Short-term postoperative outcomes of lymphadenectomy for cholangiocarcinoma, hepatocellular carcinoma and colorectal liver metastases in the modern era of liver surgery: Insights from the StuDoQ|Liver registry.

INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.

Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors.

Although therapeutic options are gradually improving, the overall prognosis for patients with hepatocellular carcinoma (HCC) is still poor. Gene therapy-based strategies are developed to complement the therapeutic armamentarium, both in early and late-stage disease. For efficient delivery of transgenes with antitumor activity, vectors demonstrating preferred tumor tropism are required. Here, we report on the natural tropism of adeno-associated virus (AAV) serotype 2 vectors for HCC. When applied intravenously in transgenic HCC mouse models, similar amounts of vectors were detected in the liver and liver tumor tissue. In contrast, transduction efficiency, as indicated by the level of transgene product, was moderate in the liver but was elevated up to 19-fold in mouse tumor tissue. Preferred transduction of HCC compared to hepatocytes was confirmed in precision-cut liver slices from human patient samples. Our mechanistic studies revealed that this preference is due to the improved intracellular processing of AAV2 vectors in HCC, resulting, for example, in nearly 4-fold more AAV vector episomes that serve as templates for gene transcription. Given this background, AAV2 vectors ought to be considered to strengthen current-or develop novel-strategies for treating HCC.

A rare case of hepatic metastasis 20 years after surgical resection of a thymoma: A case report.

INTRODUCTION: Thymoma is the most common solid, primary mediastinal tumour, accounting for 20% of mediastinal neoplasms. Malignant thymus tumours (thymomas and thymic carcinomas) metastasize primarily locally. Distant metastases, especially to liver are very rare. PRESENTATION OF CASE: We review the case of a 59 year-old female patient, who underwent resection of the thymus with a diagnosed type B2 thymoma 20 years ago. The patient was referred to our hospital with a newly discovered space-occupying lesion in the liver, which had been detected in a routine follow-up magnetic resonance imaging scan. Since a malignant tumour of the liver could not be excluded, a conventional left hemihepatectomy was performed. Histological examination revealed a liver metastasis of the type B2 thymoma, which had been removed 20 years ago. CLINICAL DISCUSSION: The case was discussed in the interdisciplinary tumour board. Based on the very long history of the primary removal of the thymoma as well as the R0 resection of the liver metastasis, a follow-up regimen with CT scans on a regular basis was recommended. CONCLUSIONS: Newly discovered lesions of the liver in patients even with a long history of a thymoma should raise the suspicion of a liver metastasis that should be surgically resected as the therapy of choice. Further, this case indicates the importance for long-term radiographic follow-up.

Liver transplantation for unresectable hepatocellular carcinoma in normal livers.

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC.

Increased CD64 expression on polymorphonuclear neutrophils indicates infectious complications following solid organ transplantation.

The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients.

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation.

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions.

Phases of organ integration and conflict in a transplant recipient: a longitudinal study using a diary.

In this paper the results from a research project on self-perception and psychological processing following transplantation of solid organs are presented. A diary at the individual case level was introduced to generate a longitudinal analysis. In the following paper we describe an evaluation of the entries of a single patient following a living donor kidney transplant. Conflicts in the relationship between the transplant recipient and the donor, who is also his wife, are clearly evident, and these are interpreted as incorporation conflicts in light of current psychoanalytic theory.

A single-center experience with liver transplantation for Wilson's disease.

Wilson's disease is an inherited disorder of copper metabolism, presenting with prominent hepatic and neurologic manifestations. There is an established place for liver transplantation in the presence of liver disease, while the indication for neurologic manifestations is debated. Between 1993 and 2005, 11 patients were liver transplanted for Wilson's disease at our institution. We retrospectively reviewed the medical records of the patients. The pathology of the explanted livers was analyzed. The patients were divided into three groups based on the evolution of the disease. Postoperative data gathered included patient and graft outcome, complications, neurologic status, and copper metabolism. Six males and five females were transplanted at a mean age of 29.7 yr (range 15-48 yr). Three patients had a fulminant presentation, two patients had decompensation of established disease, and six patients had chronic disease. Neurologic features were prominent in five patients. The pathologic analysis of the explanted graft showed cirrhosis in all patients. The five patients with fulminant and acute on chronic presentations also showed necrosis in the explant. The mean postoperative follow-up was 56.8 months (range 10-129 months). Two patients were re-transplanted. One patient died because of severe sepsis. Two patients with severe neurologic dysfunction showed significant remission of symptoms. Liver transplantation is a safe and effective treatment for both acute and chronic presentations of Wilson's disease. Acute presentation correlates with the presence of necrosis in the explanted liver. In our series, there was a relevant improvement of the neurologic features after transplantation.

Polycystic liver and kidney disease: post-transplant kidney function in patients receiving pre-emptive kidney transplantation.

The aim of the study is to evaluate the changes in kidney function after pre-emptive kidney transplantation in patients with polycystic liver and kidney disease (PLKD) and to establish whether pre-emptive kidney transplantation is warranted. Between 1998 and 2006, five patients with severe anatomical changes in both native kidneys but only mild alteration of the clearance function received combined liver and kidney transplantation. Preoperatively, Technetium-99m mercaptoacetyltriglycine (Tc99m MAG3) scintigraphy was used to evaluate separately the function of each native kidney. This examination was repeated six months after transplantation, additionally measuring the function of the transplanted kidney. Pretransplant creatinine levels were 77-115 mumol/l and Tc99m MAG3 clearance was 141-163 ml/min/1.73 sqm (74 +/- 8% of minimum-for-age values). Six months after transplant, creatinine values were not significantly different. Minimum-for-age clearance decreased by 12.5 +/- 11.5% in four patients, and increased by 26% in one patient. In four patients, the transplanted and the native kidneys assumed each about one third of total tracer clearance. In one patient, the transplanted kidney assumed 92% of the clearance function. Kidney function decreases despite pre-emptive kidney transplantation. Native kidneys are not functionally excluded and the clearance seems to be divided between native and transplanted organs. Kidney transplantation in nonuremic PLKD patients does not improve the overall kidney function and should be performed only in exceptional cases.

Successful liver transplantation in a child with Caroli's disease.

CD is a rare autosomal recessive disease, characterized by multifocal cystic dilatation of intrahepatic bile ducts. The course of the disease is characterized by intrahepatic cholelithiasis, recurrent episodes of cholangitis, because of cholelithiasis, hepatic abscesses often ending in death caused by uncontrolled infection. Other conditions such as choledochal cyst and renal cystic disease are frequently associated, and patients have a higher risk for the development of cholangiocarcinoma. Endoscopic drainage of the bile duct is palliative and ineffective. OLT appears to be the treatment of choice. In monolobar cases partial liver resection has been shown to be a curative therapeutic option. We report on the course of disease in a Turkish girl who was diagnosed with CD in the neonatal period. At the age of 8.2 yr, she received OLT and is in good health 57 months post-transplantation.

Complicated small-bowel diverticulosis: a case report and review of the literature.

While jejunoileal diverticula are rare and often asymptomatic, they may lead to chronic non-specific or acute symptoms. The large majority of complications present with an acute abdomen similar to appendicitis, cholecystitis or colonic diverticulitis but they also may appear with atypical symptoms. As a result, diagnosis of complicated jejunoileal diverticulosis can be quite difficult, and may solely depend on the result of surgical exploration. In the absence of contra-indications, diagnostic laparoscopy has the benefit of thorough examination of the abdominal contents and helps to reach an absolute diagnosis. Surgical resection of the involved small-bowel segment with primary anastomosis is the preferred treatment in patients with symptomatic complicated jejunoileal diverticular disease. An atypical presentation of complicated jejunal diverticulitis in conjunction with sigmoid diverticulitis diagnosed with laparoscopy and treated with surgical resection is presented.

Liver resection and transplantation in the management of hepatocellular carcinoma: a review.

Hepatocellular carcinoma (HCC) accounts for more than 80% of all primary liver cancers and is one of the most common malignancies worldwide. Most patients with HCC also suffer from concomitant cirrhosis, which is the major clinical risk factor for hepatic cancer and results from alcoholism, infection with the hepatitis B or hepatitis C virus, and other causes. HCC is often diagnosed at an advanced stage, when established treatment options provide limited benefit. Effective treatment for HCC includes liver resection and liver transplantation. Under most clinical circumstances, those options provide a high rate of complete response and are thought to improve survival. Partial hepatectomy is the therapy of choice in patients with HCC and a noncirrhotic liver. Usually, liver transplantation is not indicated for such patients, although in individual cases, transplantation may be considered. For most cirrhotic patients who fulfill the Milan criteria, liver transplantation is the ultimate treatment option. Liver transplantation restores liver function and ensures the removal of all hepatic foci of tumor as well as tissue with a high oncogenic potential for early tumor recurrence. Because of the present lack of available organs, living-donor liver transplantation (LDLT) is an increasingly popular alternative. LDLT enables recipients to avoid a long pretransplantation waiting time and increases the number of livers available for transplantation. It is also the most effective approach to reducing the dropout rate. Strategies to reduce tumor growth in patients who are awaiting liver transplantation are important to ensure that those individuals continue to fulfill the Milan criteria for transplantation. For that purpose, using ablative techniques or chemoembolization to control local tumor growth is useful.

Surgical impact of computerized 3D CT-based visualizations in living donor liver transplantation.

For living donor liver transplantation (LDLT), accurate diagnostic evaluation is essential. Problems arise in assessment of the vascular, bile duct anatomy, liver graft volume, and vascular territories involved. Requirements for the realization of decision-support and enhanced precision in the planning of surgery in LDLT engineering fields are a three-dimensional (3D) visualization system that improves anatomic assessment, allows for interactive surgery planning, and acts as an intraoperative guide. Thirteen LDLT candidates and three LDLT recipients were assessed by "multislice" computer-tomographic examinations. Image processing for 3D visualization included segmentation and calculation of centre lines. A hierarchical mathematical model representing the vascular and biliary tree was created, which allowed calculation of individual vascular territories. Precision of 3D computed tomography (CT)-based visualizations was superior to diagnostic modalities used currently. In addition to detection of decisive anatomic variants, computerized interactive insertion of splitting lines allowed for better planning of the surgical approach and image-guided surgery. 3D CT-based visualization in LDLT facilitates diagnostic evaluation with high accuracy. Multiple examinations, especially with regard to invasive diagnostics, may be avoided. Surgical strategy was directly influenced by the detection of vascular and biliary variants.

Splenohepatic arterial steal syndrome in liver transplantation: clinical features and management.

Well-known arterial complications after liver transplantation comprise thrombosis and major stenosis, which usually necessitate a retransplantation procedure. In our institution, in a series of 165 consecutive liver transplantations, we report the first recognized case of a splenohepatic arterial steal syndrome. This is characterized by an arterial malperfusion of the hepatic graft caused by a marked diversion of blood flow to a significantly enlarged spleen, which leads to major ischemic damage of the hepatic graft. After splenectomy the perfusion through the hepatic artery increased substantially and the graft was salvaged, with a following favorable clinical course. Splenohepatic arterial steal syndrome may ultimately result in graft loss if it is falsely diagnosed or recognized too late. A post-transplantation splenectomy represents a successful therapeutic approach; alternatively a primary arterial anastomosis to the aorta prevents the development of this condition.