Pancreatic endocrine tumors or apudomas.

INTRODUCTION AND OBJECTIVE: pancreatic endocrine tumors (PET) are difficult to diagnose. Their accurate localization using imaging techniques is intended to provide a definite cure. The goal of this retrospective study was to review a PET series from a private institution. PATIENTS AND METHODS: the medical records of 19 patients with PETs were reviewed, including 4 cases of MEN-1, for a period of 17 years (1994-2010). A database was set up with ten parameters: age, sex, symptoms, imaging techniques, size and location in the pancreas, metastasis, surgery, complications, adjuvant therapies, definite diagnosis, and survival or death. RESULTS: a total of 19 cases were analyzed. Mean age at presentation was 51 years (range: 26-67 y) (14 males, 5 females), and tumor size was 5 to 80 mm (X: 20 mm). Metastatic disease was present in 37% (7/19). Most underwent the following imaging techniques: ultrasounds, computed tomography (CT) an magnetic resonance imaging (MRI). Fine needle aspiration punction (FNA) was performed for the primary tumor in 4 cases. Non-functioning: 7 cases (37%), insulinoma: 2 cases [1 with possible multiple endocrine neoplasia (MEN)], Zollinger-Ellison syndrome (ZES) from gastrinoma: 5 (3 with MEN-1), glucagonoma: 2 cases, 2 somatostatinomas; carcinoid: 1 case with carcinoide-like syndrome. Most patients were operated upon: 14/19 (73%). Four (4/14:28%) has postoperative complications following pancreatectomy: pancreatitis, pseudocyst, and abdominal collections. Some patients received chemotherapy (4), somatostatin (3) and interferon (2) before or after surgery. Median follow-up was 48 months. Actuarial survival during the study was 73.6% (14/19). CONCLUSIONS: age was similar to that described in the literature. Males were predominant. Most cases were non-functioning (37%). Most patients underwent surgery (73%) with little morbidity (28%) and an actuarial survival of 73.6% at the time of the study.

Proliferation of antigen MIB-1 in metastatic carcinoid tumours removed at liver transplantation: relevance to prognosis.

BACKGROUND: Metastatic carcinoid tumours are difficult to manage. In spite of a multidisciplinary approach, including orthotopic liver transplantation, the recurrence rate is high with a poor prognosis. Histopathology generally fails to provide prognostic information, hence it is essential to try to identify markers of prognosis in these tumours before considering orthotopic liver transplantation. The MIB-1 antibody, which detects cell proliferative activity, has been shown to be a useful prognostic marker for a variety of neoplasms. AIMS: To assess the value of MIB-1 immunostaining as a prognostic marker of the duration to recurrence and the survival of patients undergoing orthotopic liver transplantation for metastatic carcinoid/neuroendocrine tumours of the liver. METHODS: Fourteen patients were included in the study. Formalin-fixed, paraffin-embedded tissue sections of the tumours were stained with routine haematoxylin and eosin and chromogranin. The cell proliferative activity was assessed by MIB-1 antibody labelling using the immunoperoxidase method. Results were correlated with the time of tumour recurrence and the length of patients' survival after transplantation. RESULTS: No correlation was found between MIB-1 labelling index and age, gender, clinical and histological type of tumour (i.e. carcinoid, APUDOMA, secreting or non-secreting). The patients with higher MIB-1 indices ( 5%) showed a trend toward earlier recurrence and poorer survival than those with low MIB-1 indices ( 5%). The predictive value of a MIB-1 index of 2 indicating patient survival of 24 months was 83% (five out of six patients). CONCLUSIONS: The correlation between MIB-1 index and patients' survival suggests that a high proliferative rate, as assessed by MIB-1 immunostaining, may detect those tumours with more aggressive biological behaviour. Prospective studies on a larger number of patients will be needed to determine if, in any individual tumour, this method will provide an additional parameter for a rational approach to therapy.

Enfermedad endocrino-quirúrgica pancreática en la infancia: presentación de 4 pacientes / Surgical endocrine pancreatic disease in children. Report of 4 cases

Con el objetivo de exponer las experiencias en la enfermedad endocrino-quirúrgica pancreática en la niñez, se presentaron 4 pacientes estudiados en el período comprendido entre 1970 y 1997. Se llegó al diagnóstico de nesidioblastosis en 3 pacientes menores de 1 año y en 1 paciente diabética insulinodependiente de 14 años de edad, una tumoración pancreática compatible con apudoma. Se presentaron con cuadros de hipoglicemia severa, en 3 de ellos con episodios convulsivos. Se logró diagnóstico bioquímico a través de perfil glicémico, valores de insulinemia e índice insulinogénico, con resultados anatomopatológicos e inmunohistoquímico que confirmaron el diagnóstico. Se realizó pancreatectomía subtotal como terapéutica definitiva con resultados favorables en 3 de los pacientes. La hiperglicemia inmediata se presentó como principal complicación en 2 pacientes y 1 muerte por sepsis generalizada. Se concluyó que la patología endocrino-quirúrgica pancreática en la infancia no es frecuente, pero, cuando se presenta se necesita para su atención adecuada la existencia de un equipo multidisciplinario y métodos diagnósticos donde cobra valor el índice insulinogénico y las técnicas de inmunohistoquímica, que ayudan fundamentalmente al diagnóstico de hipoglicemia con hiperinsulinismo

[Apudomas: nosographic and physiopathological aspects]. / Apudomi. Aspetti nosografici e fisiopatologici.

The authors intend to contribute to the knowledge of this complex and in part not fully defined subject of apudomas, in particular with regard to classification criteria and physiopathological aspects. After having examined the characteristics of these neoplasias (probably common embryonal origin, similar radioimmunological, immunohistochemical and ultrastructural characteristics, the capacity to convert amine precursors into amines), the authors focus on the most significant aspect of these carcinoids which, in the light of current knowledge, possess varying but undisputed degrees of biological aggressiveness. They also highlight the importance of the gastroenteric tract as an organ with an endocrine function and lastly affirm the value of the classification which, using the pancreas as the reference organ, distinguishes endocrine neoplasias in this tract into entopic and ectotopic examples.

Apudoma vesical / Bladder apudoma

Se presenta un caso de paraganglioma vesical, un tumor poco frecuente del sistema APUD

Orthotopic liver transplantation in the treatment of metastatic neuroendocrine tumors of the liver.

The place of orthotopic liver transplantation (OLT) in the management of metastatic hepatic neuroendocrine tumors has not been adequately defined. The present report is concerned with patient survival, disease recurrence, and symptom relief in 11 such patients in a single center who, at the time of transplantation, had no extrahepatic tumor. All patients obtained complete symptom relief initially but tumor recurrence was observed in 6 of the 11 cases (5 carcinoid and 1 apudoma) at a median of 11 months (range 3.5-26). Five patients have died, 4 in the carcinoid group with recurrence and one from chronic rejection in the other apudoma group. Of the 6 patients currently alive one of 2 carcinoids and one of 4 other apudomas have tumor recurrence. Recurrent deposits were found predominantly in bone and in the transplanted liver. Actuarial survival post transplant was 82% and 57% at 1 and 5 years respectively. It is concluded that OLT is effective at controlling symptoms from secreting carcinoid deposits in the liver. Although the tumor will recur in most cases, this is not necessarily associated with early return of symptoms. Prolonged disease free survival is more likely in the non carcinoid apudoma group.

Screening and surgical intervention in the multiple endocrine neoplasia patient.

Persons with multiple endocrine neoplasias (MEN) are a unique group of patients that present with various APUDomas. Screening of family members can lead to early detection of these tumors and possible cure of potentially fatal tumors. Screening for the MEN syndromes at present is limited to provocative and biochemical parameters. The gene(s) responsible for these syndromes have not, as of yet, been characterized but in the future will add greatly to the ability to identify these patients early. Early surgical intervention of these APUDomas, has lead to an improved prognosis for these tumors. The screening and the surgical approach to each syndrome are outlined.

Controversies in surgical therapy for APUDomas.

Location of gastrinomas by means of portal venous sampling is a technique in which venous blood from various sites in the portal system around the pancreas and duodenum is obtained and assayed for gastrin levels. A gradient of 50% or greater compared to systemic gastrin levels from a given location regionally identifies the site of gastrin overproduction, thereby locating the tumor. The only area in which venous sampling may help, in the authors' opinion, is in the small subset of patients who have occult gastrinoma not imaged with any other modality, in the body or tail of the pancreas that cannot be found with intraoperative ultrasound or palpation. It is considered that a secretin angiogram is equally effective and is a simpler procedure. Similarly, in insulinoma regional location of the tumor by means of a calcium angiogram has eliminated the usefulness of portal venous sampling. Controversial areas of surgical treatment of APUDomas often reflect a balance between the risks and benefits of aggressive surgery, as data to support an aggressive surgical approach to obtain improved survival often do not exist. For example, if patients with occult MTC can undergo cervical reexploration with minimal or no morbidity the potential benefit of removing malignant disease, warrants this approach. Similarly, if patients with MEN-1 can be explored safely with resection of pancreatic and duodenal tumors, then this position can be defended. On the other hand, if a subgroup of patients with MEN-2 and pheochromocytomas can be spared bilateral adrenalectomy without compromising their long-term outcome in terms of disease-free survival, then this conservative approach is warranted.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical approaches to segment I for malignant tumors (20 cases)]. / Approches chirurgicales du segment I pour tumeurs malignes (20 cas).

Seven complete and 13 partial resections of segment I (caudate lobe) were performed for malignant tumors. In all except one instance, removal of segment I was combined with other types of hepatic resection for technical or carcinologic reasons. Six were iterative hepatic resections for recurrent hepatic metastases. In two, the future remaining left lobe was hypertrophied by right portal venous embolization preoperatively. Hepatectomies were performed with intermittent portal triad clamping (mean total duration of 63 minutes, range of 20 to 120 minutes) and after preparation for total vascular exclusion. Associated partial resection of the inferior vena cava was necessary in three instances. Mean duration of operation was 285 minutes (range of 60 to 540 minutes) and mean blood loss was 1,749 milliliters (range of 200 to 5,200 milliliters). There was no postoperative mortality and the morbidity rate was low. Surprisingly, we discovered retrospectively that free margins were small (less than 5 millimeters) in 83 percent of the patients. Regardless of limited free margins and six iterative hepatectomies, eight patients were free of disease with a mean follow-up examination period of 19.2 months. Technical problems were different for each patient and a patient by patient adaptation was necessary. Left, right and central approaches were used accordingly. If resection of segment I associated with a right of left hepatectomy can currently considered as a standard hepatic resection, isolated complete resection of segment I remains a real technical challenge.

[Cushing syndrome in ACTH-producing neuroendocrine tumor of the hepatic duct]. / Cushing-Syndrom bei ACTH-produzierendem neuroendokrinen Tumor des Ductus hepaticus.

We present a patient with an ACTH producing neuroendocrine tumor of the hepatic bile duct which was detected by chance during abdominal surgery for Cushing's syndrome. Diagnostic strategy and surgical therapy in patients with neuroendocrine tumors are discussed. The diagnostic problems caused by combination with an endocrine function disorder like Cushing's syndrome are pointed out.

[Apudoma: a rare case of the laryngeal tumor]. / W sprawie rzadkiego przypadku guza krtani--apudoma.

The authors present the problem of endocrine function of some neoplasmatic tumors based on their own very rare case of the larynx apudoma. They pay attention to the value of some modern diagnostic methods including radioimmunological determination of the serum peptide hormone levels and some specific immunofluorescence assays with monoclonal antibodies.

[A case of carcinoid tumor of the breast]. / Sluchai s kartsinoiden tumor na mlechnata zhleza.

A rare tumor of the mammary gland, built up of argyrophilic cells, with numerous metastases in the axillary lymph nodes is reported. Histochemical and electron-microscopic studied unequivocally demonstrated that this tumor belonged to the APUD system. The possible histogenesis of carcinoid tumor of the mammary gland is briefly discussed.

APUD update.

Apudomas are a diffuse group of tumors that have interested surgeons for a long time. With recent developments in their radiological localization and pharmacological control, they are now treated in a truly multidisciplinary approach. In this chapter, recent developments in the radiological, surgical, and medical approaches to these tumors are reviewed. Emphasis is placed on how non-surgical developments have affected the surgical treatment of specific apudomas. Resulting changes in surgical philosophy are also reviewed.

Liver transplantation for primary and secondary hepatic apudomas.

Four patients underwent liver transplantation in the Cambridge/King's College Hospital programme for malignant primary and secondary apudomas, secreting various peptide hormones and uncontrollable by standard treatment techniques. After transplantation all patients had excellent symptomatic relief and specific peptide hormone levels fell to normal ranges. Two patients remain alive and well after 38 and 22 months, the latter with recurrence of slight tumour-related symptoms and elevation of the specific secretory product. The other two patients died from chronic graft rejection 7 and 8 months after transplantation.

Tumor carcinoide do torax: conceitos, aspectos clinicos e tratamento / Carcinoid tumor of the thorax: concept, clinical aspects and treatment

Classicamente o grupo de adenomas bronquicos inclui o tumor carcinoide. Atualmente separamos os adenomas bronquicos de origem epitelial do tumor carcinoide que se origina das celulas de Kultschizky. Estas celulas pertencem ao Sistema Endocrino Difuso (Apud Cells). Portanto, o mais correto é classificar os tumores carcinoides como "apudoma" e nao como adenomas bronquicos. Apresentamos neste estudo quatro doentes portadores de tumores carcinoides, tres com localizaçao endobronquica e um mediastinal. Os sintomas mais frequentes foram a tosse, febre e pneumonias de repetiçao. O diagnostico foi firmado pela broncoscopia com biopsia, exceto no caso de o tumor se localizar no mediastino. Nao constatamos morbidade ou mortalidade per ou pos-operatoria. Apesar e ser histologicamente benigno, o tumor carcinoide pode evoluir com comportamento maligno, dando metastases. Em nossa casuistica nenhum teve recidiva da doença num periodo de pelo menos 6 anos, no caso mais antigo

The progressive Zollinger-Ellison syndrome in multiple endocrine neoplasia.

The problem of hypergastrinemia in patients with the syndrome of multiple endocrine neoplasia (MEN type 1) has become increasingly controversial since the introduction of the antisecretory H2 antagonists for the treatment of the Zollinger-Ellison syndrome (ZES). One of the questions in the management of ZES is whether the malignant potential of the gastrinomas or the recurrent complications of ulcer will be the ultimate cause of death. Another problem is whether the association of MEN is a favorable or unfavorable factor to the prognosis of patients with ZES. Hypercalcemia contributes to excessive gastrin secretion, thereby casting doubt on the diagnosis of ZES in the presence of MEN. Patients with MEN are also more likely than patients with ZES not to have gastrinoma on an exploratory laparotomy. The existing controversy concerns the choices of therapy in instances of progressive ZES associated with MEN or when there is a failure to detect a primary gastrinoma when exploration is performed. To highlight the debate, the clinical courses of two patients, observed during two and three decades, respectively, are presented. These patients were receiving high doses of cimetidine; in addition, conventional surgical treatment for ulcer and repeated biopsies for gastrinoma were performed. After total gastrectomies (as life saving procedures), both patients are well.

[A case of malignant pancreatic apudoma producer of serotonin and pancreatic polypeptide]. / Su un caso di apudoma maligno pancreatico a produzione di serotonina e polipeptide pancreatico.

Taking as their starting point the observation of a pancreatic malignant endocrine neoplasm with mixed production of serotonin and pancreatic polypeptide, the authors go on to review the literature on the diagnosis and treatment of pancreatic apudomas. The possibility of performing an extempore intraoperative histological examination makes it possible to obtain a correct diagnosis of endocrine neoplasm and thus to proceed with surgery which could not be contemplated in adenocarcinomatous forms at an equivalent stage. Chemotherapy may then provide additional therapeutic possibilities, using specific markers for malignancies of the APUD system in order to detect possible recurrences.