[Early detection of sporadic pancreatic cancer]. / Früherkennung des sporadischen Pankreasadenokarzinoms.

The incidence of pancreatic cancer is rising. At present, pancreatic cancer is the third most common cancer-causing death in Germany, but it is expected to become the second in 2030 and finally the leading cause of cancer death in 2050. Pancreatic ductal adenocarcinoma (PC) is generally diagnosed at advanced stages, and 5-year-survival has remained poor. Early detection of sporadic PC at stage IA, however, can yield a 5-year-survival rate of about 80%. Early detection initiatives aim at identifying persons at high risk. People with new-onset diabetes at age 50 or older have attracted much interest. Novel strategies regarding how to detect sporadic PC at an early stage are being discussed.

[Type-2-diabetes and gastrointestinal cancer screening]. / Typ-2-Diabetes mellitus und gastrointestinale Krebsvorsorge.

More than 8000000 Germans suffer from diabetes. People with type-2-diabetes (T2D) are at increased risk of gastrointestinal adenocarcinomas. They often develop cancer at younger age and their tumor-specific 5-year-survival is generally shorter. Cancer has become the leading cause of death of T2D-patients. Both chronic hyperglycemia and insulin resistance can stimulate gastrointestinal (GI) tumor growth. T2D can cause colorectal, pancreatic, hepatocellular, biliary and gastric cancer as well as esophageal adenocarcinoma. Both low-risk lifestyle and gastrointestinal cancer screening are effective and reduce GI cancer risk and GI cancer mortality of T2D-patients.

[Metabolic syndrome and gastrointestinal cancer screening]. / Metabolisches Syndrom und gastrointestinale Krebsvorsorge.

Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his cancer risk is. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric and esophageal adenocarcinomas. MetS increases cancer mortality up to 2.4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Preventing and treating the MetS together with GI cancer screening is effective and decreases the burden of GI cancer mortality significantly.

[Tobacco smoking and cancer risk]. / Tabakrauchen und Krebsrisiko.

Smoking tobacco is the most important and potentially modifiable risk factor for cancer in Germany. Combining tobacco with alcohol can multiply cancer risks. Up to 30 % of cancer deaths are due to tobacco smoking. 23,3 % of 18-64 year-old Germans are current smokers; in addition, 11 % of the population are regularly exposed to secondhand tobacco smoke. Tobacco smoking is causally associated with oropharyngeal, laryngeal, nose, paranasal sinus, lung, esophageal, gastric, pancreatic, hepatocellular, biliary, colorectal, kidney, ureter, urinary bladder, uterine cervix and ovary cancers and leukemia. Smokers should be supported to stop smoking and join programmes of cancer screening. Smoking cessation effectively reduces tobacco-associated cancer risk.

[Prevention of pancreatic cancer]. / Prävention des Pankreaskarzinoms.

The incidence of pancreatic cancer is rising in Germany. At present pancreatic cancer is the third commonest cause of cancer death but is expected to become the second in 2030 and finally the leading cause of cancer death in 2050. Pancreatic ductal adenocarcinoma (PC) is generally diagnosed at far advanced stages and 5-year-survival has remained poor. Modifiable risk factors of PC are tobacco smoking, excess body weight, alcohol use, type 2-diabetes and the metabolic syndrome. Smoking cessation and -in case of obesity- intentional weight loss can reduce PC risk by as much as 50 %. Early detection of asymptomatic sporadic PC at stage IA - stage IA-PC now has a 5-year-survival rate of about 80 %- has become a realistic chance for people older than 50 years with new-onset diabetes.

Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses.

BACKGROUND & AIMS: Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment. METHODS: Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle. RESULTS: Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively. CONCLUSIONS: These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy.

Tobacco Smoking and Gastrointestinal Cancer Risk.

Background: Smoking tobacco is the most preventable cause of gastrointestinal (GI) cancer disease in Germany. The more and the longer you smoke, the higher your risk of GI cancer. About 28% of 18-64 year-old Germans are current smokers; in addition, 11% of the population is regularly exposed to secondhand tobacco smoke. Summary: Tobacco use is causally associated with esophageal, gastric, pancreatic, biliary, hepatocellular, colorectal, and anal cancers. Combining smoking with alcohol use, excess body weight, diabetes, or chronic infections synergistically enhances GI cancer risk. Smoking cessation effectively reduces tobacco-associated GI cancer risk. Key Messages: Smokers should be encouraged to stop smoking tobacco and join programs of risk-adaptive cancer screening.

[Metabolic syndrome and cancer risk]. / Metabolisches Syndrom und Krebsrisiko.

Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his risk of cancer. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric, esophageal, thyroid, breast, endometrial and renal cell cancers. MetS increases cancer mortality up to 2,4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Both a low-risk lifestyle and cancer screening are effective and decrease the burden of cancer.

Staging of rectal cancer by EUS: depth of infiltration in T3 cancers is important.

BACKGROUND: EUS is an established method for staging of rectal cancer. Nevertheless, there are few data about the significance of infiltration depth measured by EUS. OBJECTIVE: Assessment of accuracy of T and N staging by EUS with attention to infiltration depth as provided by EUS. DESIGN: Part retrospective, part prospective study. SETTING: Community and tertiary referral hospital, covering the period before neoadjuvant therapy for advanced rectal cancer was established. PATIENTS: Eighty-three patients (60% men) with untreated rectal cancer. INTERVENTION: EUS examination. MAIN OUTCOME MEASUREMENTS: We examined the correlation between EUS findings and postoperative histology. T3 cancers as diagnosed by EUS were classified into minimally invasive (1-2 mm) or advanced (>2 mm) tumors depending on the depth of infiltration beyond the muscularis propria. RESULTS: Accuracy of T staging and N status was 76% and 63%, respectively. Overstaging by EUS was more common in minimally invasive T3 by EUS (uT3) (8 of 16 [50%]) compared with advanced uT3 tumors (1 of 24 [4%]) (P=.01). Accuracy of EUS discrimination between T1/2 and T3/4 in rectal cancer for all but minimally invasive uT3 rectal tumors was 88%. LIMITATIONS: Partly retrospective analysis. CONCLUSIONS: EUS examination of rectal carcinoma determines T stage with high accuracy. Additionally, it provides information beyond T and N staging. The 50% probability of overstaging patients with minimally invasive uT3N0 by EUS may argue for managing these cancers as stage I disease, ie, to refer the patient for surgery without neoadjuvant therapy.

Excess Body Weight and Gastrointestinal Cancer Risk.

BACKGROUND: Excess body weight (EBW), defined as a body mass index (BMI) ≥25 kg/m2, has become the second most important as well as a potentially modifiable risk factor for cancer in many industrialized countries. The more excess weight people have, the higher the risk of certain cancers. Over the past several decades, EBW has been increasing globally not only among adults, but also among children and adolescents. SUMMARY: EBW is causally associated with colorectal, esophageal (adenocarcinoma), gastric (cardia), pancreatic, biliary and hepatocellular cancer. EBW when combined with tobacco smoking, risky alcohol use, or diabetes can act synergistically to cause gastrointestinal cancer. In recent years, more and more young adults (20-40 years old) were diagnosed with EBW-associated neoplasms. People with EBW should be encouraged to join cancer screening programs. KEY MESSAGES: Keeping a healthy weight is a major public health concern and reduces the risk of cancer.

[Smoking tobacco and cancer risk]. / Tabakrauchen und Krebsrisiko.

Smoking tobacco is the most important and potentially modifiable risk factor for cancer in Germany. Combining tobacco with alcohol can multiply cancer risks. Up to 30 % of cancer deaths are due to tobacco smoking. 23,3 % of 18-64 year-old Germans are current smokers; in addition, 11 % of the population are regularly exposed to secondhand tobacco smoke. Tobacco smoking is causally associated with oropharyngeal, laryngeal, nose, paranasal sinus, lung, esophageal, gastric, pancreatic, hepatocellular, biliary, colorectal, kidney, ureter, urinary bladder, uterine cervix and ovary cancers and leukemia. Smokers should be encouraged to stop smoking and join programmes of cancer screening. Smoking cessation effectively reduces tobacco-associated cancer risk.

[Type-2-diabetes and cancer risk]. / Typ-2-Diabetes-mellitus und Krebsrisiko.

Type-2-diabetes (T2D) increases the risk for several cancers and cancer has become the major cause of death of T2D-patients. T2D is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric, esophageal, oral, breast, endometrial, ovary, kidney and thyroid cancers as well as leukemias. When T2D goes along with tobacco smoking, alcohol use, physical inactivity, excess body weight, poor diet, familial risk or certain chronic infections, the cumulative cancer risk rises, and T2D-patients often suffer from cancer disease at younger age. T2D-patients should be encouraged to join cancer screening programmes even at younger age than the average non-diabetic population.

Alcohol Use and Gastrointestinal Cancer Risk.

BACKGROUND: Alcohol use is an important and potentially modifiable risk factor for gastrointestinal cancers. The more and the longer a person drinks, the higher the risk of cancer becomes. Even modest use of alcohol may increase cancer risk; 100 g of alcohol per week or less is currently considered to be the limit of low-risk use. GASTROINTESTINAL CANCER RISK: Alcohol is causally associated with oesophageal squamous cell cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and most likely also with pancreatic cancer. Alcohol when combined with tobacco smoking or excess body weight can act synergistically to cause gastrointestinal cancer. Exposure to alcohol may have contributed to the recent incidence increases of early-onset gastrointestinal cancers in some Western countries. CONCLUSIONS: People with long-term risky alcohol use should be encouraged to join cancer screening programmes. Alcohol cessation appears to be effective in reducing the alcohol-induced, increased cancer risk.

[Excess Body Weight and Cancer Risk]. / Übermäßiges Körpergewicht und Krebsrisiko.

Excess body weight (EBW) is the second most important and potentially modifiable risk factor of cancer in Germany. The longer and the more excess body weight a person has, the higher the cancer risk. About 60 % of adult Germans have EBW (BMI ≥ 25.0 kg/m²) and more than 23 % are obese (BMI ≥ 30.0 kg/m²). Excess body weight is causally associated with colorectal, esophageal (adenocarcinoma), gastric (cardia), pancreatic, biliary, hepatocellular, kidney, thyroid, breast (postmenopausal), endometrial and ovarian cancer as well as multiple myeloma and meningioma. In recent years, more and more young adults (20-40 years) were diagnosed with EBW-associated tumors. People with EBW should be encouraged to join programs of cancer screening. Keeping a healthy weight is a major public health concern in Germany.

Source attribution of community-acquired cases of Legionnaires' disease-results from the German LeTriWa study; Berlin, 2016-2019.

INTRODUCTION: Sources of infection of most cases of community-acquired Legionnaires' disease (CALD) are unknown. OBJECTIVE: Identification of sources of infection of CALD. SETTING: Berlin; December 2016-May 2019. PARTICIPANTS: Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls. MAIN OUTCOME MEASURE: Percentage of cases of CALD with attributed source of infection. METHODS: Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)). RESULTS: Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25-93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed. CONCLUSION: Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.

[Alcohol Use and Cancer Risk]. / Alkoholkonsum und Krebsrisiko.

Alcohol use is one of the most important and potentially modifiable risk factors for cancer in Germany. The more and the longer a person drinks, the higher the risk of cancer. Even modest use of alcohol may increase cancer risk. Statistically, every German drinks more than 100 gram of alcohol per week; this amount is currently considered to be the limit of low-risk use. Alcohol is causally associated with oropharyngeal and larynx cancer, esophageal squamous cell cancer, hepatocellular carcinoma, breast cancer, and colorectal cancer. People with long-term risky alcohol use should be encouraged to join programs of cancer screening. Alcohol cessation appears to be effective in reducing the alcohol-induced, increased cancer risk.

Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer.

Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors ("small molecule inhibitors") and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation. mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

Targeted medical therapy of biliary tract cancer: recent advances and future perspectives.

The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.