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)

Esophageal, gastric, and pancreatic cancers frequently present with extensive local regional disease, which can be difficult to resect or to definitively control with radiation therapy given as a single modality. In addition, these patients are at high risk for the development of distant metastasis. Neoadjuvant chemotherapy is a promising experimental approach for the use of combined modality treatments that involve a systemic component. The theoretical background for the use of chemotherapy followed by an operation or chemotherapy plus radiation in these tumors has been extensively described. For esophageal cancer, many phase II trials have demonstrated tolerance to systemic chemotherapy; chemotherapy plus radiation prior to operation has more toxicity. Definitive phase III studies testing the hypothesis that this approach is superior to operation alone have recently been performed in the United States and Europe. These data are currently being analyzed. For the use of combined modality therapy of chemoradiation, random assignment trials have demonstrated an improvement in cure rate for patients with squamous cell carcinomas of the esophagus. Preliminary data suggest a similar outcome for adenocarcinoma, but the number of patients who have been studied is smaller. Newer phase III studies involve the use of new systemic agents that have demonstrated activity in metastatic disease (such as paclitaxel) or the use of higher doses of radiation therapy. For gastric cancer, a substantial number of phase II trials have again demonstrated tolerance to preoperative chemotherapy with no increase in operative morbidity or mortality. Small-scale phase III trials have been performed that suggest an improvement in outcome. Definitive studies are in the planning stage. Finally, for pancreatic carcinoma, in which local control is an even more difficult issue, a major stumbling block remains the development of newer systemic therapies that have activity in this disease. The recent identification of gemcitabine as having modest activity as a single agent and its potential use with radiation therapy is being explored in the neoadjuvant setting.
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PMID:Neoadjuvant therapy for upper gastrointestinal tract cancers. 886 8

The standard approaches of surgery or radiotherapy cure only a minority of patients with esophageal cancer. Because of these poor results and the frequent systemic pattern of recurrences, combined-modality therapy employing chemotherapy has been extensively studied. Preoperative chemotherapy, both alone and given concurrently with radiation, has not shown a significant impact on survival and remains investigational. Concurrent chemoradiation as definitive therapy is an alternative to surgery for localized disease. Paclitaxel and vinorelbine have significant activity as single agents in metastatic disease. Paclitaxel is currently under investigation in combination therapy for metastatic disease, as a radiosensitizer for locally advanced disease, and as preoperative therapy. For palliation of locally advanced esophageal cancer, a variety of endoscopic techniques are available to relieve dysphagia. Laboratory studies have identified growth factor pathways and tumor-suppressor genes as potential new pharmacologic targets.
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PMID:Management of esophageal cancer. 888 28

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 889 33

In gastric cancer lymph node metastases at the hepatoduodenal ligament and in esophageal cancer, metastases at the celiac axis are classified as distant metastases (M1 LYMPH) and implying a poor prognosis. In pretherapeutic staging, imaging procedures such as computed tomography of the abdomen or transcutaneous ultrasonic examination are of limited value in the assessment of enlarged or metastatic lymph nodes. Conversely, laparoscopic staging with subsequent biopsy of suspicious lymph nodes provides essential diagnostic information. After exclusion of distant metastases (liver, lung, bone) in 73 patients with esophageal-(n = 21) and gastric cancer (n = 52), staging laparoscopy, including laparoscopic ultrasound, were performed during an 18-month-period (July/ 93-December/94). After laparoscopic exclusion of peritoneal seedings, the hepatoduodenal ligament was examined and enlarged lymph nodes were biopsied. In a total of 73 patients, laparoscopy revealed previously undiagnosed liver metastases in 14 and peritoneal carcinosis in 19 patients. Additionally, in eight (esophageal cancer; n = 3, gastric cancer; n = 5) of the remaining 40 patients, lymph nodes in the M1-position were regarded suspicious and biopsied. In six of these, malignant spread was observed. Thus, in a further six of 40 patients, surgically incurable situations could be detected. In esophageal and gastric cancer, staging laparoscopy, including laparoscopic ultrasound and biopsy, is a sensitive technique to assess local tumor spread and distant metastases. The detection of M1- lymph node metastases is facilitated by the use of laparoscopic ultrasound. Tumor spread, which limits surgical curability, can be properly assessed and exploratory laparotomy avoided.
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PMID:Laparoscopic lymph node assessment in pretherapeutic staging of gastric and esophageal cancer. 889 43

To define the rational extent of dissection in radical esophagectomy for esophageal cancer, survival was studied according to nodal status in 154 patients undergoing extended radical esophagectomy. The incidence of cervical metastasis in patients with upper or middle esophageal tumors did not differ between those with favorable (grade N < or = 4) or unfavorable (grade N > or = 5) lymph node status, at 28.6% vs 20%, respectively. On the other hand, in patients with lower esophageal tumors, the incidence of cervical metastasis was significantly lower in those with favorable grade (grade N < or = 4) node status than in those with unfavorable grade (grade N > or = 5) node status, at 6.5% vs 46.7%, respectively. Survival did not differ in patients with upper or middle esophageal tumors according to whether they had regional (n = 42) or distant (n = 15) lymph node metastases, the 5-year survival rates being 11.6% vs 25%, respectively. However, in patients with lower esophageal tumors, none of 10 patients with distant node metastases survived for more than 4 years, whereas the survival rate was 43.7% at 5 years for 36 patients with regional node metastases. These results show that cervical lymphadenectomy should only be performed as part of radical esophagectomy in those patients with upper or middle esophageal cancer.
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PMID:Evaluating the rational extent of dissection in radical esophagectomy for invasive carcinoma of the thoracic esophagus. 903 93

The interum results of a multicenter study on extended segmentectomy for small lung tumors and the results reported by Lung Cancer Study Group are discussed. The multi-center study was started in 1992. The inclusion criterium was the presence of a peripheral tumor of less than 2 cm in diameter on chest X-ray films. Seventy three patients were initially enlisted for the study, but 18 patients underwent lobectomy instead because of various reasons such as true or false-positive N1 or N2 disease. The remaining 55 patients were enrolled in this study. The lymph nodes around the segmental and lobar bronchi were examined during operation using fronzen section. Dissection or sampling of the mediastinal lymph nodes was documented. The amount of lung tissues resected was actually more than one segment, because the resection line far entered the adjacent one. Five patients died; one due to local recurrence, known to have the close resection line to the tumor and one of acute myocardial infarction, one of cerebral stroke, one for esophageal cancer and one due to pulmonary metastases on the non-affected side, with no evidence of local recurrence except the first patients. The interim results suggest that the extended segmentectomy is suitable for patients with N0 small tumors.
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PMID:[Extended segmentectomy for small lung cancer]. 904 15

A total of 188 cases of nonresected esophageal cancer were categorized into the following groups based on T category. (1987 UICC) and radiological classification (Japanese Society of Esophageal Diseases); Group 1: superficial or early (T2 or less) tumorous type; Group 2: advanced tumorous type, early serrated or early spiral type; Group 3: others. The response to radiotherapy was significantly related to the group. According to the proportional hazard model, the important factors predicting long-term survival were T category, radiotherapy response at the end of treatment, and group. There was a tendency to obtain better local control in group 1 patients than in group 2 patients, but cause-specific survival was the same for both groups (mainly the appearance of distant metastases). Local control was poor in group 3. If the tumor response at 40Gy was excellent in group 2 patients, the main cause of death was distant metastases, much the same as in group 1 patients. However, if response at 40Gy was not excellent, the main cause of death was local failure even though final tumor response was excellent. It seemed that therapy that may improve local control is valuable for group 3 patient, and for group 2 patients whose tumor response at 40Gy was not excellent.
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PMID:[Radiotherapy of esophageal cancer: clinical usefulness of new grouping]. 912 76

54 patients suffering from esophageal cancer have been treated in a period from 1990 to 1994. In 29 cases curative resection was possible, corresponding to a resection rate of 54%. Average age of resected patients was 62 years. According to pTNM-classification the stages T1 and T2 amounted to 45%, T3 and T4 to 55%. Lymphatic node metastases were discovered with an incidence of 55%. In patients treated conservatively more unfavourable stage distributions and increased rates of lymphatic node metastasis were shown. Transthoracal-transabdominal esophageal resection was preferred as curative management. Lethality amounted to 13.8%. In 3 of 4 lethal cases after resection autopsy confirmed absence of tumor. Lethal complications were two respiratory insufficiencies, one suture line dehiscence and one alcoholic delirium. Survival rates were calculated by life-table-method. We consider the transthoracal-transabdominal esophageal resection as an acceptable therapeutic option in esophageal cancer offering a real chance of enduring curing.
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PMID:[Transthoracic-transabdominal resection of esophageal carcinoma]. 920 10

Between 1980 and 1995, 91 (13.7%) out of 666 patients were determined by pathologic staging to have a superficial squamous-cell esophageal carcinoma of the thoracic esophagus. The male to female ratio was 3.3:1, and the mean age 60 years. Postoperative mortality was 4.3%. The median follow-up was 48 months (range 3-179). Survival was significantly decreased with increased depth of tumour invasion and presence of nodal metastases (P=0.03). Recurrent disease was prevalent in patients with submucosal tumours compared to those with mucosal tumours (P < 0.05). Only intra-epithelial and intramucosal carcinomas deserve the definition of 'early' tumours. Given the relative inaccuracy of current staging modalities and the low morbidity and mortality rates associated with surgical resection, surgery appears to be the mainstay of treatment of superficial squamous-cell esophageal cancer.
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PMID:Prognosis of early squamous cell carcinoma of the esophagus after surgical therapy. 928 73

Locally advanced esophageal cancer, potentially curable with surgery or radiotherapy-based treatment, has a poor prognosis because of the eventual development of systemic metastatic disease in the majority of patients. Local recurrence of disease after local treatment modalities is equally problematic. The use of systemic chemotherapy in the surgical and radiation-based treatment of esophageal cancer is reviewed, including the approach of preoperative chemotherapy, preoperative concurrent chemotherapy plus radiotherapy, and chemoradiotherapy as definitive treatment without surgery. The use of chemoradiotherapy has clearly been shown to be superior to radiotherapy alone in the nonsurgical management of locoregional esophageal cancer. Recent trials suggest that preoperative chemoradiotherapy may be superior to surgery alone but trials are ongoing to better define the role of combined modality therapy in the surgical management of esophageal cancer.
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PMID:Neoadjuvant therapy of esophageal cancer. 930 90


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