Prognostic significance of histologically detected lymph node micrometastases of sizes between 0.2 and 2 mm in colorectal cancer.

PURPOSE: Minimal lymph node involvement is a potential prognostic factor in colorectal cancer. The International Union Against Cancer defined tumour deposits between 0.2 and 2 mm as micrometastases and clusters and single-cell infiltrations below this cutoff as isolated tumour cells. Nevertheless, only a minority of studies discriminated metastatic involvements according to this definition. METHODS: In order to investigate the prognostic significance of micrometastases (0.2-2 mm), we performed a retrospective study enrolling 44 routinely diagnosed micrometastatic cases within 15 years which represent about 1% of our cases. These cases have been re-evaluated. RESULTS: Seven of the micrometastatic cases turned out to be macrometastases after step sectioning. Complete follow-up was available in 33 remaining cases. Collections of node-negative and macrometastatic cases served as control groups. The Kaplan-Meier curves of macro- and micrometastatic cases showed a similar adverse course (p = 0.830) especially during the first 40 months. The 5-year-survival rates were 51, 60 and 64 months for macro-, micrometastatic and node-negative cases, respectively. The difference in overall survival, however, reached only a statistical trend and was not significant (p = 0.137). After re-evaluation with step sections and cytokeratin immunohistochemistry out of an initial 91 node-negative cases, 11 (12%) cases were identified with isolated tumour cells and one (1%) case with a micrometastasis. CONCLUSIONS: Our data show that micro- and macrometastatic colorectal cancers show very similar survival rates. Therefore, efforts to improve the detection of lymph node micrometastases seem to be justified.

Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer.

AIMS: The proteases PAI-1 and uPA play a major role in extracellular matrix degradation, which facilitates tumour progression. Tumour budding is a histomorphological expression of enhanced tumour cell migration. MATERIALS AND METHODS: To investigate their prognostic value for and correlation with colon cancer, a prospective study was performed. We analysed tissue levels of uPA and PAI-1 of 55 colon cancer tumours employing a commercially available enzyme-linked immunosorbent assay (ELISA). Tumour budding was analysed on cytokeratin-stained slides. RESULTS: There was a strong correlation between uPA and tumour budding (R = 0.440; P < 0.001). uPA levels were increased in high grade tumours, whereas PAI-1 was elevated in cases with venous invasion (P = 0.004 and P = 0.028). PAI-1 values and tumour budding are associated significantly with the occurrence of distant metastases (P < 0.001 and P = 0.034, respectively). Tumour budding was significantly associated with lymph node metastases (P = 0.034). Multivariate analysis revealed PAI-1 and lymph node metastases to be independently predictive of distant metastases (P = 0.007 and P = 0.004, respectively). CONCLUSIONS: The results of our study show that tumour budding and the plasmin/plasminogen system are related. PAI-1 was independently predictive for the occurrence of distant metastasis.

Survival benefit in patients after palliative resection vs non-resection colon cancer surgery.

AIM: To evaluate survival in patients undergoing palliative resection versus non-resection surgery for primary colorectal cancer in a retrospective analysis. METHODS: Demographics, TNM status, operating details and survival were reviewed for 67 patients undergoing surgery for incurable colorectal cancer. Palliative resection of the primary tumor was performed in 46 cases in contrast to 21 patients with non-resection of the primary tumor and bypass surgery. Risk factors for postoperative mortality and poor survival were analyzed with univariate and multivariate analyses. RESULTS: The two groups were comparable in terms of age, gender, preoperative presence of ileus and tumor stage. Multivariate analysis showed that median survival was significantly higher in patients with palliative resection surgery (544 vs 233 d). Differentiation of the tumor and tumor size were additional independent factors that were associated with a significantly poorer survival rate. CONCLUSION: Palliative resection surgery for primary colorectal cancer is associated with a higher median survival rate. Also, the presence of liver metastasis and tumor size are associated with poor survival. Therefore, resection of the primary tumor should be considered in patients with non-curable colon cancer.

["Fast-Track" for laparoscopic-assisted rectum resection--what can be achieved? First results of a feasibility study]. / "Fast-Track" bei laparoskopisch assistierter Rektumresektion--was kann erreicht werden? Erste Ergebnisse einer Machbarkeitsstudie.

AIM: "Fast-track" multimodal rehabilitation is increasingly entering the perioperative management strategies in colon surgery aiming at minimized perioperative morbidity and accelerated recovery. So far little is known about the complementary effects of minimally invasive surgery along with "fast-track" rehabilitation in the treatment of rectal cancer. The aim of this pilot study was to investigate the influence of "fast-track" perioperative management on morbidity, recovery and length of hospital stay in laparoscopically-assisted rectum resections and to compare those data to earlier results. METHODS: An interdiciplinary "fast-track" multimodal rehabilitation strategy with avoidance of mechanical bowel cleansing, with a restrictive intravenous intra- and postoperative fluid regimen, forced mobilisation, and early enteral nutrition was introduced into clinical practice and applied in 16 laparoscopically-assisted rectum resections. Data were collected in the course af a prospective analysis. The mean patient age was 62 (42-79) years. RESULTS: Mean time of surgery was 245 (SD 46) min, and the mean intraoperative infusion rate was 11.2 (SD 2.6) ml/kg/BW. On day 2, 14 of the 16 patients tolerated solid food and 12 patients had had bowel movements. All patients returned to their initial body weight by day 4. The median postoperative hospital stay was 7.5 days (6-20), 12 patients were discharged between day 6 and 8. Two patients were readmitted for intestinal atony, one patient developed an anastomotic leakage. CONCLUSIONS: "Fast-track" rehabilitation is feasible in rectum surgery and seems to complement the beneficial effects of minimally invasive surgery without increasing the complication rate.

Two-dimensional tension tests in plant biomechanics--sweet cherry fruit skin as a model system.

Splitting of fruits is a function of two-dimensional tension caused by different growth rates of tissues and turgor, especially water uptake shortly before harvest. In order to analyse the mechanical properties of spheroid plant material close to stress-strain conditions in vivo, a new hydraulic two-dimensional testing device was set up. Sweet cherry (Prunus avium L.) fruit skin was chosen as a model system. The recorded pressure-deflection curves were non-linear, with a considerable initial "lag phase" and a distinct increasing end part. Taking into account the special geometry, these curves could be modelled with a newly developed analytical approach based on linear elastic material behaviour. The results demonstrated good correlation if a modulus of elasticity ranging from 160 to 250 MPa for the cherry fruit skin was chosen. In addition, a mean strength value of 47 MPa was calculated based on the theory of thin shells and spheres. The results are compared with mechanical data found for fruits and other plant material. In order to test the theoretical approach, two- and one-dimensional tension tests were performed on packaging PE foil, revealing a mean modulus of 171 MPa in bi-axial tension, and 193 and 242 MPa in uni-axial tension, depending on the test speed. The results demonstrate that it seems to be feasible to use this method to analyse the two-dimensional stress-strain conditions of spheroid plant materials such as cherry fruit skins. It may be applied as a tool for crop testing to elucidate the mechanical basis of cracking susceptibility of fruits.

The mechanical role of the endodermis in Equisetum plant stems.

The endodermis of different species of the genus Equisetum has different configurations, two or one continuous layers or a sheath only around the vascular bundles. The question whether the endodermis contributes to the mechanical stability of the aerial shoots is investigated in two ways: In a direct approach, the endodermis of segments of E. hyemale was dissected longitudinally and the mechanical stability against ovalization measured as a function of the orientation of the cuts with respect to the forces applied. A comparative approach tested the mechanical stability of eight different species of Equisetum against ovalization of the cross-section for samples, which were either fully turgescent or had reduced turgor pressure. The double-layer endodermis substantially contributed to the mechanical stability of E. affinis and E. hyemale. Equisetum arvense, E. pratense, E. sylvaticum, and E. telmateja are mechanically stabilized by their single layer of endodermis at least under conditions of low turgor pressure.

Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1.

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3C upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.

The surgical discharge summary: a lack of substantial clinical information may affect the postop treatment of rectal cancer patients.

BACKGROUND AND AIMS: The discharge summary is crucial for patient aftercare as it is the main document for communicating information on patient data between the hospital and the primary care practitioner. The aim of this study was to assess the completeness of hospital discharge summaries and to determine whether the inclusion or omission of specific items of clinical information may affect further patient care. PATIENTS/METHODS: A population based cohort study including patients with rectal cancer from April 1996 through March 1998 in the Munich region. Five hundred and thirty-seven discharge summaries were evaluated for completeness of clinical- and tumor-related information. In addition, the association between recommendation for (discharge summary) and initiation of adjuvant therapy after discharge was evaluated. RESULTS: Information about T and N category was given in 98%, about metastasis in 90%, and about residual tumor in 73% of all discharge summaries. Follow-up was recommended in only 68% of the summaries. No adjuvant therapy was administered to 5/5 patients with N+, T1/2 tumors nor to 14/17 patients with N+, T3/4 tumors if correspondent recommendations were missing. CONCLUSION: Lack of crucial information in surgical discharge summaries is not only surprisingly common, but may also negatively affect patient aftercare.

Oscillation frequencies of plant stems with apical loads.

The frequency of free oscillations of plant stems with apical loads, as found in some cereals, is different depending on whether the stems are oriented vertically or horizontally. Neglecting the stem's own weight the differential equations describing the oscillation can be solved for both cases, although in the vertical orientation only for a limited set of conditions including constant bending stiffness along the stem. Comparison with experimental data shows that the difference between the oscillation frequencies in vertical and horizontal orientations can be attributed to the fact that in the vertical orientation the top load due to gravity induces a bending moment varying with the oscillation, while in the horizontal case this bending moment is nearly constant.

Brittleness of twig bases in the genus Salix: fracture mechanics and ecological relevance.

The twig bases within the genus Salix were investigated. Brittleness of twig bases as defined in the literature neither correlates with Young's modulus nor with growth strains, which were measured for S. alba, S. fragilis and S. x rubens. For the species S. alba, S. appendiculata, S. eleagnos, S. fragilis, S. purpurea, S. triandra, S. viminalis, and S. x rubens, fracture surfaces of broken twigs were investigated and semiquantitatively described in terms of 'relative roughness' (ratio of rough area of fracture surface over whole area of fracture surface). The relative roughness clearly corresponds with the classification into brittle and nonbrittle species given in the literature. An attempt was made to quantify brittleness with mechanical tests. The absolute values of stress and strain do not correlate with the brittleness of the twig bases as defined by the relative roughness. However, the 'index stress' (ratio of stress at yield over stress at fracture) or the 'index strain' (ratio of strain at yield over strain at fracture), correlate well with the relative roughness. The graphic analysis of index stress against index strain reveals a straight line on which the eight species are ordered according to their brittleness. Depending on growth form and habitat, brittle twig bases of willows may function ecologically as mechanical safety mechanisms and, additionally, as a propagation mechanism.

[Coloproctological diseases of the pelvic floor]. / Koloproktologische Erkrankungen des Beckenbodens.

PURPOSE: The aim of this review is to describe the most frequent and important coloproctologic pelvic floor disorders. Relevant diagnostic procedures of the pelvic floor will be presented. MATERIAL AND METHODS: A host of diagnoses and symptoms such as the descending perineum syndrome, rectocele, cystocele, enterocele, uterine and vaginal descensus, anal and rectal prolapse, outlet obstruction, anismus, inertia recti and intussusception are included under the heading "pelvic floor disorders". Although symptoms are often varied, problems concerning urinary and/or faecal continence commonly lead to primary consultation of a physician. RESULTS: Quite often, apparently divergent symptoms such as constipation and incontinence are simultaneously mentioned. A clear gender disposition is observed with female patients inflicted nine-fold in comparison to male patients. The primary consultant may belong to a variety of specialities such as urology, proctology, gynaecology or dermatology, depending upon the predominant symptom. A feeling of trust is essential for the treatment of a disorder involving highly intimate regions of the body. DISCUSSION: An exact medical history and standardized proctologic evaluation consisting of inspection, palpation, rectoscopy and proctoscopy may be augmented by investigations such as anorectal manometry or endosonography. Conventional defecography has been replaced more and more by dynamic MRI of the pelvic floor in specialized institutions, enabling additional gynaecologic and urologic investigations avoiding ionizing radiation.

Micromechanics and anatomical changes during early ontogeny of two lianescent Aristolochia species.

The mechanical properties of young stems of Aristolochia macrophylla Lam. and Aristolochia brasiliensis Mart. et Zucc. were studied during elongation growth and primary differentiation. Data for the modulus of elasticity, for the viscoelastic behaviour caused by longitudinal tension and for the shear modulus resulting from torsion around a longitudinal axis were related to the underlying structural changes by quantitative analysis of stem anatomy, tissue distribution, ultrastructure, and cell wall biochemistry. The orientation of cellulose microfibrils was determined by light microscopy and small-angle X-ray diffraction, and the lignin content was determined by thioglycolic acid derivatization and spectroscopic quantification. It was demonstrated that the increase in stability during early development is due to the complementary effects of increase in cell wall material, lignification, and cellulose microfibril alignment. A detailed micromechanical model, considering internal prestresses, is proposed to explain the characteristic biphasic stress-strain behaviour as well as the strain-hardening observed.

The functional morphology of the petioles of the banana, Musa textilis.

Bananas are among the largest herbs in the world and their lightweight petioles hold up huge leaves. This study examined how the petioles manage to achieve adequate rigidity to do this, while allowing extensive and reversible reconfiguration in high winds. Morphological and anatomical examination of the petioles and leaves of Musa textilis suggested how these two apparently incompatible abilities are achieved. The hollow U-shaped section of the petiole and the longitudinal strengthening elements in its outer skin give it adequate rigidity, while its ventral curvature help support the leaf without the need for thick lateral veins. These features, however, also allow the petiole to reconfigure by twisting away from the wind, while the leaf can fold away. In addition, two sets of internal structures, longitudinal partitions and transverse stellate parenchyma plates, help prevent dorsoventral flattening, allowing the petiole to flex further away from the wind without buckling. These ideas were tested and verified by a range of mechanical tests. Simple four-point-bending and torsion tests showed that the petioles are indeed far more compliant in torsion than in bending. Axial bending tests and crushing tests showed that petioles could be flexed twice as far and were four times as resistant to dorsoventral flattening when intact than when the internal tissue is removed. The banana petiole, therefore, seems to be an excellent example of natural integrated mechanical design.

Mechanical behaviour of plant tissues: composite materials or structures?

The mechanical characteristics of the strengthening tissue of young axes of Aristolochia macrophylla were studied in successive loading-unloading cycles in tension. Elastic, viscoelastic and plastic deformations could be distinguished. After the first cycle, the material was in a state different from its original state, to which it returned only partially and/or slowly. Internal 'microstructural' prestresses are considered as an explanation for the mechanical behaviour seen in Aristolochia macrophylla and several other plants.

Methods for calculating factors of safety for plant stems.

The concept of a 'factor of safety' is used by biologists and engineers who generally agree that structures must be mechanically reliable, i.e. that structures must be capable of coping with unprecedented loads without failing. These factors can be calculated for individual structures or for a population of otherwise equivalent mechanical structures differing in their load capabilities. Objective methods for quantifying factors of safety for biological structures are nevertheless difficult to devise because (1) actual (working) loads are defined by environmental conditions that can vary widely, (2) breaking loads (capability) of otherwise mechanically equivalent structures can likewise vary as a result of developmental variation, and (3) specific criteria for failure must be determined a priori. In this paper, we illustrate and discuss two methods for computing factors of safety for plants. One method works well for individual stems or entire plants, the other is useful when dealing with a population of conspecifics exhibiting a norm of reaction. Both methods require estimates of the actual and breaking bending (or torsional) moments experienced by stems, and both are amenable to dealing with any biologically reasonable criterion for failure. However, the two methods differ in terms of the assumptions made and the types of data that need to be gathered. The advantage of the first method is that it estimates the potential for survival of an individual stem or plant. The disadvantage is that it neglects natural variation among otherwise mechanically homologous individuals. The advantage of the second (statistical) approach is that it estimates the probability of survival of a population in a particular habitat. The disadvantage of this approach is that it sheds little light on the probability of an individual's survival.

Estudios sobre la Serotonina Plaquetaria y Plasmatica en Pacientes Depressivos / Studies on platelet and plasmatic serotonin in depressive patients

En un estudio multicéntrico se determinó la concentración de serotonina plaqueraria en 47 pacientes depresivos hallándose que un 40.4 por cento de los mismos presenta valores inferiores al rango normal. Los valores obtenidos son comparables a los de un estudio preliminar. En 19 casos se determinó asimismo la concentración de serotonina extracelular en plasma. Los pacientes con cifras normales de serotonina plaquetaria arrojaron un valor de serotonina plasmática de 4.6ñ2.1 ng/ml mientras que los pacientes con cifras bajas dieron un valor de 2.2ñ1.3 ng/ml, una disminuicción estadísticamente significativa que indicaría una falla en los mecanismos de formación de este neurotransmisor. Finalmente se determinó la serotonina plaquetaria en 41 pacientes tratados con inhibidores de recaptación de la serotonina. Alrededor del 60 por cento de ellos presenta cifras notablemente inferiores a las normales. De todos modos, la presencia de pacientes con cifras normales o cercanas a las mismas indica la necesidad de evaluar las respuestas terapéuticas individuales frente a los distintos valores obtenidos

De novo expression of the cell adhesion molecule E-selectin on gastric cancer endothelium.

BACKGROUND AND AIMS: Angiogenesis and the molecular phenotype of the tumor vasculature determine tumor growth and metastasis. PATIENTS/METHODS: In a series of 58 gastric cancer patients, vascular density and the antigenic profile of endothelial cells in normal, inflamed and malignant gastric tissues were compared using immunohistochemistry. RESULTS: In both benign gastric mucosa and primary gastric cancer vascular density was inflammation-independent. However, increased vascularity in primary tumors was positively associated with a high tumor cell density suggesting tumor-induced angiogenesis (P=0.00001 ). P-selectin was expressed in most of the gastric mucosa samples on a small fraction of vessels and increased in the presence of moderate to strong leukocyte infiltrate. VCAM-1 positive mucosal vessels were rare and showed no association with inflammation. E-selectin and the EN 7/44 antigen defining budding vessels were absent on normal and inflamed endothelium. In contrast, in primary gastric cancer de novo expression of both E-selectin and the EN 7/44 antigen was observed. E-selectin positive vessels were preferentially found in vascular-rich tumor areas (P=0.0043) independently of leukocyte infiltration. Upregulation of VCAM-1 on tumor-associated endothelium was closely related to inflammation (P=0.019), while P-selectin expression resembled that in benign mucosa. CONCLUSIONS: Differentially expressed vascular molecules may influence the functional characteristics of extravasating leukocytes and represent new targets in anti-gastric cancer therapy.

Biomechanics and functional anatomy of hollow-stemmed sphenopsids. I. Equisetum giganteum (Equisetaceae).

The hollow stem of Equisetum giganteum owes its mechanical stability to an outer ring of strengthening tissue, which provides stiffness and strength in the longitudinal direction, but also to an inner lining of turgid parenchyma, which lends resistance to local buckling. With a height >2.5 m isolated stems are mechanically unstable. However, in dense stands individual stems support each other by interlacing with their side branches, the typical growth habit of semi-self-supporters.

Hebb's concept of synaptic plasticity and neuronal cell assemblies.

Both in vertebrates and in invertebrates the study of processes of plasticity in nervous systems have led to consistent models of molecular mechanisms for the so-called Hebb's synapse. Changes of synaptic efficacy will lead to changes in the properties of assemblies of nerve cells--as seen today the correlates of purport. Donald Hebb's view of the characteristics of such assemblies appears farsighted.

Young's moduli and shear moduli in cortical bone.

Young's modulus and shear modulus are determined for cortical bone from mammals and birds and for antler bone, using three-point bending at a range of span-to-depth ratios between 25 and 10. Young's modulus is obtained by extrapolating the values for the flexural modulus Eapp to infinite span-to-depth ratios. The shear modulus is obtained from the dependance of Eapp on this ratio. The main determinant for the mechanical properties is the mineral content. For mammalian bone the frequency of Haversian systems correlates negatively with stiffness and resistance to shear. However, because Haversian systems have a lower mineral content than laminar bone (the main component), material and structural determinants can not be separated at present. The ratio of Young's modulus to shear modulus is of the order of 20:1. This high value is discussed in terms of the Cook-Gordon theory of controlled crack propagation as well as in its significance for protecting hollow bones from failing upon local impact.