Feshicage The basics of bioventing are presented. Enucleation is the resection method to be chosen whenever this it is technical possible. As monolayer cell cultures have previously been shown to function differently than cells in vivo, the results of such in vitro tests may fisiopatologja accurately reflect cell response in vivo. At night, when ecosystem respiratory fluxes are dominant, 13C-depleted CO2 insuilnoma respired and thereby depletes the atmospheric del 13C-content. Management strategies for organic livestock effluents,innovative treatment and valorization.
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Contributor Information. Joyce J Shin: gro. Abstract Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin and, as a result, patients present with symptoms of hypoglycemia. Fortunately, insulinomas are usually benign and solitary, and surgical cure rates are highly favorable. Most of these tumors occur sporadically, but they can also be associated with multiple endocrine neoplasia type-1 syndrome. The diagnosis is confirmed by a supervised fast, and early detection is important.
Several preoperative and intraoperative techniques with various success rates have been employed in order to localize the lesion. When technically feasible, tumor enucleation is the procedure of choice; however, a more formal resection may be necessary for certain tumors.
In the age of laparoscopy, the role of laparoscopic surgery in the management of insulinomas is continuing to attract attention. This review will discuss the historical background, pathogenesis, diagnosis, localization and management of insulinomas. Keywords: enucleation, insulinoma, laparoscopic, localization, MEN-1 syndrome, metastatic insulinoma Insulinoma is the most common neuroendocrine tumor of the pancreas with an annual incidence of four in every 1 million persons [ 1 ].
Although rare, insulinomas have the potential to produce profound metabolic derangements, necessitating early recognition and treatment.
Generally, insulinomas occur sporadically; however, they can be associated with multiple endocrine neoplasia MEN -1 syndrome. Once the diagnosis is established, the insulinoma is preoperatively localized by various techniques in order to improve operative success. Owing to the fact that complete surgical excision is the only curative method, accurate preoperative and intraoperative localization of the insulinoma is imperative.
Historical background The pancreatic islet cells were first described by Paul Langerhans in , while still a medical student [ 2 ]. The relationship between hyperinsulinism and a functional pancreatic islet cell tumor was established by William J Mayo, who attempted the first operation for insulinoma in [ 4 ]. Unfortunately, the tumor was malignant and unresectable [ 5 ].
However, 2 years later, Roscoe Graham performed the first surgical cure of an islet cell tumor [ 6 ]. Pathogenesis Insulinomas can occur sporadically or in conjunction with MEN-1 syndrome. It is characterized by parathyroid hyperplasia, anterior pituitary adenomas and tumors of the endocrine pancreas and duodenum. First proposed by Knudson to describe the tumorigenesis of retinoblastomas, the two-hit hypothesis for tumor suppressor genes also applies to MEN-1 syndrome [ 9 ].
In patients affected with MEN-1 syndrome, the presence of MEN1 germline mutations accompanied by loss of heterozygosity at 11q13 is observed [ 10 , 11 ]. This phenomenon has suggested a role of MEN1 as a tumor suppressor gene, requiring inactivation of both alleles for clonal expansion and tumor development [ 10 , 11 ].
In addition, a variety of sporadic endocrine tumors, such as parathyroid adenomas, pancreatic insulinomas and pituitary prolactinomas, have expressed somatic mutations and loss of heterozygosity of the MEN1 alleles, demonstrating that the MEN1 gene may play the same role in nonhereditary endocrine tumors [ 10 — 13 ].
The MEN1 gene consists of ten exons spanning 9 kb of genomic DNA and encodes a amino acid protein product termed menin [ 14 ]. Menin is ubiquitously expressed in both endocrine and nonendocrine tissues and does not display significant homology to any known family of proteins [ 11 , 14 ].
In mouse models, knockout of both Men1 alleles results in embryonic lethality, whereas the heterozygous phenotype of menin inactivation in mice is remarkably similar to that of the human MEN-1 syndrome [ 17 ]. Although the combination of findings from all current research has resulted in a better understanding of menin and its role in the development of the MEN-1 syndrome, the specific mechanisms leading to the endocrine tumorigenesis of MEN-1 syndrome have not been completely elucidated [ 11 , 16 , 17 ].
Owing to these characteristics of MEN-1 syndrome-associated insulinomas, simple enucleation and local resections are less likely to be curative. Subtotal pancreatectomy in addition to enucleation of tumors identified in the head of the pancreas may be required for patients with insulinoma and MEN-1 syndrome [ 18 , 22 , 23 ]. Genetic testing for MEN-1 syndrome can complement the clinical diagnosis and should be offered to patients in whom the diagnosis is being considered.
Other family members at risk can then undergo subsequent analysis by testing selectively for the specific MEN1 mutation of the affected individual [ 26 ]. Inappropriately elevated insulin levels cause symptoms of hypoglycemia that have been classified into two major categories: neurologic neuroglycopenic and adrenergic catecholamine response TABLE 1 [ 23 , 27 , 29 , 30 ].
While symptoms are typically precipitated by fasting or exercise, they can also occur postprandially or can have no relationship to eating [ 23 ]. The most prominent and perhaps most reliable symptoms are those of the neurologic type: diplopia, blurred vision, altered mental status, abnormal behavior, amnesia, coma and seizures [ 5 , 23 , 27 , 29 , 30 ].
Symptoms caused by catecholamine response include sweating, anxiety, palpitations, weakness, tremors, hunger, nausea and feeling of warmth [ 5 , 23 , 27 , 29 , 30 ]. Another notable manifestation of insulinoma is weight gain, as patients may eat frequently to avoid symptoms [ 19 , 23 , 30 ].
Although various combinations of symptoms have been reported, the symptom complex usually follows a stereotypical repeated pattern for each individual [ 5 , 27 ]. Table 1 Features of insulinoma and frequency of clinical symptoms.
Insulinoma: pathophysiology, localization and management