Ganglioneuroblastoma During Pregnancy †Case Report

Ganglioneuroblastoma During Pregnancy – Case Report Rare case of ganglioneuroblastoma during pregnancy – case report Abstract Ganglioneuroblastoma is a very rare tumor, especially in pregnancy. So far the association between this tumor and pregnancy has not been reported. We present a case of ganglioneuroblastoma relapse at a 3rd trimester pregnant woman. Neurological symptoms developed late, increased by the effects of pregnancy on the brain tumor. Therapeutic management in this case represents a medical dilemma regarding mode setting and timing of delivery, taking into account the maternal-fetal risk-benefit. In this case caesarean section under general anesthesia was settled, with the need of postpartum brain tumor excision. Keywords: ganglioneuroblastoma, pregnancy, treatment, caesarean section Introduction Ganglioneuroblastoma is a neuroblastic tumor containing malignant elements characteristic to neuroblastoma and benign elements found in ganglioneurinoma (1). Intracranial tumors are extremely rare in pregnancy (2). By their rarity and their diagnosis in the last trimester of pregnancy, intracranial tumors have an increased risk of maternal and fetal morbidity and mortality. Cranial tumors tend to increase and become symptomatic in the last trimester of pregnancy, the causes not being entirely known. Therefore any woman with an existing neurological condition should consult her obstetrician and her neurologist before she becomes pregnant (3). Management of these cases should evaluate whether the mothers and the fetuss lives are threatened. A multidisciplinary team recommends the optimal timing for the termination of pregnancy, as determined by the fetus maturity and mothers neurological condition (4). The present study reports one case of pregnant women in the third trimester with ganglioneuroblastoma. The patient underwent caesarean section under general anesthesia at 36 weeks gestation with favorable postoperative evolution. So far, there are no well-established protocols regarding the management of intracranial tumors (especially ganglioneuroblastoma) in pregnant women. Case report I.A., 20-year-old woman, G1P1L0, was admitted to our hospital due to weak, irregular uterine contractions in her 36th week of gestation. Patient’s history: in 2005 the patient was diagnosed with right parietal lobe ganglioneuroblastoma. She had undergone surgery followed by radiochemotherapy and anticonvulsive therapy with phenytoin for about one year with favorable outcome. Six years following resection, the patient had no radiologic recurrence. The pregnant woman was taken out by a gynecologist in the first trimester of pregnancy, with the usual analyzes of pregnancy, ultrasound and regular prenatal checkups without objective neurological signs until the 3rd trimester of pregnancy. Therapeutic attitude assumed identification of neurological symptoms in order to determine the optimal treatment, maintaining a low fetal risk and continuing uncomplicated pregnancy until birth. Methods Investigation protocol included routine tests and imaging tests. Neurological examination revealed vestibular syndrome and nystagmus which recommended contrast MRI. MRI conclusions: In the right parietal lobe, postcentral, viewed a well-shaped image of 32mm in diameter, nongadolinium-enhanced, sequel looking. An area of oedema with irregular outline in white matter was surrounding it. In the right temporal lobe, adjacent to the sylvian seizure, in hyposignal T2 image showed a nodular-shaped tumor of about 7mm in diameter with discrete central heterogenity (gadolinium-enhanced). No perilesional oedema. Ventricular system located on the midline. MRI based neurosurgical consultation has determined that the tumor was operable and stated the need of postpartum surgery (excision of the brain tumor). All fetal biometric parameters studied were below the 10th percentile for gestational age, showing a linear decrease with gestation until the end of pregnancy. The difference between menstrual age and gestational age determined by ultrasound was 3 weeks and 3 days. Estimated fetal weight was 2420 g, which placed the infant in the 6th percentile. The amniotic fluid index was 7.5 cm, confirming the diagnosis of IUGR. The patient had received dexamethasone treatment with double purpose: fetal lung maturation and reduced perilesional cerebral oedema in order to decrease focal neurological symptoms. The association between IUGR, repeated variable cardiotocography decelerations and brain tumor recurrence with emphasized neurological symptoms imposed urgent caesarean section. Medical committee composed of obstetrician, anesthesiologist, neurosurgeon and neonatologist decided caesarean section under general anesthesia, which was performed 5 days after the admission of the patient. Results A 20 year-old patient, I.A., known with operated and radiochemotreated ganglioneuroblastoma eight years earliar, with ongoing pregnancy (36 weeks) was admitted to our clinic for weak uterine contractions and associated neurological symptoms (vestibular syndrome, nystagmus, slightly right motor deficit). She followed a protocol of blood tests, imaging and interdisciplinary consultations establishing the diagnosis of brain tumor, possible relapse of old pathology. Fetal biometry measurements and fetal biological parameters objectified the existence of fetal distress risk of premature birth or miscarriage. Those set the need for preoperative corticosteroid therapy (Dexamethasone) for lung maturation and perilesional brain oedema control and emergency caesarean under general anesthesia. Caesarean section was performed 5 days after admission, without early nor late intraoperative and postoperative complications. It resulted an unique live female newborn, weighing 2670g, 9 Apgar, with physiological vital functions, not requiring special follow-up. Recovery of the mother was complication-free with persistent, constant postoperative neurological symptoms. When discharged, the patient was recommended ambulatory neurosurgical exam to establish the opportunity of surgery targeting the brain tumor. Discussions Ganglioneuroblastoma is a tumor of the sympathetic nervous system that arises from primitive sympathogonia and is composed of both mature gangliocytes and immature neuroblasts and has intermediate malignant potential (5). These tumors are rare. They occur in fewer than five out of one million children each year (6). Ganglioneuroblastomas are extremely rare in adults, with only about 50 cases documented in people over the age of 20, and only five cases observed in the adult brain (7). There are no reports of ganglioneuroblastoma presenting during pregnancy in medical literature (8). Objectification of brain tumor by contrast MRI was necessary to establish the subsequent therapeutic management, although in literature there are â€Å"not enough studies to determine the safe use of contrast in pregnancy (9). MRI is probably the imaging diagnostic procedure of choice and should be performed when a brain tumor is suspected (10). Before pregnancy the patient was declared cured, as no clinical nor radiological tumor relapse existed for six years. It is likely that pregnancy-induced changes have a tumorigenic effect, due to several factors such as fluid retention, increased blood volume and hormonal changes (11). Pregnancy is an aggravating factor for brain tumours on which it acts by three mechanisms: acceleration of tumor growth, increase of peritumoral oedema and the immunotolerance to foreign tissue antigens that is proper to pregnancy (12). Normal physiological changes during the pregnancy, such as increased levels of gonadotropins and augmented fluid volume status may accelerate the growth of some types of brain tumors (13). The combination of oligohydramnios and IUGR portends a less favorable outcome, and early delivery should be considered (14). Treatment of brain tumor in pregnancy requires an integrated multidisciplinary approach, which includes neurosurgery, ophthalmology, radiology, obstetrics, neonatal pediatrics (15). Indication for type of delivery is controversial. The best moment to recommend the craniotomy and the neurosurgical removal of the tumor will depend of the mothers neurological condition, the histological tumor type as well as the gestational age. In a study published in 2011, performed on 10 patients with brain tumors diagnosed during pregnancy, prior to craniotomy, five patients had caesarean sections, two others had vaginal deliveries, in three patients the delivery took place after the brain tumor treatment(16). The caesarean section was made under general anesthesia. Studies have shown that general anesthesia remains safe and dependable for operative delivery in parturients with intracranial tumor. Tracheal intubation allows maternal hyperventilation thereby controlling raised intracranial pressure. Hemodynamic stability is readily achieved to maintain cerebral perfusion (17). Conclusions Ganglioneuroblastoma is a rare brain tumor in childhood, and appears exceptionally in pregnant women. Pregnancy and brain tumor have mutual negative effect on the patient. Brain tumors that develop in pregnant women have to be diagnosed and assessed through MRI, although the effect of gadolinium contrast on the pregnancy is yet unknown and needs further medical studies. The order of obstetrical an neurosurgical treatment of pregnant women with brain tumors requires an integrated multidisciplinary approach, including neurosurgery, radiology, obstetrics, neonatal pediatrics which have to assess all maternal-fetal risks and benefits. Lack of brain tumor reccurence 6 years after currative neurosurgical treatment was not enough to establish that the patient was cured. The patient suffered a brain tumor relapse 8 years after brain surgery probably due to metabolic and hormonal changes induced by pregnancy. References 1.Robertson H.E. Das Ganglioneuroblastom ein besonederer Typus im System der Neurome. Virchows Arch [Pathol Anat]. 1915;63: 147-168 2. Pavlidis NA. Coexistence of pregnancy and malignancy. The Oncologist 2002;7: 279-87. 3. Carmel Armon, Stephen A Berman. Neurologic Disease and Pregnancy. Medscape reference; 8 nov 2012 4. Ducray F, Colin P, Cartalat-Carel S, et al. Management of malignant gliomas diagnosed during pregnancy. Rev Neurol (Paris) 2006;162: 322–9. 5. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics 2002; 22: 911-34. 6. Linda J., Vorvick, MD and Yi-Bin Chen, MD. Also reviewed by David Zieve, MD. A.D.A.M. Medical Encyclopedia. Ganglioneuroblastoma; Last reviewed: February 7, 2012. 7. Schipper MH, van Duinen SG, Taphoorn MJ, Kloet A, Walchenbach R, Wiggenraad RG, Vecht CJ. Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands. Cerebral ganglioneuroblastoma of adult onset: two patients and a review of the literature. Clin Neurol Neurosurg. 2012 Jul;114(6):529-34. 8. Manjusha Sanjay Rathi. Ganglioneuroblastoma: First presentation during pregnancy; Program: Abstracts Orals, Featured Poster Presentations, and Posters Monday, June 17, 2013; Kings Mill Hospital, Sutton in Ashfield, United Kingdom 9. Black P, Morokoff A, Zauberman J, Claus E, Carroll R. Meningiomas: science and surgery. Clin Neurosurg. 2007;54:91-9. 10. Awada A, Watson T, Obeid T. Cavernous angioma presenting as pregnancy-related seizures. Epilepsia, 38 (7): 844-6, 1997. 11. Wlody D: Neurosurgery in the pregnant patient. Newfield P, Cottrell J, editors. Philadelphia: WW Lippincott; 1999. 12. Depret-Mosser S, Jomin M, Monnier JC, Vinatier D, Bouthors-Ducloy AS, Christiaens JL, Krivosic-Horber R. Cerebral tumors and pregnancy. Apropos of 8 cases. J Gynecol Obstet Biol Reprod (Paris). 1993; 22(1):71-80. 13. Poisson M, Pertuiset BF, Hauw JJ, Philippon J, Buge A, Moguilewsky M, et al. Steroid hormone receptors in human meningiomas, gliomas and brain metastases. J Neurooncol 1983;1:179-89. 14. Golan A, Lin G, Evron S, Arieli S, Niv D, David MP. Oligohydramnios: maternal complications and fetal outcome in 145 cases. Gynecol Obstet Invest. 1994;37:91–5. 15. Khalil E Rajab, FRCOG, FFFP Nouf Behzad N, MD, Arab Board. Brain Tumor in Pregnancy. Bahrain Medical Bulletin, Vol 35, No 1, March 2013. 16. Lynch JC, Gouvà ªa F, Emmerich JC, Kokinovrachos G, Pereira C, Welling L, Kislanov S. Management strategy for brain tumour diagnosed during pregnancy. Br J Neurosurg. 2011 Apr;25(2):225-30. doi: 10.3109/02688697.2010.508846. Epub 2010 Sep 8. 17. Lily Chang, Lian Looi-Lyons, Lydia Bartosik, Simon Tindal; Anesthesia for cesarean section in two patients with brain tumours. Canadian Journal of Anesthesia. January 1999, Volume 46, Issue 1, pp 61-65 1

From Freedom Of Contract

The modern entrant making process Is often a set of very complex agreements and usually Involves big amounts of money. The negotiations may last for months or even years. As a result, the parties will reach an agreement by piecemeal. There Is not a simple offer and an acceptance anymore, but there are offers, counteroffers, partial discussion. But when exactly the discussion is ended? For this still developing contract formation procedure, in most legal systems there are no special and adequate rules established. Since it is impossible to qualify in these cases offer and acceptance, a whole set of new problems arises: . As the agreement been concluded; 2. When was it concluded; 3. If the agreement is concluded, what are the terms of it. In this paper I will examine and discuss a very controversial topic in the theory of the formation of contracts: the relationship between parties in a situation in which an agreement has not been reached and one of the parties breaks off the negotiati ons. This can be done in several ways: one 2 can Just end the negotiations and walk away, the offered can revoke his offer, an option clause is violated etc.Since there is still no contractual liability in these cases, he question arises if there is any liability at all and if so according to what theory a party is held liable. I will analyses this problem from the point of view of two legal families: Common Law and Civil Law. In the context of this paper by Civil Law I mean the codified law systems in Western Europe and I will discuss French, German and Dutch law. We will see that there are important differences between the Common Law and the Civil Law approach to these problems.As a result of the still growing trade market between the United States and Western Europe it is of utmost importance that one is aware of these differences. I want to discuss three topics: 1 . Cross-boundary pre-contractual negotiations will bring together law and culture and reality and perception and so many problematic situations; I will give you Just some examples to show what I mean; 2. Then I will discuss the different approaches as mentioned above and even more important the different results on what is understand as pre-contractual liability; 3. He last topic will be on recent European developments in contract law in this field as realized in a proposed European Code of Contract Law. 2. Law and culture As I said before, pre-contractual negotiations will not only bring together law and ultra but also reality and perception. So it is quite possible that one party – from his particular background and legal culture – is convinced that after some meetings an agreement is reached, as the opposite party thinks these were still preliminary conversations. When this is the case severe problems will rise and immediately two questions have to be answered: 1 . According to which law the breaking off of the negotiations has to be Judged; 2. And which court has standing. In Co mmon Law countries, as a rule lawyers will take part in the conversation in a very early stage of the negotiations. s true for The Netherlands you from the start of the 3 – it is all a matter of trust. If you take your lawyers with negotiations it means you don't trust the other party so they don't trust you. The result is that you start the negotiations one step behind the other party and that is exactly not what you want.Probably this is also because English and American contracts are much longer than German, French or Dutch contracts. 1 Just one example; contrast these two standard forms of a forum selection clause: ; American clause: The exclusive forum for the resolution of any dispute under or rising out of this agreement shall be the courts of general Jurisdiction of xx and both parties submit to the Jurisdiction of such courts. The parties waive all objections based on forum non convenience; German clause: Cholinesterase Geriatricians sit xx (the only competent court is (P. 96) So when you enter into international contracting your first lessons are: 1 . Be aware of the cultural differences and legal mentality between you and the other party ; 2. Try to reach an agreement on two questions as early in the negotiations as possible: a. Which law has to be applied in case anything goes wrong (express choice of law); b. Which court has standing. A way to realize an answer to these questions in the pre-contractual stage is the use of a so called Letter of Intend or a Memorandum of Agreement.In case anything goes wrong, such a Letter or Memorandum can save a lot of time and money for both parties. According to American case law the answer of the question if the Letter or Memorandum is legally binding depends on the following factors: – The amount of details; – The language used; – Are there any escape-clauses; – Are there ‘subject to formal contract/definitive agreement' clauses; See for a comparison between American an d German contracts: Claire A. Hill and Christopher King, How do German contracts do as much with fewer words? , 79 Chicago-Kent Law Review 2004, p. 889 – 926. – Complexity of the transaction; – The way parties behave in the pre-contractual stage; – Custom. In Civil law similar factors are used. For about seven years I was honorary Judge in the Court of Rotterdam in a division on international contracts. In a surprisingly amount of cases – where contracts were actually formed – there was no provision on an express choice of law and on which court has standing. Making a choice on forehand will save time and money and the allowing factors can be taken into account. In the first place parties create certainty; both parties know what to expect in case anything goes wrong.I will take the English approach as a starting point, because this approach still resembles the classical theory on contract law. (Gigglier 2002, Cheshire and Foot 2001, Allen 19 91) In the case William Lacey (Winslow) Ltd. V. Davis [1957] 1 W. L. R. 932, 934 (Q. B. 1957) the view is expressed that a party to negotiations undertakes this work as a gamble, and its cost is part of the overhead expense of his business which he hopes will be met out of the profits of such contracts as are made. ‘ More recently the leading case on this topic is Wallboard v.Miles [1992] 1 All ERE 453. The question was if the parties can, by agreement, impose on themselves a duty to negotiate in good faith. Lord Cancer held: ‘Each party to the negotiations is entitled to pursue his (or her) own interest, so long as he avoids making misrepresentations. To advance that interest he must be entitled, if he thinks it appropriate, to threaten to withdraw from further negotiation or to withdraw in fact in the hope that the opposite party may seek to reopen negotiations by offering him improved terms.A duty to negotiate in good faith is as unworkable in practice as it is inhere ntly inconsistent with the position of the negotiating party. In spite of this rather rigid and formalistic view English law has taken on this question, there are some grounds to pursue negotiations or to recover damages in case of breaking off the negotiations. 6 Although the main contract has not been concluded, the court may held that there is a collateral contract which gives rise to some rights during the negotiating process.And even though there is no contract, a party may be entitled to restitution relief on the grounds that the other party has derived a benefit from the transaction for which he should compensate the plaintiff even if no contract has arisen (unjust enrichment). Finally a party can be held liable for loss which he inflicted on the other party in case of fraudulent misrepresentation (a claim in tort, e. G. When there was never an intention to form a contract) or negligent misrepresentation. In England one can only claim negative interests.Specific performance à ¢â‚¬â€œ that is to say forcing parties to re-open negotiations – is not possible. 3. 1. 2 AMERICAN LAW (Tanner and Hamilton, paper 2004, Track 1991) Like in English contract theory, it is generally agreed that also in the United States the existence of a duty in good faith is denied in the absence of an enforceable contract. According to American law there are three other grounds for pre-contractual liability. As in England, unjust enrichment as a basis for liability could be a ground for restitution.However, Just a few courts have entertained such claims and the prevailing view is still the alternator theory: both benefit and loss are at risk of the parties. Also the misrepresentation theory is considered to be a ground for recovering losses in the preoccupation stage in the United States, but situations in which this occurs American courts is the doctrine of promissory estoppels: one negotiating party cannot thou liability breach a promise made during negotiations, if the o ther party relied on that promise.

Financial Position of Gap Inc.

The gross margins have also Increased for fiscal 2009 here It was 40. 32 percent as compared to 2008 of 37. 5 percent and 2007 of 36. 1 1 percent. The operating margins also continue to grow for fiscal 2009 Gap had an operating margin on 12. 8 percent as compared to 10. 7 percent from 2008 and 8. 3 percent In 2007. Gap has also been able to grow Its cash not only each year but also 29. 4 percent of Its total assets as compared to 2008 where cash was only at 1. 7 billion and 22. 6 percent of total assets.Gap also has worked to reduce their debt down to ere by 2010 and they have done so, currently they have no long-term debt and 2. 3 billion in cash. The 2009 current ratio for Gap is 2. 19 as compared to 1. 88 in 2008, and 1. 67 in 2007. Gap is increasing their liquidity from year to year while net sales are still decreasing. Gaps merchandise inventory has also seen a decrease not only in value but also as a percentage of total assets 2007 Gap had merchandise inventory valued TTL . 57 billion and that represented 20. Percent. Inventory was 1. 50 billion and represented 19. Percent of total assets in 2008. In 2009 the merchandise inventory was 1. 47 billion and represented 18. 5 percent of total assets. The operating expenses for Gap have maintained constant from 2005-2009 when looking at them as a percentage of sales. The difference in percentage from year to year changed only by a few tenths of percentage. Income from operations however has increased since 2006 where it had fallen 29 percent from 2005.Operating expenses include the following: I payroll and related benefits (for our store operations, field management, striation centers, and corporate functions); I marketing I general and administrative expenses; costs to design and develop our products; I merchandise handling and receiving In dilutions centers and stores; I distribution center general and administrative expenses; I rent, occupancy, depreciation, and amortization for corporate facilities: and othe r expense (income). I gross margins previously stated. Gap had cost of goods sold at 59. 68 percent of sales in 2009 compared to 62. Percent in 2008 and 63. 89 percent in 2007. Gap has been working to drive their costs down and thus far have been successful. Cost of goods sold and occupancy expenses include the following: I the cost of merchandise; I I inventory shortage and valuation adjustments; I I freight charges; I I costs associated with our sourcing operations, including payroll and related benefits;

Sex Minority And Sexual Minority Orientation - 1156 Words

The Williams, Connolly, Pepler, and Craig (2005) study focuses on issues they feel are specific to sexual minority (lesbian, gay, and bisexual) adolescents and those that are questioning their sexuality. Williams et al. questions the way sexual orientation, victimization, psychosocial adjustment, and social support are intertwined in relation to sexual minority youth. They hypothesized that the absence of social support, from both family and friends, along with the experiences relating to being a victim, bring about a sexual minority orientation in adolescents. Additionally, Williams et al. sought to prove that victimizing experiences of sexual minority adolescents mediated the connection between psychological adjustment and social†¦show more content†¦The Williams et al. (2005) study was conducted on students from five high schools in a large south central Canadian city. There were 194 participants in total, of those half of them identified as sexual minority and questionin g adolescents, while the other half were heterosexual. The student’s ages ranged from 14 to 19, with a majority of them being of Euro-Canadian decent with two parent households. This study focused on psychosocial adjustment and social support as their main topics with various subtopics. Psychosocial adjustment included depression, externalizing symptoms, and victimization. More specifically, victimization encompassed bullying, sexual harassment and physical abuse. Lastly, for the social support aspect Williams et al. focused on the adolescent’s relationship with their mother and best friends along with their overall friendships. To conduct their research Williams et al. (2005) used well-known surveys where the students had to rate their responses on a numbered scale. In order to assess the symptoms of depression in the students, Williams et al. used the Beck Depression inventory and they used the Youth Self-Report to assess externalizing symptoms. After giving a very s pecific definition of bullying, students answered how frequently they had been bullied within the past two months. Williams et al. pulled items from the American