[Long-term follow-up of patients with suprasellar germinomas]. / Langzeitverlauf bei Patienten mit suprasellären Germinomen.

BACKGROUND: Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes. PATIENTS AND METHODS: The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas. RESULTS: Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case. CONCLUSION: Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Treatment of primary intracranial germ cell tumors: Single center experience with 42 clinically diagnosed cases.

BACKGROUND AND OBJECTIVE: Primary intracranial germ cell tumors (GCTs) are a class of heterogeneous tumors. Surgery can quickly relieve tumor compression and provide histological diagnosis. It is very difficult to treat some patients who are unable to be pathologically diagnosed. We aimed to analyze clinically diagnosed GCTs patients. METHODS: Patients clinically diagnosed as primary intracranial GCTs were included in this study. RESULTS: From 2002 to 2015, 42 patients clinically diagnosed with primary intracranial GCTs received chemotherapy and/or radiotherapy. Patients were assigned to diagnostic chemotherapy group (25 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 85.8%, 75.0% and 63.6%, respectively. There were no statistically significant difference (p value = 0.44). Patients were assigned to the group (30 cases) with secretory tumors and the group (12 cases) with non-secretory tumors based on their levels of tumor makers. The 5- year survival rates were 80.7% and 68.6%, respectively. There were no statistically significant difference (p value = 0.49).The major adverse reactions were grade III - IV bone marrow suppression with an incidence of 35.2% and grade II- III nausea/vomiting with an incidence of 45.8%. CONCLUSION: Surgical removal of tumor or biopsy is recognized as the most accurate method to determine the pathological property of tumor. But for some patients who can not be pathologically diagnosed, they can receive comprehensive treatments such as chemotherapy combined with radiotherapy, and some of them can still have good responses.

[Recurrent operations on the adrenal glands]. / Wiederholungseingriffe an den Nebennieren.

Repeat adrenalectomy may be required due to ipsilateral recurrence of benign or malignant adrenal tumors after previous total or subtotal adrenalectomy. Even for multivisceral resection in patients with adrenocortical carcinoma, complete resection of local recurrent tumor offers results similar to those of primary resection (5-year survival 40-60%). In contrast, since no benefit on long-term survival has been shown so far by tumor debulking, palliative tumor resection should only be performed individually for control of severe endocrine symptoms. The effect of endoscopic adrenalectomy in patients with large tumors (>5 cm) or suspected malignancy has still not been well examined. Further studies are required. In any case, during open or endoscopic approach, tumor spillage must be avoided to prevent local tumor cell implantation. Following subtotal adrenalectomy, the risk of ipsilateral recurrence correlates with disease, follow-up, localization, size of the adrenal remnant, and, in case of familial pheochromocytoma, probably with genotype.

Primary neuroendocrine tumors of the thymus.

Primary neuroendocrine tumors of the thymus are highly aggressive tumors that rarely occur. A little more than 200 cases have been reported, many of which were single case reports. Only a few articles contained modest series from single centers for analysis. A review of 157 cases collected from the major series reported to-date show a clinical pattern with male preponderance (male:female ratio, 3:1) and a mean age of 54 years. Most patients presented with symptoms and signs of local compression. Almost 50% of these tumors were functionally active and were associated with endocrinopathies. Several histologic variants have been described, all with similar ultrastructural features. The biologic behavior of these tumors shows a direct relation to the degree of differentiation. Whenever possible, surgical resection is the treatment of choice as adjuvant therapy is controversial and has been used with variable success. Potential therapies exploit the presence of somatostatin receptors on a variety of these tumors. Use of radiolabeled Octreotide for radionuclide therapy has yielded tumor inhibition in animal models and may have clinical application. Fifty-one percent of the patients survived 3 years, 27% survived 5 years, and less than 10% survived beyond 10 years. Histologic grade, tumor extension, and early detection are the most important factors affecting survival. Other prognostic factors that impact outcome include presence of endocrinopathy, incomplete resectability, nodal status, and presence of distant metastasis.

Results of treatment of pituitary disease in multiple endocrine neoplasia, type I.

OBJECTIVE: The aim of the present study was to examine the clinical and pathological features of pituitary disease in patients with multiple endocrine neoplasia, Type I (MEN I) and to assess the prognosis. METHODS: Fifty-two patients with pituitary disease and MEN I were studied retrospectively. Medical records were reviewed, and all of the patients known to be alive were sent a questionnaire to ascertain current disease status. RESULTS: In 12 patients, pituitary disease was the initial manifestation of MEN I. The most common lesion was prolactinoma, followed, in frequency, by acromegaly and nonsecretory adenoma. Thirty-four of the patients had surgical treatment at the Mayo Clinic, Rochester, MN, as primary treatment, 3 had radiotherapy, and 12 received no specific therapy. Twelve patients had adjunctive radiotherapy postoperatively. Of the 34 patients receiving surgical treatment, 33 had adenoma and 1 had adenoma and pituitary hyperplasia. Immunocytochemical examination demonstrated that many tumors showed reactivity for more than one pituitary hormone. On survival analysis, no excess pituitary-related mortality was found, either in the surgically treated group or in the group as a whole. CONCLUSION: On the basis of this study, we conclude that pituitary disease is frequently the initial manifestation of MEN I; that adenomas, particularly prolactinomas, are the rule and hyperplasia is rare; that a significant proportion of tumors are plurihormonal; and that excess pituitary-related mortality is not a factor in patients with MEN I.

Unusual peptide-secreting tumors in adolescents and children.

Endocrine tumors of the pancreas and intestine are uncommon but challenging lesions. Those tumors that arise in the pancreas are typically derived from one of the various cell types of the islet of Langerhans and secrete the peptide associated with the cell type. In general, the primary tumors are small, relatively slow growing, and many are benign. However, certain tumors are malignant, more aggressive, and metastasize early, such as gastrinomas, glucagonomas, and VIPomas. Many of these tumors can be multicentric, and some may arise in the duodenum of small intestines. Tumors that arise more often in the intestine are carcinoids and VIPomas. The endocrine effects of many of these tumors such as VIPomas or gastrinomas can be life-threatening. A markedly elevated level of a specific peptide will generally be sufficient to establish the diagnosis. Often, the greatest challenge is localizing the tumor(s). The only opportunity for cure is complete surgical excision. Palliation can be accompanied through tumor reduction, surgically of with antineoplastic agents (eg, doxorubicin and 5-fluorouracil). Palliation from symptoms also can be accomplished by blockade of the peptide's secretion of effects. The prognosis is variable and depends on cell type, resectability, and presence of metastases.

Endocrine complications of pediatric brain tumors: case series and literature review.

The survival rate for childhood cancer, including brain tumors, is increasing. As a result, long-term sequelae of chemotherapy and radiotherapy are also increasing. The purpose of this study was to determine the frequency of endocrine complications of therapy for brain tumors in pediatric patients. Endocrinopathy was observed in 19 of 20 (95%) of patients with supratentorial midline tumors. Fifty-seven patients with nonmidline tumors (22 supratentorial, 35 posterior fossa) were followed for a mean of 4.6 +/- 2.4 years. Twenty-two endocrinopathies occurred in 16 patients treated as follows: one of 23 patients (0.4%) had surgery alone, zero of four (0%) had chemotherapy alone, eight of 18 (44%) had radiotherapy alone, and seven of 12 (58%) had both radiotherapy and chemotherapy. Endocrine disturbance was particularly common after craniospinal radiation (10 of 18 [55%]). Growth failure occurred in none of 23 patients who had surgery alone, in one of four patients who had chemotherapy (25%), in 11 of 18 patients who had radiotherapy (61%), in seven of 12 patients who received both radiotherapy and chemotherapy (58%), and in 12 of 18 patients who had craniospinal radiation (67%). In conclusion, endocrine and growth disturbances are uncommon with surgery alone, although they occurred in 53 and 60%, respectively, of patients treated with cranial irradiation for a brain tumor. This finding underscores the importance of routine endocrinology follow-up for all brain tumor patients receiving cranial irradiation. Literature review and endocrine surveillance recommendations are included.

Surgical treatment of pituitary adenomas in elderly patients.

Partly due to increased life expectancy, more and more patients over 60 years of age present with neurosurgical problems. In each case you have to decide to operate a patient or not. Describing the management in pituitary adenomas we conclude that also in elderly people operative therapy via the transsphenoidal approach can be done with a low risk in most cases.

Management of huge pituitary adenomas.

Management of huge pituitary adenoma (more than 5 cm in diameter) is one of the most important issues on the treatment of pituitary tumors. We have analyzed the therapeutic modality and the result of our cases. From 1967 to 1983, 50 patients with huge adenoma (14.1%) out of a total 354 pituitary adenomas were surgically treated. The operative mortality was 25% for radical transcranial (TC) approach (10/40), 14% (1/7) for transsphenoidal (TS) approach and 0% (0/3) for combined two stage operations. From long-term follow-up, excellent prognoses were observed in only 44% of the patients treated by radical TC operation. After 1984, we have employed partial removal by TS surgery at the first stage, followed by reoperation by TS or TC surgery with or without radiotherapy or bromocriptine in case by case. Seventeen huge pituitary adenomas out of a total 700 pituitary adenomas were operated. There was no mortality nor major complications. The two stage operation with initial TS surgery is recommended for the management of huge pituitary adenomas.

Functioning adrenal tumours in children and adolescents: an institutional experience.

BACKGROUND: The purpose of the present paper was to carry out an audit of clinicopathological profile and treatment outcome in 13 children with functioning adrenal tumours. METHODS: The medical records of 13 children with functioning adrenal tumours who were managed between June 1990 and January 1999 were reviewed. Demographic data, clinical features, biochemical and localization studies, operative details and follow-up records were studied. Children with neuroblastoma were excluded. RESULTS: The mean age was 7.4 +/- 5.3 years. Seven patients had Cushing's syndrome (CS), two patients had virilizing tumours, three patients had phaeochromocytoma (PCC) and one patient had Conn's syndrome. All patients (except one child with CS) were treated surgically. Two children with adrenocortical carcinoma (ACCa) died during the perioperative period. Histopathological diagnosis was adrenal cortical adenoma (ACAd) in four patients, ACCa in five patients and PCC in three patients. Two ACCa patients died of metastases at 12 and 14 months, respectively, while the third is alive and well at 30 months. Children with ACAd are alive and well at 91, 56, 32 and 27 months postoperatively. Children with PCC are free of disease (normal urinary metanephrines) at 63, 18 and 8 months after surgery but require antihypertensive drugs in low doses. CONCLUSION: The outcome of surgery is good in cases of ACAd and PCC. Although outcome is poor in ACCa, surgery remains the mainstay of treatment and offers good palliation.

[Neuro-endocrine tumors of the gastrointestinal tract: epidemiology, classification, prognosis, diagnosis and therapeutic modalities]. / Neuroendokrine Tumoren des Gastrointestinaltraktes.

The neuro-endocrine tumors of the gastrointestinal tract comprise a heterogeneous group of slow-growing malignancies with great differences regarding their localization, tissue of origin and their entopic and ectopic production of hormones. They can be subdivided in carcinoid tumors and endocrine tumors of the pancreas. According to their secreted products they manifest as endocrinological syndromes or as local space-occupying tumors. This review focuses, besides summarizing the available epidemiological data and describing tumor localization and classification, on the differing symptom complexes and the prognosis of the various tumor entities. Furthermore, the value of available diagnostic techniques and the role of different therapeutic modalities like surgery, radiation, biotherapy and cytostatic chemotherapy are discussed.

Surgical management of gastrointestinal endocrine tumours.

The surgical management of gastrointestinal endocrine tumours must involve a multidisciplinary approach. The importance of accurate diagnosis, rendering the patient safe, and, in our opinion, localizing the tumour(s) before embarking on surgery cannot be overemphasized. Surgery is the only available treatment for cure. Occult primary tumours are now rarely a problem with novel imaging techniques, which can also improve detection and hence clearance of local spread. Surgical management in extensive metastatic or multicentric disease is less rigidly defined, and is dependent on the endocrine syndrome. A better understanding of tumour pathology, for example in MEN 1, has not always simplified matters. An appreciation of the benefit of chemotherapy, use of somatostatin analogues and hepatic artery embolization are vital to target appropriate palliative surgery. Hepatic transplantation may have an increasing role in the future. Surgical strategies must adapt to new medical treatments. If therapeutically relevant, advances in tumour biology (for example somatostatin receptor subtypes and growth factors) will influence surgical strategies in the future.

[Surgery of primary unilateral adrenal gland tumors--results of 154 patients]. / Die Chirurgie primärer unilateraler Nebennierentumoren--Ergebnisse von 154 Patienten.

Surgical resection of adrenal neoplasias with endocrine activity is principally indicated. In adrenal neoplasias without endocrine activity, surgical removal is indicated in relation to tumor size. Surgical access and extent of resection are the major problems related to adrenal surgery. From 1980 to 1996, in 154 patients (62 m, 92 f) primary and unilateral adrenal tumors (139 benign, 15 malign) were resected. 93 resections were performed transperitoneally, 13 extraperitoneally, and 48 retroperitoneoscopically. Subtotal adrenal resections were performed in 23 benign tumors smaller than 4 cm. Perioperative lethality was 0%, morbidity was 31.8%. Malignancy was correlated to tumor size: In 114 tumors smaller than 5 cm, no malign neoplasia was found, whereas in 40 tumors larger than 5 cm, 15 specimen were malign. Operating time of the retroperitoneoscopic method was significantly longer than of open procedures (p < 0.05). Postoperative analgotic medication was significantly reduced after endoscopic surgery compared to transperitoneal or extraperitoneal surgery (p < 0.0001). No tumor recurrences occurred after subtotal adrenal resections (mean follow up: 5.7 [1.3 years]). In patients with adrenal carcinomas, 5-year-survival was approximately 15%. In adrenal neoplasias smaller than 5 cm, malignancy is extremely rare. Therefore, less aggressive surgery with a lower morbidity (extraperitoneal approach) and reduced postoperative pain (retroperitoneoscopic approach) including function preserving resection is indicated in these lesions. Due to the high incidence of malignancy, adrenal tumors larger than 5 cm should principally be treated by conventional transperitoneal surgery.

Paraneoplastic Cushing's syndrome as an adverse prognostic factor in patients who die early with small cell lung cancer.

The potential role of paraneoplastic Cushing's syndrome (CS) was assessed on the clinical course of patients with small cell lung cancer. A retrospective comparison was done of complications and survival rates according to the presence or absence of CS in patients with small cell lung cancer who died within 90 days of initial administration of chemotherapy. The setting was a comprehensive cancer center. Eleven patients with clinical and/or biochemical features of CS were identified from among 90 patients who presented between 1979 and 1989 with previously untreated small cell lung cancer. The group with CS and the control patients were compared in terms of clinicopathologic prognostic factors, treatment, and outcome. Patients with CS were comparable to the control patients in all prognostic factors, including tumor stage and cancer treatment. Eighty-two percent of patients with CS (nine of 11) died within 14 days of initiation of chemotherapy compared with 25% of the control patients (19 of 77). The median survival from initiation of chemotherapy was 12 days for the 11 patients with CS and 27 days for the 77 control patients. In 45% of the patients with CS (five of 11), death was attributed to opportunistic fungal or protozoal infection compared with 8% of control patients (six of 77). Paraneoplastic CS is a previously unrecognized adverse prognostic factor for patients with small cell lung cancer. Those with both small cell lung cancer and CS have severe opportunistic infections soon after the initiation of chemotherapy, leading to clinical deterioration and death before antineoplastic benefit from chemotherapy can be achieved. Biochemical control of CS for at least 1 to 2 weeks before initiation of chemotherapy may ameliorate the poor prognosis.

Pituitary apoplexy: endocrine, surgical and oncological emergency. Incidence, clinical course and treatment with reference to 799 cases of pituitary adenomas.

Authors analyzed retrospectively the incidence of pituitary apoplexy in a series of 799 pituitary adenomas with respect to the long term follow-up of the patients. Focal vascular abnormalities in histological specimens of tumours, regarded as morphological suggestion of past apoplexy (haemorrhage, ischaemic infarction or necrosis), were established in 113 out of 783 surgical cases (14.4%). Acute clinical onset, justifying the clinical diagnosis of pituitary apoplexy, occurred in 39 patients only (5% of the whole series), 19 of them were subjected to urgent surgical decompression due to severe neurological deficit. The haemorrhagic character of apoplexy was established in most cases requiring immediate surgery. The detailed clinical picture of this condition and its management are discussed with respect to the long term prognosis. On this basis the authors suggest the necessity of surgical treatment in every case of pituitary apoplexy, taking into account not only neurological recovery, but also endocrine and oncological aspects of the disease. The observation that pituitary apoplexy may be a "marker" of tumour invasiveness (even in small, "enclosed" adenomas) is highlighted.

[Conventional operation for therapy of incidentaloma]. / Konventionelle Operation zur Therapie des Inzidentaloms.

AIM: The increasing detection rate of incidentalomas imposes not only the question about the necessity of treatment but also with introduction of laparoscopic adrenalectomy the question about operative strategy. Own patients and literature are analysed and discussed. PATIENTS: Between 1985 and 1996 203 patients have been operated on for adrenal disease including 21 patients with incidentaloma. RESULTS: Biochemical analysis revealed latent hormonal activity in 9 patients. All patients were operated conventionally. Pathohistology demonstrated 1 adrenal carcinoma, 9 adrenocortical adenomas, 2 myelolipomas, 2 adrenal cysts, 2 nodular hyperplasias and 5 pheochromocytomas. Postoperative morbidity was 5% and mortality 0%. CONCLUSION: Small and hormonally latent active tumors can be operated laparoscopically or conventionally via dorsal approach. In case of suspected malignancy conventional operation is the more reliable procedure.

Malignant endocrine tumours in childhood and adolescence--results of a retrospective analysis.

BACKGROUND: Malignant endocrine tumours (MET) are rare neoplasms in childhood and data on such tumours are scarcely available. The aim of this retrospective study was to collect data over a period of 11 years (1984-1995) and to give the basis for a prospective study. PATIENTS AND METHOD: 180 departments of paediatrics, nuclear medicine and children's surgery were asked for reporting of patients with MET by a questionnaire. 35% of the departments answered (however, 75% of the paediatric departments). RESULTS: 96 children with MET were reported: 73 with thyroid cancer (50 papillary, 15 follicular, 7 medullar, 1 anaplastic; 1:1,9 boys to girls, both mean and median age 11 3/4 years), 12 with adrenocortical cancer and 11 with other malignant endocrine tumours. Metastases were found at diagnosis in 41 of 65 children with papillary or follicular carcinoma. 37 patients (pts.) are in first continuous complete remission (CCR), 4 in partial remission (PR) and in 24 (!) children the remission state or the outcome is not known. 6 of 7 children with medullary cancer have had metastases at diagnosis. 1 patient is in CCR, 1 patient is living in PR, 1 in relapse. 4 children are lost of follow up (lfu.). In sex-ratio no difference was found in 12 pts. suffering from adrenocortical cancer (mean age 5 1/4 years, median age 2 1/2 years). 11 tumours showed hormonal activity. 5 children disclosed metastases at diagnosis. All patients were treated by surgery, 6 received chemotherapy additionally. 4 children are living in CCR, 3 pts. in remission of unknown state, 4 died (all of them with metastases at diagnosis), 1 patient is lfu. The other MET reported: 8 carcinoids (7 x appendix, 1 x lung), 2 phaeochromocytomas, 1 islet cell cancer. 8 pts. are in CCR, 2 are lfu. The child with the islet cell carcinoma died. CONCLUSIONS: Since only 35% of the clinics answered this retrospective analysis cannot give any statement about the incidence of MET in children. As to the prognosis thyroid cancer seems to have a favourable prognosis in childhood and adolescence. In contrast, metastatic adrenocortical cancer is incurable in this age group. Carcinoids of the appendix can be treated curatively by appendectomy. To better understand the biology of MET in children and adolescence and to achieve a better prognosis for some types of these tumours, much more data are needed. For these reason a multicenter prospective therapy study for childhood MET seems to be necessary.