Clinical significance of personalized tacrolimus dosing by adjusting to donor CYP3A-status in liver transplant recipients.

Donor's CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period. METHODS: The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy. RESULTS: The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A-status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P < 0.0001). Acute rejection episodes (3.6 vs 23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P > 0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mL-1 (20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated with high tacrolimus concentrations (>20 ng mL-1 ) in the first week after transplantation (13/27 of control and 2/9 of CYPtest patients). CONCLUSION: CYP3A-status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).

[Surgery of peritoneal surface malignancies - surgical cytoreduction and hyperthermic intraperitoneal chemotherapy]. / A peritoneális felszín tumorainak sebészete ­ citoreduktív sebészet és hipertermiás intraperitoneális kemoterápia.

Peritoneal carcinosis has historically been considered as inoperable, although the technique of its resesection together with high dose intraperitoneal chemotherapy potentiated by heat has been described decades ago. It has not became a widely practiced routine except in specialized centers - the complex technique, weakly standardized but resource demanding chemotherapy, lacking financial background and the many times questionable clinical benefit at a cost of high surgical load might have been the key factors. Refined technology, developing chemotherapy protocols together with growing clinical evidence are now more sharply delineating the range of indications where the procedure might be beneficial, increases survival, or is the only curative therapy. These include tumors of the appendix and pseudomyxoma peritonei, mesothelioma, and selected cases of ovarian, colorectal and gastric cancer. In addition to technical description of the intervention, we summarize the currently valid indications and describe our institutional protocol for the treatment of appendiceal malignancies.

Optimizing Survival for Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Report and Current Perspectives.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options. METHODS: We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed. RESULTS: A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

[Antegrade colonic enema is a choice for the treatment of faecal incontinence and constipation]. / Anterograd vastagbélátmosás az incontinentia és az obstipatio kezelésének egyik lehetosége.

UNLABELLED: Faecal incontinence and constipation cannot always be treated successfully by conservative or surgical methods. In these cases regular retrograde colonic enema can reduce the symptoms of the patients and can establish pseudocontinence. The authors present a method of colon cleaning which has been used successfully. The method was introduced in clinical practice by Malone in 1990. The antegrade enema is administered through the appendicostomy. In cases, where the appendectomy was performed earlier, a neoappendix was created from the coecal wall and used for the irrigation of the colon. During procedure the patients injected tap water (300-450 ml) through the (neo-)appendicostomy with a thin catheter. After a short time period this was followed by passing of the stool. The procedure was performed on twelve patients, five female, and seven male patients (mean age: 39.2 years). The indications for the procedure were the following: faecal incontinence induced by denervation of the pelvic floor in three patients, sphincter trauma in two patients and congenital sphincter malformation in two cases. In addition, combined symptoms of faecal incontinence and constipation caused by pelvic floor denervation in three patients. Finally, intractable constipation was the reason in two patients. After irrigation, the stool was passed, but the functional result was rather variable. Eight out of twelve patients were satisfied with the result, two patients reported improvement in the constipation, but it failed in one case. In another case, the appendicostomy could not have been used due to surgical complications. The stricture of the (neo-)appendicostomy was observed in two cases. Significant reflux occurred only in one case. CONCLUSION: after adequate patient selection this method can be applied with success.