Helmut Friess

Technische Universität München, München, Bavaria, Germany

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Publications (559)2567.82 Total impact

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    ABSTRACT: Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.
    Digestive and Liver Disease 02/2013; · 2.89 Impact Factor
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    ABSTRACT: Locoregional interventional bridging therapy (IBT) is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC). However, the prognostic value of IBT in patients with advanced HCC is still undefined. The aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT) in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging. A total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT. There was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P = 0.25). However, tumor response following IBT (≥50% tumor necrosis rate at explant pathology) resulted in a significantly better outcome 5 years post-LT (96%) than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001). Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001). None of macromorphological HCC features, but only the absence of increased (18)F-fluoro-deoxy-glucose ((18)FDG) uptake on pretransplant positron emission tomography (PET) was identified as independent predictor of postinterventional tumor response (P<0.001). Our results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET assessment may identify those patients with advanced HCC that will benefit from post-IBT tumor response and may, thereby, achieve excellent posttransplant outcome.
    PLoS ONE 01/2013; 8(1):e53960. · 3.53 Impact Factor
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    ABSTRACT: Computer-based simulators for ultrasound training are a topic of recent interest. During the last 15 years, many different systems and methods have been proposed. This article provides an overview and classification of systems in this domain and a discussion of their advantages. Systems are classified and discussed according to the image simulation method, user interactions and medical applications. Computer simulation of ultrasound has one key advantage over traditional training. It enables novel training concepts, for example, through advanced visualization, case databases, and automatically generated feedback. Qualitative evaluations have mainly shown positive learning effects. However, few quantitative evaluations have been performed and long-term effects have to be examined.
    Simulation in healthcare: journal of the Society for Simulation in Healthcare 01/2013; · 1.59 Impact Factor
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    ABSTRACT: BACKGROUND: The glycoprotein MFG-E8 mediates phagocytic clearance of apoptotic cells and influences the pathogenesis and progression of inflammatory diseases. MFG-E8 was shown to attenuate the progression of inflammation and to improve survival in septic rats. Accumulating evidence suggests an immunomodulatory link between MFG-E8 and the pro-inflammatory chemokine fractalkine, which may determine the severity of pain, fibrosis, and inflammation in chronic pancreatitis (CP). METHODS: The expression and localization of MFG-E8 was investigated in CP (n = 62), and normal pancreas (NP; n = 34) by QRT-PCR, Western-blot and immunohistochemistry analyses. Results were correlated with mRNA expression of fractalkine, CX3CR1, and with the presence and degree of pain and fibrosis. Human pancreatic stellate cells (hPSCs) were isolated from CP tissues and evaluated for MFG-E8 mRNA expression after fractalkine stimulation. RESULTS: MFG-E8-mRNA was significantly overexpressed in CP and isolated hPSCs when compared to NP. Western-blot and immunohistochemistry analysis confirmed accumulation of MFG-E8 in CP, with noticeably increased MFG-E8 immunoreactivity in tubular complexes. MFG-E8 expression correlated significantly with fractalkine expression, severe fibrosis, and the presence of pain in CP patients. Stimulation of hPSCs with fractalkine led to a significant increase in MFG-E8 expression. CONCLUSIONS: In the present study, we demonstrated for the first time that MFG-E8 is significantly up-regulated in CP patients and together with fractalkine correlated noticeably with severe fibrosis and the presence of pain. hPSCs overexpress MFG-E8 upon fractalkine stimulation in vitro, which underlines the suggested immunmodulatory link in CP and may be a key mechanism in CP fibrogenesis and pain generation. Taken together, these novel findings suggest that MFG-E8 blockade may be a promising tool for future immunotherapy in CP to attenuate both fibrosis and pain sensation.
    BMC Gastroenterology 01/2013; 13(1):14. · 2.11 Impact Factor
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    ABSTRACT: OBJECTIVES:: The aim of this study was to independently validate a genomic signature developed both to assess recurrence risk in stage II patients and to assist in treatment decisions. BACKGROUND:: Adjuvant therapy is recommended for high-risk patients with stage II colon cancer, but better tools to assess the patients' prognosis accurately are still required. METHODS:: Previously, an 18-gene signature had been developed and validated on an independent cohort, using full genome microarrays. In this study, the gene signature was translated and validated as a robust diagnostic test (ColoPrint), using customized 8-pack arrays. In addition, clinical validation of the diagnostic ColoPrint assay was performed on 135 patients who underwent curative resection (R0) for colon cancer stage II in Munich. Fresh-frozen tissue, microsatellite instability status, clinical parameters, and follow-up data for all patients were available. The diagnostic ColoPrint readout was determined blindly from the clinical data. RESULTS:: ColoPrint identified most stage II patients (73.3%) as at low risk. The 5-year distant-metastasis free survival was 94.9% for low-risk patients and 80.6% for high-risk patients. In multivariable analysis, ColoPrint was the only significant parameter to predict the development of distant metastasis with a hazard ratio of 4.28 (95% confidence interval, 1.36-13.50; P = 0.013). Clinical risk parameters from the American Society of Clinical Oncology (ASCO) recommendation did not add power to the ColoPrint classification. Technical validation of ColoPrint confirmed stability and reproducibility of the diagnostic platform. CONCLUSIONS:: ColoPrint is able to predict the development of distant metastasis of patients with stage II colon cancer and facilitates the identification of patients who may be safely managed without chemotherapy.
    Annals of surgery 01/2013; · 7.19 Impact Factor
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    ABSTRACT: Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown. Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients. In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients. Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.
    PLoS ONE 01/2013; 8(3):e60529. · 3.53 Impact Factor
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    ABSTRACT: Objective: The cytoprotective enzyme heme oxygenase 1 (HO-1) is highly up-regulated in acute pancreatitis (AP). In this study, we tested its metabolites as potential therapeutic agents for AP in rats. Methods: Acute necrotizing pancreatitis was induced by retrograde intraductal injection of sodium taurocholate in rats. Biliverdin hydrochloride (BV HCl) (50 μmol/kg subcutaneously), the carbon monoxide, donor methylene chloride (MC) (500 mg/kg orally), or iron-chelating desferrioxamine (DFO) (125 mg/kg subcutaneously) were administered in a therapeutic manner starting with the first dose 4 hours after taurocholate injection to mimic the effects of HO-1 metabolites. Results: Administration of BV HCl, MC, or DFO showed significant reduction of inflammatory activity in comparison to controls leading to lower myeloperoxidase activity in the pancreas, less edema, lower ascites volumes, and preservation of tissue integrity (P < 0.05). Administration of either BV HCl or MC markedly increased 5-day survival rate (70% and 75% vs 40%; P < 0.05), whereas DFO had no significant effect on survival (60%). When given in therapeutic manner, all 3 substances led to diminished nuclear factor κB activity in the pancreas (P < 0.05). Conclusions: Therapeutic use of BV HCl and MC led to marked reduction of mortality in experimental pancreatitis. Thus, HO-1 metabolites may present a novel therapeutic approach in AP treatment.
    Pancreas 01/2013; 42(2):265-271. · 3.01 Impact Factor
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    ABSTRACT: BACKGROUND: Preoperative radio(chemo)therapy (pR(C)T) significantly reduces the local recurrence risk and is therefore recommended in stage II/III rectal cancer. However, this multimodal treatment approach may be associated with late adverse effects. To determine the impact of pR(C)T on long-term anorectal, sexual, and urinary function, we performed a systematic review and meta-analysis. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for studies reporting on long-term functional outcome after rectal cancer resection with pR(C)T. Only studies that reported anorectal, sexual, and/or urinary function after rectal cancer resection in TME-technique with pR(C)T were eligible for inclusion. RESULTS: Twenty-five studies, including 6,548 patients, were identified. Methodological quality of the eligible studies was low. The majority of studies reported higher rates of anorectal (14/18 studies) and male sexual dysfunction (9/10 studies) after pR(C)T. Few studies examined female sexual dysfunction (n = 4). Meta-analysis revealed that stool incontinence occurred more often in irradiated patients (risk ratio (RR) = 1.67; 95 % confidence interval (CI), 1.36, 2.05; p < 0.0001) and manometric results were significantly worse after pR(C)T (mean resting pressures (weighted mean difference (WMD) = 15.04; 95 % CI, 0.77, 29.31; p = 0.04) and maximum squeeze pressures (WMD = 30.39; 95 % CI, 21.48, 39.3; p < 0.0001)). Meta-analysis of erectile dysfunction revealed no statistical significance (RR = 1.41; 95 % CI, 0.74, 2.72; p = 0.3). Six of eight studies and meta-analysis demonstrated no negative effect of pR(C)T on urinary function (RR = 1.05; 95 % CI, 0.67, 1.65; p = 0.82). CONCLUSIONS: Although quality of studies on long-term functional outcome is limited, current evidence demonstrates that pR(C)T negatively affects anorectal function after TME.
    Annals of Surgical Oncology 12/2012; · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND: The current trend in surgery toward further trauma reduction inevitably leads to increased technological complexity. It must be assumed that this situation will not stay under the sole control of surgeons; mechanical systems will assist them. Certain segments of the work flow will likely have to be taken over by a machine in an automatized or autonomous mode. METHODS: In addition to the analysis of our own surgical practice, a literature search of the Medline database was performed to identify important aspects, methods, and technologies for increased operating room (OR) autonomy. RESULTS: Robotic surgical systems can help to increase OR autonomy by camera control, application of intelligent instruments, and even accomplishment of automated surgical procedures. However, the important step from simple task execution to autonomous decision making is difficult to realize. Another important aspect is the adaption of the general technical OR environment. This includes adaptive OR setting and context-adaptive interfaces, automated tool arrangement, and optimal visualization. Finally, integration of peri- and intraoperative data consisting of electronic patient record, OR documentation and logistics, medical imaging, and patient surveillance data could increase autonomy. CONCLUSIONS: To gain autonomy in the OR, a variety of assistance systems and methodologies need to be incorporated that endorse the surgeon autonomously as a first step toward the vision of cognitive surgery. Thus, we require establishment of model-based surgery and integration of procedural tasks. Structured knowledge is therefore indispensable.
    Surgical Endoscopy 12/2012; · 3.31 Impact Factor
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    ABSTRACT: PURPOSEValidity of the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems for gastric cancer has been evaluated in several studies, mostly in Asian patient populations. Only few data are available on the prognostic implications of the new classification system on a Western population. Therefore, we investigated its prognostic ability based on a German patient cohort.Patients And methodsData from a single-center cohort of 1,767 consecutive patients surgically treated for gastric cancer were classified according to the seventh edition and were compared using the previous TNM/UICC classification. Kaplan-Meier analyses were performed for all TNM stages and UICC stages in a comparative manner. Additional survival receiver operating characteristic analyses and bootstrap-based goodness-of-fit comparisons via Bayesian information criterion (BIC) were performed to assess and compare prognostic performance of the competing classification systems.ResultsWe identified the UICC pT/pN stages according to the seventh edition of the AJCC/UICC guidelines as well as resection status, age, Lauren histotype, lymph-node ratio, and tumor grade as independent prognostic factors in gastric cancer, which is consistent with data from previous Asian studies. Overall survival rates according to the new edition were significantly different for each individual's pT, pN, and UICC stage. However, BIC analysis revealed that, owing to higher complexity, the new staging system might not significantly alter predictability for overall survival compared with the old system within the analyzed cohort from a statistical point of view. CONCLUSION The seventh edition of the AJCC/UICC classification was found to be valid with distinctive prognosis for each stage. However, the AJCC/UICC classification has become more complex without improving predictability for overall survival in a Western population. Therefore, simplification with better predictability of overall survival of patients with gastric cancer should be considered when revising the seventh edition.
    Journal of Clinical Oncology 12/2012; · 17.88 Impact Factor
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    ABSTRACT: Abstract Objective. Many patients experience problems with sexual functioning after renal transplantation (RTx). Research on the sexual functioning of the partners of those patients and the consequences for relationship satisfaction and quality of life is lacking. This study sought to explore changes in sexual and relationship functioning from before to after RTx in patients and their partners. Material and methods. Twenty-nine patients (mean ± SD age 53.4 ± 14.2 years) and 13 partners (age 57.1 ± 11.6 years) provided data 12-15 months after RTx. They retrospectively evaluated sexual and relationship functioning as well as general life satisfaction before RTx and, in comparison, in the most recent months. Results. Among the patients, most items on sexual experience indicated deterioration in sexual functioning. Among their partners, the wish for sexual activity with the patient and the actual frequency of sexual activity decreased from before to after RTx. The rate of partners indicating high personal importance for intercourse decreased from 83.3% to 69.2%, as did the rate of partners stating high sexual satisfaction (from 63.6% to 41.7%). Despite these trends, most patients and partners reported high relationship and life satisfaction after RTx. Conclusions. Partners of patients who had received a kidney transplant seem to be affected by negative changes in the patients' sexual functioning. Nonetheless, many couples maintain high relationship and life satisfaction.
    Scandinavian Journal of Urology and Nephrology 12/2012; 46:431-436. · 1.06 Impact Factor
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    ABSTRACT: PURPOSE: Neural invasion/NI is a histopathological feature of colon cancer/CC which receives little consideration. Therefore, we performed a morphological and functional characterization of NI in CC. EXPERIMENTAL DESIGN: NI was investigated in 673 patients with CC. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of CC-cells (HT29, HCT-116, SW620, DLD-1) was compared to pancreatic cancer/PC- (T3M4 and SU86.86) and rectal cancer/RC-cells (CMT-93) in the in-vitro 3D-neural-migration assay and analyzed via live-cell-imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and NGF was quantified in CC and PC nerves. Dorsal root ganglia/DRG of newborn rats were exposed to supernatants of CC-, RC- and PC-cells and neurite density was determined. RESULTS: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in CC. In the 3D migration assay, CC- and RC-cells demonstrated much less neurite-targeted migration when compared to PC-cells. Supernatants of PC- and RC-cells induced a much higher neurite density than those of CC-cells. Accordingly, NGF, Artemin and GAP-43 were much more pronounced in nerves in PC than in CC. CONCLUSIONS: I is not an independent prognostic factor in CC. The lack of a considerable biological affinity between CC-cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in CC may explain the low prevalence and impact of NI in CC.
    Clinical Cancer Research 11/2012; · 8.19 Impact Factor
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    ABSTRACT: OBJECTIVES:: Individualized risk assessment in patients with UICC stage II colon cancer based on a panel of molecular genetic alterations. BACKGROUND:: Risk assessment in patients with colon cancer and localized disease (UICC stage II) is not sufficiently reliable. Development of metachronous metastasis is assumed to be governed largely by individual tumor genetics. METHODS:: Fresh frozen tissue from 232 patients (T3-4, N0, M0) with complete tumor resection and a median follow-up of 97 months was analyzed for microsatellite stability, KRAS exon 2, and BRAF exon 15 mutations. Gene expression of the WNT-pathway surrogate marker osteopontin and the metastasis-associated genes SASH1 and MACC1 was determined for 179 patients. The results were correlated with metachronous distant metastasis risk (n = 22 patients). RESULTS:: Mutations of KRAS were detected in 30% patients, mutations of BRAF in 15% patients, and microsatellite instability in 26% patients. Risk of recurrence was associated with KRAS mutation (P = 0.033), microsatellite stable tumors (P = 0.015), decreased expression of SASH1 (P = 0.049), and increased expression of MACC1 (P < 0.001). MACC1 was the only independent parameter for recurrence prediction (hazard ratio: 6.2; 95% confidence interval: 2.4-16; P < 0.001). Integrative 2-step cluster analysis allocated patients into 4 groups, according to their tumor genetics. KRAS mutation, BRAF wild type, microsatellite stability, and high MACC1 expression defined the group with the highest risk of recurrence (16%, 7 of 43), whereas BRAF wild type, microsatellite instability, and low MACC1 expression defined the group with the lowest risk (4%, 1 of 26). CONCLUSIONS:: MACC1 expression predicts development of metastases, outperforming microsatellite stability status, as well as KRAS/BRAF mutation status.
    Annals of surgery 11/2012; 256(5):763-771. · 7.19 Impact Factor
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    ABSTRACT: OBJECTIVE:: We have developed a multifactorial histopathological prognostic score (PRSC) for patients with gastric cancer treated with neoadjuvant chemotherapy before surgery for the accurate discrimination of patient subgroups with differing outcomes. BACKGROUND:: For patients with gastric cancer who undergo multimodal treatment, the postoperative staging classifications used for nontreated tumors may not accurately predict patient prognosis. METHODS:: We evaluated 428 gastric carcinoma specimens after a cisplatin-based chemotherapy. The factors for the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) ypT-category, ypN-category, and histopathological tumor regression were assigned a value from 1 to 3 as follows: ypT0 to 2 = 1 point; ypT3 = 2 points; ypT4 = 3 points; ypN0 = 1 point; ypN1 to 2 = 2 points; ypN3a to 3b = 3 points; less than 10% residual tumor per tumor bed = 1 point; 10% to 50% residual tumor per tumor bed = 2 points; and greater than 50% residual tumor per tumor bed = 3 points. A 3-tiered PRSC based on the sum value was established (group A: 34 points; group B: 5-7 points; group C: 8-9 points) and was found to correlate with patient prognosis. RESULTS:: The PRSC showed a clear discrimination of 3 significantly different prognostic groups (group A: 76 patients; group B: 210 patients; group C: 142 patients; P < 0.001). In multivariate analyses, including the completeness of resection, tumor diameter, lymphatic vessel invasion, tumor grading, and Lauren classification, the PRSC was the only independent prognostic factor for overall survival (hazard ratio [HR] = 2.03; 95% confidence intervals [CI], 1.49-2.78; P < 0.001). It was slightly superior to the UICC/AJCC staging system (HR = 1.66; 95% CI, 1.20-2.27; P = 0.002) when analyzed with tumor regression as an additional independent factor (HR = 1.27; 95% CI, 1.01-1.62; P = 0.044) included in the analysis. CONCLUSIONS:: The proposed PRSC reveals the most accurate prediction of survival for patients with gastric carcinoma after neoadjuvant chemotherapy followed by surgery. The PRSC clearly identifies 3 subgroups with different prognoses and may be helpful for therapeutic decisions.
    Annals of surgery 09/2012; · 7.19 Impact Factor
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    ABSTRACT: Introduction: The glial-cell-line-derived neurotrophic factor (GDNF) family member neurturin (NRTN) and its receptor GFRα2 play a deciding role in the normal development of pancreatic parasympathetic innervation. In this study, we aimed at investigating the role of NRTN/GFRα2 axis in pancreatic neuropathy in human chronic pancreatitis (CP). Methods: Expression of NRTN/GFRα2 was compared between normal human pancreas (NP) and CP tissues via immunohistochemistry, immunoblotting and QRT-PCR and correlated to abdominal pain sensation. To elucidate the impact of NRTN in pancreatic neuroplasticity, neuronal phenotype and glial density were quantified via an in vitro neuroplasticity assay in dissociated newborn rat dorsal root ganglia (DRG) cultured 1) in CP tissue extracts depleted from NRTN, 2) in NP, 3) in untreated CP tissue extracts and 4) CP extracts in which nerve growth factor (NGF), glial-cell-derived-neurotrophic factor (GDNF) or transforming growth factor-β1 (TGFβ1) was depleted Results: NRTN and GFRα2 were highly upregulated in CP, especially in intrapancreatic nerves and the extracellular matrix. CP tissue demonstrated increased amounts of mature multimeric NRTN and elevated levels of GFRα2. The noticeable neurotrophic effect of CP tissue extracts upon DRG neurons was diminished upon blockade of NRTN from these extracts, However, blockade of NRTN from CP extracts did not influence the density of DRG glia cells. Conclusion: The NRTN/GFRα2 axis is activated during the course of CP and represents a major key player in the reactive neural alterations in CP. This is the first study to provide functional evidence for the contribution of neurotrophic factors to neuroplasticity in CP.
    AJP Gastrointestinal and Liver Physiology 09/2012; · 3.65 Impact Factor
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    Martin Loos, Helmut Friess
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    ABSTRACT: Advances in surgical technique and better perioperative management have significantly improved patient outcomes after liver surgery. Even major hepatectomy can be performed safely with low morbidity and mortality. Post-resection liver failure is among the most feared complications after extended hepatectomy. In order to increase the future liver remnant (FLR) and to expand the pool of candidates for surgical resection, Schnitzbauer et al recently presented a new 2-stage surgical approach which combines right portal vein ligation (rPVL) with in situ splitting (ISS) of the liver parenchyma. In comparison to other current strategies, such as interventional portal vein embolization, hypertrophy of the FLR was more pronounced (median volume increase = 74%; range: 21%-192%) and more rapid (after a median of 9 d; range: 5-28 d) after rPVL and ISS. In this commentary, we discuss the technical aspects and clinical impact of rPVL combined with ISS. Based on the reported data, this new 2-stage therapeutic approach represents a promising new strategy for patients with locally advanced liver disease, previously regarded as marginally resectable or even unresectable, potentially enabling curative resection. However, morbidity is significant and mortality not negligible.
    World journal of gastrointestinal surgery. 07/2012; 4(7):163-5.
  • Journal of Clinical Oncology 07/2012; 30(23):e209-12. · 17.88 Impact Factor
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    ABSTRACT: The small actin-binding protein destrin is one of the key regulators involved in remodeling of the actin cytoskeleton, a process crucial for cytokinesis, cell migration and polarized cell growth as well as for cancer cell migration and invasion. A novel ex vivo nerve invasion model mirroring perineural cancer cell invasion as a key feature of pancreatic ductal adenocarcinoma has been previously established. Using this model, highly nerve-invasive clones of human pancreatic cancer cell lines have been obtained. Genome-wide transcriptional analyses of these cells revealed up-regulation of destrin in highly versus lowly nerve-invasive pancreatic cancer cells. Increased expression of destrin in these nerve-invasive cells was validated using quantitative RT-PCR and immunoblotting; concomitant changes in cell morphology were demonstrated using immunofluorescence analysis. Silencing of destrin by two specific siRNA oligonucleotides in Panc-1 pancreatic cancer cells decreased invasiveness and migration, and reduced proliferation of these cells. Destrin is upregulated in nerve-invasive pancreatic cancer cells and its expression might be related to perineural invasiveness.
    Pancreatology 07/2012; 12(4):350-7. · 2.50 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the five most lethal malignancies worldwide and survival has not improved substantially in the past 30 years. Desmoplasia (abundant fibrotic stroma) is a typical feature of PDAC in humans, and stromal activation commonly starts around precancerous lesions. It is becoming clear that this stromal tissue is not a bystander in disease progression. Cancer-stroma interactions effect tumorigenesis, angiogenesis, therapy resistance and possibly the metastatic spread of tumour cells. Therefore, targeting the tumour stroma, in combination with chemotherapy, is a promising new option for the treatment of PDAC. In this Review, we focus on four issues. First, how can stromal activity be used to detect early steps of pancreatic carcinogenesis? Second, what is the effect of perpetual pancreatic stellate cell activity on angiogenesis and tissue perfusion? Third, what are the (experimental) antifibrotic therapy options in PDAC? Fourth, what lessons can be learned from Langton's Ant (a simple mathematical model) regarding the unpredictability of genetically engineered mouse models?
    Nature Reviews Gastroenterology &#38 Hepatology 06/2012; 9(8):454-67. · 10.43 Impact Factor
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    ABSTRACT: Background/Aims: Measurement of serum lactate remains the most frequently applied laboratory investigation to diagnose acute mesenteric (intestinal) ischemia. The present review aims at critically questioning the widespread measurement of serum lactate to diagnose acute mesenteric ischemia in clinical practice and at drawing attention to more novel markers of intestinal ischemia. Methods: An electronic search of multiple databases was performed with the key words 'lactate', 'marker', 'mesenteric', 'intestinal' and 'ischemia' to detect all relevant studies. Additionally, the references of published articles were also reviewed. Results: Serum lactate is an unspecific marker of tissue hypoperfusion and undergoes significant elevation only after advanced mesenteric damage. While L-lactate is the routinely measured stereoisomer of lactate, the other stereoisomer, D-lactate, has been shown to bear a somewhat higher specificity, which is still not comparable to the extremely specific nature of ischemia markers from other organs (e.g. cardiac ischemia). Larger studies are currently lacking to reliably advocate the routine clinical usage of novel markers like mucosal damage markers such as intestinal fatty acid-binding protein. Conclusion: Based on current evidence, the level of no single serum marker, including serum lactate, is elevated early and specifically enough in the serum to diagnose acute mesenteric ischemia.
    Digestive surgery 06/2012; 29(3):226-35. · 1.37 Impact Factor

Publication Stats

12k Citations
2,567.82 Total Impact Points

Institutions

  • 2007–2014
    • Technische Universität München
      • Clinic and Polyclinic for Surgery
      München, Bavaria, Germany
    • Otto-von-Guericke-Universität Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
  • 2013
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2012
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
    • Helmholtz Zentrum München
      • Institut für Pathologie
      München, Bavaria, Germany
  • 2009–2012
    • Deutsches Herzzentrum München
      München, Bavaria, Germany
  • 2010–2011
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2002–2011
    • Universität Heidelberg
      • Institute of Pathology (Mannheim)
      Heidelberg, Baden-Wuerttemberg, Germany
    • Heidelberg University
      Tiffin, Ohio, United States
    • Southeast University (China)
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2002–2010
    • University of Liverpool
      • Cancer Research Centre
      Liverpool, ENG, United Kingdom
  • 2007–2009
    • Beth Israel Deaconess Medical Center
      • Center for Vascular Biology Research
      Boston, MA, United States
  • 2006–2009
    • German Cancer Research Center
      • Division of Functional Genome Analysis
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2004–2007
    • Geisel School of Medicine at Dartmouth
      • Department of Medicine
      Hanover, New Hampshire, United States
  • 2003–2007
    • University of California, Los Angeles
      • Department of Surgery
      Los Angeles, CA, United States
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
    • Peking Union Medical College Hospital
      • Department of General Surgery
      Beijing, Beijing Shi, China
  • 2002–2005
    • Northwestern University
      • Department of Surgery
      Evanston, IL, United States
  • 1994–2003
    • University of California, Irvine
      • • Department of Medicine
      • • Division of Endocrinology
      Irvine, CA, United States
  • 2001–2002
    • University of Nebraska at Omaha
      • • Department of Pharmaceutical Sciences
      • • Eppley Institute for Research in Cancer and Allied Diseases
      Omaha, NE, United States
    • Inselspital, Universitätsspital Bern
      • Department of Visceral Surgery and Medicine
      Bern, BE, Switzerland
    • General Hospital of Shenyang Military Region
      Feng-t’ien, Liaoning, China
  • 1995–2002
    • Universität Bern
      • Visceral and Transplantation Surgery Research Group
      Bern, BE, Switzerland
    • University of Nagasaki
      • Department of Surgery II
      Nagasaki, Nagasaki, Japan
  • 1993–1998
    • Universität Ulm
      • Institute of General Medicine
      Ulm, Baden-Württemberg, Germany