Elevated Serum Levels of CCL23 Are Associated with Poor Outcome after Resection of Biliary Tract Cancer.

Background: Surgical tumor resection is the only potentially curative treatment option for patients with biliary tract cancer (BTC). However, 5-year survival rates are still below 50% mainly due to tumor recurrence. The preoperative identification of ideal surgical candidates has remained a major challenge and easily accessible algorithms including parameters of the individual tumor biology are missing. Chemokine (C-C motif) ligand 23 (CCl23) has been associated with tumor progression in hepatocellular carcinoma (HCC), but its role in the context of BTC is largely unknown. Here, we evaluated circulating levels of CCL23 as potential diagnostic and prognostic biomarker in patients with resectable BTC. Methods: CCl23 serum levels were analyzed by multiplex immunoassay in a cohort of 119 BTC patients receiving surgical tumor resection as well as 50 healthy control samples and 11 patients with primary sclerosing cholangitis (PSC). Results: Baseline serum CCL23 levels were significantly elevated in BTC patients compared to PSC patients as well as healthy controls. CCL23 increased the diagnostic sensitivity and specificity of established tumor markers including CA19-9 and correlated with patients' age and makers of systemic inflammation. Elevated preoperative CCL23 levels were associated with a significantly impaired postoperative outcome. BTC patients with a preoperative CCL23 level above the optimal prognostic cut-off value of 702.4 pg/ml showed a median OS of only 110 days compared to 501 days for patients with low initial CCL23 levels. The prognostic value of circulating CCL23 was confirmed in Cox-regression analysis. Conclusion: Serum levels of CCL23 are elevated in patients with BTC, and high preoperative CCL23 levels were associated with an impaired postoperative survival. CCL23 serum levels could help to identify the ideal surgical candidates for BTC resection in the future.

Prevalence of chronic obstructive pulmonary disease among 48,061 digestive tract cancer patients in Europe.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) shares common risk factors with digestive tract malignancies such as esophageal cancer. However, the prevalence and geographic distribution of COPD in patients with gastrointestinal (GI) cancer is only poorly understood. METHODS: We used the IQVIA's Oncology Dynamics (OD) database to identify a total of 48,061 patients with GI cancer (4,229 esophagus, 7,568 stomach, 27,300 colon, and 8,964 rectum cancer) from Germany, France, Italy, Spain and the UK. RESULTS: The prevalence of COPD among the 48,061 patients with GI cancer was 12.5% (5,983/48,061). We observed significant differences in frequencies of COPD between the different cancer sites with the highest COPD prevalence among patients with esophageal (25.5%) or gastric cancer (13.4%) and lowest prevalence in colon (11.0%) or rectal (9.8%) cancer patients. Moreover, rates of COPD strongly varied between digestive tract cancer patients from different countries. Interestingly, Spain (16.8%) and Germany (13.4%) had the highest COPD prevalence while prevalence of COPD was lowest in the UK (8.4%). Finally, we showed that the proportion of digestive tract cancer patients with COPD was highest among male patients (15%) and those >80 years (20.6%) when compared to all other patients. CONCLUSIONS: In this analysis, we show that COPD is found at high frequencies in patients with digestive tract cancer in Europe. We demonstrate that prevalence varies according to digestive tract cancer sites and European countries.

Current Trends in Inpatient Care and In-Hospital Mortality of Cholangiocarcinoma in Germany: A Systematic Analysis between 2010 and 2019.

Background: Cholangiocarcinoma (CCA) is a rare malignant disease of the biliary tract with an increasing incidence and a high mortality worldwide. Systematic data on epidemiological trends, treatment strategies, and in-hospital mortality of CCA in Germany are largely missing. However, the evaluation and careful interpretation of these data could help to further improve the treatment strategies and outcome of CCA patients in the future. Methods: Standardized hospital discharge data from the German Federal Statistical Office were used to evaluate epidemiological and clinical trends as well as the in-hospital mortality of CCA in Germany between 2010 and 2019. Results: A total of 154,515 hospitalized CCA cases were included into the analyses. The number of cases significantly increased over time (p < 0.001), with intrahepatic CCA (62.5%) being the most prevalent tumor localization. Overall, in-hospital mortality was 11.4% and remained unchanged over time. In-hospital mortality was significantly associated with patients' age and tumor localization. The presence of clinical complications such as (sub)acute liver failure, acute respiratory distress syndrome (ARDS), or acute renal failure significantly increased in-hospital mortality up to 77.6%. In-hospital mortality was significantly lower among patients treated at high annual case volume centers. Finally, treatment strategies for CCA significantly changed over time and showed decisive differences with respect to the hospitals' annual case volume. Conclusions: Our data provide a systematic overview on hospitalized CCA patients in Germany. We identified relevant clinical and epidemiological risk factors associated with an increased in-hospital mortality that could help to further improve framework conditions for the management of CCA patients in the future.

The Spectrum of Co-Diagnoses in Patients with Colorectal Cancer: A Retrospective Cohort Study of 17,824 Outpatients in Germany.

Background: The prognosis of colorectal cancer (CRC) patients is determined to a decisive extent by comorbidities. On the other hand, anti-cancer treatments for CRC are associated with relevant toxicities and may therefore cause additional comorbidities. Methods: This retrospective cohort study assessed the prevalence of various diseases in patients 12 months before and 12 months after an initial diagnosis of colorectal cancer (ICD-10: C18, C20) in 1274 general practices in Germany between January 2000 and December 2018. The study is based on the Disease Analyzer database (IQVIA), which contains drug prescriptions, diagnoses, and basic medical and demographic data. Patients with and without CRC were matched by sex, age, and index year. Results: We identified several diagnoses with a significantly higher prevalence among CRC patients 12 months prior to the index date compared to controls. These diagnoses included gastrointestinal hemorrhage, hemorrhoids, perianal venous thrombosis, and abdominal and pelvic pain, as well as functional intestinal disorders. In contrast, the prevalence of lipid metabolism disorder, depression, hypertension, coronary heart disease, or acute bronchitis was significantly lower in CRC cases. After diagnosis of CRC, we found a significantly higher prevalence of anemia, polyneuropathies, functional intestinal disorders, and chronic kidney disease among CRC patients compared to the control group, while the prevalence of acute upper respiratory infections of multiple and unspecified sites and acute bronchitis was significantly lower in CRC patients compared to non-CRC patients. Conclusions: In the present study, we identified a variety of diseases occurring at higher or lower frequencies in CRC patients compared to matched controls without CRC. This might help to select patients for early CRC screening and improve the clinical management of CRC patients.

Serum Levels of CXCL13 Are an Independent Predictor of Survival Following Resection of Biliary Tract Cancer.

BACKGROUND: The prognosis of biliary tract cancer (BTC) has remained very poor. Although tumor resection represents a potentially curative therapy for selected patients, tumor recurrence is common, and 5-year survival rates have remained below 50%. As stratification algorithms comprising the parameters of individual tumor biology are missing, the identification of ideal patients for extensive tumor surgery is often challenging. The CXC chemokine family exerts decisive functions in cell-cell interactions and has only recently been associated with cancer, but little is known about their function in BTC. Here, we aim to evaluate a potential role of circulating CXCL1, CXCL10 and CXCL13 in patients with resectable BTC. METHODS: Serum levels of CXCL1, CXCL10 and CXCL13 were measured by multiplex immunoassay in a cohort of 119 BTC patients undergoing tumor resection and 50 control samples. RESULTS: Circulating levels of CXCL1, CXCL10 and CXCL13 were all significantly elevated in BTC patients compared to healthy controls and increased the diagnostic power of established tumor markers such as CA19-9 when used in combination. Importantly, elevated levels of CXCL13 both before and after tumor resection identified a subgroup of patients with significantly impaired outcomes following tumor resection. As such, BTC patients with initial CXCL13 levels above the ideal prognostic cut-off value (25.01 pg/mL) had a median overall survival (OS) of 290 days compared to 969 days for patients with low initial CXCL13 levels. The prognostic value of circulating CXCL13 was further confirmed by uni- and multivariate Cox regression analyses. Finally, the individual kinetics of CXCL13 before and after tumor resection were also indicative of patient outcomes. CONCLUSION: Our data support a fundamental role of the CXC chemokine family in BTC and identified circulating levels of CXCL13 as a previously unrecognized marker for predicting outcomes following the resection of BTC.

Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer.

BACKGROUND: Tumor resection represents the only potentially curative therapy for patients with biliary tract cancer. Nevertheless, disease recurrence is observed in about 50% of patients, leading to a 5-years survival rate of less than 50%. The Golgi protein 73 (GP73), a type II Golgi transmembrane protein, exerts important functions of intracellular protein processing and transportation. Circulating GP73 has recently been suggested as a prognostic marker following resection of hepatocellular carcinoma (HCC) but its role in the context of BTC has remained unknown. In this study, we evaluate a potential role of circulating GP73 as a novel biomarker in patients with resectable BTC. METHODS: GP73 serum levels were measured by immunoassay in n = 97 BTC and n = 40 HCC patients as well as n = 31 healthy controls. Results were correlated with clinical data. RESULTS: Serum GP73 levels were significantly elevated in BTC patients compared to healthy controls but lower compared to HCC patients. The combination of GP73/CA19-9 showed a sensitivity and specificity of 83.5% and 90.3% regarding the differentiation of BTC patients and healthy controls. BTC patients with baseline GP73 levels above the ideal cut-off value (42.47 ng/mL) showed a significantly reduced median overall survival (193 days) compared to patients with preoperative GP73 levels below this cut-off (882 days). These results were confirmed in uni- and multivariate Cox-regression analysis including several clinicopathological parameters such as age, ECOG performance status, tumor stage as well as established tumor markers and parameters of liver and kidney function. CONCLUSIONS: GP73 represents a previously unrecognized biomarker in the patients with resectable BTC that identifies patients with an impaired postoperative outcome. If larger clinical trials confirmed these findings, measurement of GP73 serum levels might become a novel tool in the challenging preoperative stratification process of patients with resectable BTC.

Prevalence of Lung Metastases among 19,321 Metastatic Colorectal Cancer Patients in Eight Countries of Europe and Asia.

BACKGROUND: Colorectal cancer is one of the most common malignancies in the Western world, and is responsible for about 10% of annual cancer-related deaths. Especially for UICC stage IV, the probability of survival is significantly reduced. Little is known about risk factors for specific metastatic patterns of colorectal cancer that may also influence patients' overall survival. METHODS: We used data from the IQVIA oncology dynamics (OD) database to determine the prevalence of pulmonary metastases in 19,321 patients with UICC stage IV colorectal cancer in eight European and Asian countries. RESULTS: In total, 6132 of 19,321 (31.7%) study patients had lung metastases, with a higher prevalence among patients with rectal (37.5%) than colon (30.1%) cancer. When compared to China as the country with the lowest lung metastases prevalence, the odds for lung metastases were highest in UK (OR: 2.02, 95%CI: 1.80-2.28), followed by Italy (OR: 1.86, 95%CI: 1.52-2.27), Spain (OR: 1.85, 95%CI: 1.64-2.09), and Germany (OR: 1.47, 95%CI: 1.26-1.71). CONCLUSION: The prevalence of pulmonary metastases in UICC stage IV colorectal cancer varies widely among the different analyzed countries. Although the present data are purely descriptive, a possible combination of ethnic, environmental, and health care system-associated differences could be discussed as the underlying cause. Further studies are needed to investigate the reasons for differences in the prevalence of lung metastases.

Incidence of Cancer in Patients with Irritable Bowl Syndrome.

(1) Background: Irritable bowel syndrome (IBS) represents one of the most common disorders of gut-brain interaction (DGBI). As recent data has suggested an increased cancer incidence for IBS patients, there is an ongoing debate whether IBS might be associated with a risk of cancer development. In the present study, we evaluated and compared incidence rates of different malignancies including gastrointestinal cancer in a large cohort of outpatients, with or without IBS, treated in general practices in Germany. (2) Methods: We matched a cohort of 21,731 IBS patients from the IQVIA Disease Analyzer database documented between 2000 and 2019 in 1284 general practices to a cohort of equal size without IBS. Incidence of cancer diagnoses were evaluated using Cox regression models during a 10-year follow-up period. (3) Results: In 11.9% of patients with IBS compared to 8.0% without IBS, cancer of any type was diagnosed within 10 years following the index date (p < 0.001). In a regression analysis, this association was confirmed in female (HR: 1.68, p < 0.001) and male (HR = 1.57, p < 0.001) patients as well as in patients of all age groups. In terms of cancer entity, 1.9% of patients with and 1.3% of patients without IBS were newly diagnosed with cancer of digestive organs (p < 0.001). Among non-digestive cancer entities, the strongest association was observed for skin cancer (HR = 1.87, p < 0.001), followed by prostate cancer in men (HR = 1.81, p < 0.001) and breast cancer in female patients (HR = 1.80, p < 0.001). (4) Conclusion: Our data suggest that IBS might be associated with cancer of the digestive organs as well as with non-digestive cancer entities. However, our findings do not prove causality and further research is warranted as the association could be attributed to life style factors that were not documented in the database.