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C Gebhardt

Publications and source records attributed to C Gebhardt.

At least 19 recordsLinked to original sources

Enhanced spontaneous transmitter release is the earliest consequence of neocortical hypoxia that can explain the disruption of normal circuit function.

After the onset of an acute episode of arrested circulation to the brain and consequent cerebral hypoxia, EEG changes and modifications of consciousness ensue within seconds. This in part reflects the rapid effect of hypoxia on the neocortex, where oxygen deprivation leads to impaired neuronal excitability and abnormal synaptic transmission. To identify the cellular mechanisms responsible for the earliest changes in neocortical function and to determine their time course, we have used patch-in-slice recording techniques to investigate the effects of acute hypoxia on the synaptic and intrinsic properties of layer 5 neurons. Coronal slices of mouse somatosensory cortex were maintained at 37 degrees C and challenged with episodes of hypoxia (3-4 min of exposure to 95% N(2), 5% CO(2)). In recordings with cell-attached patch electrodes, activation of ATP-sensitive potassium channels first became detectable 211 +/- 11 sec (range, 185-240 sec; n = 6 patches) after the onset of hypoxia. Similar recording techniques revealed no alterations in the properties of Na(+) currents in the first 4 min after the onset of hypoxia. The earliest hypoxia-induced disturbance was a marked increase in the frequency of spontaneous EPSCs and IPSCs, which began within 15-30 sec of the removal of oxygen. This rapid synaptic effect was not sensitive to TTX and was present in Ca(2+)-free perfusate, indicating that the hypoxia had a direct influence on the vesicular release mechanisms. The incoherent, massive increase in miniature PSCs would be expected to deplete the readily releasable pool of vesicles in cortical terminals, and to thereby markedly distort the neuronal interactions that underlie normal circuit function.

Adenosine Triphosphate↗

The expression of substance P and its neurokinin-1 receptor mRNA in the bovine corpus luteum of early developmental stage.

Related to all leukocytes, 90% of eosinophils are recruited into the bovine corpus luteum of early developmental stage. We here describe a simultaneous appearance of substance P (SP)-positive fibre-like structures and the neurokinin-1 (NK-1) receptor mRNA for SP. Substance P was depicted by using indirect immunohistology and immunofluorescence localization. The dot blot analysis confirmed the presence of SP at the protein level. Using nested reverse transcribed-polymerase chain reaction (RT-PCR) analysis, a 358 bp long partial bovine receptor mRNA for SP (NK-1) was sequenced in the spinal cord. The mRNA for SP and for the NK-1 receptor were then detected in the corpus luteum of early developmental stage with RT-PCR and nested RT-PCR. We conclude: The production of SP and the expression of NK-1 receptor mRNA may be involved in the selective recruitment of eosinophils into the bovine corpus luteum of early developmental stage.

Animals↗

Prognostic importance of isolated peritumoral lymphangiosis carcinomatosa in lymph-node-negative colorectal carcinoma.

BACKGROUND: The prognostic value of microinvasion of lymph vessels and lymph nodes has become increasingly important; there is a wide range in prognosis of patients with nodal-negative tumor stages after curative resection for colorectal cancer. AIM: Detection of the prognostic importance of isolated lymph-vessel invasion as a possible precursor of lymph-node metastasis in patients with nodal-negative tumor stages. PATIENTS/METHODS: Retrospective analysis of 894 patients with R0-resected colorectal cancer, uni- and multivariate analysis of tumorbiologic prognostic factors, immunohistochemical proof of tumor cells in negative lymph nodes (pN0) using the epithelial marker HEA-125 (human epithelial antigen). RESULTS: The incidence of lymph-vessel invasion (L) was 37.7% in total. A pN0,L1 status was found in 144 patients (16.1% of all analyzed patients). Comparing patients with pN0,L1 status to those with pN+,L0 status showed that both groups have similar rates of overall survival and tumor relapse. Lymph-node status, lymph-vessel invasion, depth of tumor infiltration (pT) stage, and age were detected as independent prognostic factors by multivariate analysis. After reanalysis of 54 cases primarily classified as 18.5% pN0,L1, microinvasion in lymph nodes was detected by immunohistochemistry. We found a higher rate of tumor relapse (approximately 20%) for those patients. In regard to the overall survival rate, however, there was no difference when compared to patients without immunohistochemical proof of microinvasion. CONCLUSION: Isolated lymph-vessel invasion in nodal-negative tumor stages and a lymph-node-positive tumor status have equivalent prognostic importance in colorectal cancer.

Aged↗

Keratinocyte-specific onset of serine protease BSSP expression in experimental carcinogenesis.

Malignant transformation of mouse skin by chemical carcinogens and tumor promoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, is a multistage process leading to the formation of squamous cell carcinomas. In an effort to identify target genes whose expression is associated with skin tumorigenesis we combined elements of suppression subtractive hybridization with differential screening to isolate genes that are differentially upregulated in mouse skin after short-term treatment with 12-O-tetradecanoylphorbol-13-acetate and that exhibit a high constitutive expression in squamous cell carcinomas. Here, we report the detailed analysis of one of these cDNAs encoding the serine protease BSSP in mouse skin. Phorbol ester application increases BSSP expression in keratinocytes of the epidermis and the hair follicle several-fold starting 4 h post- treatment. Transcriptional activation of BSSP by 12-O-tetradecanoylphorbol-13-acetate was found to be independent of c-Fos expression and resistant to downregulation by glucocorticoids. By monitoring BSSP expression throughout experimental skin carcinogenesis we found strong constitutive expression in hyperplastic epidermis as well as in proliferatively active keratinocytes of benign and malignant skin tumors. These results establish a novel link between expression of an as yet ill-defined serine protease and skin carcinogenesis.

Animals↗

Organization of genes controlling disease resistance in the potato genome.

Nineteen single dominant genes (R genes) for resistance to viruses, nematodes, and fungi have been positioned on the molecular map of potato using DNA markers. Fourteen of those genes are located in five "hotspots" for resistance in the potato genome. Quantitative trait loci (QTL) for resistance to late blight caused by the oomycete Phytophthora infestans, to tuber rot caused by the bacterium Erwinia carotovora ssp. atroseptica, and to root cyst nematodes have been identified on all 12 potato chromosomes. Some QTL for resistance to different pathogens are linked to each other and/or to resistance hotspots. Based on the genetic clustering with R genes, we propose that some QTL for resistance have a molecular basis similar to single R genes. Mapping potato genes with sequence similarity to cloned R genes of other plants and other defense-related genes reveals linkage between candidate genes, R genes, and resistance QTL. To explain the molecular basis of polygenic resistance in potato we propose (a) genes having structural similarity with cloned R genes and (b) genes involved in the defense response. The "candidate gene approach" enables the identification of markers highly useful for marker-assisted selection in potato breeding.

Animals↗

Prognostic factors in the operative treatment of ductal pancreatic carcinoma.

BACKGROUND AND AIMS: The average 5-year survival rate following resection of a ductal adenocarcinoma of the pancreas is 10%, worldwide. Despite increasing resection rates, only about 20% can be operated on with curative intent. A differential histopathological analysis of the resected tumors may help to justify expanding the surgical procedure by extended lymph-node dissection. PATIENTS/METHODS: Between January 1986 and December 1995, a total of 113 patients underwent resection with curative intent for a ductal pancreatic carcinoma with regional lymph-node dissection. All histological findings were reviewed and reclassified in accordance with the 1997 Union Internationale Contra la Cancrum (UICC) classification. Survival data for all of these patients were obtained from family doctors and registration offices. Independent prognostic factors were statistically analyzed. RESULTS: Of the 113 patients, 93 received an R0 resection. The postoperative mortality rate was 2.2% (2 of 93). More than one-half of the tumors had a diameter of between 2.1 cm and 4 cm. Among the 22 tumors measuring up to 2 cm in diameter, 41% already had lymph-node metastasis and 86% invasion of the lymphatic vessels. Carcinomas measuring between 4.1 cm and 6 cm were all associated with lymph-vessel invasion. Perineural invasion was present in 50% of the tumors. A noteworthy finding was the fact that 64% of the 25 tumors with negative lymph nodes had lymph-vessel invasion, and 48% perineural invasion. The cumulative 5-year survival rate of the R0-resected patients was 10. 5%. Patients with lymph-node-negative stages survived significantly longer (26.5%) than patients with lymph-node-positive stages (5%). Furthermore, a significant difference was seen between pN1a and pN1b (16.7% vs 2.2%). Multivariate analysis identified tumor grading, tumor size and lymph vessel invasion as independent prognostic factors. CONCLUSIONS: Apart from the factors tumor size and tumor grading, lymph-vessel invasion appears to be of special significance for the long-term prognosis. Already in the pN0 stage, the latter was present in 64% of the cases and must be considered a precursor of lymphogenic metastasization. Since lymph-vessel invasion was demonstrated in 86% of tumors measuring less than 2 cm, the therapeutic consequence for all ductal pancreatic tumors is an extended lymphatic and soft tissue dissection that goes beyond the regional lymph-node stations.

Aged↗

Pathomorphological and histological prognostic factors in curatively resected ductal adenocarcinoma of the pancreas.

The fate of patients with potentially resectable carcinomas is not only determined by the pTNM tumor stage, but also possibly by tumor-biological factors. The aim of this study was to identify these prognostic factors in patients undergoing primary curative (R0) resection. The study retrospectively analyzed 113 patients with ductal adenocarcinoma who were operated on between 1986 and 1995. R0 resection was able to be performed in 93 patients. Lymph node metastases were found in 73%. The rates of lymph vessel and perineural invasion were 83.5% and 45%, respectively. Among the 25 carcinomas without lymph node metastases, 64% already had lymph vessel invasion and 48% had perineural invasion. The cumulative 5-year survival rate of the 91 surviving patients analyzed was 10.5%. Depending on the tumor stage we found a significant difference in 5-year survival rates between patients without lymph node metastases (26.5%) and those with lymph node involvement (5%) (P = 0.008). A multivariate analysis only identified lymph vessel invasion (L0/1), tumor size (< or = or < or =2 cm), and tumor grading (G) to have significant and independent prognostic value. Lymph vessel invasion, tumor size, and tumor grading proved to be independent factors determining long-term prognosis.

Adenocarcinoma↗

[Is resection of left-sided ductal pancreatic carcinoma of value?]].

UNLABELLED: The ductal adenocarcinoma of the left part of the pancreas is concerned to be incurable. With the aid of the own patient material and the data from the literature an analysis was made to find out whether this negative prognostic assessment can be accepted. METHODS: The findings of 60 patients with tumors in the corpus/cauda region of the pancreas served as a basis for the investigation (observation time: 1986-1998). The resected tumors were reclassified according to the UICC from 1997. The survival rates were calculated with the method of Kaplan-Meier. RESULTS: Only 12 (20%) of the 60 tumors were resectable, in 6 cases only by multivisceral resection. A R0-resection was possible in 8 cases. 11 of these 12 patients had already a lymph vessel invasion (L1) and 50% an involvement of lymph nodes (pN1). After curative resection the median survival time was 17 months, after palliative resection 4 months and in cases with inoperability only 3.6 months. The survival time is identical with the results after operative treatment of carcinomas of the pancreatic head. CONCLUSIONS: Stage related the prognosis of the left sided pancreatic carcinoma is comparable with the results after similar therapy of the pancreatic head carcinoma. Therefore therapeutic nihilism is not indicated.

Adenocarcinoma↗

Two cDNAs representing alleles of the nitrate reductase gene of potato (Solanum tuberosum L. cv. Desirée): sequence analysis, genomic organization and expression.

Two, different, full-length cDNAs, StNR2 and StNR3, of 3049 and 3066 nucleotides, respectively, were isolated from a Solanum tuberosum L. cv. Desirée leaf cDNA library by an RT-PCR approach. Conceptual translation of the longest open reading frame of each cDNA showed that they could encode a protein of 911 amino acids in each case with an M(r) of 102.6 and 102.5 kDa, respectively, and with 99.7% identity with each other. The cDNAs have a high degree of sequence similarity with all higher plant nitrate reductases (NRs) and possess structural characteristics expected of NADH-NR proteins, consistent with enzyme activity data. Southern analysis of genomic DNA suggested the presence of a single NR gene in the potato genome whilst studies using the mapping population F1840, and the full-length StNR2 cDNA as hybridization probe, identified a single NR locus within the potato genome that is located on chromosome XI. The two cDNAs identified here are probably derived from two transcribing alleles of this single gene. Distribution of total NR transcript and of NADH-NR activity, in different organs of compost-grown plants, depended on the level of nitrate supplied: at low nitrate level transcript and activity were detected only in leaf and stem tissue whilst at high nitrate level they could also be detected in root and stolon. An RT-PCR approach was used to differentiate between the transcripts derived from the two identified alleles and to show that the pattern of transcription of the two identified alleles of the potato nia gene, in the organs studied, is the same.

Amino Acid Sequence↗

Recessive and dominant genes interfere with the vascular transport of Potato virus A in diploid potatoes.

Resistance to Potato virus A (PVA) was examined in a diploid cross involving Solanum tuberosum subsp. andigena as a resistance source. Hypersensitive resistance (HR) to PVA cosegregated with extreme resistance (ER) to Potato virus Y conferred by the dominant gene Ry(adg) on chromosome XI. Hence, HR to PVA was controlled by a novel, dominant resistance gene closely linked to Ry(adg), or Ry(adg) recognized both viruses but conferred a different type of resistance to each virus. The HR prevented systemic infection with PVA following mechanical inoculation but not following graft inoculation. Another, recessive gene, ra, that may be linked or even allelic with Ry(adg) fully blocked vascular transport of PVA in graft-inoculated plants. Hence, a possibility exists that the genes for the three types of resistance to potyviruses may reside at the same, resistance gene-rich chromosome region syntenic in solanaceous species and might be related. The gene ra acted against all of the three PVA strains tested and, therefore, the avirulence determinants could not be mapped. However, also, PVA strain-specific resistance was found in the progeny. It was overcome by mutations introduced into the viral genome-linked protein and the helper component proteinase and/or the coat protein.

Biological Transport↗

Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals.

Recently, different research groups reported conflicting results with regard to an association of dopamine 4 receptor (DRD4) genotypes and the personality dimension of novelty seeking (NS). High scores for NS seemed to be associated with long alleles of a DRD4 polymorphism. Furthermore, an association between personality traits and the dopamine 2 (DRD2) receptor gene was reported. NS and persistence (PS) high scores seemed to be associated with alleles of DRD2. We examined 109 (78 female and 31 male) normal healthy individuals using Cloninger's Temperament and Character Inventory (TCI) in order to replicate these findings. We genotyped a 48 base pair variable number of tandem repeats (from two to eight repeats) polymorphism in the third exon of DRD4 and a Cys311Ser polymorphism in exon 7 of DRD2. We tested alleles and genotypes of DRD4 (allele 7 absent or present; genotype 4,4 versus 4,7), and Ser/Cys and Cys/Cys genotypes of DRD2 for associations with TCI values. NS and the alleles and genotypes of DRD4 did not show any association. In associating the genotypes of DRD2 with TCI scales (NS, harm avoidance, reward dependence and PS), we also found no association. Recent findings associating NS with DRD4 could not be replicated. With regard to DRD2, we tested a different polymorphism as published recently and could not find an association of TCI scales with the gene. The present results therefore do not provide evidence that the DRD2 and DRD4 receptor genes contribute a common and relevant effect to personality traits.

Adult↗

SUT2, a putative sucrose sensor in sieve elements.

In leaves, sucrose uptake kinetics involve high- and low-affinity components. A family of low- and high-affinity sucrose transporters (SUT) was identified. SUT1 serves as a high-affinity transporter essential for phloem loading and long-distance transport in solanaceous species. SUT4 is a low-affinity transporter with an expression pattern overlapping that of SUT1. Both SUT1 and SUT4 localize to enucleate sieve elements of tomato. New sucrose transporter-like proteins, named SUT2, from tomato and Arabidopsis contain extended cytoplasmic domains, thus structurally resembling the yeast sugar sensors SNF3 and RGT2. Features common to these sensors are low codon bias, environment of the start codon, low expression, and lack of detectable transport activity. In contrast to LeSUT1, which is induced during the sink-to-source transition of leaves, SUT2 is more highly expressed in sink than in source leaves and is inducible by sucrose. LeSUT2 protein colocalizes with the low- and high-affinity sucrose transporters in sieve elements of tomato petioles, indicating that multiple SUT mRNAs or proteins travel from companion cells to enucleate sieve elements. The SUT2 gene maps on chromosome V of potato and is linked to a major quantitative trait locus for tuber starch content and yield. Thus, the putative sugar sensor identified colocalizes with two other sucrose transporters, differs from them in kinetic properties, and potentially regulates the relative activity of low- and high-affinity sucrose transport into sieve elements.

Amino Acid Sequence↗

Genome scan for susceptibility loci for schizophrenia.

OBJECTIVE: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHODS: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. CONCLUSIONS: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Adult↗

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Adult↗

Development of SCAR markers to the PVY resistance gene Ryadg based on a common feature of plant disease resistance genes.

Sequence-characterized amplified regions (SCARs) were developed, based on nucleotide differences within resistance gene-like fragments isolated from a potato plant carrying the Ryadg gene, which confers extreme resistance to potato Y potyvirus (PVY). It originates from Solanum tuberosum subsp. andigena, and a susceptible potato plant. SCARs were tested using 103 potato breeding lines and cultivars with diverse genetic backgrounds derived from Europe, North America, and Japan. Two markers showed high accuracy for detection of the Ryadg gene. The SCAR marker RYSC3 was generated only in genotypes carrying Ryadg. The SCAR marker RYSC4 was detected in all genotypes carrying Ryadg but also in four PVY-susceptible genotypes. Neither marker was detected in genotypes carrying other Ry genes originating from different species than S. tuberosum subsp. andigena. Therefore, these SCAR markers should be powerful tools in marker-assisted selection for Ryadg in potato breeding programs, and should also be useful for cloning of the Ryadg gene.

Breeding↗

Anoxic decrease in potassium outward currents of hippocampal cultured neurons in absence and presence of dithionite.

The effect of brief anoxia on voltage dependent K(+)-currents of hippocampal cultured neurons was studied. The oxygen scavenger dithionite (hydrosulphite) was previously used for creating zero oxygen pressure. However, dithionite consumes O(2) in parallel with generation of superoxide radicals and is a strongly reducing agent. In this study anoxia was produced by perfusion of the neurons with a solution bubbled with nitrogen for 1 h using a chamber with an argon layer isolating the anoxic bath flow from atmospheric oxygen in presence and absence of dithionite. Oxygen partial pressure of dithionite-free solution was determined by oxygen dependent quenching of the phosphorescence of Pd-coproporphyrin to be 0.15+/-0. 02 Torr (values are given as mean+/-S.D., n=6). Slow (I(K))- and fast (I(A))-inactivating K(+)-currents were measured with the patch clamp technique in the whole cell configuration. Exposure of the neurons to anoxia reversibly decreased the amplitude of I(K) at a test pulse of 0 mV to 77+/-12% (n=7) in absence and to 83+/-7% (n=6) in presence of 2 mM dithionite; the amplitude of I(A) decreased to 78+/-11% in absence and to 82+/-9% in presence of 2 mM dithionite. Voltage dependence of activation and inactivation shifted 5 min after exposure to anoxia reversibly by about 6 mV in depolarizing direction. The decay times of inactivation were insensitive to anoxia. Dithionite had no significant effects on K(+)-currents. In 15 of 21 neurons not employed for analysis on K(+)-currents, a reversible increase in holding current under dithionite was observed. In absence of dithionite in 4 of 19 neurons the holding current reversibly increased during anoxia. Although dithionite does not affect K(+)-currents, changes in holding current show that the dithionite may affect neurons independently of oxygen deprivation.

Animals↗

Cystic neoplasms of the pancreas--cystadenomas and cystadenocarcinomas.

INTRODUCTION: Among the rare cystic pancreatic tumors, serous and mucinous cystadenoma and mucinous cystadenocarcinoma are most often diagnosed. CASE: We report on a total of 21 patients with cystic neoplasms who underwent surgery, 11 of whom had mucinous cystadenocarcinoma. Of the 10 remaining patients, serous and mucinous cystadenoma were diagnosed in two groups of five. A common feature of all cystic neoplasms is slow growth, leading to clinical symptoms at an advanced stage, with tumors frequently becoming enormous. RESULTS: In approximately half of the cases, diagnosis was possible by means of ultrasound, computed tomography and, in three instances, by preoperative percutaneous aspiration. Differential diagnosis of pseudocysts proved to be most difficult. CONCLUSION: Given the low operative risk, resection should always be performed in instances where findings cannot be clearly identified. Moreover, compared with ductal pancreatic carcinomas, the prognosis of a cystadenocarcinoma after early resection is extremely favorable, so that postponing resection might reduce the patient's prospects of being cured.

Adult↗

Multivisceral resection of advanced colorectal carcinoma.

BACKGROUND AND AIMS: In about 10% of patients with carcinoma of the colorectum, the tumour has already invaded contiguous organs or else inflammatory tumorous adhesions involving neighbouring structures are found. In such a situation, the question arises whether one should perform a multivisceral resection, the usefulness of which in terms of surgical risk and late oncological results have been investigated in the present study. PATIENTS AND METHODS: A total of 173 patients with colorectal carcinoma who underwent a multivisceral resection during the period between 1984 and 1995 are reported. Excluded from the study were patients with recurrent tumour or distant metastases. RESULTS: In the majority of cases (63%), the primary tumour originated in the sigmoid colon or rectum. In 102 patients, only a single neighbouring organ was additionally involved, while the remaining patients had involvement of two or more contiguous organs. In 140 patients, the resection was curative, while in the remaining patients an R1/2 situation presented. In the curative group, tumour infiltration was confirmed histologically in 55% of the cases, while in the remaining patients a peritumourous adhesion had mimicked tumour invasion. Postoperative surgical complications occurred in only 1.4% of the interventions, a figure identical to the incidence of complications seen with conventional limited operations. The same applied to the postoperative 30-day mortality rate of 3.6%. The 5-year survival rate of the overall group of patients undergoing multivisceral resection was 42%, that of the subgroup undergoing curative surgery was 51%, and that of the subgroup receiving only palliative resection was 0%. Calculation of the stage-related 5-year survival rates for Union Internationale Contra la Cancrum stage-II and stage-III tumours revealed figures of 58% and 43%, respectively. After non-extended resection, the respective survival rates were identical (60% and 41%). CONCLUSION: An identical surgical risk and survival rates for curative resection, equally as good as those seen with conventional, non-extended procedures, justify the liberal use of multivisceral resection in the surgical treatment of colorectal carcinomas directly invading neighbouring organs.

Abdominal Muscles↗