Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience

Forty-five patients with biochemically documented primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome types 1 or 2 were surgically treated from 1960 through 1980. Hyperplasia occurred in 69% of the patients, single adenoma in 27%, and double adenomas in 4%. All but two patients with hyperplasia underwent subtotal parathyroidectomy. In this group, the cure rate was 93% and the incidence of permanent postoperative hypoparathyroidism 23%. In the adenoma group, treatment included excision of the adenoma and biopsy of at least one other gland. The cure rate was 76%, with no postoperative hypoparathyroidism. Analysis of patients with persistent hyperparathyroidism suggested that failure to recognize multiple gland disease was the principal cause of postoperative hypercalcemia. In view of the high incidence of hypocalcemia after subtotal parathyroidectomy, approximately 500 mg of tissue should be cryopreserved to allow transplantation should hypocalcemia ensue postoperatively.     

Carcinoids associated with multiple endocrine neoplasia syndromes

Carcinoids occur in association with MEN types 1 and 2. To determine the relationship between carcinoids and MEN, we reviewed nine patients with carcinoids and other endocrine tumors. Analyzing these 9 patients and 56 other patients previously described in the literature, we found several clinically important relationships. In contrast to the usual midgut and hindgut origin, most carcinoids associated with MEN (69 percent) are of foregut origin (thymus 24 percent, bronchus 27 percent, stomach 3 percent, and duodenum 14 percent). Carcinoids are more commonly associated with MEN type 1 than MEN type 2 (59 patients and 6 patients, respectively). Thymic carcinoids associated with MEN are more common in men (15 versus 2), and most (82 percent) are malignant. Bronchial carcinoids associated with MEN are more common in women (15 versus 4), and most (74 percent) are benign. There is a strong association between thymic carcinoids and parathyroid tumors and between bronchial carcinoids and pituitary tumors. Most patients with carcinoids and hyperparathyroidism (82 percent) have had parathyroid hyperplasia or multiple parathyroid adenomas. Thus, carcinoids may occur in association with both MEN type I and MEN type II. MEN should be suspected in patients with foregut carcinoids. Patients with MEN and ectopic ACTH production should be considered to have bronchial carcinoids if they are female and thymic carcinoid if they are male. The thymus should be routinely removed in patients with MEN type I because of the possible presence of an ectopic parathyroid gland in this tissue and to prevent subsequent development of a carcinoid tumor.     

Duodenopancreatic resections in patients with multiple endocrine neoplasia type 1

OBJECTIVE: To review the authors' 7-year experience with a surgical approach for pancreatic and duodenal neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN 1) designed to remove all gross tumor with limited complications, preserving pancreatic function. SUMMARY BACKGROUND DATA: MEN 1 is an autosomal dominant familial neoplasia syndrome characterized by the development of NETs of the duodenum and pancreas. Some tumors are clinically insignificant or follow a benign course, although a subset pursues a malignant, lethal natural history; the risk of surgical management must be appropriate to the disease course. METHODS: The clinical, biochemical, genetic, and pathologic data were retrospectively reviewed for 21 consecutive MEN 1 patients undergoing pancreatic resection for NETs between 1993 and 1999 at one institution. Age at operation, presenting symptoms, results of preoperative and intraoperative localization studies, major and minor complications, and pathology, including metastases, were analyzed. RESULTS: The surgical approach was selected based on the location and size of the tumors. Five patients required pancreaticoduodenectomy, 11 patients underwent non-Whipple pancreatic resections, and 5 underwent simple enucleation of benign NETs. The incidence of regional lymph node metastases was 33%. CONCLUSIONS: Major pancreatic procedures can be performed safely in most patients with MEN 1 and NETs. Because NETs are the most common MEN 1-related cause of death in the authors' kindreds, an aggressive surgical approach, including early intervention before malignant spread and major pancreatic resection where indicated, appears justified.     

Gastrointestinal manifestations of multiple endocrine neoplasia type 2

OBJECTIVE: To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. SUMMARY BACKGROUND DATA: The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. METHODS: From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. RESULTS: Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. CONCLUSIONS: Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.     

Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1

Background

Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined.

Methods

A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed.

Results

We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence.

Discussion

Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.     

Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1

OBJECTIVE: To evaluate the outcome of an aggressive surgical approach for duodenopancreatic neuroendocrine tumors (PETs) associated with multiple endocrine neoplasia type 1 (MEN1). SUMMARY BACKGROUND DATA: The management of PETs is still controversial in the setting of the autosomal dominant inherited MEN1 syndrome. METHODS: MEN1 patients that had either biochemical evidence of functioning PETs or visualized nonfunctioning PETs larger than 1 cm in size on imaging were operated. Since 1997, patients were followed annually by biochemical testing and imaging studies. RESULTS: Twenty-six genetically confirmed MEN1 patients underwent duodenopancreatic resection for functioning (n = 17) or nonfunctioning (n = 9) PETs. Ten (38%) patients had malignant PETs as characterized by the presence of lymph node (10 patients) and/or distant metastases (2 patients). The surgical approach was selected based on the type, location, and size of PETs. Four Zollinger-Ellison syndrome (ZES) patients required pylorus preserving pancreaticoduodenectomy (PPPD) as initial or redo procedure, 20 patients underwent other duodenopancreatic resections, and 2 patients had simple enucleations of PETs. After median 83 months (range, 5-241 months), 24 patients were alive and 2 patients died of an unrelated cause. All patients with insulinoma or vipoma and 7 of 11 patients with ZES were biochemically cured, including the ZES patients who underwent PPPD. However, 19 of 26 (73%) patients developed new small PETs (<1 cm) in the pancreatic remnant, but no patient had yet detectable metastases on imaging. CONCLUSIONS: Early and aggressive surgery of PETs in MEN1 patients prevents the development of liver metastases, which are the most life-threatening determinant. PPPD might be the procedure of choice for MEN1-ZES, which has to be proven in large scale studies.     

Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1

HYPOTHESIS: Three-gland parathyroidectomy with trans-cervical thymectomy and cryopreservation is the preferred initial surgical approach for hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with multiple endocrine neoplasia type 1 who underwent 1 or more surgical procedures for HPT from January 1, 1973 to April 30, 2004. RESULTS: At initial parathyroid surgery, 16 (43%) of 37 patients had fewer than 3 parathyroid glands resected (group 1); 16 (43%) had at least 3 but fewer than 4 glands (group 2), and 5 (14%), 4 or more glands (group 3). Follow-up of at least 6 months after initial surgery was complete for 31 (84%) of 37 patients. CONCLUSIONS: Recurrent HPT in patients with multiple endocrine neoplasia type 1 is frequent if fewer than 3 glands are removed at initial parathyroidectomy. Optimal surgical intervention must balance the risk of recurrent hypercalcemia with the morbidity of permanent hypoparathyroidism. Three-gland parathyroidectomy, transcervical thymectomy, and parathyroid cryopreservation constitute our preferred initial surgical procedure.     

Thymic carcinoids in multiple endocrine neoplasia type 1.

OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved.     

Prominent corneal nerves in patients with multiple endocrine neoplasia type 2A: Diagnostic implications

We examined corneal nerves of 22 patients from 10 families with multiple endocrine neoplasia type 2A (MEN-2A). According to the findings in slit-lamp biomicroscopic examination and photographic documentation, the increased visibility of corneal nerves were classified into 5 grades (Grade 0=invisible to Grade 4=as thick as in MEN-2B). All eyes of normal subjects, 19 of 20 eyes of patients with anterior keratoconus, and 11 of 12 eyes of patients with non-hereditary medullary thyroid carcinoma (MTC) were either grade 0 or 1, and the remaining 2 eyes were evaluated as grade 2. Of the 44 eyes of MEN-2A patients, 5 (11.4%) eyes were grade 0, 11 (25%) eyes were grade 1, 19 (43.2%) eyes were grade 2, 8 (18.2%) eyes were grade 3, and 1 (2.3%) eye was grade 4. Thus, more than 60% of eyes of MEN-2A patients showed pathologically thickened corneal nerves of varying degree (grade 2 or higher). There was no definite relationship between the grade of corneal nerve thickening and the patient's age or presence of pheochromocytoma. Differences in the grade of corneal nerve thickening were observed among affected members belonging to the same MEN-2A family, but unaffected members of the family never showed prominent corneal nerves of grade 2 or higher. Our findings suggest that MTC patients with thickened corneal nerves might actually be MEN-2A patients and should be carefully followed for other components of this syndrome.

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Resumen La presencia de nervios corneanos prominentes es un hallazgo constante en casos de neoplasia endocrina múltiple tipo 2B (NEM 2B). Recientemente encontramos un paciente con NEM 2A y nervios corneanos prominentes, lo cual nos indujo a estudiar la incidencia del engrosamiento de los nervios corneanos en los pacientes con NEM 2A. Examinamos los nervios de 22 pacientes provenientes de 10 familias con alto riesgo de NEM 2A. Según los hallazgos en el examen biomicroscópico con la lámpara de hendidura y la documentación fotográfica, la apariencia aumentada de los nervios corneanos fue clasificada en 5 grados (Grado 0=invisibles, Grado 4=tan gruesos como en el NEM 2B). La totalidad de los ojos en los individuos normales, 19 de 20 ojos en pacientes con queratocono anterior y 11 de 12 ojos de pacientes con carcinoma medular no hereditario de la glándula tiroides (CMT) fueron grado 0 o 1, y los 2 ojos restantes fueron clasificados como grado 2. De los 44 ojos de los pacientes con NEM 2A, 5 (11.4%) fueron grado 0, 11 (25%) grado 1, 19 (43.2%) grado 2, 8 (18.2%) grado 3 y 1 (2.3%) grado 4. O sea, que más de 60% de los ojos de los pacientes con NEM 2A demostró engrosamiento patológica de los nervios corneanos de grado variable (Grado 2 o más alto). No se halló relación definitiva entre el grado del engrosamiento y la edad del paciente o la presencia de feocromocitoma. Se observaron diferencias en cuanto al grado de engrosamiento entre los miembros afectados de una misma familia con NEM 2A, pero los miembros no afectados no exhibieron prominencia grado 2 o mayor de los nervios. Nuestros hallazgos sugieren que pacientes con CMT y engrosamiento de los nervios corneanos pueden realmente tener NEM 2A y que deben ser seguidos cuidadosamente para investigar la presencia de otros componentes de este síndrome.

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Résumé Nous avons examiné les nerfs cornéens chez 22 patients issus de 10 familles à haut risque de MEN 2A. Suivant les résultats de l'examen biomicroscopique à la lampe à fente et les clichés photographiques, l'augmentation de la visibilité des nerfs cornéens a été classée en 5 grades (grade 0=invisible, grade 4=aussi épais que lors de la MEN 2B). Les yeux de tous les sujets normaux, 19 sur 20 yeux des patients avec antécédent de kératite et 11 des 12 yeux des patients ayant un carcinome médullaire de la thyroïde non héréditaire (MTC) étaient de grade 0 ou 1 et les 2 yeux restants étaient évalués de grade 2. Sur les 44 yeux des patients atteints de MEN 2A, 5 yeux (11.4%) étaient classés grade 0, 11 yeux (25%) grade 1, 19 yeux (43.2%) grade 2, 8 yeux (18.2%) grade 3 et 1 oeil (2.3%) grade 4. C'est-à-dire que plus de 60% des yeux des patients atteints de MEN 2A présentaient des nerfs cornéens anormalement épaissis à des degrés variables (grade 2 ou plus). Nos résultats suggèrent que les patients atteints de MTC qui présentent un épaississement des nerfs cornéens peuvent être en réalité atteints de MEN 2A et doivent être soigneusement suivis à la recherche d'autres anomalies de ce syndrome.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia type 2A.

OBJECTIVE: To describe our surgical technique for, and results of, subtotal adrenalectomy for phaeochromocytoma in multiple endocrine neoplasia (MEN) type 2. DESIGN: Retrospective study. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 6 patients (four women and 2 men, mean age 35 years, range 31-46) with MEN type 2 who presented between 1993 and 1996. INTERVENTIONS: Cortical sparing adrenalectomy (n =4) together with contralateral total adrenalectomy in bilateral disease (n = 2). MAIN OUTCOME MEASURES: Morbidity, mortality, adrenal function postoperatively, and recurrence. RESULTS: Cortical sparing adrenalectomy leaving adequate adrenal reserve was possible in all cases. There was no operative morbidity or mortality. Mean follow-up was 40 months (range 1347). One patient developed a recurrent phaeochromocytoma 24 months after subtotal adrenalectomy. CONCLUSIONS: Subtotal adrenalectomy with preservation of adequate adrenal cortical reserve was feasible in all cases. Long term follow-up is necessary to establish its definitive place in the treatment of familial phaeochromocytoma.     

Presymptomatic screening for medullary thyroid carcinoma in patients with multiple endocrine neoplasia type 2A

Presymptomatic screening of medullary thyroid carcinoma in MEN IIA families enables the early diagnosis of this tumor with its significant morbidity. Biochemical screening consists of basal and stimulated serum calcitonin evaluation. Genetic screening is based on DNA analysis using linked DNA markers. Thyroidectomy at an occult tumor stage may be curative. Calcitonin measurement was carried out in 58 apparently unaffected family members at risk and 11 MEN IIA patients. Calcitonin elevation was detected in nine individuals. All nine underwent thyroidectomy. Histologic examination confirmed medullary thyroid carcinoma in eight patients and in one case C cell hyperplasia. Postoperatively, eight patients (89%) are clinically and biochemically tumor-free (mean follow-up 30 months). DNA screening results in one affected family are presented. DNA analysis allowed recognition of one apparently unaffected individual at risk as a MEN IIA gene carrier. One family member at risk was found not to carry the gene and may be excluded from further screening.

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Resumen El tamizaje presintomático del carcinoma medular de la glándula tiroides en familias con síndrome NEM 2A hace posible el diagnóstico precoz de este tumor, el cual en forma característica se asocia con significativa morbilidad. El tamizaje bioquímico consiste en la determinación de los niveles calcitonina sérica basal y estimulada. El tamizaje genético se basa en el análisis de ADN utilizando marcadores ligados al ADN. La tiroidectomía que se realiza cuando el tumor es todavía clínicamente oculto puede ser curativa. La determinación de calcitonina fue realizada en 58 familiares aparentemente no afectados pero de reconocido riesgo y en 11 pacientes con síndrome NEN 2A; se detectó calcitonina elevada en 9 individuos, y todos los nueve fueron sometidos a tiroidectomía. El examen histológico confirmó carcinoma medular en 8 e hiperplasia de células C en 1. Postoperatoriamente 8 pacientes (89%) se hallan clínica y bioquimicamente libres de tumor (promedio del seguimiento, 30 meses). Se presentan los resultados del tamizaje de ADN en una familia afectada. El análisis de ADN permitió el reconocimiento de un individuo aparentemente no afectado pero de riesgo como portador del gen NEM 2A. Un familiar con riesgo fue marcado como no portador del gen y puede ser excluído de tamizajes ulteriores.

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Résumé Le dépistage du cancer médullaire de la thyroïde avant l'apparition des symptômes dans les familles MEN 2A facilite le diagnostic de cette maladie accompagnée d'une morbidité non négligeable. Le dépistage biochimique consiste en une évaluation de la calcitonine basale et stimulée. Le dépistage génétique comporte une analyse de l'ADN qui utilise des marqueurs spécifiques des liaisons d'ADN. La thyroïdectomie a des chances d'être curative au stade de tumeur occulte. La calcitonine a pu ètre mesurée chez 58 membres d'une famille atteinte mais sans symptômes et chez 11 patients MEN 2A. La calcitonine était élevée chez 9. Tous ces patients ont eu une thyroïdectomie et un cancer médullaire a été retrouvé chez 8 et une hyperplasie des cellules C chez le neuvième. Postopérativement, 8 patients (89%) sont sans tumeur clinique et biologique (suivi moyen: 30 mois). Les résultats du dépistage par l'ADN chez une famille atteinte sont présentés et a permis d'identifier un seul membre apparemment non symptomatique qui était à risque de porter le gêne MEN 2A. On a déterminé également qu'un membre n'était pas porteur du gêne; il peut être exclu de tout examen de dépistage ultérieur.

     

Simultaneous bilateral laparoscopic adrenalectomy: a surgical option for multiple endocrine neoplasia (MEN 2) patients with bilateral pheochromocytomas

Multiple endocrine neoplasia (MEN 2) is a rare disorder. Of this group, 42% develop a pheochromocytoma of which 60% will have bilateral involvement. Although the benefits of unilateral laparoscopic adrenalectomy have been well documented, fewer cases of simultaneous bilateral laparoscopic adrenalectomy have been reported. We present the cases of three patients with MEN 2 who underwent successful simultaneous bilateral laparoscopic adrenalectomy after their initial presentation with bilateral pheochromocytoma. Although the management of bilateral pheochromocytomas has traditionally been approached via open laparotomy or bilateral posterior incisions, the bilateral laparoscopic approach should be considered a viable alternative for patients requiring surgical intervention. Clinical outcomes and complications are similar to open laparotomy. Simultaneous bilateral laparoscopic adrenalectomy is a safe and effective procedure that results in a more rapid recovery and a shorter hospital stay for patients with bilateral pheochromocytomas originating from MEN 2.     

Laparoscopic surgery in patients with sporadic and multiple insulinomas associated with multiple endocrine neoplasia type 1

There have recently been reports of a limited number of laparoscopic procedures in patients with clinically manifest hyperinsulinism. However, the precise role of laparoscopy remains unknown. Between January 1998 and September 2003, 11 consecutive patients (10 women and 1 man; mean age, 40 years; age range, 22–66 years) with sporadic insulinoma and two female patients (25 and 40 years old) with multiple insulinomas associated with multiple endocrine neoplasia type 1 (MEN-1) were operated on using the laparoscopic approach. Endoscopic ultrasonography was used to localize the tumor preoperatively in 90% of patients with sporadic insulinoma. In patients with MEN-1, computed tomography and octreoscan-111In demonstrated multiple tumors. Laparoscopic ultrasonography (LapUS) was performed in all patients for operative decision-making. Of 11 patients with sporadic insulinoma, laparoscopic enucleation (LapEn) was planned in 8 patients, but in 1 patient, the use of LapUS missed the tumor and the patient was converted to open surgery. Mean operating time after LapEn (seven patients) was 180 minutes, and the mean blood loss was 200 ml. The mean hospital stay was 5 days. In three of the 11 patients, laparoscopic spleen-preserving distal pancreatectomy (LapSPDP) was performed; the mean operative time was 240 minutes, and the mean blood loss was 360 ml. Postoperative complications occurred in three of seven patients after LapEn (three pancreatic fistulas managed conservatively, and one case of bleeding requiring reoperation). LapSPDP was performed in both patients with MEN-1; in one patient with splenic vessel preservation (SVP), the operating time was 210 minutes and blood loss was 650 ml, with a hospital stay of 6 days. In another patient without SVP, the operating time was 150 minutes and blood loss was 300 ml. The latter patient developed a 4-cm splenic infarct managed conservatively, and the hospital stay was 14 days. LapEn and LapSPDP are feasible and safe and achieved cure in patients with sporadic insulinoma and multiple insulinomas associated with MEN-1. However, the risk of pancreatic leakage after LapEn remains high, and LapSPDP without SVP may be associated with splenic infarct.     

多发性内分泌肿瘤2型的诊断和外科处理

目的 探讨多发性内分泌肿瘤2型（multiple endocrine neoplasia,MEN2）的诊断和外科处理方法.方法 回顾性研究1997年6月至2006年6月我院诊断和治疗的MEN2患者28例的临床资料.结果 MEN2a型25例,其中23例分属7个家系,均有RET基因11外显子634编码子突变;MEN2b型3例,无家族史,为RET基因16外显子918编码子突变.MEN2a型中22例有甲状腺肿物伴降钙素升高,其中17例经病理证实为甲状腺髓样癌;12例合并嗜铬细胞瘤,其中5例为多发性,2例恶性;5例合并甲状旁腺功能亢进症,3例无临床症状及生化改变.3例MEN2b型均为甲状腺髓样癌合并黏膜神经瘤病和马凡样体形,其中1例伴双侧肾上腺嗜铬细胞瘤.MEN2a型中12例接受双侧甲状腺全切除＋双侧颈淋巴清扫,5例行甲状腺肿物切除;甲状旁腺病变在甲状腺手术时一并处理;9例接受11次肾上腺肿瘤摘除术,3例为双侧肾上腺手术.3例MEN2b型均行双侧甲状腺全切除＋双侧颈淋巴清扫.结论 MEN2型以甲状腺髓样癌为主要病变,基因筛查可帮助早期诊断.根治性甲状腺切除能预防和治疗甲状腺髓样癌.     

Metastatic pheochromocytoma associated with multiple endocrine neoplasia syndrome type II.

Pheochromocytoma is a rare adrenal medullary tumor of chromaffin cell origin that presents a syndrome of alpha- and beta-adrenergic receptor stimulation due to secretion of epinephrine and norepinephrine. This tumor occurs sporadically in the population and is also associated with multiple endocrine neoplasia syndrome type II (MEN II). Although malignant pheochromocytoma is associated with sporadic tumors, those associated with familial MEN syndromes are rarely malignant. We report a case of a rare metastatic pheochromocytoma in a patient with MEN IIA. Surgical debulking, which has been shown to benefit many patients with metastatic neuroendocrine tumors, was attempted in this patient. Palliation, with symptom relief, was provided. The options for treatment of metastatic pheochromocytoma are discussed.