Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy: A case report and review of literature

BACKGROUNDPrimary extra-gastrointestinal stromal tumors (E-GIST) of the liver are rare. The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect. Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care. However, under specific circumstances, a cytoreductive approach may represent a therapeutic option. We describe herein the case of an 84-year-old woman who presented with a tender, protruding epigastric mass. Abdominal computed tomography scan revealed a large, heterogeneous mass located across segments III, IV, V, and VIII of the liver. The initial approach was transarterial embolization of the tumor, which elicited no appreciable response. Considering the large size and central location of the tumor and the advanced age of the patient, non-anatomic complete resection was indicated. Due to substantial intraoperative bleeding and hemodynamic instability, only a near-complete resection could be achieved. Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver. Considering the risk/benefit ratio for therapeutic options, debulking surgery may represent a strategy to control pain and prolong survival.CASE SUMMARYHere, we present a case report of a patient diagnosed with E-GIST primary of the liver, which was indicated a cytoreductive surgery and adjuvant therapy with imatinib.CONCLUSIONE-GIST primary of the liver is a rare conditional, the treatment is with systemic therapy and total resection surgery. However, a cytoreductive surgery will be necessary when a complete resection is no possible.     

Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology - The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors...     

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in the guinea-pig trachea with the selective muscarinic receptor antagonist tripitramine

1. The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M₂-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M₂ receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference.
2. It was found that tripitramine antagonized methacholine-induced contractions of the guinea-pig lung strip with a pK_B value of 8.76±0.05. Both the parallel shifts of the concentration-response curves and the slope of the Schild plot being not significantly different from unity (when antagonist preincubation was for 2 h) indicated the involvement of a single population of receptors in the contractile response. From the pK_B values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Roffel et al., 1993), this single population of receptors can only be classified as M₂-like.
3. Tripitramine antagonized methacholine-induced negative chronotropic and inotropic responses in guinea-pig right and left atria with apparent pK_B values of 9.4–9.6. However, such values were only obtained when antagonist preincubation was relatively long and/or antagonist concentration relatively high (e.g. with 1 h at 100 or 300 nM but 3 h at 30 nM). It thus appears that low concentrations of tripitramine do not readily equilibrate with M₂ receptors in guinea-pig atria nor with M₂-like receptors in the guinea-pig lung strip.
4. Tripitramine increased electrical field stimulation-induced cholinergic twitch contractions in guinea-pig trachea in concentrations of 0.3–100 nM, by blocking prejunctional muscarinic inhibitory autoreceptors; with higher concentrations, twitch contractions were progressively diminished, as a result of blocking postjunctional M₃ receptors (apparent pK_B value 6.07±0.15). The pEC₂₀ value (−log concentration that increases twitch by 20% of maximum) was 8.29±0.08, which would suggest that M₄ receptors are involved in this response.
5. Oxotremorine-induced inhibition of the release of prelabelled [³H]-acetylcholine from guinea-pig trachea, under conditions where there is no auto-feedback, was blocked by tripitramine (2 h preincubation) with a pK_B value of 8.56±0.06. The slope of the corresponding Schild plot was not significantly different from unity, which together with the parallel shifts of the concentration-response curves indicated the involvement of a single muscarinic receptor subtype.
6. Since the pK_B value for tripitramine at prejunctional receptors in guinea-pig trachea is in between the affinities towards M₂ and M₄ receptors, correlation plots were constructed to compare the pK_B values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Kilbinger et al., 1995) to reported affinities at M₁–M₄ receptors. This showed rather similar distribution patterns of the data points around the line of equality in the case of M₂ and M₄ receptor subtypes. However, the correlation coefficient was markedly better for M₂ (0.9667) than for M₄ (0.5976). Since recent evidence suggests that M₄ receptors are not expressed in cholinergic nerves from guinea-pig trachea, it is concluded that prejunctional muscarinic autoinhibitory receptors in this tissue exhibit an atypical M₂ type character, with a pharmacological profile distinct from cardiac M₂ receptors.

     

A versatile shuttle cosmid vector for the efficient construction of genomic libraries and for the cloning of fungal genes

A shuttle cosmid vector, pANsCos1, has been constructed for Escherichia coli and filamentous fungi. This vector contains two cos sequences separated by a single XbaI restriction site. pANsCos1 allows the efficient construction of representative genomic libraries from as little as 15–20 g of genomic DNA. Due to the presence of a functional hygromycin B phosphotransferase gene (hph) transformation of fungal protoplasts with pANsCos1, or derivatives of it, results in the formation of hygromycin B-resistant transformants. The T7 and T3 RNA polymerase promoter sequences flanking the cloning site, in combination with two adjacent NotI sites facilitate genomic walking and the rapid construction of restriction maps of cloned inserts.Dedicated to Professor Dr. K. Esser on the occasion of his 70th birthday     

DNA repair synthesis following irradiation with 254-nm and 312-nm ultraviolet light is not diminished in fibroblasts from patients with dysplastic nevus syndrome

The DNA excision repair capacity of 23 primary fibroblast lines from patients with dysplastic nevus syndrome was investigated and DNA repair synthesis (unscheduled DNA synthesis) was determined after UV exposure. Seventeen fibroblast lines from normal donors served as controls. The dose/response experiments included up to ten dose levels and two wavelength ranges: UV-C (using a low-pressure mercury lamp emitting predominantly 254-nm light) and UV-B (artificial sunlamp radiation centering around 312-nm light). For each dose level, silver grains over fibroblast nuclei were counted by visual inspection. Twelve cell lines were also evaluated for both UV wavelength ranges using a new semi-automatic image analyzing system. This system included components for rapid sequential identification of both fibroblast nuclei and silver grains sited above them. Silver grains over 100 nuclei were determined for each UV dose level. Dose/response curves were established and analyzed by linear regression. As a quantitative term for assessing DNA excision repair capacity of a cell line we calculated the linear increase (G ₀) in the number of grains per nucleus, when the UV dose was multiplied by the factor e (i.e. 2.72). The sensitivity of grain detection and resolution ofoverlapping grains was approximately threefold better in visual than in automatic counting, especially when there were more than 70 grains over nuclei. The time recired for visual conting, however, was tenfold that of automatic counting. The varianceweighted meanG ₀ ^v,w of all fibroblast lines from patients with dysplastic nevus syndrome was found to be 79.1 (±1.8-grains/nucleus, that of fibroblast lines from normal donors was 74.2 (±1.7) grains/nucleus. This difference revealed a slightly better repair capability for cell lines from patients but was at the borderline of detection and, therefore, should not be overinterpreted. From the experimental accuracy achieved by determination of the varianceweighted means of the two groups, we would have been able to detect a difference of 7 and more grains [> 2 x (_normal + _patients)]. The variance-weighted meanG _o ^v,w of all fibroblast lines from patients with dysplastic nevus syndrome was found to be 76.4 (±1.4) grains/nucleus, whereas that of fibroblast lines from normal donors was only 66.6 (±1.8) grains/nucleus. This difference was statistically significant and, contrary to expectation, revealed better, not worse post-UV DNA repair capability in cell lines from patients that in those from normal donors. From the experimental accuracy achieved by determination of the variance-weighted means of the two groups, we would have been able to detect a difference of 6.4 or more grains [> 2 x (_normal + _patients)]. Variation between cell lines belonging to the same group was expressed by the standard deviation. On average, the standard deviation was in the range 18.2–21.1 grains/nucleus. This variation did not reflect experimental inaccuracy but different responses of individual cell lines to UV irradiation. On the basis of our data, we consider the hypothesis that patients with dysplastic nevus syndrome are prone to melanoma development because of a general defect in post-UV DNA repair to be improbable.This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136     

Lead-induced blockade of kainate-sensitive receptor channels

The effects of bivalent lead on ion channels activated by kainate and -amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) were studied using Xenopus oocytes microinjected with mRNA from rat brain. Lead reduced kainate-induced membrane currents in a reversible and dose-dependent manner, without affecting membrane currents induced by AMPA. Lead decreased the kainate currents with a concentration of 0.1 mol/l to 0.93 ± 0.01 and with a concentration of 100 mol/l to 0.41 ± 0.04 of the control values. The blocking effect of lead on kainate responses was voltage dependent. The inhibition was strongest at - 90 mV to - 70 mV and became weaker at more positive membrane potentials. The effect of lead on the kainate-induced membrane currents remained unchanged when the concentration of kainate was increased. Hence lead probably represents a noncompetitive channel-blocking agent for non-N-methyl-d-aspartate (NMDA) receptor channels activated by kainate.     

Leukocyte activation by isolated hyperthermic liver and limb perfusion due to malignancy

Fourteen patients with liver tumor malignancy and sixteen patients with malignant melanoma localized to one limb were studied regarding leukocyte activation with the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and formation of cytokines (TNF- and Il-6) during the surgical treatment. Patients undergoing liver resection (n=10), abdominal hysterectomy (n=10), or hip replacement surgery (n=10) served as control groups. Isolated hyperthermic liver perfusion was performed with cytostatic-containing perfusate (melphalan and cisplatinum). Patients with recurrent malignant melanoma confined to one limb underwent isolated hyperthermic limb perfusion with cytostatic-containing perfusate (melphalan). Blood samples for determination of PMN elastase, neopterin, TNF-, and IL-6 were drawn from the patients preoperatively, 1 minute before the start of the perfusion, 60 and 120 minutes after the start of the perfusion, and 24 hours postoperatively. Samples from the perfusate were drawn 60 minutes after the start of the perfusion. High concentrations of plasma PMN clastase were found both in patients undergoing liver and limb perfusion and in patients undergoing liver resection surgery. Elevated concentrations of Il-6 were found in the patients undergoing liver perfusion and in patients undergoing liver resection. In none of the patients were there increased concentrations of neopterin or TNF-. The perfusate contained high concentrations of PMN elastase, neopterin, and IL-6. This study also demonstrated that major surgery leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN elastase and IL-6 was seen in response to perfusion and to surgical trauma.

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Resumen Catorce pacientes con tumores malignos del hígado y 16 pacientes con melanoma maligno localizado en una extremidad fueron estudiados en relación con la activación de leucocitos con liberación de elastasa de PMN y de neopterina y la formación de citocinas (FNT- e IL-6) en el curso del tratamiento quirúrgico. Pacientes sometidos a resección del hígado (n=10), histerectomía abdominal (n=10) y reemplazo de cadera (n=10) sirvieron como grupos control. Se realizó perfusión hipertérmica aislada del hígado con perfusato citostácico (melfalán y cisplatino). Los pacientes con melanoma maligno recurrente confinado a una extremidad fueron sometidos a perfusión hipertérmica aislada de la extremidad con perfusato citostácico (melfalán). Se tomaron muestras de sangre para determinación preoperatoria de elastasa de PMN, neopterina, FNT- e IL-6, un minuto antes de comenzar la perfusión, 60 y 120 minutos después del comienzo de la perfusión y 24 horas después de la operación. Se tomaron muestras del perfusato a los 60 minutos luego del comienzo de la perfusión. Se encontraron altas concentraciones de elastasa de PMN tanto en los pacientes sometidos a perfusión hepática o de la extremidad, como en los pacientes sometidos a resección hepática. Se encontraron concentraciones elevadas de IL-6 en los pacientes sometidos a perfusión hepática y en los pacientes sometidos a resección del hígado. En ningún paciente se encontraron concentraciones aumentadas de neopterina o de FNT-. El perfusato contenía altas concentraciones de elastasa de PMN, neopterina e IL-6. Se encontró un aumento en la elastasa de PMN y en la IL-6 en respuesta a la perfusión y al trauma quirúrgico.

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Résumé Quatorze patients ayant une tumeur maligne du foie et 16 patients ayant un mélanome malin localisé à une extrémité ont été étudiés en ce qui concerne l'activation des leucocytes associée à un relargage d'élastase PMN et de néoptérine ainsi que la formation de cytokinines (TNF- et IL-6) pendant le traitement chirurgical. Trente patients avant eu soit une résection hépatique (n=10), soit une hystérectomie abdominale (n=10) ou une prothèse de hanche (n=10) ont servi de témoins. On a perfusé le foie avec un perfusât de cytostatiques (mélphalane et cis-platine). Les patients ayant un mélanome malin d'une extrémité ont eu une perfusion isolée hyperthermique avec une perfusion de cytostatique (mélphanane). Des échantillons du sang ont été retirés pour déterminer les taux d'élastase PMN, de la néoptérine, du TNF-, et de l'IL-6 en préopératoire, une minute avant le début de la perfusion, 60 et 120 minutes après le début de la perfusion, et 24 heures postopératoirement. Des échantillons ont été retirés 60 minutes après le début de la perfusion. Des concentration élevées d'élastase PMN ont été retrouvées à la fois chez les patients ayant une perfusion hépatique et de l'extrémité et chez les patients ayant eu une résection du foie. Des concentration élevées en IL-6 ont été retrouvées chez le patient ayant une perfusion du foie et chez le patient ayant une résection hépatique. Les concentrations en néoptérine et en TNF- n'étaient pas élevées. Le liquide de perfusion contenait des concentrations élevées en élastase PMN, néoptérine et en IL-6. Cette étude démontre aussi que la chirurgie majeure est associée avec des concentrations élevées en PMN elastase et IL-6. Une augmentation en PMN-élastase et en IL-6 a été retrouvée en réponse à la perfusion et au traumatisme chirurgical.

     

Neurobiological and anthropological aspects of compulsions and rituals

Obsessions and compulsions frequently accompany motor and vocal tics in Gilles de la Tourette syndrome (GTS). The occurrence of motor tics and compulsions helps to understand the neurobiological foundation of repetitive behavior patterns. Based on a review of the literature and our own studies in GTS, we suggest that simple motor tics are caused by a stimulus-dependent disinhibition of stereotypies encoded in the head of the caudate, while more complex compulsions are associated with a serotonergic disinhibition of frontocortical-striatal circuits in GTS and obsessive-compulsive disorder. These findings indicate that obsessions and compulsions do not simply result from a lack of cortical control of phylogenetically primitive behavior patterns. Rather, an activation of the orbitofrontal cortex seems to be essential for the induction of anxiety and the disinhibition of subcortical stereotypies. The neurobiological findings may help to clarify why compulsions differ from cultural rituals. Cultural rituals are performed cyclically, represent important social conflicts and are usually not accompanied by fear or anxiety. Obsessions, on the other hand, seem to be generated in a self perpetuating cycle of cortico-subcortical activation and are associated with anxiety and ineffective repetition of stereotypies.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Malignes Histiocytom der Haut mit multivesiculärer Vacuolisierung

Zusammenfassung Bei einem 47 jährigen Patienten entwickelten sich am rechten Bein mehrere rasch wachsende Tumoren von distal nach proximal. Histologisch und elektronenmikroskopisch zeigten die Tumorzellen morphologische Besonderheiten, die für ihre histiocytäre Provenienz sprechen. Auffallend war die große Anzahl polymorpher cytoplasmatischer Membranstrukturen und großer Vacuolen, die massenhaft kleine Vesikel enthielten. Diese Strukturen werden als transformierte multivesiculäre Körper gedeutet; ihre Entstehung vollzieht sich im Rahmen einer bizarr übersteigerten Membranaktivierung einer malignen Zellrasse. Bemerkenswert ist die rasche und völlige Remission durch Radiotherapie.

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Multivesicular vacuolization in malignant histiocytoma of the skin

Summary A 47-year-old patient developed several rapidly growing tumours in his right leg. Histologic and electron microscopic examination revealed morphological characteristics suggesting the histiocytic origin of the tumour cells. An important finding was the striking number of pleomorphic membraneous inclusions and large vacuoles containing numerous small vesicles. These cytoplasmic inclusions are interpreted as transformed multivesicular bodies. Their formation may be an expression of an increased and bizarre membraneous activity of a malignant cell race. Radiotherapy resulted in a remarkably rapid and complete remission.

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Auszugsweise vorgetragen beim 4th European Meeting on Electron Microscopy Applied on Cutaneous Pathology, Heidelberg, 6. und 7. Mai 1977: Multivesicular Vacuolization in Malignant Histiocytoma.