Long-term Outcome of Incisional Hernia Repairs Using the Erlangen Inlay Onlay Mesh (EIOM) Technique.

BACKGROUND: The objective of this study was to investigate the long-term outcome of incisional hernias treated with the Erlangen Inlay Onlay Mesh (EIOM) repair technique, taking into account recurrence, complications, and patient satisfaction. METHODS: A total of 163 patients treated in the surgical department of Erlangen university hospital with the EIOM repair between the years 1996 and 2009 were evaluated retrospectively. RESULTS: The collected data revealed a mean follow-up period of 70 (18-190) months. Incisional hernia recurrence after EIOM repair was observed in 6 (3.7%) patients after a mean observation period of 70 mo (18-190) postoperatively. The recurrence rate increased significantly when the body mass index (BMI) was higher than 32 kg/m2. Here, a recurrence rate of 10.5% for BMI> 32 versus 1.7% with BMI ≤32 was reported. There were no significant differences in hernia recurrence if haven been operated by an assistant under supervision or by a consultant. In regard to patient satisfaction, 91% of patients included in this study were satisfied with the surgical outcome. CONCLUSIONS: The EIOM procedure is a safe surgical technique that can be used for the treatment of all, also for giant incisional abdominal wall hernias regardless of the size, BMI, or position of the incisional hernia.

Management of the focal nodular hyperplasia of the liver: evaluation of the surgical treatment comparing with observation only.

BACKGROUND: Long-term results of both surgery and observation for patients with focal nodular hyperplasia (FNH) in a large single-center experience do not exist. Accordingly, the aim of this study was to compare long-term outcomes in patients with FNH who underwent either elective hepatectomy or observation alone. METHODS: A retrospective single-institution analysis of 185 patients with FNH, treated from 1990 to 2009, was performed. RESULTS: Seventy-eight patients underwent elective hepatectomy and 107 patients observation alone, with a median follow-up period of 113 months. There was no perioperative mortality. Postoperative complications were recorded in 12 patients, and 92% of patients reported symptomatic reductions. Among observation patients, 9 (13%) developed additional symptoms; tumor enlargement was seen in 3 patients (4%). CONCLUSIONS: Elective liver resection for FNH is a safe procedure at high-volume centers. This single-center experience showed that 13% of observed patients had protracted symptoms. This justifies the therapeutic algorithm that elective surgery should be considered in symptomatic patients or in those with marked enlargement.

Indications and long-term outcome after elective surgery for hepatocellular adenoma.

The management of hepatocellular adenoma (HA) is dependent on several parameters, which are influencing the decision for further management. The aim of this study was to evaluate the clinical presentation, indications, and long-term outcome of surgical treatment in a single-institution analysis. Forty-nine patients underwent elective hepatectomy for HA between 1990 and 2007. Analysis parameters included demographic data, lesion number and size, diagnostic method, mode of surgery, and postoperative outcome. Mean follow-up was 108 months. Thirty-six patients underwent hormone therapy and four patients had a history of cancer before surgical treatment. The mean tumor diameter was 9.8 cm. Mild or moderate postoperative complications were recorded in 16 patients. There was no perioperative mortality. Symptoms were relieved in 95 per cent of the patients. Intratumoral hemorrhage was detected in 21 specimens (43%); malignant transformation was detected in zero specimens. Among patients with HA with clinical symptoms, tumor diameter greater than 5 cm and in male patients the indication for surgery should be given because of the high risk of tumor-related complications. Elective liver resection for HA is a safe procedure and results in a good long-term outcome.

Necrosis and angioinvasion predict adverse outcome in pancreatic neuroendocrine tumors after curative surgical resection: results of a single-center series.

BACKGROUND: The prediction of outcome in pancreatic neuroendocrine tumors (P-NETs) still represents a challenge. Several clinicopathologic parameters have been proposed to predict adverse outcome. The aim of this study was to evaluate the impact of tumor necrosis and angioinvasion on the outcome after curative R0 resection of P-NETs. METHODS: We reviewed our institutional experience over the last 30 years. A total of 82 patients with a mean age of 54 years (range 17-83 years) underwent surgical resection of P-NETs during the period from 1964 to 2006. There were 41 men and 41 women. The patients' outcomes after R0 surgical treatment were analyzed in relation to the presence or absence of tumor cell necrosis and angioinvasion as judged by histologic methods. RESULTS: The overall (n = 82) 5-year survival was 52.4% (± 6.0%). Forty-eight of the patients underwent a R0 resection successfully. These patients showed a 5-year survival of 59.04% (± 7.8%); the median survival was 101 ± 36 months. Necrosis status was documented on 47 of the R0 resected patients (97.9%). The survival median of patients with tumor cell necrosis was significantly shorter than those without necrosis (41 ± 25 vs. 173 ± 69 months, respectively, P = 0.006). The patients' mean 5-year survival was also significantly decreased (28.9 ± 15.0% vs. 68.5.6 ± 8.9%). Angioinvasion status was documented on 43 of the R0 resected patients (90.0%). The median survival of these patients was decreased from 173 ± 51 to 54 ± 18 months when angioinvasion was observed in the histological sections (P = 0.104). The patients' mean 5-year survival was also decreased from 69.2 ± 9.3% to 35.9 ± 14.0%. CONCLUSIONS: Long-term survival of patients with P-NETs is influenced by various pathologic factors. Among our patients, there was not a significant difference in overall survival based on the diameter of the primary tumor or the lymph node status after R0 surgical resection. The presence of necrosis in the TNM and World Health Organization classification for pancreatic endocrine tumor was associated with significant poor overall survival in each classification category. Hence, necrosis represents an independent variable for poor prognosis.

Angiolipomatous mesenchymal hamartoma (angiolipomatosis) of the sigmoid mesocolon.

BACKGROUND: Primary mesenteric tumors are exceedingly rare and may thus pose a diagnostic challenge. They encompass both benign and malignant neoplasms as well as reactive and idiopathic tumefactive fibroinflammatory lesions. METHOD AND RESULTS: A 70-year-old man who was diagnosed with sigmoid colon cancer was found to have a large non-homogeneous predominantly fatty retroperitoneal soft tissue mass on computerized tomography (CT) scan. The mass was attached to the aorta and have encased the inferior mesenteric artery and extended into the sigmoid mesocolon. Histological examination of the mass showed ill-defined lipoma-like mature fatty tissue traversed by paucicellular fibrous septa entrapping small nerves and containing remarkably increased venous blood vessels reminiscent of soft tissue angiomatosis without evidence of malignancy. The histological features were consistent with an angiolipomatous hamartomatous mesenchymal proliferation. CONCLUSIONS: Angiolipomatous hamartoma might be histogenetically related to soft tissue angiomatosis. To our knowledge, this case represents the first well documented lesion of this type at this location and must be distinguished from other fat-containing masses, particularly angiomyolipoma, sclerosing mesenteritis and mesenteric liposarcoma.

Definition of the "Drug-Angiogenic-Activity-Index" that allows the quantification of the positive and negative angiogenic active drugs: a study based on the chorioallantoic membrane model.

Since the introduction of the angiogenic therapy by Folkman et al. in the 1970'ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the "Drug-Angiogenic-Activity-Index" of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the "Drug Angiogenic Activity Index" by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {ΔVIS[Drug]-ΔVIS[Control]} / Δ VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a -1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the "Drug-Angiogenic-Activity-Index" in the preclinical phase will give us an impact of effectiveness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family.

Antiviral re-treatment of IFN-ribavirin non-responders for recurrent post-transplantation hepatitis C.

BACKGROUND: The aim of the study was to compare the efficacy and tolerability of pegylated interferon (PEG-IFN) plus ribavirin (RIB) and PEG-IFN monotherapy after unsuccessful initial therapy with interferon-α2b (IFN) plus RIB after recurrent post-transplantation hepatitis C. METHODS: Twenty-four patients with either no response (n = 10) or relapse (n = 14) after treatment with IFN plus RIB were prospectively randomized in the two treatment arms: 1) PEG-IFN monotherapy at a dosage of 0.8 µg/kg per week (n = 12) and 2) PEG-IFN (0.8 µg/kg per week) plus RIB (800-1200 mg/d) (n = 12). RESULTS: Twenty-one patients (86%) were treated for at least six months. Three patients are still being treated. At the end of therapy, 18 patients (75%) were HCV RNA negative. Five (45%) patients in PEG-IFN and five (50%) in PEG-IFN plus RIB arms had sustained virological response. Two patients (10%) died from recurrent hepatocellular carcinoma. The histologic activity indices significantly improved in both treatment arms. In the PEG-IFN arm, one patient experienced an acute rejection and discontinued therapy. CONCLUSIONS: Both treatment arms showed to be effective, well tolerated and lead to an improvement in histologic outcome. Because of lower rates in side effects and equal outcome, PEG-IFN monotherapy is an adequate option for antiviral re-treatment.

Malignant progression of invasive tumour cells seen in hypoxia present an accumulation of beta-catenin in the nucleus at the tumour front.

Of all processes involved in tumour progression, local invasion and formation of metastases are the clinically most relevant but the scientifically least well understood at their molecular level. The loss of cell adhesion, then tumour cell migration with changes in the cytoskeleton, invasion and metastatic dissemination are the steps of the "metastatic cascade". The E-cadherin-catenin complex plays a key role in cell adhesion thus building the first step in malignant progression. In many epithelial cancers, E-cadherin is lost concomitantly with tumour progression. Thus beta-catenin dissociates in the cytoplasm and accumulates in the nucleus as a transcription factor. Recent experimental progress has identified that tumour hypoxia not only induces tumour angiogenesis, but also modulates malignant progression to initiate tumour invasion and metastasis. It was hypothesised that hypoxia within tumours causes dysfunction of the E-cadherin-catenin complex with an accumulation of beta-catenin in the nucleus and produces an invasive phenotype of tumour cells. For this purpose fertilized chicken eggs were incubated for ten days in normoxic conditions. Subsequently colon carcinoma cells (SW-480) were placed on the chorioallantoic membrane. During the following six days the eggs were incubated either in normoxic conditions or in stepwise decreasing hypoxic conditions. SW-480 colon carcinoma cells did not invade the epithelial layer in normoxic conditions. beta-catenin was membrane bound or in the cytoplasm. The nuclei were regularly omitted. In contrast, an invasion through the epithelial layer into the mesoderm was already seen after three days when incubated in hypoxic conditions. beta-catenin was membrane bound in non-invasive regions of the tumour nodule but there was an accumulation of beta-catenin in the nucleus in the invasive tumour front. Hypoxia seems to be responsible for accumulation of beta-catenin in the nucleus which is accompanied by a more invasive phenotype of tumour cells at the tumour front.

Surgical treatment of mass-forming intrahepatic cholangiocarcinoma: an 11-year Western single-center experience in 107 patients.

Hepatic resection is the only cure for intrahepatic cholangiocellular carcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcome of patients with ICC. We retrospectively studied the records of 67 patients who underwent laparotomy for ICC from January 1995 through December 2005. Univariate and multivariate analyses were conducted for several variables to evaluate their influence on the outcome. Forty-five patients underwent hepatic resection. In 19 patients, the tumors were found to be unresectable at the time of laparotomy. Median 2- and 5-year survival rates in the 45 resected patients were 62% and 35%, respectively. For 36 patients who underwent curative resection, the 2- and 5-year survival were 67% and 41%, respectively; with a median survival of 43 months. The overall 5-year recurrence-free survival was 30%. The 90-day postoperative mortality rate was 4% and morbidity 28%. Multivariate analyses confirmed resection margin, lymph node involvement, blood loss, and blood transfusion to be independent significant variables for overall survival. Predictors of longer recurrence-free survival were lymph node involvement, vascular infiltration, blood loss, and transfusion. Surgical treatment of ICC by curative hepatic resection in patients without nodal invasion provides good long-term results. In contrast, incomplete tumor removal does not provide a survival benefit. An improved quality of preoperative staging was able to increase the resectability rate to acceptable 70%.

Hypoxia generates a more invasive phenotype of tumour cells: an in vivo experimental setup based on the chorioallantoic membrane.

Of all processes involved in carcinogenesis, local invasion and the formation of metastases are the clinically most relevant but the scientifically least well understood at their molecular level. Recent experimental progress has identified that tumour hypoxia not only induces tumour angiogenesis, but also modulates the expression of several genes that have been implicated in tumour invasion and metastasis. Here we developed an in vivo model to understand a number of molecular pathways and cellular mechanisms for tumour invasion in hypoxia. For this purpose fertilized chicken eggs were incubated for 10 days in normoxic conditions. Subsequently colon carcinoma cells (SW-480) were placed on the chorioallantoic membrane. During the following 6 days the eggs were incubated either in normoxic conditions or in stepwise decreasing hypoxic conditions. SW-480 colon carcinoma cells did not invade the epithelial layer in normoxic conditions. In contrast an invasion through the epithelial layer in to the mesoderm was already seen after 3 days when incubated in hypoxic conditions. The chorioallantoic membrane assay described in this paper allows investigating tumour invasion and its cellular mechanisms under defined hypoxic conditions.

Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization.

AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.