numberDRKS00029682.

Objectives Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. Methods Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. Results Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0–7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6–187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2–116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3–28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0–9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8–85.6) and 53.5% (50.9–56.1), respectively (OR 0.25, 95% CI 0.08–0.75, p = 0.001). Conclusions Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Purpose In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. Methods Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. Results MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13–3.37, P = 0.63) and 1.44 (95% CI 0.66–3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14–0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89–1.58, P = 0.26). Conclusion Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Background and Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC. Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire. Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p

Purpose To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. Methods This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. Results Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). Conclusion Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer.

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome 8q24 at rs2585176 (P = 1.09 x 10(-09)). On chromosome 5p13 we found cis-eQTL effects with an up-regulation of PTGER4 expression in GC risk allele carrier (P = 9.27 x 10(-11)). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 x 10(-47)). In addition, we found trans-eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 x 10(-09)). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk-conferring GC pathomechanisms.

Die Ergebnisse, die im Zusammenhang mit einer R1-Situation bei einem resezierten Magenkarzinom in der Literatur berichtet werden, sind nicht einheitlich. Eine R1-Situation verschlechtert die Prognose fur das Langzeituberleben der Patienten. Dies ist vor allem fur niedrige T‑Stadien und einer Lymphknotenmetastasierung mit 0 bis ≤3 Lymphknotenmetastasen signifikant. In hoheren Tumorstadien und bei ausgedehnter Lymphknotenmetastasierung ist der Uberlebensunterschied zwischen R0- und R1-Resektion geringer bzw. nicht mehr signifikant. Die Haufigkeit einer R1-Resektion liegt bei ca. 5 % (1,8–9 %, AEG-Tumoren ≥10 %). Die Daten beziehen sich vor allem auf den oralen und aboralen Schnittrand, Angaben zum zirkumferenziellen Schnittrand finden sich selten. Das Risiko eines histologisch positiven Schnittrandes steigt mit der Grose des Tumors (≥5 cm), einem T3/4- und oder pN2/pN3-Stadium. Schlecht differenzierte, Siegelringzell- oder muzinose Adenokarzinome und Karzinome vom Bormann-Typ 3+4 fuhren ebenfalls zu einer erhohten R1-Rate. Zur Erzielung einer R0-Resektion stellt eine intraoperative histologische Schnellschnittuntersuchung den Standard dar. Bei einer Tumorinfiltration sollte die sofortige Nachresektion vorgenommen werden. Findet sich die R1-Diagnose erst in der definitiven Histologie, gilt die Nachresektion zur Erzielung einer R0-Resektion in Publikationen als Standard. Trotzdem erfolgt eine Reoperation nur selten. Nur eine Studie berichtet uber 122 Patienten mit 100 % Reoperationen, die bei 50 Patienten (41 %) erfolgreich (R0) durchgefuhrt wurden. Fur die R0-Gruppe konnte das mediane Uberleben von 18 auf 23 Monate verlangert werden. Fur postoperative additive Masnahmen (Chemo‑, Strahlen- und Radiochemotherapie) finden sich nur sporadische Literaturdaten und keine Evidenz.

e13591 Background: In Germany, a serious illness is the main cause of malnutrition. Various studies have already shown that the length of time in hospital for various diseases and operations in malnourished patients increases. This leads to a deterioration in the quality of life of the patient and results in considerable costs for the health care system. Methods: In order to investigate the relationship between nutritional status and length of hospital stay, a patient group of 363 patients who had a tumor with the primary tumor in the gastrointestinal tract was first identified. All patients had an NRS score of 3 or greater and a meaningful laboratory with regard to protein and albumin levels and / or results of a bioelectrical impedance analysis. The average length of stay for these patients was determined depending on the various parameters. Results: The present study shows that malnourished patients have to stay in the hospital for between 2 and 11.1 days longer. When evaluating the NRS score, the protein and albumin level as well as the BCM and the ECM / BCM index, a longer hospital stay of malnourished patients compared to those who were not malnourished was demonstrated. The BMI is an insufficient parameter to describe the nutritional status. An extension of the length of hospital stay cannot be demonstrated only on the basis of the BMI. Conclusions: Since an inadequate nutritional status obviously affects the length of hospital stay in oncological patients, they should be examined early for malnutrition. The length of stay can be shortened through nutritional therapy measures, which also leads to a significant reduction in costs.

e16143 Background: Colorectal cancer is one of the most common types of cancer in Germany. Colonoscopy is certainly one of the most efficient diagnostic methods in preventing and early detection of colorectal cancer. Nevertheless, acceptance of colonoscopy as a useful screening method among the population in Germany is moderate, with around 22% of those entitled to claim. Methods: In order to better assess the reasons for the low level of acceptance, patients who presented themselves from March 2016 to June 2017 in the General Surgery Clinic of the Johanniter Hospital Stendal were randomly selected and interviewed using a questionnaire. These randomized patients did not suffer from colorectal cancer. The questionnaire asked whether the patients had participated in Colon Cancer Screening and if not for what reasons. Respondents were asked to choose among 8 preselected reasons or give their own. The options for not having participated in colorectal cancer screening were: lack of knowledge about the offer of colorectal cancer screening, fear of the examination, fear of cancer as an outcome, lack of time for the examination, didn't get an appointment for the exam, place of examination is too far away, excessive travel costs, examination makes no sense, and other (free text entry). Results: A total of 238 questionnaires were completed, 235 of which could be evaluated with regard to gender and age. The proportion between women and men was balanced (m 123, w 112). Surprisingly, contrary to expectations, significantly more respondents participated in colorectal cancer screening than not. There were no differences between females and males. The participation rate in colorectal cancer screening was 71%, which was significantly higher than expected. A significantly lower rate was found in respondents ages between 55 to 60 years old, with 41% of men and 67% of women having participated in a colorectal screening. Asked specifically about the reasons why they did not take advantage of the preventive medical check-up, the men of the affected age group (55-60 years) gave: fear of the examination, fear of cancer as an outcome, and examination makes no sense. Conclusions: The results underline the importance of determining why the acceptance of colorectal cancer screening has not yet reached the desired level. Considering and discussing these three main reasons show that there are opportunities to continuously increase awareness of the importance of participation rates in colonoscopy as a screening method for colorectal cancer through target public education.

The primary tumor side is emerging as a prognostic factor for patients with liver metastatic colorectal cancer (mCRC). In a combined analysis of data from 2 randomized studies, the addition of selective internal radiation therapy to first-line chemotherapy in patients with mCRC was associated with statistically and clinically significant overall survival gains for patients with a right-sided primary tumor. Background: The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. Results: In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002). Conclusion: The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain. (C) 2018 Elsevier Inc. All rights reserved.

Acute cholecystitis is a common disease, and laparoscopic surgery is the standard of care.Optimal timing of surgery for acute cholecystitis remains controversial: either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics.The ACDC ("Acute Cholecystitis-early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy") study is a randomized, prospective, open-label, parallel group trial. Patients were randomly assigned to receive immediate surgery within 24 hours of hospital admission (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence of predefined relevant morbidity within 75 days. Secondary endpoints were as follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3) change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of hospital stay.Morbidity rate was significantly lower in group ILC (304 patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate to open surgery and mortality did not differ significantly between groups. Mean length of hospital stay (5.4 days vs 10.0 days; P0.001) and total hospital costs (€2919 vs €4262; P0.001) were significantly lower in group ILC.In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (NCT00447304).

Hintergrund: Die Adenokarzinome des osophagogastralen Ubergangs stellen eine eigene Entitat dar. Die Prognose ist im Vergleich zu den distalen Magenkarzinomen schlechter. Multizentrische Daten der Versorgungsforschung sollen die aktuelle Behandlungssituation besonders auch nach Etablierung der neoadjuvanten Verfahren zeigen. Patienten und Methode: Im Rahmen der prospektiven multizentrischen Beobachtungsstudie QCGC 2 (Deutsche Magenkarzinomstudie 2) wurden im Zeitraum vom 01. 01. 2007 bis 31. 12. 2009 544 Adenokarzinome des osophagogastralen Ubergangs (AEG 1–3) erfasst. Ergebnisse: Die Patienten wurden in 108 (76,6 %) der 141 beteiligten Kliniken operiert. Bei 391 (82,5 %) Patienten war eine R0-Resektion moglich. Fast 60 % der AEG-Tumoren wurden in Kliniken operiert, die weniger als 10 Kardiakarzinome/Untersuchungszeitraum (3 Jahre) behandelten. Endosonografiert wurde in 283 Fallen (53 %), und die Rate der neoadjuvanten Behandlung lag bei 34,4 % (n = 187). Eine intraoperative Schnellschnittuntersuchung erfolgte bei 242 Patienten (60,8 %). Bei dem sehr heterogenen Eingriffsmuster wurde neben einem eingeschrankten transthorakalen Vorgehen (20 %) eine Rate mediastinaler Lymphadenektomien von 47 % beobachtet. Die Hospitalletalitat betrug 6,6 %. Die Adenokarzinome des osophagogastralen Ubergangs zeigten stadienunabhangig ein signifikant kurzeres medianes Uberleben (25 Monate) als die distalen Karzinome des Magens (38 Monate). Auch die 5-JUR sind mit 33,1 % fur die AEG-Patienten deutlich schlechter gegenuber 41,4 % fur Patienten mit einem distalen Magenkarzinom. Ein Uberlebensvorteil durch eine neoadjuvante Behandlung konnte im vorliegenden Krankengut nicht signifikant nachgewiesen werden. Schlussfolgerung: Die flachendeckenden Ergebnisse nach Behandlung der Karzinome des osophagogastralen Ubergangs konnen auch nach der Etablierung multimodaler Verfahren nicht zufriedenstellen. Besonders moderne diagnostische und operative Strategien mussen breiter eingesetzt bzw. geandert werden. In dieser Hinsicht erscheint eine Zentralisierung dieser Entitat sinnvoll.

To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A subgroup of 67 xenograft models was treated with cetuximab, bevacizumab and oxaliplatin as single agents. Mutation status of KRAS (G12, G13, A146T), BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allelespecific real-time PCR. KRAS codon 61 was assessed by conventional sequencing. AREG and EREG expression levels were analyzed by real-time PCR expression assays. In the treatment experiment we observed response rates of 27% (18/67) for cetuximab, 3% (2/67) for bevacizumab, and 6% (4/67) for oxaliplatin. Classification based on KRAS, BRAF and PIK3CA mutation status identified 15 of the responders (sensitivity 83%, confidence interval at p = 0.05 (CI): 59% - 96%), and 38 nonresponders (specificity 78%, CI: 63% - 88%). If any mutation except in KRAS codon 13 were considered, the classifier reached sensitivity of 94% and specificity of 69%. We improved specificity of the classifiers to 90% and 86% respectively by adding AREG and EREG RNA expression thresholds retrospectively. In patient-derived xenograft models, we found a predictive classifier for response to cetuximab that is more accurate than established biomarkers. We confirmed its potential performance in primary human tumors. For patients, the classifier’s sensitivity promises increased response rates and its specificity limits unnecessary toxicity. Given the scope of our xenograft models across all UICC stages, this applies not only to mCRC but also to the adjuvant setting of earlier stages. The xenograft collection allows to mimic randomized phase II trials and to test novel drugs effectively as single agents or in combinations. It also enables the development of highly accurate companion diagnostics as demonstrated by us for cetuximab.

In diesem Beitrag werden die Ergebnisse ausgewahlter deutscher multizentrischer Beobachtungsstudien zur chirurgischen Therapie des Magenkarzinoms der letzten 2 Dekaden vergleichend dargestellt. Insgesamt werden dabei 6035 Patienten mit einem Magenkarzinom, die in den Zeitraumen 1986 bis 1989, 01–12/2002 und 2007–2009 flachendeckend in deutschen Kliniken erfasst wurden, in die Analyse einbezogen. Neben den wichtigsten peri- und fruhpostoperativen Kriterien wird in dieser Studie besonders die Entwicklung onkologischer Langzeitergebnisse untersucht. Berucksichtigung finden sowohl die Fortschritte im diagnostischen und operationstechnischen Bereich als auch der Stellenwert der speziell im letzten Untersuchungszeitraum etablierten, multimodalen Therapiekonzepte.

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p

Die kontrastverstärkte Mehrschicht-Computertomographie (MSCT) hat sich als das Standard-Schnittbildverfahren sowohl zur Diagnostik als auch zur Therapiekontrolle von Leberläsionen durchgesetzt. Zur Abklärung der lokalen Verhältnisse vor einer Leberteilresektion kann die diffusionsgewichtete Magnetresonanztomographie (DWI-MRT) wichtige zusätzliche Befunde liefern. Um das Kriterium der R0-Resektion zu erfüllen, erscheint ein Sicherheitsabstand von 0,5 mm ausreichend. Eine neoadjuvante Chemotherapie mit dem Ziel, die Tumorgröße zu verringern, kann parallel zur Pfortaderembolisation durchgeführt werden, ohne dass die perioperative Morbidität und Mortalität beeinträchtigt wird. Bezüglich des Managements primär resektabler Lebermetastasen besteht dringender Studienbedarf. Trotz der eher geringen Evidenz wird die adjuvante Chemotherapie in Deutschland derzeit breiter befürwortet als die perioperative Chemotherapie. Auch bezüglich der präoperativen Therapie bei Patienten mit (noch) nicht resektablen Lebermetastasen besteht erheblicher Studienbedarf. Bei KRAS-Wildtyp-Tumoren werden mit einer Cetuximab/Chemotherapie-Kombination hohe Ansprechraten (im Sinne einer metrischen Verkleinerung der Metastasen) erzielt. Bevacizumab/Chemotherapie-Kombinationen führen zu hohen pathohistologischen Komplett- und Partialremissionen. Welches der beste Parameter zur Erfolgsbeurteilung einer präoperativen Therapie ist, ist derzeit noch unbekannt, weshalb Vergleichsstudien mit dem Überleben als hartem Endpunkt durchgeführt werden müssen.

Die sich mit dem wissenschaftlichen Erkenntniszuwachs und den gesellschaftlichen Rahmenbedingungen standig wandelnden Voraussetzungen fur medizinische Behandlungsablaufe haben in den letzen Jahren das Interesse an der Ergebnisqualitat dieser Prozesse unter klinischen Alltagsbedingungen verstarkt. Im Hinblick auf die Entwicklung der chirurgischen Therapie des Magenkarzinoms liegen in Deutschland zwei prospektive multizentrische Beobachtungsstudien vor, die Deutsche Magenkarzinomstudie (GGCS ’92) und die Qualitatssicherungsstudie der Ostdeutschen Arbeitsgruppe fur Qualitatssicherung und regionale Entwicklung in der Chirurgie e.V. (EGGCS ’02). Aufgrund des Studiendesigns sind die beiden Untersuchungen gut vergleichbar. Insgesamt konnte im Vergleich mit der GGCS ‘92 eine Verbesserung der peri- und fruhpostoperativen Behandlungsqualitat des Magenkarzinoms in den zwischen den Studien liegenden 12 Jahren konstatiert werden. Die onkologischen Langzeitergebnisse sind jedoch fur das gesamte Patientenkollektiv mit einer Funfjahresuberlebenswahrscheinlichkeit von ca. 40% nach wie vor unbefriedigend. In den letzten Jahren hat sich zunehmend die Erkenntnis durchgesetzt, dass auch beim Magenkarzinom eine multimodale Therapie ein Weg zur Verbesserung dieser Resultate sein kann. Diese Entwicklungen waren der Anlass, die neue Qualitatssicherungsstudie fur Magenkarzinome zu initiieren. Bei der Uberarbeitung der Erfassungsbogen wurde besonderer Wert auf die gegenuber 2002 detaillierte Erfassung der multimodalen Therapiekonzepte gelegt. Mit Hilfe der im Januar 2007 beschlossenen Unterstutzung der Studie durch den Konvent der leitenden Krankenhauschirurgen sollte ein hoher Erfassungsgrad der bundesweit behandelten Magenkarzinome moglich sein.

Even though adjuvant systemic therapy significantly increases 5-year survival rates for resectable gastric or gastroesophageal carcinoma, quality assurance research has shown that in practice it is often not given. The European standard, perioperative chemotherapy, is based on results of the MAGIC trial (3 cycles of ECF - epirubicin, cisplatin, 5-FU as infusion before and after surgery). It is to be expected that oral capecitabine will replace infusional 5-FU in perioperative treatment, as in the palliative setting. This change has already taken place in many institutions. For metastatic and locally advanced esophageal and gastric carcinoma, the results of clinical trials over recent years have led to the following concrete changes: the importance of platinum has been confirmed. Oxaliplatin can replace cisplatin. Capecitabine can replace 5-FU. If docetaxel is given in addition to platinum/5-FU, this doubles 2-year survival (with significant toxicity). Targeted drugs such as cetuximab, panitumumab, and bevacizumab are currently undergoing clinical trials.

A standardized procedure for dealing with nonresectable liver metastases does not currently exist. It is important that an interdisciplinary approach to treatment be taken, in order to look for the optimum solution for each individual patient. High response rates appear to be important, in order to make more patients with nonresectable liver metastases 'resectable' and thus provide a chance of cure. A series of randomized phase II-III trials found a clear increase in response rates and an improvement in the R0 resection rate as a result of more intensive therapy (triple chemotherapy or combination chemotherapy plus cetuximab or bevacizumab). In the NO16966 trial, too, under blinded conditions, more liver metastasis resections were carried out among patients who had received bevacizumab than among patients in the control arm without bevacizumab, although the response rates in the two arms were the same. A gap of 6-8 weeks between the last dose of bevacizumab and surgery is clinically optimal from the point of view of perioperative safety. If neoadjuvant treatment is given, then resection should be carried out as soon as the metastases are resectable. If the patient's response is not adequate, then consideration should be given to an adaptation or change of the treatment regimen. Regular evaluation for secondary resectability is important. Surgically, in addition to 2- or multi-stage surgery, other possible techniques include portal embolization and intraoperative ablation. The goal remains R0 resection. In order to minimize complications, clinicians must select patients carefully, take account of comorbidities, and know the critical resection volume.

Das Kolonkarzinom gehort zu den haufigsten Tumorentitaten und wird bei der Mehrheit der Patienten im lokalisierten Stadium diagnostiziert. Das Rezidivrisiko schwankt je nach Stadium zwischen 10 und 80%, kann aber bei Risikopatienten mit einer postoperativen Chemotherapie in relevantem Mase gesenkt werden. Im Stadium III ist die adjuvante Chemotherapie eindeutig indiziert, sofern keine Kontraindikationen vorliegen. Im Stadium II hat die Chemotherapie einen nur marginalen Effekt auf das rezidivfreie Uberleben und wird daher nicht routinemasig empfohlen. Bei Vorliegen von Risikofaktoren wie Perforation, unzureichender Anzahl untersuchter Lymphknoten etc. kann die Chemotherapie jedoch auch im Stadium II eine relevante Verbesserung bringen und sollte individuell mit den Patienten diskutiert werden. Es wird die Kombination aus Oxaliplatin plus 5-FU/Folinsaure (FOLFOX) empfohlen. Alternativ konnen auch orale Fluoropyrimidine als Monotherapie gegeben werden.

Das multimodale Management sowie innovative chirurgische Techniken haben die Therapie und Prognose von Patienten mit Lebermetastasen vollig verandert und deutlich verbessert. Ob Patienten mit resektablen Lebermetastasen eine neoadjuvante und/oder adjuvante Chemotherapie erhalten sollten, wird derzeit noch kontrovers diskutiert. Ist eine R0-Resektion moglich (primar oder nach Vorbehandlung), sollte diese aus chirurgischer Sicht ohne Verzogerung erfolgen. Eine limitierte Resektion (Subsegment/Segment/nichtanatomische Resektion) ist adaquat, wenn die Metastasen komplett entfernt werden konnen, und hat den Vorteil des Erhalts von mehr funktionalem Lebergewebe, um im Fall eines Rezidivs eine Zweit-und eventuell Drittresektion vornehmen zu konnen. Ein geringer Sicherheitsabstand (

Background: The optimum regimen for advanced gastric cancer requires definition. This multicentre phase II study evaluated docetaxel-cisplatin combination in advanced gastric cancer. Methods: Chemotherapy-naïve patients with locally advanced or metastatic disease received docetaxel plus cisplatin (75/75 mg/m2) every 21 days for up to 9 cycles. Endpoints included tumour response, time to progression, overall survival and toxicity. Results: Of 113 patients recruited, 88 were completely evaluable. The median age was 58 years, and most patients had metastatic disease. The overall response rate was 29.6%. Five patients (5.7%) achieved a complete response and 21 patients (23.9%) had a partial response. Tumour control, including stable disease, was achieved in 57 patients (64.8%). The median time to progression and median overall survival time was 4.8 and 8.7 months, respectively. The major toxicity was haematological: 37.5% of patients experienced grade 3–4 neutropenia, whereas febrile neutropenia was observed in only 2% of patients. Conclusion: Docetaxel-cisplatin was active with a predictable and manageable toxicity profile.

The prognostic impact of isolated lymphovascular invasion (LVI) after radical resection of rectal cancer is controversially discussed. However, it could be relevant to decide for an adjuvant treatment.The aim of the analysis was, based on the data of an observational study, to determine the prognostic relevance of the isolated LVI.Patients after radical resection of rectal cancer with no hemangioinvasion were subdivided in three groups: I-no LVI, no lymph node metastases (LNM); II-positive LVI, no LNM; III-positive LNM. Five-year local recurrence rate, distant metastases-free and disease-free survival were determined uni- and multivariate.Patients, n = 846, were studied (I, n = 471; II, n = 75; III, n = 300). The univariate comparison between the groups revealed the following 5-year results: local recurrence rate: 9.4 vs 10.0 vs 14.0%; distant metastases-free survival: 84.1 vs 82.5 vs 49.3%; disease-free survival: 83.2 vs 80.7 vs 45.5%. The differences between groups I and III were significant, but not between groups I and II. The determined higher disease-free survival rate in group II vs group III was significant (P = 0.041), but the differences in local recurrence rate and rate of distant metastases did not reach statistical significance. The multivariate analysis revealed no impact of the isolated LVI on the oncological outcome.The isolated LVI has no independent prognostic impact on the local recurrence rate and long-term survival after radical resection of rectal cancer. Based on this finding, no indication for an adjuvant treatment in these patients can be derived.

Conclusion. The aortic stop-flow technique was associ- ated with a high toxicity rate but no improvement in the tumor response and survival was seen in comparison to the systemic chemotherapy of the historical group. De- spite detectable pharmacokinetic advantages, the aortic stop-flow technique is therefore not considered to be feasible for palliative chemotherapy in patients with pancreatic carcinoma for routine use. Abstract Purpose. Systemic palliative chemotherapy provides only a disappointing response and almost no prolonga- tion of the survival time in patients with pancreatic carcinoma. Isolated perfusion may lead to a higher con- centration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects. The aim of the study was to investigate the feasibility of the aortic stop-flow technique using commercially available tools in patients with advanced pancreatic carcinoma. Methods. Seventeen patients with either unresectable or metastasized pancreatic carcinoma (diagnosed by histologic investigation) were enrolled in the study. In total, a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m 2 of mitomycin C (Medac, Hamburg, Germany) was carried out 22 times. The cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. The tumor response was assessed using computed tomography and a tumor marker (CA19-9) every 4 weeks. Results. While 12 patients underwent one cycle, in 5 patients two complete perfusions were performed. Mi- tomycin C concentration was 10-fold higher within the regional compared with the systemic compartment at its maximum. The area under the curve (AUC) was 4.02 times larger. The degree of toxicity was considerable: World Health Organization grade I/II in 8/17, III/IV in 9/17 cases. Three treatment-related deaths were docu- mented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission (CR), 2 partial remissions (PR)). In 3 subjects, a stable disease (SD) and in 11 individuals tumor progression (PD) was registered. The median survival was 4.1 months.

Peritoneal recurrence after resection of colorectal carcinoma is still a major concern. We investigated whether the novel cytostatic drug, CPT-11 (Irinotecan), delivered intraperitoneally (i.p.) and intravenously (i.v.), could inhibit intraperitoneal tumor spread in a rat model.We induced intraperitoneal tumor growth using a tumor cell transfer model (10(6) cells) and divided the rats into the following five groups of eight: group IP1, given CPT-11 i.p. immediately after intraperitoneal tumor cell transfer; group IV1, given CPT-11 i.v. immediately after intraperitoneal tumor cell transfer; group IP2, given CPT-11 i.p. on postoperative days (PODs) 5, 10, and 15; group IV2, given CPT-11 on PODs 5, 10, and 15; and a control group. The rats were killed 30 days after tumor cell transfer, and the tumor weight, number of nodes in the greater omentum and peritoneum, presence of metastases in the liver and lungs, and ascites volume were determined.CPT-11 inhibited peritoneal tumor growth significantly. The direct intraoperative intraperitoneal application induced a more pronounced effect than the early postoperative intraperitoneal application, but both these application modes were superior to the intravenous route, which had no significant effect.CPT-11 was highly efficacious against peritoneal carcinomatosis in this experimental model. The combination of CPT-11 with other cytostatic agents and drugs generating different effector mechanisms may diminish or even prevent intraperitoneal tumor growth.

Background: An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma. Methods: Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (MitomedacTM, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. Results: The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months. Conclusion: Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.

Background: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen. Patients and Methods: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m2 of gemcitabine and 25 mg/m2 of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer. Results: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m2, and docetaxel, 45 and 40 mg/m2; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects ≧ grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity. Conclusion: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m2 of gemcitabine and 35 mg/m2 of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial.