Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.

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Resumen Entre 33 individuos con tumores pancréaticos endocrinos como componente del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1), 19 pacientes (58%) tenían hipergastrinemia, 7 (21%) hiperinsulinismo y 7 (21%) lesiones clínicas no funcionantes. En la totalidad de los pacientes sometidos a cirugía pancreática fue hallado por lo menos un tumor, incluso en aquellos con examenes de localización negativos anteriores a la operación. Estos pacientes también albergaban tumores macroscópicos, así como numerosos microadenomas; con frecuencia las lesiones demostraron inmunocoloración con diferentes hormonas, principalmente polipéptido, insulina, glucagón y somatostatina. Se encontraron lesiones endocrinas duodenales en 4 de cada 5 pacientes investigados, las cuales colorearon con gastrina y anticuerpos a la somatostatina. Se practicó resección pancreática distal (principalmente resección subtotal) en 18 pacientes, eventualmente combinada con enucleación del tumor (cuando éste se hallaba ubicado en la cabeza del páncreas) o duodenectomía; solamente unos pocos pacientes fueron sometidos a simple enucleación del tumor o al procedimiento de Whipple. El resultado a largo plazo fue más favorable en los pacientes con hiperinsulinismo, puesto que sólo uno presentó recurrencia clínica. Los pacientes con hipergastrinemia exhibieron apenas una disminución transitoria de los valores de gastrina sérica luego de la cirugía pancreática. Cuarenta y siete por ciento del conjunto tuvo o desarrolló metástasis, en tanto que la extensión local del tumor se presentó en 57% de los casos con lesiones no funcionantes. Nueve pacientes murieron por progresión de la neoplasia en el curso del seguimiento. En acuerdo con sugerencias previas, se considero quo la cirugía está indicada en pacientes con NEM-1 e hiperinsulinismo, aún en los casos en que no se visualiza radiológicamente la lesión, pero que la indicación puede ser ampliada para incluir también pacientes con sólo marcadores bioquímicos, tales como niveles elevados de gastrina, indicativos de la presencia de tumores macroscópicos. Esta estrategia debe ser aplicada principalmente en aquellos pacientes con historia familiar agresiva, con lo cual tal vez se reduce el riesgo de progesión maligna del tumor.

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Résumé Parmi 33 patients ayant une tumeur pancréatique endocrine due à une néoplasie endocrine multiple de type 1 (MEN-1), 19 (58%) avaient une hypergastrinémie, 7 (21%) un hyperinsulinisme et 7 (21%) une lésion cliniquement muette. On a mis en évidence au minimum une grosse tumeur chez tous les patients, y compris chez ceux dont les examens préopératoires de dépistage tumoral étaient négatifs. Les patients étaient également porteurs de tumeurs macroscopiques et de nombreux microadénomes. Les lésions montraient souvent un immunomarquage positif pour de multiples hormones, principalement le polypeptide pancréatique, l'insuline, le glucagon et la somatostatine. Des lésions endocrines duodénales furent retrouvées chez 4 des 5 patients explorés; elles montraient un immunomarquage avec les anticorps angigastrine et anti-somatostatine. Une résection pancréatique distale, le plus souvent subtotale, a été réalisée chez 18 patients. Elle était éventuellement complétée par une énucléation tmorale de la tête ou par une duodénotomie. Peu de patients ont bénéficié d'une simple énucléation ou d'une intervention de Whipple. L'évolution postopératoire à long terme a été plus favorable en cas d'insulinome puisque seul un patient a eu une récidive clinique. Les patients atteints de gastrinome n'ont présenté que transitoirement une diminution des taux sériques de gastrine après la chirurgie pancréatique. Quarante sept pour cent de ces patients avaient ou ont développé des métastases contre 57% des patients porteurs de lésions sans traduction clinique. Neuf patients sont décédés en raison de l'extension tumorale au cours du suivi. Conformément à des suggestions antérieures, la chirurgie semble indiquée chez les patients atteints de MEN-1 avec hyperinsulinisme même si la radiologie ne visualise pas de lésion. Mais cette indication peut être élargie aux patients dont seuls les paramètres biologiques sont en faveur d'une grosse tumeur (dont l'hypergastrinémie). Cette stratégie pourrait convenir particulièrement aux patients ayant des antécédents familiaux importants; elle permettrait peut-être de réduire le risque d'extension tumorale.

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

Pancreatic head well-differentiated endocrine tumor

The authors report a case of a small pancreatic head well-differentiated endocrine tumor. A 44-year-old woman was revealed to have a large cystic tumor in the pancreatic head area. Resection revealed a well-differentiated endocrine tumor 7 mm in diameter confined to the pancreatic head and obstructing the proximal portion of the pancreatic duct, resulting in cystic dilatation of the duct, mimicking a cystic tumor of the pancreatic head.     

Pancreatic cystic tumors

Cystic tumors of the pancreas are less frequent than other tumors in neoplastic pancreatic pathology, but in recent years the literature has reported an increasing number. After the first report by Becourt in 1830, cystic tumors were classified into 2 different types by Compagno and Oertel in 1978: benign tumors with glycogen-rich cells and mucinous cystic neoplasms with overt and latent malignancy. The WHO classification of exocrine tumors of the pancreas, published in 1996, is based on the histopathological features of the epithelial wall, which are the main factor in differential diagnosis with cystic lesions of the pancreas. Thanks to the knowledge acquired up to now, a surgical procedure is not always required because the therapeutic choice is conditioned by the correct classification of this heterogeneous group of tumors. Clinical signs are not really useful in the clinical work up, most patients have no symptoms and when clinical signs are present, they may help us to pinpoint the organ of origin but never to identify the type of pathology. In the last few years, the great improvement in imaging has enabled us not only to discriminate cystic from solid lesions, but also to identify the features of the lesions and label them preoperatively. More invasive diagnostic procedures such as fine needle aspiration and intracystic fluid tumor marker level are not really useful because they are not sensitive and the cystic wall can show different degrees of dysplasia and de-epithelialization. These are the reasons for sending the entire specimen to pathology. Good cooperation between surgeons, pathologists, radiologists and gastroenterologists is mandatory to increase the chances of making a proper diagnosis. Therefore, we must analyze all the information we have, such as age, sex, clinical history, location of the tumor and radiological features, in order to avoid the mistake of treating a cystic neoplasm as a benign lesion or as a pseudocyst, as described in the literature. Except for inoperable cases due to the critical condition of the patient or non-resectable lesions, surgical treatment differs with the diagnosis. Cystic tumors of the pancreas, therefore, are a heterogeneous group of tumors, with a real problem regarding differential diagnosis between neoplastic and inflammatory lesions. Even with a proper work up, some perplexity may remain about the nature of the lesion and in these cases the surgical procedure has a therapeutic value as well as playing a diagnostic role. The role of surgery is central in the treatment of these tumors because it could be curative when complete resection is possible. In this way, the lack of good therapeutic results with chemotherapy and radiotherapy force the surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms represent a new and, from the epidemiological point of view, important chapter in the world of cystic tumors. The margin of resection is important and the surgeon has to be aware that in order to have a curative resection, total pancreatectomy is sometimes required. In the last few years the therapeutic approach has changed thanks to new knowledge of the biological behavior of these tumors. In fact, from a surgical approach in all cases, we are now discussing the possibility of a follow-up not only for asymptomatic serous cystadenomas but also for the little branch side intraductal papillary mucinous neoplasms (IPMNs) in critical patients. A follow-up could be planned even for solid pseudopapillary tumors but it seems risky to leave untreated big tumors in young patients without a certain diagnosis and with so few studies reported in the literature.     

Pancreatic islet cell tumors

Tumors arising from the pancreatic islet cells represent a heterogeneous group of lesions. Some tumors present with well-characterized syndromes, while others appear to be nonfunctioning. Eighty-four patients with pancreatic islet cell tumors operated on at the Cleveland Clinic during a 35-year period were reviewed. The tumor types include 21 nonfunctioning tumors, 41 insulinomas, 16 gastrinomas, two vasoactive intestinal polypeptide (VIP)-omas, two carcinoids, and two probable cases of pancreatic parathyrinoma. Eleven patients had multiple endocrine neoplasia type I syndrome. Preoperative localization was possible in 63% of patients in whom it was attempted. Complete mobilization of the head and distal pancreas with bimanual palpation of the entire gland is critical for intraoperative tumor localization. Distal pancreatectomy is favored for tumors in the body and tail. In the head of the pancreas, small, benign lesions require enucleation, and large or malignant lesions necessitate a Whipple procedure. The operative morbidity rate was 24%, and the mortality rate was 3.6%. The 10-year survival rate was 54.7% for nonfunctioning lesions, 68.4% for gastrinomas, and 92.4% for insulinomas. At this time surgery represents the only way to cure these lesions.     

Management of duodenal-pancreatic endocrine tumors

Endocrine tumors of pancreas and duodenum have a common diagnostic and therapeutic approach. Surgery has a key role to play in the management of patients with such tumors. According to a particular patient, this role is to get under control a secretory syndrome which is refractory to medical therapy, to eradicate a malignant or a premalignant tumor, to produce cytoreduction by debulking, or to palliate complications due to massive regional extension of a malignant tumor.     

胰腺内分泌肿瘤的外科治疗

目的:探讨胰腺内分泌肿瘤的临床特点和外科治疗方法。
方法:对收治的胰腺内分泌肿瘤33例患者的临床资料进行回顾性。
结果:33例中胰岛素瘤18例,无功能性胰岛细胞瘤9例,胃泌素瘤4例,胰高血糖素瘤2例。其中29例进行根治行切除,4例因肿瘤无法切除而放弃手术,总手术切除率为87.8%,术后发生胰瘘5例,肠梗阻2例,无住院期间死亡病例。26例平均随访时间为（4.7±3.5）年（9个月至14年）,其中恶性14例患者总的1年和3年生存率为71.4%和50.0%,在随访期间19例良性患者全部存活。
结论:手术切除是胰腺内分泌肿瘤最为理想的治疗方法。术前定性及术中定位尤为重要,术中胰腺探查结合术中B超是定位的关键。选择合适的术式有助于避免术后并发症的发生。

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胰腺神经内分泌肿瘤的MSCT表现

目的探讨胰腺神经内分泌肿瘤的多层螺旋CT（MSCT）表现特点。方法回顾性分析13例经手术病理证实的胰腺神经内分泌肿瘤的cT表现。男7例,女6例,平均年龄49．2岁,均行cT平扫加增强扫描。结果13例中,胰岛素瘤5例,胃泌素瘤2例,非功能性神经内分泌肿瘤6例。13例患者共发现15个病灶,胰头占3／15、胰颈占1／15、胰体占3／15、胰尾占8／15。CT平扫呈等密度5个,低密度10个,其中混杂密度占6／15。平扫7个病灶局部突出或隆起于胰腺轮廓外。增强扫描动脉期明显强化8个,中度强化5个,轻度强化2个;胰腺期7个病灶强化程度同动脉期。结论胰腺神经内分泌肿瘤的CT表现具有一定的特征,结合临床资料,做出术前诊断可能性较大。     

Anatomic distribution of pancreatic endocrine tumors

Pancreatic endocrine tumors are grouped together by their common histologic, cytochemical, and ultrastructural features. Although useful conceptually, this paradigm has been unable to predict the anatomic location of different tumor types. Successful surgical excision of these tumors would be facilitated by an improved understanding of their anatomic distribution. Based on the available data, a bimodal distribution of pancreatic endocrine tumors was identified. Cluster 1 (gastrinomas, pancreatic polypeptide (PP)-secreting tumors, somatostatinomas) had 75% of tumors to the right of the superior mesenteric artery, whereas cluster 2 (insulinoma, glucagonoma) had 75% of tumors to the left of the superior mesenteric artery (p less than 0.05). This distribution is similar to that distribution predicted based on the volume density of the corresponding islet cells for insulinoma, glucagonoma, and PP-secreting tumors, but not for somatostatinoma. These findings suggest that pancreatic endocrine tumors are derived from similar cytologic precursors as pancreatic islet cells, and their distribution may be a consequence of embryologic development from either the ventral (cluster 1) or dorsal (cluster 2) pancreatic buds.