Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy.

PURPOSE: This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS: The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS: Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS: Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.

[Individualized curative treatment for malignant diseases through liver transplantation]. / Individualisierte kurative Therapie bei malignen Erkrankungen durch Lebertransplantation.

BACKGROUND: For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions. OBJECTIVE: This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies. RESULTS AND CONCLUSION: Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.

Liver Transplantation for Incidental Cholangiocarcinoma or Combined Hepatocellular Carcinoma/Cholangiocarcinoma-Own Experiences and Review of the Literature.

BACKGROUND: Data about liver transplantation for mixed tumors from hepatocellular carcinoma to cholangiocarcinoma are limited. Furthermore, the diagnosis of intrahepatic cholangiocarcinoma or combined tumors in a cirrhotic liver is considered a contraindication for transplantation. Our aim was to evaluate the long-term outcomes of patients with incidental cholangiocarcinoma or combined tumors after liver transplantation. METHODS: In our descriptive analysis, data were evaluated from all patients since 2010 who received a liver transplant due to an assumed hepatocellular carcinoma at Jena University Hospital. Survival rates were determined using the Kaplan-Meier method. RESULTS: Between January 2010 and December 2022, an incidental intrahepatic cholangiocarcinoma was found in eight patients post-transplant. Four combined hepatocellular and cholangiocarcinoma and four sole intrahepatic cholangiocarcinomas were found. A recurrence through distant metastases from combined hepatocellular- and cholangiocarcinoma was found in one patient at one year after transplantation. Another patient developed a pulmonary primary tumor independently one year post-transplant. The recurrence rate was at 14.3%. While two patients died, the 1- and 5-year overall survival rates post-transplant were 87.5% and 75%, respectively. CONCLUSION: Patients with intrahepatic cholangiocarcinoma or combined hepatocellular- and cholangiocarcinoma could profit from liver transplantation.

Robot-assisted Radical Cystectomy with Orthotopic Neobladder Reconstruction: Techniques and Functional Outcomes in Males.

BACKGROUND: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. OBJECTIVE: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. DESIGN, SETTING, AND PARTICIPANTS: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. SURGICAL PROCEDURE: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. MEASUREMENTS: The outcomes measured were UC and EF at 12 mo. RESULTS AND LIMITATIONS: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58-70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88-7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55-11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91-0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25-0.89; p < 0.02) were inversely associated with EF. CONCLUSIONS: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. PATIENT SUMMARY: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery.

Interleukin-10-592 polymorphism: impact on relapse and survival after allogeneic hematopoietic stem cell transplantation in children with hematological malignancies.

PURPOSE: Interleukin-10 (IL-10) potentially can promote the development of alloimmunity. The aim of this study was to investigate if the IL-10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT) and if that has an impact on event-free survival (EFS) and overall survival (OS). METHODS: A cohort of 211 children with acute lymphoblastic leukemia (n = 99), acute myeloid leukemia (n = 69), myelodysplastic syndrome (n = 31) or chronic myeloid leukemia (n = 12) who underwent hematopoietic stem cell transplantation (HSCT) in a single center and their respective donors were genotyped of IL-10 gene for rs1800872 using TaqMan real-time polymerase chain reaction. RESULTS: The IL-10-592 CC genotype was detected in 107 of the 211 donors (50.7%) and in 106 of the 211 patients (50.2%). Genotype AC was found in 95 donors (45.0%) and in 90 patients (42.7%). Nine donors (4.3%) and 15 patients (7.1%) were homozygous for AA. Ultimately, we observed a significantly reduced incidence of relapse rate (RR) in patients who were transplanted from a donor with the IL-10-592 CC genotype (19% versus 43% (AC) versus 49% (AA); P = 0.0007). In addition, a significant increase of EFS (P = 0.004) and OS (P = 0.006) was detected if the IL-10-592 CC genotype is present in the donor. The occurrence of the IL-10-592 CC genotype, in either donors or recipients, had no significant impact on acute and chronic graft-versus-host disease. In addition, the IL-10-592 genotype of the recipients was not relevant for the RR (P = 0.47434), the EFS (P = 0.840), and the OS (P = 0.535). CONCLUSION: The IL-10-592 CC genotype in the donor was associated with a significant decrease of RR which led to a significant increase of EFS and OS after HSCT. This is the first study to describe an association of the IL-10 gene polymorphism with RR, EFS, and OS after HSCT. Selecting a donor with the IL-10-592 CC genotype could be a useful therapeutic strategy for improving the outcome after allogeneic HSCT.