Anti-EGFR Reintroduction and Rechallenge in Metastatic Colorectal Cancer (mCRC): A Real-World Analysis.

BACKGROUND AND AIMS: In patients with Rat sarcoma proto-oncogene (RAS) wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) antibodies have been established in first- and further therapy lines. Due to limited treatment options upon disease progression, anti-EGFR re-exposure is increasingly employed in real-world oncology. The aim of this study was to assess clinical implementation and utility of anti-EGFR retreatment strategies in real-world mCRC patients. METHODS: In this monocentric retrospective study, we included 524 patients with CRC and identified patients who received an anti-EGFR-based treatment as well as anti-EGFR rechallenge (progression on first-line anti-EGFR therapy) or reintroduction (discontinuation due to intolerance/toxicity/other). RESULTS: In total, 143 patients received an anti-EGFR-based first- or second-line treatment, showing a similar overall survival (OS) compared to the non-anti-EGFR treatment group (38.3 vs. 39.6 months, p = 0.88). Thirty-three patients met the inclusion criteria for anti-EGFR re-exposure and were either assigned to rechallenge (n = 21) or reintroduction (n = 12) subgroups. The median FU after re-exposure was 45.8 months. Cetuximab and Panitumumab were used in 21 and 12 patients, respectively, and the main chemotherapy at re-exposure was FOLFIRI in 39.4%. Anti-EGFR re-exposure was associated with a distinct trend towards a better outcome (median OS 56.0 vs. 35.4 months, p = 0.06). In a subgroup comparison, reintroduction was associated with a higher OS and PFS in trend compared to the rechallenge (mOS 66 vs. 52.4, n.s., mPFS 7.33 vs. 3.68 months, n.s.). CONCLUSIONS: This retrospective study provides real-world evidence underscoring that anti-EGFR re-exposure strategies might benefit patients independently of the reason for prior discontinuation.

Low Platelet Count Predicts Reduced Survival in Potentially Resectable Hepatocellular Carcinoma.

The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We retrospectively reviewed 128 patients who underwent hepatic resection for HCC at a tertiary academic centre (2007−2019). Patient data were modelled by regression analysis, and platelet count was treated as a continuous variable. 89 patients had BCLC 0/A tumours and 39 had BCLC B tumours. Platelet count was higher in patients with larger tumours and lower in patients with higher MELD scores, advanced fibrosis, and portal hypertension (p < 0.001 for all listed variables). After adjusting for BCLC stage and tumour diameter, low platelet count associated with reduced overall survival (hazard ratio 1.25 per 50/nL decrease in platelet count, 95% confidence interval (CI) 1.02−1.53, p = 0.034) and increased perioperative mortality (odds ratio 1.96 per 50/nL decrease in platelet count, 95% CI 1.19−3.53, p = 0.014). Overall, low platelet count correlates with increased liver disease severity, inferior survival, and excess perioperative mortality in resectable HCC. These insights might be applied in clinical practice to better select patients for resection.

[Education of Abdominal Organ Procurement Surgeons in Germany - Challenges and Possible Solutions]. / Ausbildung von Entnahmechirurgen abdomineller Organe in Deutschland ­ Herausforderungen und Lösungsansätze.

The procurement of abdominal organs is a highly specialised operation, which marks the first important step for a successful transplantation. The article gives an overview of the organisation and the current state of the education of procurement surgeons in Germany. We comment on current challenges and discuss these in an international context.

The Epidemiology of Acute Liver Failure.

BACKGROUND: Acute liver failure (ALF) is a life-threatening event associated with high mortality. Currently, only estimates are available for its incidence. The aim of the study was to assess the incidence of ALF in Germany, using the accounting data of the largest statutory health insurance company, which represents 26.5 million people. METHODS: The analysis included patients insured from 1 January 2014 to 31 December 2018. Coding with the International Statistical Classification of Diseases and Related Health Problems and the German operation and procedure codes were used to identify the patients, whose age, sex, liver transplantations (LT), and fatal outcomes were then recorded and extrapolated to the total population. As a validity check, the extrapolated LT results were compared with the LT that were actually performed. RESULTS: The calculated incidence of ALF was 1.13/100 000 person-years, representing 4652 cases. Women were more often affected (52% versus 48%, p < 0.001). The overall rate of mortality within 3 months was 47%. A total of 203 LT were recorded in 176 patients. Men received 41% of the LT, women 59% (p < 0.137). The 1-year overall mortality rate after LT was 20%. The 203 calculated transplantations corresponded to 228 actually performed transplantations. CONCLUSION: The incidence of ALF was higher than previously estimated for Germany, with only a very low rate of LT despite high mortality. When extrapolating ny, it must be borne in mind that those insured by the company concerned do not represent a valid sample.

Conversion From Sirolimus to Everolimus in Long-Term Liver Graft Recipients.

Immunosuppression by inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach after liver transplantation. The mTOR inhibitor sirolimus was used in selected liver graft recipients despite safety concerns and lack of approval. Everolimus is another mTOR inhibitor approved after liver transplantation. It is currently unknown, whether conversion of sirolimus to everolimus is safe in long-term liver graft recipients. Long-term liver graft recipients treated with sirolimus were converted to everolimus. A systematical analysis of biochemical and clinical data before and after conversion was performed. Sixteen patients were included (female/male, 8/8). Median (range) age at conversion was 66 years (49-78 years), and patients were converted at a median (range) of 10.1 years (4.0-22.3 years) after liver transplantation. In the majority of patients, no dose adjustment was needed after conversion. No rejection and no cytomegalovirus replication episodes were observed. Furthermore, no differences were found with respect to kidney function, diabetes mellitus, or blood pressure before and after conversion. Bilirubin serum concentration was lower, whereas aspartate aminotransaminase, alanine aminotransferase, and triglycerides serum concentrations were higher after conversion to everolimus. Neither clinical- nor graft-associated significant complications were observed after conversion from sirolimus to everolimus in long-term liver graft recipients. Everolimus-based immunosuppression may be offered to patients after liver transplantation formerly treated with sirolimus.