Deubiquitylating enzyme USP9x regulates radiosensitivity in glioblastoma cells by Mcl-1-dependent and -independent mechanisms.

Glioblastoma is a very aggressive form of brain tumor with limited therapeutic options. Usually, glioblastoma is treated with ionizing radiation (IR) and chemotherapy after surgical removal. However, radiotherapy is frequently unsuccessful, among others owing to resistance mechanisms the tumor cells have developed. Antiapoptotic B-cell leukemia (Bcl)-2 family members can contribute to radioresistance by interfering with apoptosis induction in response to IR. Bcl-2 and the closely related Bcl-xL and Mcl-1 are often overexpressed in glioblastoma cells. In contrast to Bcl-2 and Bcl-xL, Mcl-1 is a short-lived protein whose stability is closely regulated by ubiquitylation-dependent proteasomal degradation. Although ubiquitin ligases facilitate degradation, the deubiquitylating enzyme ubiquitin-specific protease 9x (USP9x) interferes with degradation by removing polyubiquitin chains from Mcl-1, thereby stabilizing this protein. Thus, an inability to downregulate Mcl-1 by enhanced USP9x activity might contribute to radioresistance. Here we analyzed the impact of USP9x on Mcl-1 levels and radiosensitivity in glioblastoma cells. Correlating Mcl-1 and USP9x expressions were significantly higher in human glioblastoma than in astrocytoma. Downregulation of Mcl-1 correlated with apoptosis induction in established glioblastoma cell lines. Although Mcl-1 knockdown by siRNA increased apoptosis induction after irradiation in all glioblastoma cell lines, USP9x knockdown significantly improved radiation-induced apoptosis in one of four cell lines and slightly increased apoptosis in another cell line. In the latter two cell lines, USP9x knockdown also increased radiation-induced clonogenic death. The massive downregulation of Mcl-1 and apoptosis induction in A172 cells transfected with USP9x siRNA shows that the deubiquitinase regulates cell survival by regulating Mcl-1 levels. In contrast, USP9x regulated radiosensitivity in Ln229 cells without affecting Mcl-1 levels. We conclude that USP9x can control survival and radiosensitivity in glioblastoma cells by Mcl-1-dependent and Mcl-1-independent mechanisms.

Notch receptors in human choroid plexus tumors.

Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3 has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (p<0.0001) and Notch4 (p=0.046) was significantly higher, whereas Notch2 expression was significantly lower (p<0.0001) in nCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (p<0.0001 each). Expression of Notch2 and Notch4 showed a shift from a prevailing membranous/cytoplasmic expression in nCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.

Executive functions recover earlier than episodic memory after microsurgical transsphenoidal resection of pituitary tumors in adult patients--a longitudinal study.

Pituitary tumors may lead to cognitive dysfunction, and the most prevalent deficits are impaired memory and attention. To investigate whether memory and executive functions improve after surgical treatment we performed a prospective longitudinal study comprising 106 patients with pituitary tumors. Psychometric evaluation was performed with the d2-Letter Cancellation test, the Trail Making test, the Digit Span test and the Intelligence Structure test-Verbal Memory test at three timepoints: preoperatively, and at 3 months and 12 months after surgery. The preoperative and postoperative maximum suprasellar tumor extension and hormone status was assessed in all participants. The main finding was that concentration, working memory, and attentional speed improved significantly within the first 3 months after surgery (p<0.05), while improvement of episodic memory was not observed until 12 months after surgery (p<0.001). In the patients harbouring non-functioning adenomas, prolactinomas or other sellar lesions, the most important factor promoting improvement of neurocognitive function was the removal of the suprasellar tumor extension.

Demographic factors and the presence of comorbidities do not promote early detection of Cushing's disease and acromegaly.

OBJECTIVE: The aim of the study was to analyze the time-to-diagnosis interval in patients with Cushing's disease (CD) and acromegaly (AC), to assess factors that promote early disease detection and to investigate the medical fields diagnosing the pathologies. METHODS: 33 CD and 52 AC patients operated over 10 years received a self-designed disease-related questionnaire. Data about symptoms and their duration prior to diagnosis, education level, age, gender and place of residence (i. e. rural vs. urban, size of the city) were collected. RESULTS: The mean time-to-diagnosis interval was 6.0 years in CD and 5.8 years in AC patients. The vast majority of 67% of all investigated patients was diagnosed after they changed their primary health care provider or during a hospital stay owing to comorbidities caused by their underlying disease. Only 33% of all cases were diagnosed by their primary physician. In both groups neither gender, age, place of residence, education level, typical comorbidities (e. g. hypertension or diabetes) nor distinctive symptoms and bodily changes of the underlying disease (e. g. prognathism, acral enlargement, weight gain, buffalo hump) were significant factors promoting early detection. CONCLUSIONS: Apparently, patient-related factors do not affect the time-to-diagnosis interval, but rather the change of the primary health care provider. Knowledge of the disease among physicians is prerequisite to early detection. Due to the deleterious sequelae of delayed diagnosis, information programmes in the medical community are of paramount importance. Institution of screening programmes should be evaluated.

Are there gender-specific differences concerning quality of life in treated acromegalic patients?

OBJECTIVE: Acromegaly is associated with deleterious comorbidities that can remain irreversible even after successful cure has been achieved and lead to a persistently impaired Quality of Life (QoL). The aim of the study was to assess frequency and degree of persistent comorbidities and complaints after treatment of acromegaly and to investigate their impact on QoL. Another scope of interest was to determine gender-specific factors that influence perceived QoL in men and women. METHODS: We developed an Acromegaly Comorbidities & Complaints Questionnaire (ACCQ) consisting of 8 items (e. g. acral enlargement, joint complaints, hypertension, diabetes) known to affect QoL in order to assess frequency and degree of comorbidities. Additionally, the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Short-form 36 (SF-36) questionnaire were handed out to 55 treated acromegalic patients. RESULTS: Both genders suffer from a lasting impairment in quality of life to a considerable degree. Complaints impairing manual skills (e. g. acral enlargement, arthralgias) were the most frequent findings (73% of all participants) in both genders. Multivariate analyses revealed that in men numbness of fingers and persistent joint-complaints were decisively responsible for impaired QoL. In women, it was the persistence of hypertension. CONCLUSIONS: Persistent joint complaints have adverse effects on QoL after treatment of acromegaly in men, possibly because they lead to impairment of manual motor skills and a handicap in their working life. Women seem to perceive late effects of hypertension as a manifest health threat.

Erythropoietin receptor expression in normal and neoplastic choroid plexus.

BACKGROUND: The erythropoietin receptor (EpoR) is expressed widely throughout the human CNS, including the choroid plexus. Recent studies have shown that EpoR is also expressed in various human tumors, including carcinomas, meningiomas and gliomas. Thereby, the Epo-EpoR pathway plays a role in inhibition of apoptosis and tumor growth, infiltration, angiogenesis and metastasis as well as treatment resistance and is a potential target in oncological treatment. Lower levels of EpoR have been associated with shorter survival in high grade gliomas and higher risk of tumor recurrence in meningiomas. METHODS: Since the EpoR status in human choroid plexus tumors (CPT) is not known, we investigated 57 CPT from 43 cases including 14 recurrent tumors and compared them with 23 samples of normal choroid plexus (CP). CPT samples consisted of choroid plexus papillomas/CPP (n = 41), atypical CPP (n = 15) and choroid plexus carcinoma/CPC (n = 1). EpoR expression was determined by immunohistochemistry using semi-quantitative scoring for staining intensity and was validated in exemplary cases using western blot and RT-PCR. RESULTS: EpoR expression was observed in all samples of normal and neoplastic CP with significantly lower expression levels in CPT (p < 0.001). CONCLUSION: No significant correlation was found between EpoR expression and age, gender, WHO grade, number of mitosis or tumor recurrence. EpoR expression in CPT is in line with its expression in normal CP and with previous reports on EpoR expression in other glial neoplasms. Association of EpoR levels in CPT with survival, as known in astrocytic gliomas, remains to be determined.

Predictive factors for neurocognitive function and Quality of Life after surgical treatment for Cushing's disease and acromegaly.

BACKGROUND: Cushing's disease (CD) and acromegaly (AC) are associated with impairment in quality of life (QoL) and neurocognition that can persist after successful treatment. AIM: To investigate the influence of current disease status (remission vs no remission) on neurocognitive function and QoL in treated CD and AC patients and to determine predictive factors (e.g. demographic, clinical, neurosurgical, endocrinological) for post-operative neurocognition and QoL. SUBJECTS AND METHODS: Twenty-four CD and 37 AC patients underwent neuropsychological testing 1 to 10 yr following surgical therapy. Additionally, QoL was assessed. An overnight 2-mg dexamethasone suppression test in CD and IGF-I and GH levels in AC patients were assessed to determine current disease status. The results were compared with 28 sex-, education- and age-matched healthy controls (HC). RESULTS: Impaired QoL was more pronounced than neurocognitive decrease in both pathologies compared to HC. This finding was independent of the current status of disease. In AC, persistent comorbidities were associated with impaired QoL (p<0.05). Older age at operation in AC patients was a significant predictor for adverse effects on psychomotor speed and attentional functions (p<0.05). In CD persistent hypocortisolism, not hypercortisolism, had adverse effects on neurocognition (p<0.01). CONCLUSIONS: The current status of disease plays a subordinate role in postoperative outcome concerning QoL and neurocognition in either pathology. A possible explanation might be the considerably improved endocrinopathy after treatment compared to untreated patients, even if no cure is achieved. The lasting impairments might be explained by irreversible changes that have occurred during the active phase of the disease.

Cerebral low-grade lymphoma and light chain deposition disease: exceedingly high IgG levels in the cerebrospinal fluid as a diagnostic clue.

Herein, we report the case of a 72-year-old male with an exceedingly rare manifestation of a low-grade lymphoma in the brain associated with light chain deposition disease (LCDD). The patient presented with epileptic seizures. Magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions in the right parietal lobe that were suspicious of vasculitis, low-grade glioma, or neurosarcoidosis. In the cerebrospinal fluid (CSF), but not in the serum, highly elevated IgG was found. A stereotactic biopsy of one cerebral lesion was performed. Histopathology revealed a low grade lymphoplasmacytic B-cell lymphoma with light chain deposition disease (LCDD). Bone marrow biopsy and laboratory workup did not show any systemic involvement. LCDD exclusively affecting the brain is an exceedingly rare finding. It can be associated with low-grade B-cell lymphoma. This is the first report of LCDD exclusively affecting the brain in an elderly patient. Compared with the two younger patients previously reported, the course of the disease was of a slow-evolving nature. In constellations of highly elevated IgG in CSF and multiple white matter lesions, LCDD should be considered as underlying pathology.

Glioblastoma with granular cell astrocytoma features: a case report and literature review.

We present the case of a 69-year old patient with a contrast enhancing, partially cystic lesion of the right temporal lobe, involving the ventricle and extending into the occipital lobe. The resected tumor showed histological features of a glioblastoma with granular cell astrocytoma features, lacking amplification of the EGFR gene region and IDH1R132H mutation. Literature review of 59 cases showed a 12-month overall survival of 11.7% for high-grade and 40% for low-grade granular cell astrocytomas. In 35% more than one cerebral lobe was affected. These extended mass effects may explain the worse prognosis despite the relatively bland histology of the granular cell component.

Surgical technique and validation of outcome assessment in sagittal synostosis.

BACKGROUND: Aim of the study was to evaluate the outcome of children operated for sagittal synostosis, with special attention paid to the postoperative aesthetic result, as seen from the parents' and the treating medical doctors' perspective, and to assess the time point for operative correction. METHODS: A retrospective chart review of 87 patients operated over 15 years was performed. Data included age at the time of operation, perioperative complications, duration of hospital stay, intraoperative blood loss, transfusion volume, neurological outcome, and postoperative skull growth. Aesthetic outcome was assessed at 6, 12 and 18 months after surgery separately by the treating medical team and the children's parents. RESULTS: Sagittal synostosis was diagnosed in 98.9% of cases in the first six months of life. We performed the same operative technique in all children with bilateral total removal of parietal bones. The median age at operation was 5 months. There was no correlation between age at the time of operation and blood loss (p<0.602). 5.7% of the children presented with significant postoperative skull asymmetries. All of these children had undergone operation in the first four months of life (p<0.01). The evaluation of the postoperative aesthetic outcome as seen by parents and doctors was highly convergent, with 79.3% of children in the excellent or good outcome group CONCLUSIONS: Our results suggest that the feasible time period for the method used by us is around the 5th - 6th month of life, with satisfying results. With regard to the aesthetic outcome assessment we recommend our approach using validation by parents as a valuable new principle.

Benign meningioma developing late lung metastases: case report and review of the literature.

Here we report the case of a 65-year-old female with a histologically benign parietal falcine meningioma who developed multiple lung metastases 15 years after tumor resection. The meningioma was initially incompletely resected due to invasion of the sagittal sinus. Since it was diagnosed as a benign meningothelial meningioma Grade I WHO, the residual tumor was followed with serial imaging without adjuvant treatment. The patient subsequently developed lung lesions later identified as metastases. The lung lesions were successfully removed surgically and histologically diagnosed as meningothelial meningioma Grade I WHO. A repeat brain MRI revealed the known residual meningioma with no signs of interval tumor growth, but did demonstrate occlusion of the sagittal sinus. In the further course, the residual meningioma was completely removed. A review of the literature revealed only 15 well-documented cases of benign meningiomas that metastasized in an interval of up to 12 years after primary tumor resection. This case illustrates that histologically benign meningiomas Grade I WHO with stable disease of the primary tumor have the potential to develop hematogenous metastases even after a long time interval.

Sellar neuroblastoma mimicking a pituitary tumour: case report and review of the literature.

Neuroblastomas of the sellar region are exceedingly rare. Only 2 cases have previously been reported. Management of these tumours depends on the tumour's primary site, the patient's age and histopathological features. We are reporting the case of a 43-year-old woman who developed progressive bitemporal hemianopsia and visual loss, accompanied by amenorrhea and hyponatremia. Laboratory findings revealed a slightly elevated prolactin level. Cranial MR-imaging displayed an intrasellar and suprasellar lesion with a maximum diameter of 2.5 cm that was suspicious for a pituitary adenoma or tuberculum sellae meningioma. The tumour was approached via a pterional trepanation. Intraoperatively, the tumour was highly vascularized and adhesive to the optic chiasm, the floor of the third ventricle, the hypothalamus and the hypophyseal stalk. Postoperatively, vision improved and prolactin dropped to normal values, but hyponatremia persisted. Histopathological examination revealed a neuroblastoma with strong positivity for synaptophysin and chromogranin, MAP-2 protein and NeuN-antigen in the immunohistochemistry. No pituitary hormone receptors were expressed. The MIB-1 labelling index was positive in 5% of the cell nucleoli. In the further course, the patient underwent radiotherapy of the neuroaxis. A brief review of the literature is presented.

Meningitis as a presentation of macroprolactinoma.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea and consecutive meningitis are well recognised clinical features of macroprolactinomas invading the skull base and are mainly observed under a dopamine-agonist therapy regimen. To our knowledge, a clinical case of primary meningitis due to an untreated macroprolactinoma, without any history of rhinorrhea, has not been reported previously in the English literature. CASE REPORT: A 64-year-old patient presented with acute meningitis. He had no prior episode of CSF rhinorrhea. Neuroradiological imaging revealed a pituitary tumour with invasion and destruction of the skull base. Massive hyperprolactinaemia was proof of a prolactinoma. The patient underwent transsphenoidal adenomectomy. The skull base defect was sealed with a fascia lata graft. In the postoperative course, no further episode of meningitis and no CSF rhinorrhea occurred. The invasive residual tumour was successfully treated with cabergoline. CONCLUSION: Macroprolactinomas can present with meningitis without any prior history of CSF rhinorrhea. Surgical repair of the skull base defect is the treatment of choice in order to prevent further episodes of meningitis. Pituitary tumours should be considered as a cause of otherwise unexplained meningitis.

No evidence for WT1 involvement in a beta-catenin-independent activation of the Wnt signaling pathway in pituitary adenomas.

The overexpression of Wilms' tumor gene product WT1, which acts as a tumor suppressor or oncogene, has been reported in various malignancies. Recent studies have shown that the interaction partner Wnt-4 is upregulated in pituitary adenomas dependent on the Pit-1 lineage (somatotrophs, lactotrophs, and thyrotrophs). However, no data on WT1 expression in nontumorous pituitary tissue or pituitary adenomas is available to date. We investigated WT1 expression in 90 paraffin-embedded pituitary adenomas, including eight atypical adenomas, and in 28 nontumorous pituitary glands by immunohistochemistry. WT1 is absent in epithelial cells of all nontumorous pituitary glands and in 87 out of 90 pituitary adenomas. Only two GHomas (including one atypical adenoma) and one gonadotropin-producing adenoma expressed WT1 in the cytoplasm of single tumor cells without nuclear staining. There is no evidence that WT1 does regulate the Wnt-4/beta-catenin-independent pathway which is activated in the Pit-1-expressing subset of pituitary adenomas.

Quantitative assessment of postoperative blood collection in brain tumor surgery under valproate medication.

BACKGROUND: The aim of the study was to evaluate whether valproate (VPA) increases the risk of bleeding complications in patients undergoing brain tumor surgery. METHODS: A retrospective chart review of 85 patients operated on between January and December 2005 was performed. 19 patients received VPA, 22 patients were given other anti-epileptic drugs (AEDs), 44 patients received no AEDs. Data analyzed included intraoperative blood loss, transfusion, important comorbidity factors and concomitant diseases. Preoperative and postoperative laboratory data included hemoglobin, hematocrit, fibrinogen, platelet count, INR, prothrombin time, partial thromboplastin time and RBC count. The tumor volume was evaluated by preoperative MRI and CT scans of the brain. All 85 patients underwent a native CT scan of the brain on the first day after the operation. The volume of the resection cavity and the volume of blood were documented. RESULTS: We could show that the volume of the tumor had a significant effect on the amount of blood in the tumor cavity, whereas VPA medication had no effect. CONCLUSIONS: In our dataset, we found that tumor size had a significant effect on postoperative blood volume. In contrast, no serious bleeding complications occurred in the patients receiving VPA. Therefore, the present study does not provide any evidence for the need to discontinue VPA medication prior to and during surgery.

Atypical type II silent corticotrophic adenoma developing into Cushing's disease upon second recurrence.

Herein, we report the case of a 73-year old male patient who presented with two recurrences of a pituitary adenoma within a period of 15 years. The first tumor resection 15 years ago revealed a non-functioning pituitary macroadenoma. 11 years later, the first recurrence of the tumor was reoperated. Throughout the early course of the disease, he suffered from secondary adrenal insufficiency and required replacement therapy with hydrocortisone. Currently, he presented with the second recurrence and clinical examination revealed signs of Cushing's disease. This was clearly confirmed by endocrinological evaluation. A retrospective analysis of all histological and immunohistochemical slides rendered an adenoma exhibiting chromophobia, ACTH-positivity and features of atypia such as elevated p53 and Ki67 expression as well as nuclear polymorphism. According to the revised WHO classification it was classified as atypical type II silent corticotroph adenoma at the time of the first and second surgery. The specimen removed during the recent surgery displayed the same histological features and was classified as corticotroph adenoma. The combination of an atypical type II adenoma and the switch in the hormone status to an endocrinologically active adenoma makes this case exceedingly rare.

Objective criteria for successful transsphenoidal removal of suprasellar nonfunctioning pituitary adenomas. A prospective study.

BACKGROUND: Despite ample experience with transsphenoidal surgery, objective data on which suprasellar tumour expansion and growth pattern allows for radical adenoma resection are still sparse. Hence, we have performed a prospective study to establish the predictive value of tumour dimension and shape for the intra-operative descent of the diaphragma, the completeness of tumour resection and the outcome of patients harbouring pituitary adenomas with suprasellar extension. METHOD: Included in the study were 105 patients with nonfunctioning pituitary adenomas and suprasellar extension who underwent primary transsphenoidal surgery between January 1998 and December 2005. The precise suprasellar extension, the degree of dumbbell-shape, the configuration of the adenomas and the depth of the pituitary fossa were evaluated. Completeness of resection was assessed by MRI at 3 months postoperatively. FINDINGS: The mean cranio-caudal diameter of the tumours was 28.0 mm (range 9.2-57.8 mm). On average, the suprasellar extension measured 11.9 mm (range 2.1-25.8 mm). Total removal of the suprasellar tumour was accomplished in 83% (87 of 105) of the patients. A second operation for residual adenoma was only indicated in 2 cases. The vertical intracranial extension was the strongest independent predictor of subtotal resection (p < 0.001). Irregular and multilobular configuration was a second highly-significant and independent predictor for incomplete resection (p < 0.003). In contrast, dumbbell-shape and shallow pituitary fossa were not independent predictive factors for incomplete tumour resection. The complication rate was very low. None of our patients suffered postoperative rhinorrhea, meningitis or visual deterioration. CONCLUSIONS: One-stage transsphenoidal surgery allows total or near-total resection of most suprasellar pituitary adenomas with low surgical morbidity. Quantitative assessment of tumour dimension and configuration contributes to establishing guidelines for the selection of the appropriate approach and prediction of surgical outcome.

Spontaneous cerebrospinal fluid rhinorrhea in untreated macroprolactinoma--an indication for primary surgical therapy.

BACKGROUND: Medical therapy is usually indicated as first-line treatment for prolactinomas. Surgery is generally reserved as second-line therapy if prolactinomas are non-responsive to dopamine agonists (DA) or DA therapy is not tolerated. Herein, we draw attention to the rare occurrence of spontaneous CSF rhinorrhea in prolactinomas requiring primary surgical therapy. Only 8 cases of confirmed prolactinomas with spontaneous rhinorrhea have been reported in the literature so far. CASE REPORTS: Two out of 267 surgical cases with pituitary adenomas presented with spontaneous rhinorrhea. Both patients harbored invasive prolactinomas. In both cases, the defect was exposed using a transsphenoidal procedure and was sealed with fascia lata. RESULTS: Urgent surgical repair of the leak prevented meningitis. In one case, a second operation was required due to recurrent rhinorrhea under postoperative dopamine-agonist therapy of the residual tumor. The clinical course was otherwise uncomplicated. CONCLUSION: Certain clinical settings still require primary surgical therapy of prolactinomas. Spontaneous rhinorrhea caused by invasive macroprolactinomas represents a mandatory indication for initial surgery. Early detection and surgical repair of a CSF leak is crucial for a favorable clinical outcome.

Fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in malignant melanoma. Diagnostic comparison with conventional imaging methods.

PURPOSE: To assess the diagnostic value of fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in screening for melanoma metastases. MATERIAL AND METHODS: The case records of 94 melanoma patients who had been examined by whole-body FDG-PET between 1995 and 1999 were evaluated retrospectively. Forty patients showed evidence of lymphogenous and 42 of hematogenous metastasis. The maximal interval between PET and the diagnostic procedure under comparison was 2 weeks. Confirmation of the findings was based on histology or the clinical or radiological course. RESULTS: In 24 patients, all diagnostic examinations including CT had been performed within 2 weeks from PET. In no case did PET change the staging. In 13 patients, PET agreed with morphological diagnosis in the number of metastatically invaded organs. This included 3 patients without metastases. The estimated number of organs invaded by metastases was higher with PET in 5 patients and higher with morphological imaging techniques in 6 patients. Among the PET findings with higher or equivocal counts of organs with metastases there were 2 confirmed false-positive findings. CONCLUSION: In a selected patient population, FDG-PET was found to be inferior to CT for diagnosing lung and liver metastases. The supplementary use of FDG-PET is not generally of value once metastasis has been established.

Positron emission tomography using 18F-fluorodeoxyglucose in advanced stages of malignant melanoma: a comparison of ultrasonographic and radiological methods of diagnosis.

The diagnostic and therapeutic impact and the cost-effectiveness of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) will depend on the role for which the tests are used. In 68 patients with advanced malignant melanoma, original sets of FDG-PET images from various institutes were compared with findings obtained by ultrasonography, conventional radiology, computed tomography (CT) and magnetic resonance imaging. In 22 patients, all examinations were undertaken within 2 weeks and strategies of staging were analysed. In 46 patients, only some of these examinations were performed within this time period, and comparison of methods was restricted to the examined organs. The occurrence of metastasis, without specifying the number of foci, was detected by either conventional staging with CT or by PET in 20 of 22 patients. None of these patients were up- or down-staged by FDG-PET compared with CT staging. In the 68 patients as a whole, FDG-PET detected fewer pulmonary and hepatic metastases and fewer cerebral foci, but more lymph node and bone metastases than conventional radiology or CT. For the detection of lymph node or skeletal metastases, false-positive FDG-PET findings were taken into account when compared with follow-up data. In advanced melanoma, FDG-PET did not influence the pattern of subsequent diagnostic testing. Thus, indications for FDG-PET include pre-metastatic melanoma, localized lymph node metastases and monitoring of the response to treatment.