Gastrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges.

This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.

[Utility of single photon emission computed tomography-computed tomography in selective sentinel lymph node biopsy in patients with melanoma]. / Utilidad de la tomografía de emisión de fotón único-tomografía computarizada en la biopsia selectiva del ganglio centinela en pacientes con melanoma.

OBJECTIVE: To assess the contribution of SPECT-CT lymphoscintigraphy in selective sentinel lymph node biopsy (SLNB) in patients with newly diagnosed malignant melanoma. MATERIAL AND METHODS: A prospective study was made between July 2009 and October 2010. It included 63 patients diagnosed with melanoma (32 men and 31 women) with mean age of 55 years (range: 25-88) and inclusion criteria for SLNB. The melanomas were located as follows: 28 in trunk, 5 in head and neck, 16 in upper limbs and 17 in lower limbs. Three patients had two melanomas. Preoperative lymphoscintigraphy was performed after pericicatricial/perilesional injection of 74MBq of (99m)Tc-labeled nanocolloid human serum albumin, obtaining early planar images, late whole body study and sectorial images and SPECT-CT in the area of interest. Planar scintigraphy findings were compared with SPECT-CT. RESULTS: The sentinel node (SN) was localized by planar imaging in 62/63 (98%) of patients. SPECT-CT study located the SN in all the patients with a detection rate of 100%. The number of SNs detected with SPECT-CT was higher than with the planar study in 27 patients. The SPECT-CT provided additional information (change in location and/or in its accuracy in the localization of location uncertain SN) in 14/63 (22.2%) patients, involving changes in the surgical approach and lymph node staging. CONCLUSION: SPECT-CT detects a higher number of SN than planar lymphoscintigraphy in patients with melanoma. Its contribution is more relevant in the melanomas located on the trunk, head and neck. SPECT-CT modified the SN location by 22% compared to planar scan findings, facilitating a correct surgical approach.

123I-MIBG, 18F-DOPA and 18F-FDG in a patient with MEN2 syndrome and recurrent pheochromocytoma.

Pheochromocytoma is a rare tumor located in the medulla of the adrenal gland that is characterized by high catecholamine synthesis. Surgery is the treatment of choice and is usually curative if appropriately diagnosed and excised. Imaging methods, both morphological and functional, are of great importance in presurgical evaluation. We report the case of a female patient with multiple endocrine neoplasia syndrome type 2, with bilateral adrenalectomy due to two pheochromocytomas and progressive elevation of urinary metanephrine. Magnetic resonance imaging showed a nodular image in the right adrenal fossa. The patient was referred to our unit in order to confirm suspicion of recurrence. Due to the absence of pathological findings in the (123)I-MIBG scintigraphy and high suspicion of recurrence, PET/CT imaging with (18)F-DOPA and (18)F-FDG were performed, and the diagnosis was confirmed.

[Effectivity and clinical impact of (18)F-FDG-PET in the diagnosis of unsuspected second primary tumors]. / Efectividad e impacto clínico de la PET-(18)F-FDG en el diagnóstico de segundos tumores primarios insospechados.

OBJECTIVE: This study has aimed to determine the capacity and clinical impact of the (18)F-FDG-PET to detect previously unsuspected second primary tumors. MATERIAL AND METHODS: This is a retrospective cross-sectional study of 1984 consecutive scans performed between March 2004 and March 2005, identifying those studies that had reported the presence of hypermetabolic lesions, that had not been previously suspected or detected and that could be suggestive of second primary tumors. Diagnosis was made histopathologically or by clinical and radiological follow-up for a period exceeding one year. RESULTS: 62 findings suggestive of second primary tumors were detected in 58 patients (3.1%). The reasons for the study for this group of patients were diverse, the most common being the differential diagnosis of solitary pulmonary nodules. A total of 43.5% of lesions were not followed-up. We confirmed the existence of 35 lesions, either by pathology study (21 lesions, 13 second primary tumors, the incidence in our population was 0.65%) or clinical and radiological follow-up (14 lesions, none of which corresponded to second primary tumors). The total clinical impact was the discovery of unexpected 14 lesions in 12 patients. CONCLUSION: The presence of second primary tumors on (18)F-FDG-PET is relatively common. These lesions should be monitored clinically for accurate diagnosis. In a high percentage, they correspond to unexpected second primary tumors in an early stage and therefore amenable to curative treatment or for which tumor treatment planning may be modified.

[Unsuspected bronchial carcinoid tumor detected in a somatostatin receptor scintigraphy in a patient with multiple endocrine neoplasia syndrome type 1 and hypergastrinemia]. / Hallazgo incidental de un tumor carcinoide bronquial en gammagrafía de receptores de somatostatina de paciente con síndrome de neoplasia endocrina múltiple tipo 1 e hipergastrinemia.

Multiple Endocrine Neoplasia type 1 syndrome (MEN1) is characterized by the presence of tumors in parathyroid glands, anterior pituitary gland, endocrine pancreas and duodenum. However, other tumors may also occur. One of them is the carcinoid tumor, which in this context, is more common in the gastrointestinal tract. Less common is the presence of carcinoid tumors of bronchial origin, which with histologic confirmation, may occur in 5-8% of cases and that appears more frequently in patients with hypergastrinemia. We report a patient with MEN1 syndrome, hypergastrinemia and an incidental finding in a somatostatin receptor scintigraphy of an unsuspected bronchial carcinoid tumor that was confirmed histologically.

Value of the negative PET-FDG in the middle term follow-up of differentiated thyroid cancer in patients with negative 131 I-Na scan and elevated thyroglobulin serum levels.

OBJECTIVE: This study has aimed to analyze the evolution of patients diagnosed with differentiated thyroid carcinoma (DTC) with a negative (131)I-Na whole body scan (WBS), high levels of serum thyroglobulin (Tg) and negative (18F)fluorodeoxyglucose positron emission tomography (PET-FDG) study. MATERIAL AND METHODS: Twenty-three patients diagnosed and treated for DTC were studied retrospectively. Patients were aged between 23 and 83 and had shown, between January 2001 and December 2002, negative WBS, Tg values in a range of suspected recurrence or metastasis (Tg>2 ng / mL with thyroid hormone withdrawal) and a negative PET-FDG study. The patients were monitored clinically, radiologically and analytically for a minimum period of 4 years. After this, a new evaluation was made of their state of disease with a control WBS, also observing the evolution of Tg. All WBS were performed with a 185 MBq diagnostic dose of (131)I-Na. RESULTS: In 18/23 patients, Tg decreased and in 5 it increased. Four patients (17%) were free of active disease (negative WBS Tg<2 ng / mL). A total of 16 patients (70%) were free of disease according to the WBS but had elevated Tg. Three patients (13%) had disease and high levels of Tg, two of them with positive WBS and the third with (99m)Tc-MIBI scan and CT positive. CONCLUSIONS: Most patients with a negative WBS, high Tg serum levels and negative FDG PET had good evolution, with descending Tg levels, normal levels even being reached in a significant percentage of them.

[Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test]. / Evaluación de la eficacia y del impacto clínico de la PET-18F-FDG en el diagnóstico de recurrencia del carcinoma medular de tiroides con calcitonina elevada y pruebas de imagen negativas.

AIM: To evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. MATERIAL AND METHODS: We performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60 minutes after intravenous injection of 333-434 MBq of (18)F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years) RESULTS: Sensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's "t" test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3). CONCLUSIONS: In patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients.

[Use of 18F FDG-PET in patients with suspicion of recurrent differentiated thyroid cancer by elevated antithyroglobulin antibodies levels and negative ¹³¹I scan]. / Uso de la PET-18F-FDG en pacientes con sospecha de recurrencia de cáncer diferenciado de tiroides por anticuerpos anti-tiroglobulina elevados y rastreo ¹³¹I negativo.

AIM: To evaluate the utility of (18F)FDG-PET for patients diagnosed of differentiated thyroid carcinoma who present risk of disease and invaluable levels of thyroglobulin (Tg) by the presence of antibodies antithyroglobulin (AbTg). MATERIAL AND METHODS: Retrospective study of 7 women of 40 years old and histological diagnosis of differentiated thyroid cancer (7 papillary tumours) that were sent to our department for the accomplishment of(18F)FDG-PET study because of suspicion of disease, due to ¹³¹I negative and high levels of AbTg, between the year 2002 and 2007. 11 PET scans were obtained after the intravenous injection of 370-434 MBq of (18F)FDG in normoglycemia conditions and previous administration of muscle relaxant, hydration and diuretic. The results of (18F)FDG-PET scans were confirmed by pathologic examination or clinical outcome and radiographic examination for more than 24 months. RESULTS: The prevalence of recurrence in our population was 57.14%. All patients presented levels of Tg lower than 3 ng/dl and AbTg superior to 200 UI/ml. Three patients had precedent thyroiditis. Out of 11 scans performed 3 of them were negative and 8 cases were found positive. It ruled out the existence of disease in three patients and localized the presence of recurrence in 4 patients. CONCLUSION: (18F)FDG-PET CONCLUSION: 18F-FDG-PET is a useful diagnostic tool for the detection of recurrence as well as to rule out the existence of disease with a high accuracy, in patients with differentiated thyroid carcinoma with ¹³¹I whole body scan negative but with pathological elevation of antithyroglobulin antibodies.

[18F-FDG PET-CT in a case of solitary plasmacytoma of the soft palate]. / Tomografía por emisión de positrones con ¹8F-fluorodeoxy-glucosa en un caso de plasmocitoma solitario de paladar blando.

Solitary plasmacytoma is an uncommon tumor of plasma cells that can appear in the head and neck. It must be differentiated from multiple myeloma because of its initial presentation. A case of solitary plasmacytoma on the palate is presented. Furthermore, role of ¹8F-fluorodeoxyglucose Positron Emission Tomography (¹8F-FDG-PET) in its initial staging is analyzed.

[A colon adenocarcinoma and a pharyngeal carcinoma incidentally detected by means of (18)F-FDG PET in a patient diagnosed of lung cancer]. / Adenocarcinoma de colon y carcinoma faríngeo detectados incidentalmente mediante (18)F-FDG PET en paciente diagnosticado de cáncer de pulmón.

It is not uncommon to find two or more tumors in the same patient, usually based on similar etiologic factors or the use of radiotherapy and/or chemotherapy. This occurs quite often in the case of lung cancer. In this sense, the positron emission tomography with (18)F-FDG (FDG-PET) is widely used for the diagnosis and treatment of cancer patients. It is also especially useful in patients with solitary pulmonary nodule, bronchogenic carcinoma, head and neck cancer, colon cancer, tumors of unknown origin, lymphomas, etc. Its capacity to detect previously unsuspected second or third primary tumors has also been demonstrated. We report a clinical case showing how two synchronous cancers were incidentally detected in a 73-year old patient diagnosed with lung cancer and referred for (FDG-PET) study.

[Clinical impact of FDG-PET in patients with suspected recurrent ovarian cancer]. / Impacto clínico de la PET-FDG en pacientes con sospecha de recurrencia de cáncer de ovario.

AIM: To evaluate the efficacy and clinical impact of FDG-PET in patients with suspected recurrent ovarian cancer. METHODS: Between October 2001 and October 2006, we retrospectively studied 49 FDG-PET performed in 40 women (age: 52.4 +/- 12.2 years) with ovarian cancer, who had suspicion of recurrent disease by positive morphologic imaging tests (MIT) or increased tumour markers and negative MIT. All patients underwent whole body FDG-PET after the injection of 370-434 MBq of (18)FDG. The results were confirmed by histology in 31 cases, and by clinical-radiological follow-up in 18. RESULTS: Prevalence of disease was 79.6 %. We obtained a global sensitivity and positive predictive value of 87.2 % and 87.2 %, and an accuracy of 79.6 %. Results led to a change in the patient's management in 25 cases (51 %). Subgroup results were: Sensitivity of 81.8 % in patients with increased tumour markers and negative MIT, and 89.3 % in patients with operable malignant lesions. CONCLUSIONS: FDG-PET has high sensitivity and clinical impact in patients with suspicion of recurrent ovarian cancer. Better results were obtained in patients with increased tumour markers and negative MIT.

[Evaluation of efficacy and clinical impact of FDG-PET on patients with potentially resectable non-small cell lung cancer]. / Evaluación de la eficacia y el impacto clínico de la PET-FDG en los pacientes con carcinoma broncopulmonar no microcítico candidatos a cirugía.

AIMS: We have evaluated the efficacy and clinical impact of FDG-PET for staging patients with potentially resectable non-small cell lung cancer (NSCL) in CT. MATERIALS AND METHODS: We have prospectively studied 115 patients (104 M/11 F and mean age: 59 years old) with diagnosis of potentially resectable NSCL, (resectable criteria: Stage

[Bone metastases from unknown primary. FDG-PET detection of two synchronous tumors]. / Metástasis óseas de tumor primario desconocido. Detección mediante PET-FDG de dos tumores sincrónicos.

A 60-year-old woman presented with noncardiac chest pain over months and negative laboratory findings. Conventional imaging methods and bone scintigraphy detected bone lesions suggesting metastatic disease from an unknown primary tumor. An 18FDG-PET scan performed to orient the search for the primary tumor found focal lesions suggesting lymphoma and identified a focal thyroid lesion and a cervical lymph node accessible for biopsy. The biopsy of this lymph node incidentally detected a papillary differentiated thyroid cancer (DTC), since the existence of a non-Hodgkin's lymphoma was confirmed after a new biopsy. After confirming the presence of a lymphoma, 18FDG-PET enabled the initial staging of the tumor, the evaluation of the response to treatment, and follow-up for detection of recurrence. On the other hand, 18FDG-PET incidentally detected a DTC.

[Patients treated for differentiated thyroid cancer with negative 131I whole-body scans and elevated thyroglobulin levels: a possible course]. / Pacientes tratados por carcinoma diferenciado de tiroides con rastreos de 131I negativos y niveles de tiroglobulina elevada. Una evolución posible.

OBJECTIVE: To verify the existence of patients with treated differentiated thyroid cancer (DTC) with negative 131I whole-body scanning (WBS) and high serum thyroglobulin (Tg) in the follow-up who evolve towards normalization without other therapy interventions. MATERIAL AND METHODS: Retrospective revision of the periodic examinations established in the protocol for patients with DTC, analyzing the levels of Tg found with IRMA annually in those with hormonal treatment and every 1-5 years in absence of previous hormonal treatment to WBS. Minimum surveillance of 2 years. Those who had elevated levels of Tg and WBS and other negative imaging tests in their course were selected. The characteristics of the patients selected were analysed in those whose Tg levels evolved to normalization without specific medical or surgical treatment (Group I) and those who did not reach normalization of Tg (Group II). RESULTS: A total of 130 patients (17.93 %) with high levels of Tg and negative WBS were detected. Group I: 31 patients (4.28 %), 11 men and 20 women; average age at the moment of the diagnosis of 33.4 years (rank: 5-60); average surveillance: 12.4 years (+/- 7.4). HISTOLOGY: 27 papillary and 4 follicular carcinoma. Average ablation dose: 3.260 GBq (88,1 mCi); average total I131 dose: 6.850 GBq (185.13 mCi). Tg normalization average time: 8.2 years. Group II: 99 patients (13.65 %), 27 men and 72 women. Average age of 40.4 years (rank: 7-76). Average surveillance: 9.8 years. HISTOLOGY: 86 papillary and 13 follicular carcinoma. Average ablation dose: 3.266 GBq (88.28 mCi); average total 131I dose: 9.363 GBq (253,06 mCi). Two of the patients in group I had negative PET-FDG. There were 13 patients in whom progressive reduction of the levels of thyroglobulin without reaching normalization with negative PET-FDG was detected. CONCLUSIONS: In patients with radiated DTC, deferred normalization of the levels of the serum thyroglobulin is possible. Empirical treatments cannot be considered the only factor that contributes to this result, which can occur without the administration of high-doses of 131I.

[Evaluation of efficacy and clinical impact of positron emission tomography with 18F fluoro-deoxyglucose in patients with suspicion of recurrent head and neck cancer or distant metastases]. / Evaluación de la eficacia y el impacto clínico de la tomografía de emisión de positrones con 18F-FDG en pacientes con sospecha de recurrencias locales y metástasis de carcinomas de cabeza y cuello.

AIMS: To evaluate the efficacy and clinical impact of Positron Emission Tomography with FDG (FDG-PET) in patients with suspected recurrent head and neck cancer or distant metastases. MATERIALS AND METHODS: Sixty patients (12 women and 48 men) with suspicion of recurrent head and neck cancer and ambiguous conventional imaging modalities. In all patients a whole body scan was performed with FDG-PET in fasting patients following i.v. administration of 370-444 MBq FDG. The results were confirmed by histology and clinical evolution (follow-up period > 12 months) and imaging test. RESULTS: Prevalence of recurrence was 66.6 %. FDG-PET was positive in 40/60 patients, with confirmation in 39 cases, and 18 were true negative (TN). We have found 2 false positive and 1 false negative. Overall sensitivity, specificity, PPV, NPV and accuracy were 97.5 %, 90 %, 95.12 %, 94.7 % and 95 %, respectively. FDG-PET changed the modality of treatment in 34 patients (clinical impact 56.6 %) CONCLUSIONS: FDG-PET has high clinical impact in patients with suspicion of recurrent head and neck cancer, and should be incorporated in the diagnostic protocols before making a therapy decision.

[Evaluation of efficacy and clinical impact of FDG-PET on patients with suspicion of recurrent cutaneous melanoma]. / Evaluación de la eficacia y el impacto clínico de la PET-FDG en los pacientes con sospecha de recurrencia de melanoma maligno.

AIMS: To evaluate the efficacy and clinical impact of positron emission tomography with 18F-FDG (FDG-PET) in patients with suspected recurrent melanoma. MATERIALS AND METHODS: We studied 105 patients with melanoma and suspicion of recurrent melanoma by clinical symptoms in 38 cases or equivocal/positives morphological tests (TC, MR, US) in 77 cases. In all patients a whole body scan was performed with FDG-PET (ECAT HR +) after an intravenous injection of 444-518 MBq of 18F-FDG, in normoglucemia conditions, and previous administration of muscular relaxant, hydration and diuretic. Images were evaluated by 2 dxpert nuclear physicians and were analysed qualitatively and semiquantitatively. In 48 cases the results were confirmed by histology and clinical evolution (follow-up period >12 months) and imaging tests in 57 cases. RESULTS: Prevalence of recurrent melanoma was 63.8 %. Sensitivity, specificity, PPV, NPV and accuracy of FDG-PET was 97 %, 97.2 %, 98.5 %, 82 % y 94.7 % respectively. FDG-PET had led to a management change in 48 cases (38 %). CONCLUSIONS: FDG-PET has high clinical impact in patients with suspicion of recurrent melanoma, and should be incorporated in the diagnosis protocols, before making therapeutic decision.

[Evaluation of efficacy and clinical impact of positron emission tomography with 18F fluoro-deoxyglucose (FDG) in patients with suspicion of recurrent laryngeal carcinoma]. / Evaluación de la eficacia y el impacto clínico de la tomografía de emisión de positrones (PET) con 18F fluoro-desoxiglucosa (FDG) en pacientes con sospecha de recurrencia de carcinoma de laringe.

AIMS: To evaluate the efficacy and clinical impact of FDG-PET in patients with suspected recurrent laryngeal carcinoma. MATERIALS AND METHODS: 15 patients, with suspicion of recurrent laryngeal carcinoma and ambiguous conventional imaging modalities. In all patients a whole body scan was performed with FDG-PET in fasting patients following i.v. administration of 370-444 MBq FDG. The results were confirmed by histology and clinical evolution (follow-up period > 12 months). RESULTS: Prevalence of recurrence was 86.6%. FDG-PET was positive in 13 patients, with confirmation in all cases, and 2 were true negative (TN). Overall sensitivity, specificity, PPV, NPV and accuracy were 100%. FDG-PET changed the modality of treatment in 10 patients (clinical impact 63.3%). CONCLUSIONS: FDG-PET has high clinical impact in patients with a suspicion of recurrent laryngeal carcinoma, and should be incorporated to the diagnostic protocols before making a therapy decision.

[F-18-fluordeoxyglucose positron emission tomography on patients with differentiated thyroid cancer who present elevated human serum thyroglobulin levels and negative I-131 whole body scan]. / PET con 18FDG en pacientes con cáncer diferenciado de tiroides que presentan niveles elevados de tiroglobulina sérica y rastreos con 131I negativos.

UNLABELLED: This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. MATERIAL AND METHODS: Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH > or = 30 microIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy (99mTc-MIBI) was done in 14 patients and morphologic imaging in 26 by CT scan. RESULTS: Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. CONCLUSIONS: These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.