Biomedical subjects

Lars Wolfram

Publications and source records attributed to Lars Wolfram.

5 recordsLinked to original sources

PubMed2006

Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy.

AIM: To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS: Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three (41%) of the 106 patients were staged as pT((1/2)), 63 (59%) as pT((3/4)), 51 (48%) as pN(0), and 55 (52%) as pN(1). The study population included 59 (56%) patients exhibiting G((1/2)), and 47 (44%) patients with G(3) tumors. Patients received no adjuvant chemo- or radiation therapy and were followed up for a median of 12 (range: 3.5 to 139) mo. RESULTS: Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as "tumor free" by conventional histopathology in 73 (69%) out of the 106 patients. Twenty-nine (57%) of 51 patients staged histopathologically as pN(0) had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free (relative risk 2.92, P=0.005) and overall (relative risk 2.49, P=0.009) survival. CONCLUSION: The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports may help to improve risk stratification of patients with pancreatic cancer.

Adult↗

PubMed2006

Effectiveness of radical en-bloc-esophagectomy compared to transhiatal esophagectomy in squamous cell cancer of the esophagus is influenced by nodal micrometastases.

PURPOSE: The appropriate surgery for curable squamous cell cancer (SCC) of the esophagus is discussed controversially. PATIENTS AND METHODS: Transthoracic esophagectomy (TTE) with radical en-bloc-lymphadenectomy was performed in 79/120 patients (66%). Due to severe comorbidity, 41/120 patients (34%) underwent less traumatizing transhiatal esophagectomy. Lymph nodes were stained using mAb BER-Ep4. RESULTS: pN0 status was found in 54 patients (45%) and pN1 status in 66 patients (55%). In the pN0 subgroup, 30 out of 54 patients (55.6%) had occult tumor cells in lymph nodes detected with BER-Ep4. pN1 patients had additional BER-Ep4 positive cells in histopathologically negative lymph nodes in 41 out of 66 patients (59.2%). Median disease-specific survival was 31.4 and 16.8 months for the transthoracic and transhiatal groups, respectively (P = 0.129). pN0 patients lived longer after transthoracic resection (P = 0.0349), and in the subgroup without lymph node micrometastases this effect was even stronger (P = 0.025). In contrast, in pN0 patients with nodal microinvolvement, TTE did not entail a survival benefit when compared with the transhiatal group (P = 0.333). CONCLUSION: TTE results in improved outcome in the absence of lymph node micrometastases. Poor survival in patients with lymphatic micro-dissemination indicates systemic disease and the need for adjuvant treatment.

Adult↗

PubMed2006

Sequential changes in vessel formation and micro-vascular function during bone repair.

BACKGROUND: Angiogenesis, the process of new vessel formation from a pre-existing vascular network, is essential for bone development and repair. New vessel formation and microvascular functions are crucial during bone repair, not only for sufficient nutrient supply, transport of macromolecules and invading cells, but also because they govern the metabolic microenvironment. Despite its central role, very little is known about the initial processes of vessel formation and microvascular function during bone repair. METHODS: To visualize and quantify the process of vessel formation and microvascular function during bone repair, we transplanted neonatal femora with a substantial defect into dorsal skin-fold chambers in severe combined immunodeficient (SCID) mice for continuous noninvasive in-vivo evaluation. We employed intravital microscopic techniques to monitor effective microvascular permeability, functional vascular density, blood flow rate and leukocyte flux repeatedly over 16 days. Oxytetracyclin and v. Kossa/v. Giesson staining was performed to quantify the calcification process in vivo and in vitro. RESULTS: Development of a hematoma surrounding the defect area was the initial event, which was accompanied by a significant increase in microvascular permeability and blood flow rate. With absorption of the hematoma and vessel maturation, permeability decreased continuously, while vascular density and tissue perfusion increased. Histological evaluation revealed that the remodeling of the substantial defect prolonged the in-vivo monitored calcification process. INTERPRETATION: The size of the initial substantial defect correlated positively with increased permeability, suggesting improved release of permeability-inducing cytokines. The unchanged permeability in the control group with boiled bones and a substantial defect corroborated these findings. The adaptation to increasing metabolic demands was initially mediated by increased blood flow rate, later with increasing vascular density through increased tissue perfusion rate. These insights into the sequence of microvascular alterations may assist in the development of targeted drug delivery therapies and caution against the use of permeability-altering drugs during bone healing.

Animals↗

PubMed2006

Long-term follow-up in small duct chronic pancreatitis: A plea for extended drainage by "V-shaped excision" of the anterior aspect of the pancreas.

BACKGROUND: A pancreatic duct diameter (PDD) ranging from 4 to 5 mm is regarded as "normal." The "large duct" form of chronic pancreatitis (CP) with a PDD >7 mm is considered a classic indication for drainage procedures. In contrast, in patients with so-called "small duct chronic pancreatitis" (SDP) with a PDD <3 mm extended resectional procedures and even, in terms of an "ultima ratio," total pancreatectomy are suggested. METHODS: Between 1992 and 2004, a total of 644 patients were operated on for CP. Forty-one prospectively evaluated patients with SDP underwent a new surgical technique aiming at drainage of the entire major PD (longitudinal "V-shaped excision" of the anterior aspect of the pancreas). Preoperative workup for imaging ductal anatomy included ERCP/MRCP, visualizing the PD throughout the entire gland. The interval between symptoms and therapeutic intervention varied from 12 to 120 months. Median follow-up was 83 months (range, 39-117 months). A pain score as well as a multidimensional psychometric quality-of-life questionnaire was used. RESULTS: Hospital mortality was 0%. The perioperative (30 days) morbidity was 19.6%. Postoperative, radiologic imaging showed an excellent drainage of the entire gland and the PD in all but 1 patient. Global quality-of-life index increased in median by 54% (range, 37.5%-80%). Median pain score decreased by 95%. Twenty-seven patients (73%) had complete pain relief. Sixteen patients (43%) developed diabetes, while the exocrine pancreatic function was well preserved in 29 patients (78%). CONCLUSION: "V-shaped excision" of the anterior aspect of the pancreas is a secure and effective approach for SDP, achieving significant improvement in quality of life and pain relief, hereby sparing patients from unnecessary, extended resectional procedures. The deterioration of exocrine and endocrine pancreatic functions is comparable with that observed during the natural course of the disease.

Adult↗

PubMed2005

Long-term observation reveals time-course-dependent characteristics of tumour vascularisation.

Functional properties of tumour vasculature influence the process of metastasis and play a role in generating a heterogeneous metabolic microenvironment, which contributes to genetic instability and inefficiency of tumour therapies. Morphological and functional properties of tumour vasculature may vary from tumour onset to late-stage disease. The aim of this study was to identify the dynamic alteration in tumour microcirculation in a chronic observation model. Invasively-growing, non-disseminating, green fluorescent protein transfected, human bone marrow derived endothelial cells, were implanted into cranial windows of severe combined immunodeficient mice. Intravital fluorescence microscopy was performed over a period of 85 days to measure permeability, leucocyte-endothelial interaction (LEI) and tissue perfusion rate as functional parameters. Vessel density, branching pattern and scanning electron microscopy were monitored as morphological parameters. Concordant with an increasing count of transendothelial pores, the results show that the initial event following tumour cell implantation was a significant increase in the permeability of pre-existing vessels. The variations in newly formed vessels were characterised by sequentially-occurring functional and morphological alterations with the development of characteristics typical of tumour vessels, such as increased count of trifurcations and variation in vessel calibre by more than 100%. In parallel with the increasing vessel volume per area, the tissue perfusion rate increased until day 61. It is concluded from the step-specific sequential functional and morphological alterations that the efficiency of adjuvant therapies depends not only on their intrinsic efficiency but also on the timing of their initiation.

Animals↗