Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.
Baillieres Best Pract Res Clin Endocrinol Metab 2000 Dec
PMID:Diagnosis and treatment of medullary thyroid cancer. 1128 39

Patients with advanced, recurrent, or metastatic gynaecological malignancies constitute a heterogenous population with diverse symptomatology. Progressive abdominopelvic disease can result in vaginal or diffuse pelvic bleeding, pain, and visceral or lymphovascular obstruction. Gynaecological cancer can also develop debilitating metastases, in particular to bone, central nervous system, or chest. Radiation therapy is a local-regional treatment modality, that, when applied judiciously, can lead to substantial symptomatic relief and tumour response. Individualized application is necessary, balancing efficacy and patient convenience versus treatment intensity, expected duration of palliation and potential toxicity. Important factors to consider are a patient's performance status, extent and sites of tumour, specific symptoms, and life expectancy. The optimal incorporation of radiotherapy is best achieved in the context of a multidisciplinary approach that addresses all facets of palliative care in patients with incurable gynaecological malignancies, to maximize their quality of life and functional level.
Best Pract Res Clin Obstet Gynaecol 2001 Apr
PMID:Palliative radiation therapy for gynaecological malignancies. 1135 1

Gynaecological malignancies affect the respiratory system both directly and indirectly. Malignant pleural effusion is a poor prognostic factor: management options include repeated thoracentesis, chemical pleurodesis, symptomatic relief of dyspnoea with oxygen and morphine, and external drainage. Parenchymal metastases are typically multifocal and respond to chemotherapy, with a limited role for pulmonary metastatectomy. Pulmonary tumour embolism is frequently associated with lymphangitic carcinomatosis, and is most common in choriocarcinoma. Thromboembolic disease, associated with the hypercoagulable state of cancer, is treated with anticoagulation. Inferior vena cava filter placement is indicated when anticoagulation cannot be given, or when emboli recur despite adequate anticoagulation. Palliative care has a major role for respiratory symptoms of gynaecological malignancies. Treatable causes of dyspnoea include bronchospasm, fluid overload and retained secretions. Opiates are effective at relieving dyspnoea associated with effusions, metatases, and lymphangitic tumour spread. Non-pharmacological therapies include energy conservation, home redesign, and dyspnoea relief strategies, including pursed lip breathing, relaxation, oxygen, circulation of air with a fan, and attention to spiritual suffering. Identification and treatment of gastroesophageal reflux, sinusitis, and asthma can improve many patients' coughs. Chest wall pain responds to local radiotherapy, nerve blocks or systemic analgesia. Case examples illustrate ways to address quality of life issues.
Best Pract Res Clin Obstet Gynaecol 2001 Apr
PMID:Pulmonary medicine and palliative care. 1135 3

Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression.
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PMID:Current options for palliative treatment in patients with pancreatic cancer. 1138 53

The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs, but also in a high percentage of small-cell lung cancers, stromal ovarian tumors, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the C-terminal CCK-receptor binding tetrapeptide sequence-Trp-Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of the gastrin or cholecystokinin families or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied and optimized in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in preclinical models. Best tumor uptake and tumor to nontumor ratios were obtained with members of the gastrin family, because of their superior selectivity and affinity for the CCK-B receptor subtype. Radiometal-labeled derivates of minigastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and healthy human volunteers. Preclinical therapy experiments in MTC-bearing animals showed significant antitumor efficacy. In a subsequent clinical study, 45 MTC patients with metastatic MTC were investigated; 23 had known and 22 had occult disease. CCK-B receptor scintigraphy was performed with (111)In-diethylenetriamine pentaacetic acid-d-Glu(1)-minigastrin. The normal organ uptake was essentially confined to the stomach (and, to a lesser extent, to the gallbladder and, in premenopausal women, to normal breast tissue) as a result of CCK-B receptor specific binding and to the kidneys, as excretory organs. All tumor manifestations known from conventional imaging were visualized as early as 1 hour postinjection, with increasing tumor to background ratios over time; at least 1 lesion was detected in 20 of 22 patients with occult disease (patient-based sensitivity, 91%). Among them were local recurrences and lymph node, pulmonary, hepatic, splenic, and bone (marrow) metastases. Eight patients with advanced metastatic disease were injected in a dose-escalation study with potentially therapeutic activities of a (90)Y-labeled minigastrin derivative at 4 to 6-week intervals (30-50 mCi/m(2) per injection for a maximum of 4 injections). Hematologic and renal toxicities were identified as the dose-limiting toxicities at the 40 and 50 mCi/m(2) levels. Two patients experienced partial remissions, and 4 experienced stabilization of their previously rapidly progressing disease. These data suggest that CCK-B receptor ligands may be a useful new class of receptor-binding peptides for diagnosis and therapy of a variety of (CCK-B receptor expressing) tumor types. They allow for sensitive and reliable staging of patients with metastatic MTC. Initial therapeutic results are promising, but nephrotoxicity is a major concern to be solved.
 ...
PMID:Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies. 1196 5

In 30-50% of patients the liver is a preferred site of distant disease for many malignant tumours. Due to the high incidence, most of the available data relate to metastases arising from colorectal primaries. Surgical resection is at present the only treatment offering potential cure. The achievable 5-year survival rate is 30%. However, only 10-15% of patients with colorectal liver metastases can undergo potentially curative liver resection. Therefore, accurate staging is an important prerequisite in selecting patients who would benefit from surgery. Recurrence of hepatic metastases after potentially curative resection occurs in up to 60% of the cases. Results demonstrate that re-resection of liver metastases can provide long-term survival rates in a carefully selected group of patients without extrahepatic disease. Because of the high rate of recurrences following an apparently curative resection several authors investigated the use of adjuvant chemotherapy (systemic, intraportal, and hepatic arterial infusion). Until recently none had shown effectiveness. Pre-operative chemotherapy seems to be a promising approach in patients with liver metastases initially considered unsuitable for radical surgery. Recently, neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management with the aim of improving the results in resectable liver metastases. Interventional strategies (ethanol injection, cryosurgery, laser-induced thermotherapy, radio-frequency ablation) and combined modalities (surgical/interventional) are additive methods which may help to improve treatment results in the future.
Best Pract Res Clin Gastroenterol 2002 Apr
PMID:Resection and local therapy for liver metastases. 1196 40

Nuclear medicine is engaged with the detection of pathological processes with the help of radionuclides. An interesting approach is to target antigens, symporters, or receptors with diagnostic and therapeutic radionuclides. Different peptide receptors like somatostatin, bombesin/GRP or VIP are (over)expressed on cancer cells, and are therefore an ideal target for the diagnosis and therapy in nuclear medicine with radiolabeled peptides. The somatostatin analogue OctreoScan [octreotide coupled with diethylene-triamine-pentaacetate (DTPA)] can be labeled with In-111 and is widely used in nuclear oncology for the staging of different tumors (e.g., carcinoids). Other peptides like neurotensin, bombesin/GRP, and VIP are under (pre)clinical investigations. The staging of metastatic medullary thyroid cancer (MTC) with the conventional radiological procedures is sometimes difficult. The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic MTC indicates the presence of tumor, but its localization is often not possible. This reaction of the tumor cells to the pentagastrin stimulation test suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in over 90% of MTCs, but in a high percentage of small cell lung cancers, stromal ovarian, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our recent work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the C-terminal CCK receptor binding tetrapeptide sequence -Trp-Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of the gastrin- or cholecystokinin families, or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied and optimized in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in preclinical models. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family, due to their superior selectivity and affinity for the CCK-B receptor subtype. Radiometal-labeled derivatives of minigastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and healthy human volunteers. Preclinical therapy experiments in MTC-bearing animals showed significant antitumor efficacy. In a subsequent clinical study, 75 MTC patients with metastatic MTC were investigated; 43 suffered of known, 32 of occult disease. CCK-B receptor scintigraphy was performed with (111)In-DTPA-D-Glu(1)-minigastrin. The normal organ uptake was essentially confined to the stomach (and to a lower extent, to the gallbladder and, in premenopausal women, to normal breast tissue) as a result of CCK-B receptor specific binding, and to the kidneys as excretory organs. All tumor manifestations known from conventional imaging were visualized as early as 1 h p.i., with increasing tumor-to-background ratios over time; at least one lesion was detected in 29/32 patients with occult disease (patient-based sensitivity 91%). Among them were local recurrences, lymph node, pulmonary, hepatic, splenic, and bone (marrow) metastases. Eight patients with advanced metastatic disease were injected in a dose-escalation study with potentially therapeutic activities of a (90)Y-labeled minigastrin derivative at 4-6-weekly intervals (30-50 mCi/m(2) per injection for a maximum of four injections). Hematologic and renal were identified as the dose-limiting toxicities at the 40 and 50 mCi/m(2) levels. Two patients experienced partial remissions, 4 stabilization of their previously rapidly progressing disease. These data suggest that CCK-B receptor ligands may be a useful new class of receptor binding peptides for diagnosis and therapy of a variety of (CCK-B receptor expressing) tumor types. They allow for a sensitive and reliable staging of patients with metastatic MTC. Initial therapeutic results are promising, but nephrotoxicity is a major concern to be solved.
 ...
PMID:Cholecystokinin-B (CCK-B)/gastrin receptor targeting peptides for staging and therapy of medullary thyroid cancer and other CCK-B receptor expressing malignancies. 1265 27

Prognosis depending on clinical presentation The prognosis of carcinomas of unknown primary site (CUP) is poor, with median survival of 8 months. Prognosis is better for specific clinical forms. Recent predictive models rely on the general status of the patient and simple biological parameters (lacticodehydrogenase or alkaline phosphatase levels) refine the prognostic assessment of CUP except in certain specific clinical forms. Treatment of specific clinical forms Cervical node metastases revealing an unfound epidermoid carcinoma require surgical node excision and radiotherapy. Axillary node metastases in woman require lymph node excision and systemic adjuvant therapy, similar to that used in breast cancer. The management of peritoneal serous papillary carcinomatosis in women consists in chemotherapy as in ovarian cancer, combined with debulking surgery. Median line syndrome requires radiotherapy or chemotherapy (with a cisplatin-etoposide combination or the regimen used for treatment of germ-cell tumours). Other therapeutic possibilities Excluding these forms, no chemotherapy regimen is a gold standard. Best supportive care is an acceptable option. There is little data on locoregional treatments.
 ...
PMID:[Prognosis and possibilities of treatment of inaugural metastases]. 1287 31

Vulvar cancer is a rare disease. Squamous-cell carcinomas account for 90% of vulvar cancers. The main mode of spread is lymphogenic to the inguinofemoral lymph nodes. Therefore, elective uni- or bilateral inguinofemoral lymphadenectomy is part of the standard treatment in combination with radical (wide) local excision of the vulvar tumour. Lymph drainage studies in relation to the biological behaviour of vulvar cancer are presented, as well as the anatomy and surgery of the groin. The sentinel lymph node procedure is a relatively new method of staging in vulvar cancer which may lead to the omission of inguinofemoral lymphadenectomy in those patients identified as not having inguinofemoral lymph node metastases. The accuracy of this technique appears to be high, but its safety still has to be proven. Moreover, the role of additional histopathological techniques for the examination of the sentinel lymph nodes needs to be established.
Best Pract Res Clin Obstet Gynaecol 2003 Aug
PMID:Groin surgery and the sentinel lymph node. 1296 33

Radiotherapy may be used in the treatment of vulval cancer as an alternative to surgery in unfit patients, as an adjuvant to surgery in patients with poor prognosis tumours and for the treatment of inoperable, recurrent and metastatic disease. High-energy X-rays, electrons and both superficial mould and interstitial brachytherapy may be integrated in the regimen to produce the maximum tumour control and minimum morbidity. Concomitant chemoradiotherapy has a high response rate and may be used before surgery to reduce the morbidity of otherwise sphincter-sacrificing procedures. This chapter presents the historical development of radiotherapy for vulval cancer, the role of radiotherapy in the treatment of the primary tumour and also the loco-regional nodes, both for prophylaxis and for proven node metastasis. Techniques for delivering radiotherapy are then discussed and are followed by protocols detailing radiotherapy and chemotherapy doses for different clinical situations.
Best Pract Res Clin Obstet Gynaecol 2003 Aug
PMID:Radiotherapy and chemoradiotherapy for carcinoma of the vulva. 1296 37


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