Gender comparison of clinical, histopathological, therapeutic and outcome factors in 185,967 colon cancer patients.

INTRODUCTION: Colorectal carcinomas represent the third most common cause of cancer-related deaths in Germany. Although the incidence is significantly higher in men compared with women and gender is a well-established crucial factor for outcome in other diseases, detailed gender comparisons for colon cancer are lacking. METHODS: This retrospective population-based cohort study included all patients diagnosed with colon cancer in Germany between 2000 and 2016 who were included in the common dataset of colorectal cancer patients from the quality conference of the German Cancer Society. We compared clinical, histopathological, and therapeutic characteristics as well as overall and recurrence-free survival. RESULTS: A total of 185,967 patients were included in the study, of which 85,685 were female (46.1%) and 100,282 were male (53.9%). The proportion of women diagnosed with colon cancer decreased from 2000 to 2016 (f: 26.6 to 40.1%; m: 24.9 to 41.9%; p < 0.001), and the proportion of very old patients was especially high in women (f: 27.3%; m: 15.6%; p < 0.001). The localization in women was more right-sided (f: 45.0%, m: 36.7%; p < 0.001), and women had a higher tumor grading and a higher UICC stage (especially stage III nodal-positive) at diagnosis of primary colon cancer (UICC III: f: 22.7%, m: 21.0%; p < 0.001). We could detect a significantly better overall (hazard ratio: 0.853, lower 95%: 0.841, upper 95%: 0.864; p < 0.001) and recurrence-free survival (hazard ratio: 0.857, lower 95%: 0.845, upper 95%: 0.868; p < 0.001) in women compared with men, even though women received chemotherapy less frequently compared with men (f: 26.1%, m: 28.1%; p < 0.001). CONCLUSION: We could detect several variables that differed significantly between men and women regarding clinical, histopathological, therapeutic, and outcome factors. We believe that it is crucial to consider gender as a key factor in the diagnosis and treatment of colon cancer. Sex-specific diagnostic tools could lead to an earlier diagnosis of colon cancer in women, and ways to increase the rate of chemotherapy in women should be evaluated. Furthermore, we recommend stratifying randomized trials by gender.

Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience.

BACKGROUND: Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS: Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS: HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS: Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.

A Closing Chapter: Hepatitis C Genotype 3 Elimination in Liver Transplant; Sofosbuvir/Daclatasvir in a Hard-to-Treat Population.

OBJECTIVES: Historically, hepatitis C virus genotype 3 infection has not been as hard to treat as genotype 1 using interferon-based therapy. Now, genotype 3 infection can be treated using interferon-free regimes such as the combination of sofosbuvir and daclatasvir, which is a highly successful and reliable therapeutic option before liver transplant. However, real world data are rather limited regarding the use of antivirals (sofosbuvir/daclatasvir) for hepatitis C virus genotype 3 recurrence after liver transplant. Here, we present the results of antiviral treatment with sofosbuvir and daclatasvir in patients with genotype 3 recurrence after liver transplant and also viewed published data, to finally close the chapter on genotype 3 elimination. MATERIALS AND METHODS: We analyzed 11 patients who received liver transplants due to hepatitis C virus genotype 3-associated cirrhosis at our center. Two patients were nadve for any antiviral therapy. All patients received antiviral treatment with sofosbuvir/daclatasvir for 12 weeks after liver transplant, with 1 patient also having ribavirin. The endpoint was hepatitis C virus RNA-free survival after 12 weeks of therapy. Secondary endpoints were preservation of renal and liver function and incidence of adverse events. RESULTS: All patients were free of hepatitis C virus RNA by at least 8 weeks after therapy initiation. Elevated transaminases and gamma-glutamyltransferase at the beginning of therapy normalized quickly during treatment. Synthesis and excretion were stable at all dates. Patients displayed no severe adverse effects, especially regarding renal function and blood counts. Sustained virologic response rates at week 12 were achieved in all 11 patients. CONCLUSIONS: Hepatitis C virus could be eliminated in all patients after liver transplant with 12-week sofosbuvir/daclatasvir therapy. Sofosbuvir combined with daclatasvir is safe and reliable for recurrent hepatitis C virus genotype 3 infection. Our results have closed the chapter on genotype 3 recurrence after liver transplant in our outpatient clinic.

Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin.

BACKGROUND: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered. PATIENTS AND METHODS: At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks. RESULTS: End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P<.001. One of the predominant and most relevant AEs was the development of anemia in 43.1% of 10 patients receiving RBV, which was a significant result (P<.001). RBV co-medication had to be reduced in 11 (55%) patients and then stopped in 8 (40%) patients because of AEs. No significant difference was observed among the groups regarding kidney function. CONCLUSION: The SOF/LDV combination is a reliable therapy of recurrent HCV infection after LT. It is easy to administer and to achieve SVR in immunocompromised patients without interactions with immunosuppressive medications. Considering the high rate of AEs, frequent discontinuation of RBV treatment, and the 100% SVR, the use of RBV as co-medication in a 12-week SOF/LDV regimen does not seem to be justified after LT.

Gender Mainstreaming and Transplant Surgery.

BACKGROUND: Gender differences in medicine are gaining in importance. In transplant surgery, not only the patient's gender but also that of the donor play an important role in the outcome of transplantation due to sociocultural and genetic factors. METHODS: This review article gives an overview of the latest investigations into gender-related influences in the field of visceral transplantation. For this purpose, a systematic review of the literature was performed. RESULTS: In general, women are less often evaluated for and subjected to transplantation worldwide. Significantly poorer outcome can be observed in women with liver transplantation following hepatitis C cirrhosis. Furthermore, female renal grafts are less favorable in terms of outcome and survival. Gender disparities affect transplant medicine due to subtle gender-specific immunological factors. Sociocultural factors also lead to differences in the clinical treatment of men and women, which may influence overall survival. CONCLUSION: For a better understanding of gender-specific differences in transplant medicine and a possible improvement in outcome, further research in this field is necessary.

Clinical application of modern ultrasound techniques after liver transplantation.

Liver transplantation has been established as a first-line therapy for a number of indications. Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are methods of choice during the postoperative period as a safe and fast tool to detect potential complications and to enable early intervention if necessary. CEUS increases diagnostic quality and is an appropriate procedure for the examination of vessels and possibly bile ducts. This article presents the state of the art of ultrasound application during the early period after liver transplantation. It addresses common vascular complications and describes the identification of postoperative abnormal findings using ultrasound and CEUS.