Staging Of Gastrointestinal Cancers Research Articles

Effect of in vivo loss of GDF-15 on hepatocellular carcinogenesis

Growth/differentiation factor-15(GDF-15) is a divergent TGF-beta family member that is expressed following liver injury and carcinogen exposure. GDF-15 expression is highly associated with gastrointestinal cancer stage, size, and metastasis and has been implicated in inhibition of tumor growth and increased tumor invasiveness. The current study sought to determine the effect of GDF-15 ablation on the development of hepatocellular carcinoma (HCC) in vivo. Male mice genetically deleted for the gene encoding GDF-15 (Gdf15 (-/-) mice) and wild-type controls were exposed to the hepatocarcinogen diethylnitrosamine (DEN). Mice were killed at 6 months of age and their livers dissected and processed for histology. Tumor number and size relative to total liver area examined were determined. At 6 months of age, tumors were identified in 16 of 20 (80%) Gdf15 (-/-) mice and 16 of 19 wild-type mice (84%). No significant difference in tumor-occupied area was observed in Gdf15 (-/-) mice versus wild-type mice. In addition, no difference in invasiveness was observed in HCC arising in Gdf15 (-/-) as compared to wild-type mice. In wild type mice strong immunohistochemical staining for GDF-15 was noted on small HCC foci, whereas a loss of GDF-15 expression was found in a number of advanced HCC tumors. Although highly expressed in association with multiple gastrointestinal cancers, and lost in some advanced HCC, genetic ablation of GDF-15 has no apparent effect on HCC tumor formation rate, growth rate or invasiveness in diethylnitrosamine-induced HCC in vivo.

Complications of Endoscopic Ultrasonography (EUS) and EUS-Guided Fine Needle Aspiration (EUS-FNA): A Prospective Investigation in a Large Series of Patients

Background: EUS and EUS-FNA has been classically considered low-risk procedures. However, most studies are retrospective and therefore, the real incidence of complicactions could be underestimated. Aim: to prospectively investigate the incidence and predictive factors of complications after EUS and EUS-FNA. Patients and methods: Patients undergoing EUS or EUS-FNA from October 2005 to October 2006 were included. The procedure was performed under conscious sedation with continuous hemodynamic monitorization. Antibiotics were administered when a cystic lesion was sampled. Patients were systematically contacted by phone at 24 hours,1 week and 1 month after the procedure to ask for abdominal pain, fever or any other complain. Complications were considered severe when lead to stop the procedure or required hospitalization. Results: 740 patients were included. EUS-FNA was performed in 219 of them (29%). Indications were: gastrointestinal cancer staging (31%), lung cancer staging (4%), study of pancreatic lesions (26%), unexplained cholestasis (11%), submucosal tumors (14%) and other (14%). A total of 23 complications (3.1%) were observed. Within the severe complications (n = 9, 1.2%), 6 were related to the endoscopic technique itself (pancreatitis, n = 2; duodenal perforation, n = 1; GI bleeding, n = 1; sepsis n = 1: and hematoma of the piriform sinus, n = 1), and the remaining 3 to the sedation. Not severe complications were observed in 1.9% of patients: self-limited fever (n = 5), desaturation (n = 2), arrhythmia (n = 2), and other (n = 5). A previous history of cirrhosis (6% vs 1%; p = 0.04) and the duration of the procedure (42 vs 34 min; p < 0.05) were associated with a higher risk of developing severe complications. Conclusion: EUS and EUS-FNA are safe procedures. Cirrhosis and the duration of the procedure are associated with a higher risk of severe complications.

Accuracy of EUS with and without Preoperative Chemoradiation in Correlation with Pet Staging of Gastrointestinal Cancers

Accuracy of EUS with and without Preoperative Chemoradiation in Correlation with Pet Staging of Gastrointestinal Cancers

Endoscopic staging of low-grade gastric malt lymphoma

Endoscopic ultrasonography (EUS) has already proven useful in the assessment of submucosal lesions, and the staging of gastrointestinal cancer, particularly gastric MALT-type lymphoma. The goal of this paper was EUS staging. 24 patients (10 females, 14 males) with a median age of 56 years and possibly gastric MALT lymphoma (25 cases) were studied using videoendoscopy, biopsies, and echoendoscopy with 7.5- and 20-MHz radial EUS, and also with 12- and 20-MHz miniprobes (MPs). Nineteen patients were definitely evaluated (7 females, 12 males) as having 20 MALT-type lymphomas, as five patients were post-hoc disregarded when an invasive, high-grade gastric lymphoma (3c) or plasmocytoma (2c) was subsequently demonstrated. Of these 19 patients, all had T1 lesions except for two with T2 lesions; one patient had a gastroduodenal T1 lymphoma. Echographic findings with MPs were compared to EUS (gold standard) and histology both before and after eradication. Then, patients were followed up every 1-3-6 months using videoendoscopy and MPs. Echoendoscopy correctly identified T stages in 90% of cases. MPs identified T stages in 88% of cases, and N stages in 33% of cases, with results being slightly inferior to those obtained with conventional EUS (91 vs. 45%); they were consequently used for follow-up. After eradication, all but two patients are in complete remission and have been followed every 1-3-6 months using MPs without echographic abnormalities, except for a patient who relapsed.

Clinical, radiological and pathological staging of gastrointestinal cancer

Staging is the process that determines the spread of a malignant tumour, thereby providing prognostic information. It can be assessed by clinical, radiological and pathological means. Before accurate staging is undertaken, a diagnosis of cancer is required, which is usually made by histological examination of biopsy material; this may include imaging techniques to localize and sample the lesion. Once a diagnosis of malignancy is established, the extent of local invasion and the presence of distant metastases must be determined; this is usually undertaken using imaging methods. This contribution discusses the TNM system, staging of oesophageal and gastric carcinoma, staging of carcinoma of the small intestine, and staging of carcinoma of the anal region.

Endoscopic Ultrasound for Luminal Malignancies

Luminal gastrointestinal (GI) tract cancers are responsible for substantial morbidity and mortality. Since the first pairing of ultrasonography with endoscopy in 1980, technologic advances and the increased availability of trained endosonographers have propelled endoscopic ultrasonography (EUS) to the forefront of luminal GI cancer staging. In this article we discuss the role of EUS for evaluating luminal GI cancers.

Mediastinal adenopathy: finding the answer with endoscopic ultrasound‐guided fine‐needle aspiration biopsy

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS FNA) is a relatively new imaging modality that has been reported to be useful for mediastinal nodal staging of lung cancer and for the evaluation of mediastinal adenopathy of unknown cause. However, the technique is not commonly used in Australia. A retrospective review of all patients who had mediastinal EUS FNA was undertaken. Of a total of 787 patients who had undergone endoscopic ultrasound (EUS) studies from November 1999 to March 2004, 27 patients were identified to have had mediastinal EUS FNA. Details were recorded including study indication, history of malignancy, source of referral, prior attempts for tissue diagnosis, EUS and EUS FNA findings, complications, surgical pathology if available and clinical outcome after diagnosis. Mediastinal EUS FNA was performed on an outpatient basis and no complications were recorded. Diagnostic material was obtained from all patients with a mean number of three passes. Nodal stations sampled included left paratracheal, subcarinal, aortopulmonary window and inferior mediastinum. Indications for the studies included mediastinal adenopathy of uncertain cause (17), lung cancer staging (7) and gastrointestinal cancer staging (3). EUS FNA confirmed malignancy in 16/27 patients, sarcoidosis in three patients, tuberculosis in one patient and seven patients were deemed to have reactive adenopathy. Primary cytopathological diagnosis of malignancy was determined by EUS FNA in nine patients. EUS FNA is a safe, efficient and effective modality for mediastinal staging of lung cancer and for the diagnosis of mediastinal adenopathy of uncertain origin. EUS FNA has the potential to significantly impact on patient management, avoiding more invasive procedures as well as unnecessary operations.

Deteriorating Stage Profile of Gastrointestinal Cancer in Finland

The prognosis of patients with gastrointestinal (GI) cancer is mainly due to the stage of the tumor at the diagnosis. Regardless of several innovations in diagnostic and therapeutic gastroenterology, there is no longitudinal data of the trends of stage profile of patients with gastrointestinal cancer in Finland. To study the incidence by stage of GI cancer in Finland in the past 15 yr in the entire country as well as in two subpopulations with different population profile: in a population with a small number of residents over 65 yr of age (Jorvi district) and in a population with a large number of residents over 65 yr of age (Kanta-Häme district). The hospital discharge records of patients with upper or lower GI cancer between 1986 and 2000 were evaluated in Finland as well as in Jorvi and Kanta-Häme hospital districts. The data were obtained from the National Research and Development Centre for Welfare and Health, from the Centre of Statistics and from the Finnish Cancer Registry. The relative incidence of a localized esophagogastric cancer against more severe stages decreased from 37.9% to 29.3% in the entire country, from 40.8% to 19.1% in Kanta-Häme, and from 44.2% to 33.3% in Jorvi area. Respectively, the relative incidence of localized colorectal cancer decreased from 53.6% to 48.0% in the entire country, from 49.7% to 42.5% in Kanta-Häme, and from 54.5% to 48.4% in Jorvi area. During the past 15 yr the incidence by stage of both upper and lower GI cancer is deteriorating in the entire country as well as in areas with low and high percentage of residents over 65 yr of age indicating the increase of the more severe cases. The deterioration has become more pronounced in the 1990s, which requires a careful scrutiny of the function of primary diagnostic services.

The Clinical and Pathological Staging of Gastrointestinal Cancer

Staging is defined as the determination of the extent of spread of a malignant tumour. Such a determination can be made both clinically and pathologically. In this article, both of these assessments will be addressed for each of the major forms of gastrointestinal cancer.

Endoscopic ultrasonography.

Over the past two decades, endoscopic ultrasonography (EUS) has undergone a transition from being a novel imaging technique to a clinical diagnostic test that is necessary for the optimal management of gastrointestinal diseases. EUS has established itself as an important diagnostic modality, mainly for the detection and staging of gastrointestinal cancers. As EUS has become more widespread, research has gradually shifted towards studies that explore the effect of EUS on patient management and outcome. These outcome studies have examined the primary clinical applications of EUS, such as esophageal, gastric, pancreatic, and colorectal cancer staging, as well as the role of EUS in the diagnosis of inflammatory pancreatic diseases. Widespread use of EUS has recently led to studies that examine complications associated with the performance of the procedure. Endosonographers have continued efforts to define a clinical role for EUS in other gastrointestinal diseases, such as portal hypertension. EUS-guided fine-needle aspiration (FNA) is continuing to develop into a powerful diagnostic tool for the management of lung cancer and other mediastinal diseases. New applications for EUS-FNA are also emerging. Finally, investigators are continuing to explore the remaining frontier of EUS-guided therapy.

Endoscopic ultrasonography.

Endosonography is primarily a diagnostic imaging modality, but new therapeutic applications are being developed. Miniprobe technology (ultrasound catheter probes) has led to new clinical applications. The staging of gastrointestinal cancers remains the major accepted indication for endosonography. Other conditions, such as chronic pancreatitis, portal hypertension, and inflammatory bowel diseases, are also being evaluated with endosonographic imaging.

Gastrointestinal cancer staging by endoscopic ultrasound: Esophagus and gastric

Endoscopic ultrasound (EUS) is the latest major innovation in gastrointestinal endoscopy. The coupling of ultrasound with endoscopy allows visualization of the gastrointestinal mucosa and adjacent structures in such exquisite details heretofore unavailable with any other imaging modalities. EUS has made major impact on the practice of digestive diseases, particularly in the evaluation of esophageal and gastric cancer. EUS is now universally accepted as the imaging modality of choice for precise local-regional staging of these 2 malignancies. The application of EUS in esophageal and gastric cancer are described.

Endoscopic Ultrasound

Endoscopic ultrasound was introduced in the early 1980s. Today, endoscopic ultrasound remains the most accurate modality for local staging of gastrointestinal cancers but the emphasis is now on what findings will impact patient care. At the same time, a new era of interventional endoscopic ultrasound that might also be called image-directed therapies is emerging. The future looks bright for the further application of endoscopic ultrasound in gastrointestinal endoscopy. This article provides the current status and a glimpse into the future of endoscopic ultrasound.

Improving diagnostic staging laparoscopy using intraperitoneal lavage of δ-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis

Background: Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. Methods: Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine–induced colon carcinoma tumor cells (CC531, 5 × 105) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given δ-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO3) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. Results: Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light–induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. Conclusions: Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with δ-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci. (Surgery 1999;126:469-73)

Improving diagnostic staging laparoscopy using intraperitoneal lavage of [delta ]-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis

Background: Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. Methods: Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine–induced colon carcinoma tumor cells (CC531, 5 × 105) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given δ-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO3) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. Results: Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light–induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. Conclusions: Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with δ-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci. (Surgery 1999;126:469-73)

The Importance of Staging Laparoscopy for the Treatment of Gastric Cancer

Staging laparoscopy is a safe and efficient technique for staging of gastrointestinal cancer. Given the remarkable therapeutic relevance and the low morbidity associated with this technique, it seems justified to perform staging laparoscopy in patients with nonobstructed, nonbleeding advanced gastric cancer. Laparoscopy can avoid the hazards of unnecessary exploratory laparotomy in asymptomatic patients. Laparoscopy and laparoscopic ultrasound appear to be superior to otherpreoperative imaging modalities. Accurate evaluation of neo-adjuvant therapy protocols clearly necessitates precise stagingto warrant a valuable assessment of the efficacy of the protocol. We provide an overview on the recent experience with laparoscopy in the staging of patients with gastric cancer on the basis of our own experience in comparison to reports in the literature.

Radiologic staging of gastrointestinal cancer.

Pre-operative staging should define the probable course of a patient's disease, separate the resectable from the unresectable patients, and identify the patients who are candidates for induction therapy. Pre-operative staging must be well tolerated and should provide new or important information that will affect the proposed treatment plan. For some diseases such as colon cancer, pre-operative staging is largely unnecessary, but it can be of great value for other tumors such as pancreatic cancer. Currently, many imaging techniques are available to evaluate gastrointestinal cancers, and each provides information necessary for directing treatment. Although no individual technique can stage patients with complete accuracy, combinations of the various imaging techniques can be used to increase accuracy and promote appropriate decisions about an individual's treatment options. The use of current imaging techniques for staging primary lesions, regional spread, and the intra-abdominal metastatic spread of the most common gastrointestinal malignancies are reviewed.

Gastrointestinal cancer staging by endoscopic ultrasonography.

Gastrointestinal cancer staging by endoscopic ultrasonography.

Isoechoic tumor extension improves the accuracy of endoscopic ultrasound gastrointestinal cancer staging

Isoechoic tumor extension improves the accuracy of endoscopic ultrasound gastrointestinal cancer staging

Immunological significance of lymphoreticular infiltration in gastrointestinal cancer.

The 60 patients of gastrointestinal cancer comprising this study were in the age range of 29--70 years with 39 males and 21 females. The primary sites of cancer were: gallbladder 19, colon 13, stomach 12, anorectum 8, and liver 8. The stage of tumor spread was localized in 32 and metastatic in 28 cases. Round cell infiltration scores were classified semiquantitatively from O-V. Cellular immunity as expressed by the blood lymphocyte count and DNCB reactivity was also studied. Round cell infiltration was dense in the localized group (P less than 0.0005). The mean lymphocyte counts in all the primary sites of gastrointestinal cancer were significantly higher in the localized group as compared to metastatic group. The DNCB reactivity showed anergy in six cases and poor response in the remaining 22 cases of metastatic group. There was a statistically significant correlation between lymphoreticular infiltration, peripheral blood lymphocyte count, and the DNCB reactivity. Diminished round cell infiltration, lymphopenia, and depressed DNCB response indicate an advanced stage of gastrointestinal cancer.