Sven Jonas

Liver resection for hepatocellular carcinoma in patients with cirrhosis.

Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy.

Tumor-associated angiogenesis and lymphangiogenesis correlate with progression of intrahepatic cholangiocarcinoma.

OBJECTIVES:Little is known about the function of tumor-associated neovascularization in the progression of intrahepatic cholangiocarcinoma (IHC). This study was conducted to evaluate the influence of tumor-associated angiogenesis and lymphangiogenesis on progression of IHC.METHODS:We analyzed tissue specimens of IHC (N=114) by immunohistochemistry using the endothelial-specific antibody CD31 and the lymphendothelial-specific antibody D2-40 and subsequently quantified microvessel density (MVD) and lymphatic microvessel density (LVD). To analyze the influence of tumor-associated angiogenesis and lymphangiogenesis on tumor progression, tumors were allocated according to mean MVD and LVD, respectively, into groups of “high” and “low” MVD and LVD, respectively, and various clinicopathological characteristics as well as recurrence and survival data were analyzed.RESULTS:IHC revealed an induction of tumor-associated angiogenesis and lymphangiogenesis. Tumors of “high” MVD displayed more frequently advanced primary tumor stages and multiple tumor nodes. Furthermore, patients with tumors of “high” MVD had an inferior curative resection rate and suffered more frequently from recurrence. A “high” LVD was correlated with increased nodal spread, and patients with “high” LVD tumors more frequently developed recurrence. In the univariate analysis, MVD and LVD revealed significant influence on survival, and MVD was identified as an independent prognostic factor for survival in the multivariate analysis. The 5-year survival of patients with “low” MVD tumors was 42.1%, compared with 2.2% in patients with “high” MVD tumors (P<0.001).CONCLUSIONS:This study suggests a critical function of tumor-associated angiogenesis and lymphangiogenesis for progression of IHC. Therefore, antiangiogenic and antilymphangiogenic approaches may have therapeutic potency in this tumor entity.

Co-morbid mental health conditions in cancer patients at working age - prevalence, risk profiles, and care uptake

This study examined the prevalence of mental health conditions in cancer patients, the role of socioeconomic position in relation to that, and the use of professional mental health care.

Focus on parathyroid carcinoma

Parathyroid carcinoma is a malignant neoplasm affecting 05-2 per cent of all patients with primary hyperparathyroidism that was first described by de Quevain in 1904. To day it continues to defy diagnosis and treatment. It is difficult to diagnose in part because of its rarity, lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism. As a result initial surgical treatment is inadequate essentially leading to disease recurrence where complete cure is unlikely. En bloc surgical resection remains the only curative treatment, and high priorities are improving diagnostic methods, and clinical staging for resection once the disease is suspected. Margin status at resection is related to prognosis. Thus, a trend towards aggressive surgical management has improved outcomes. The recurrence rate of parathyroid carcinoma is as high as 80% with survival rates <50% at 10 years. Results of chemotherapy are disappointing. However, recent trials using radiation therapy are promising, but require further study.

Is perioperative low molecular weight hydroxyethyl starch infusion a risk factor for delayed graft function in renal transplant recipients

BACKGROUND Crystalloid or colloid fluids may be utilized during kidney transplantation. Histopathological and clinical data indicate that hydroxyethyl starch (HES) may have nephrotoxic potential. METHODS This retrospective single-centre cohort study screened 192 and included 113 patients who underwent renal transplantation between 2003 and 2007 at University of Leipzig Medical Faculty, Germany. The primary outcome parameter was delayed graft function (DGF). Patients were divided into two groups. Patients in group CRYS (N = 73) received crystalloid solution (acetated Ringers or normal saline) only. Patients in the group HES (N = 40) received a minimum of 500 mL 6% HES 130/0.4 and additional crystalloid solution by discretion of the transplant team. RESULTS Patients in both groups did not differ with respect to demographic data and American Society of Anesthesiologists Physical Status Classification System scores, except for the donor age, which was significantly lower in the group HES. The rate of DGF was not found to be different in group CRYS (31.5%) when compared to group HES (32.5%) (P = 1.00, n.s.). CONCLUSION In this single-centre retrospective cohort study, infusion of low molecular weight 6% HES 130/0.4 during and after renal transplantation was found to have no significant negative effect upon the rate of DGF.

Early retirement in cancer patients with or without comorbid mental health conditions: A prospective cohort study

The authors investigated whether cancer patients who have comorbid mental health disorders (MD) are at greater risk of early retirement compared with those who do not have MD.

Expression and functional coupling of liver β2 - adrenoceptors in the human hepatocellular carcinoma.

Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. There are now multiple lines of evidence demonstrating that the β-adrenoceptor (β-AR) signaling plays an important role in the progression and metastasis of cancer and may become a novel target for cancer therapy. Little information exists regarding the status of β-ARs and their postreceptor intracellular signaling cascade in the development of human HCC. This study was conducted to detect the expression signal transduction of the β-ARs in liver membranes obtained from patients with HCC and elucidate their possible implication on HCC development. Methods: The β-AR density and subtype distribution were determined by receptor binding studies. Protein levels of the β2-AR and Gsα protein were determined by Western blot analysis. The receptor coupling efficiency and biochemical activities of the adenylate cyclase (AC) was also determined. Results: In HCC liver membranes, the β2-AR density was higher than the density in the nonadjacent nontumor liver membranes. The β2-AR protein expression was 1.5-fold increased as compared with nonmalignant controls, and positively correlated with the receptor density. The Gsα protein expression as well as the receptor, AC and G protein-stimulated activation of the cAMP formation was reduced in HCC. Conclusion: The β2-AR was upregulated in human HCC. Despite this upregulation of the receptor, there was an altered postreceptor signal transduction in HCC liver. The mechanisms responsible for this change in the growth of HCC and the nature of this alteration remain unclear.

Spectrum of benign lesions mimicking a malignant stricture at the liver hilum.

There is a broad spectrum of benign disorders of the biliary system that resemble hilar cholangiocarcinoma (HCCA) in terms of clinical, pathologic, and imaging findings. No unifying features were found to characterize patients with benign hilar obstruction and distinguish these patients from those with cholangiocarcinoma. Imaging plays a vital role in aiding the differentiation of benign and malignant disease, defining the location and extent of the process, as well as directing biopsy. However, even when lesions at the liver hilum are detected with the highest sensitivity, none of the imaging modalities can reliably characterize and confirm the underlying type of disease. Excessive reliance on cholangiographic or endoscopic biopsy results is dangerous, because tissue sampling is not always diagnostic and a potentially resectable malignancy can be overlooked. Therefore, the preferred treatment option to patients with suspicious hilar lesions should remain resection for presumed malignancy. Local resection with adequate reconstruction excludes a malignant lesion, and provides means of biliary decompression with low mortality and morbidity rate.

Antibody-Mediated Rejection of Arterialised Venous Allografts Is Inhibited by Immunosuppression in Rats

Objectives and Design We determined in a rat model (1) the presence and dynamics of alloantibodies recognizing MHC complexes on quiescent Brown-Norway (BN) splenic cells in the sera of Lewis (LEW) recipients of Brown-Norway iliolumbar vein grafts under tacrolimus immunosuppression; and (2) the presence of immunoglobulins in the wall of acute rejected vein allografts. Materials and Methods Flow cytometry was used for the analysis of day 0, 14 and 30 sera obtained from Lewis recipients of isogeneic iliolumbar vein grafts (group A) or Brown-Norway grafts (group B, C) for the presence of donor specific anti-MHC class I and II antibodies. Tacrolimus 0.2 mg/kg daily was administered from day 1 to day 30 (group C). Histology was performed on day 30. Results Sera obtained preoperatively and on day 30 were compared in all groups. The statistically significant decrease of anti MHC class I and II antibody binding was observed only in allogenic non-immunosuppressed group B (splenocytes: MHC class I - day 0 (93%±7% ) vs day 30 (66%±7%), p = 0.02, MHC class II - day 0 (105%±3% ) vs day 30 (83%±5%), p = 0.003; B-cells: MHC class I - day 0 (83%±5%) vs day 30 (55%±6%), p = 0.003, MHC class II - day 0 (101%±1%) vs day 30 (79%±6%), p = 0.006; T-cells: MHC class I - day 0 (71%±7%) vs day 30 (49%±5%), p = 0.04). No free clusters of immunoglobulin G deposition were detected in any experimental group. Conclusion Arterialized venous allografts induce strong donor-specific anti-MHC class I and anti-MHC class II antibody production with subsequent immune-mediated destruction of these allografts with no evidence of immunoglobulin G deposition. Low-dose tacrolimus suppress the donor-specific antibody production.

Immunosuppressive protocol with delayed use of low-dose tacrolimus after aortic transplantation suppresses donor-specific anti-MHC class I and class II antibody production in rats.

BACKGROUND Arterial allografts are used as vascular conduits in the treatment of prosthetic graft infection. Immunosuppression decreases their rupture risk rate. However, immunosuppression can be unprofitable in florid infection. Previously, we confirmed inhibition of cell-mediated destruction of rat aortic grafts by delayed use of tacrolimus. In this work, we studied the influence of this protocol on the antibody-mediated rejection. MATERIAL AND METHODS Flow cytometry was used for the retrospective analysis of day 0, 14, and 30 sera obtained from Lewis rat recipients of isogeneic fresh infrarenal aortic grafts (group A) or Brown-Norway rat aortic grafts (group B,C,D) for the presence of donor-specific anti-MHC class I and II antibodies. Tacrolimus in daily dose of 0.2 mg/kg was administered from day 1 to day 30 (group C) or from day 7 to day 30 (group D). RESULTS Inhibition of fluorescence-labeled anti-BN MHC class I and MHC class II antibodies binding to BN-splenocytes was observed only by day 14 and day 30 sera of allogeneic non-immunosuppressed Lewis rats (group B). The day 30 sera significantly decreased anti-MHC I (42±3%) and anti-MHC II antibody binding (56±3%) compared to day 0 (76±9%, p=0.005 and 79±5%, p=0.003, respectively). Deposition of immunoglobulins G into the tunica media was observed only in non-immunosuppressed aortic allografts on day 30. CONCLUSIONS Fresh aortic allografts induce donor-specific anti-MHC class I and anti-MHC class II antibody production. Delayed administration of tacrolimus completely suppressed antibody production and antibody-mediated destruction of aortic allografts.