Neoplasms of the esophagus and stomach

doi:10.1053/j.semnuclmed.2004.03.005

Seminars in Nuclear Medicine

Volume 34, Issue 3, July 2004, Pages 198-208

https://doi.org/10.1053/j.semnuclmed.2004.03.005 Get rights and content

Abstract

Esophageal cancer is one of the most lethal of all neoplasms. During the last two decades, there have been significant changes in the epidemiology and treatment of esophageal cancer. The incidence of adenocarcinoma is increasing whereas that of squamous cancer is decreasing. Surgery, the mainstay of treatment of esophageal cancer, has been used with neoadjuvant chemoradiotherapy to improve prognosis in patients with localized disease. Accurate staging is essential for selection of the best mode of therapy and to predict prognosis. In addition, with widespread use of neoadjuvant therapy, accurate assessment of response to therapy has become very important because responders have better a prognosis than nonresponders. Anatomical imaging methods, such as computed tomography and endoscopic ultrasonography, that are commonly used to evaluate esophageal cancer have shortcomings in demonstrating the true extent of disease and in assessing or predicting response to therapy. Positron emission tomography (PET) with 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) has been shown to be a useful adjunct to anatomical imaging methods. For initial staging of esophageal cancer, the combination of PET and endoscopic ultrasonography with fine-needle aspiration biopsy has been suggested to be the most effective strategy. For restaging and monitoring response to therapy, FDG-PET has been shown to be superior to conventional imaging. The incidence of gastric cancer is decreasing worldwide, but it is also a highly lethal cancer. Similar to esophageal cancer, noninvasive staging of this cancer is unsatisfactory. Approximately one-third of the patients thought to have limited disease and to be candidates for surgery by conventional staging methods, are found to have advanced disease at surgery. Only a few published studies have evaluated gastric cancer with FDG-PET. These studies suggest that FDG-PET may be useful in evaluating gastric cancers of intestinal type and nonmucinous tumors.

Section snippets

Esophageal cancer

The incidence and prevalence of esophageal cancer are increasing in the Western World. Whereas the incidence of squamous cell carcinoma is stable or decreasing, that of adenocarcinoma of the esophagus and gastroesophageal junction is increasing. Cancer of the esophagus is asymptomatic in its early stages; most cases are diagnosed at an advanced stage, when tumor has spread beyond the esophagus, which is the main reason for the overall poor prognosis of this cancer. Because of the inaccuracy of

Gastric cancer

Despite a universal decrease in the incidence and mortality of gastric cancer, it remains the second most common cause of cancer-related death in the world. The overall 5-year survival rate of gastric cancer is less than 25%.38 One of the important predisposing factors for the development of gastric cancer is repeated infection with H. pylori. Gastric cancer is classified based on its macroscopic appearance or histologic characteristics. There are two major subgroups; the intestinal type that

References (43)

J Romagnuolo et al.
Helical CT versus EUS fine needle aspiration for celiac nodal assessment in patients with esophageal cancer
Gastrointest Endosc
(2002)
B Kumbasar
Carcinoma of esophagusRadiologic diagnosis and staging
Eur J Radiol
(2002)
T Lerut et al.
Cancer of the esophagus and gastro-esophageal junctionPotentially curative therapies
Surg Oncol
(2001)
M.I Block et al.
Improvement in staging of esophageal cancer with the addition of positron emission tomography
Ann Thorac Surg
(1997)
J.D Luketich et al.
The role of positron emission tomography in staging esophageal cancer
Ann Thorac Surg
(1997)
S.C Rankin et al.
Computed tomography and positron emission tomography in the pre-operative staging of oesophageal carcinoma
Clin Radiol
(1998)
H.W.D Yeung et al.
FDG-PET in esophageal cancerincremental value over computed tomography
Clin Pos Imaging
(1999)
K Kim et al.
Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography
Ann Thorac Surg
(2001)
M.B Wallace et al.
An analysis of multiple staging management strategies for carcinoma of the esophagusComputed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy
Ann Thorac Surg
(2002)
S Law et al.
Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagusA perspective randomized trial
J Thorac Cardiovasc Surg
(1997)

H Kato et al.

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer

Am J Surg

(2002)

J.R Kroep et al.

positron emission tomography using 2-deoxy-2-¹⁸F]-fluoro-D-glucose for response monitoring in locally gastroesophageal cancerA comparison of different analytic methods

Mol Imaging Biol

(2003)

P Flamen et al.

The utility of positron emission tomography for the diagnosis and staging of recurrent esophageal cancer

J Thorac Cardiovasc Surg

(2000)

A Jemal et al.

Cancer Statistics, 2004

CA Cancer J Clin

(2004)

H Vermund et al.

Neoadjuvant chemoradiation therapy in patients with surgically treated esophageal cancer

Acta Oncol

(2001)

S.M Wren et al.

Positron emission tomography in the initial staging of esophageal cancer

Arch Surg

(2002)

W.E Fickling et al.

Endoscopic ultrasound and upper gastrointestinal disorders

J Clin Gastroenterol

(2003)

F.L Flanagan et al.

Staging of esophageal cancer with FDG-PET

AJR

(1997)

A.C Kole et al.

Positron emission tomography for staging oesophageal and gastroesophageal malignancy

Br J Cancer

(1998)

D McAteer et al.

Evaluation of ¹⁸F-FDG positron emission tomography in gastric and oesophageal carcinoma

Br J Radiol

(1999)

P Flamen et al.

Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma

J Clin Oncol

(2000)

Cited by (48)

LMX1B involved in the radioresistance, proliferation and migration of esophageal cancer cells
2019, Biomedicine and Pharmacotherapy
Esophageal cancer (EC) is one of the most difficult malignancies to cure. The radioresistance remains a major obstacle for effective treatment of EC.
Esophageal cancer radioresistant cell lines were screened by the cumulative dose of radiation assays. qRT-PCR and Western blotting assays were used to detect the expression of LMXIB in EC. The survival fraction experiments were performed to test the effects of LMXIB in the radioresistance of EC. Following, the ionizing radiation and clonogenic, cell proliferation, wound healing and Flow cytometry apoptosis assays were used to characterize the properties of these cell lines.
We found that the LMX1B gene, encoding a LIM-homeodomain transcription factor, is expressed in a higher level in the radio-resistant EC cell lines. The following radiation assays revealed that LMX1B promotes the radioresistance of EC cells. Moreover, LMX1B plays roles in the proliferation, cell migration and apoptosis of EC cells.
All these results indicated that LMX1B is a key regulator involved in the radioresistance of EC, which might be used as a biomarker to guide the clinical therapy of EC.
Positron Emission Tomography/Computed Tomography in Esophageal Carcinoma: Applications and Limitations
2017, Seminars in Ultrasound, CT and MRI
Squamous cell carcinoma and adenocarcinoma represent approximately 98% of esophageal malignant tumors. During the last 30 years, the incidence of adenocarcinoma has increased in Western countries (including the USA) where adenocarcinoma currently represents more than 60% of esophageal malignancies, although, worldwide, squamous cell carcinoma continues to be the predominant histologic type. Integrated positron emission tomography or computed tomography with 2-[fluorine18] fluro-2-deoxy-d-glucose is used in many institutions routinely as a tool in the initial staging and then repeated after therapy for the assessment of response to neoadjuvant therapy and detection of recurrent disease in patients with esophageal carcinoma. As with any other imaging modality, 2-[fluorine18] fluro-2-deoxy-d-glucose-positron emission tomography or computed tomography has strengths and limitations that should be understood in order to maximize its utility.
Imaging of oesophageal cancer with FDG-PET/CT and MRI
2015, Clinical Radiology
Citation Excerpt :
Conversely, false-positive results may result from benign lesions, such as leiomyoma or secondary inflammation caused by chemotherapy, radiation treatment, Candida infection, gastro-oesophageal reflux disease, oesophageal spasm, Barrett's oesophagus, or bacterial infection with peptic strictures.30–35 However, non-malignant PET hypermetabolism is often linear in shape involving a long cranio-caudal segment with relatively low intensity and, therefore, can often be easily distinguished from more focal and intense malignant lesions.29,36 Another consequence of the poor spatial resolution of PET and the poor contrast resolution of CT, is the limited role of these techniques in evaluating the depth of invasion (e.g. T-stage) of oesophageal cancers.37
Integrated 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (FDG) PET/CT and magnetic resonance imaging (MRI) with functional features of diffusion-weighted imaging (DWI) are advancing imaging technologies that have current and future potential to overcome important limitations of conventional staging methods in the management of patients with oesophageal cancer. PET/CT has emerged as an important part of the standard work-up of patients with oesophageal cancer. Besides its important ability to detect unsuspected metastatic disease, PET/CT may be useful in the assessment of treatment response, radiation treatment planning, and detection of recurrent disease. In addition, high-resolution T2-weighted MRI and DWI have potential complementary roles. Recent improvements in MRI protocols and techniques have resulted in better imaging quality with the potential to bring improvement in staging, radiation treatment planning, and the assessment of treatment response. Optimal use and understanding of PET/CT and MRI in oesophageal cancer will contribute to the impact of these advancing technologies in tailoring treatment to the individual patient and achieving best possible outcomes. In this article, we graphically outline the current and potential future roles of PET/CT and MRI in the multidisciplinary management of oesophageal cancer.
Extended staging of oesophageal cancer using FDG-PET - A critical appraisal
2012, European Journal of Radiology
Citation Excerpt :
Thus, while usually superior to CT alone, comparison of FDG PET with EUS appear to be somewhat mixed, showing PET to have a relatively low accuracy in several studies [3,34]. On the other hand, the specificity of FDG PET in detecting regional node disease is generally high, with false positive results being unusual, generally related to an inflammatory disease (including sarcoidosis), causing increased FDG uptake, and also to an heterogeneous primary tumour uptake mimicking a nodal disease [34,35]. The relatively low accuracy emphasized in some papers is due to a relatively low sensitivity.
Oesophageal cancer (OC) is a highly aggressive tumour with unfavorable prognosis due to early stages metastases. Treatment and survival rates are highly correlated with tumour wall invasion, lymphatic involvement and metastatic spread. Thus, an accurate staging at initial diagnosis is fundamental for optimal management. In the present review article the potential role of the FDG-PET in the staging of OC is discussed.
A systematic review of all papers published in PubMed until June 2010 was performed.
Endoscopic ultrasound (EUS) is helpful for T and N staging but not for M staging. CT plays a complementary role to EUS in T staging, especially in excluding T4 disease. However, in N staging, CT relies on “size criteria” (<1cm = benign, >1cm = malignant) which reduces its sensitivity and specificity.
FDG-PET has been demonstrated to be a very helpful tool in staging and re-staging OC. Most OCs demonstrate high FDG accumulation and are usually well detected with PET. Unfortunately, PET cannot reveal very small lesions due to its limited spatial resolution, therefore limiting the usefulness of PET in T staging. In N staging, an FDG positive node is highly likely to contain disease. However, FDG-PET cannot reliably separate the primary site from closely adjacent nodes.
The real and unquestionable additional diagnostic value of FDG-PET in comparison to CT and EUS is in evaluating distant metastases.
It appears reasonable to include FDG PET/CT in the diagnostic algorithm of patients with OC in order to better define the optimal therapeutic approach.
Evaluation of the Hsp90 inhibitor NVP-AUY922 in multicellular tumour spheroids with respect to effects on growth and PET tracer uptake
2009, Nuclear Medicine and Biology
Molecular targeting has become a prominent concept in cancer treatment and heat shock protein 90 (Hsp90) inhibitors are suggested as promising anticancer drugs. The Hsp90 complex is one of the chaperones that facilitate the refolding of unfolded or misfolded proteins and plays a role for key oncogenic proteins such as Her2, Raf-1, Akt/PKB, and mutant p53. NVP-AUY922 is a novel low-molecular Hsp90 inhibitor, currently under clinical development as an anticancer drug. Disruption of the Hsp90-client protein complexes leads to proteasome-mediated degradation of client proteins and cell death.
The aim of the current study was to use a combination of the multicellular tumour spheroid (MTS) model and positron emission tomography (PET) to investigate the effects of NVP-AUY922 on tumour growth and its relation to PET tracer uptake for the selection of appropriate PET tracer. A further aim was to evaluate the concentration and time dependence in the relation between growth inhibition and PET tracer uptake as part of translational imaging activities.
MTS of two breast cancer cell lines (MCF-7 and BT474), one glioblastoma cell line (U87MG) and one colon carcinoma cell line (HCT116) were prepared.
Initially, we investigated MTS growth pattern and ³H-thymidine incorporation in MTS after continuous exposure to NVP-AUY922 in order to determine dose response. Then the short-term effect of the drug on the four PET tracers 2-[¹⁸F] fluoro-2-deoxyglucose (FDG), 3′-deoxy-3′-fluorothymidine (FLT), methionine and choline was correlated to the long-term effect (changes in growth pattern) to determine the adequate PET tracer with high predictability.
Next, the growth inhibitory effect of different dose schedules was evaluated to determine the optimal dose and time. Finally, the effect of a 2-h exposure to the drug on growth pattern and FDG/FLT uptake was evaluated.
A dose-dependent inhibition of growth and decrease of ³H-thymidine uptake was observed with 100% growth cessation in the dose range 7–52 nM and 50% ³H-thymidine reduction in the range of 10–23 nM, with the most pronounced effect on BT474 cells.
The effect of the drug was best detected by FLT. The results suggested that a complete cessation of growth of the viable cell volume was achieved with about 50% inhibition of FLT uptake 3 days after continuous treatment.
Significant growth inhibition was observed at all doses and all exposure time spans. Two-hour exposure to NVP-AUY922 generated a growth inhibition which persisted dose dependently up to 10 days. The uptake of FDG per viable tumour volume was reduced by just 25% with 300 nM treatment of the drug, whereas the FLT uptake decreased up to 75% in correlation with the growth inhibition and recovery.
Our results indicate a prolonged action of NVP-AUY922 in this cell culture, FLT is a suitable tracer for the monitoring of the effect and a FLT PET study within 3 days after treatment can predict the treatment outcome in this model. If relevant in vivo, this information can be used for efficient planning of animal PET studies and later human PET trial.
Impact of the introduction of integrated PET-CT into the preoperative staging pathway of patients with potentially operable oesophageal carcinoma
2008, Clinical Radiology
Citation Excerpt :
Accurate staging is essential to guide appropriate treatment and can help predict prognosis and select patients likely to most benefit from multimodal therapy. Treatment options include radiotherapy alone, combination chemoradiotherapy, surgery alone, or chemoradiotherapy followed by surgery.2 TNM staging is used, which considers local spread of tumour (T), regional lymph node involvement (N), and distant metastases (M).
To retrospectively evaluate the role of integrated positron emission tomography computed tomography (PET-CT) in oesophageal carcinoma staging, in predicting prognosis and its influence on surgical management.
Twenty-five consecutive patients with potentially operable, biopsy-proven oesophageal malignancy who undergoing PET-CT from September 2004 to April 2007 were included in this study. Chi-square and Fisher's exact tests were used to compare the accuracy of N staging with PET-CT and CT/endoscopic ultrasound (EUS) using postoperative loco-regional nodal histology as the reference standard. The prognostic value of primary tumour maximum standardized uptake value (SUVmax) was derived using logistic regression.
Seventeen men and eight women with a mean age of 62 years were studied. All tumours showed abnormal 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (FDG) uptake. Fifteen patients underwent surgical resection. There was high concordance between N staging at CT/EUS (14/15) and final histology. PET-CT N staging was discordant with final nodal histology in over half of the patients (8/15). PET-CT detected occult metastases in three patients (12%) that were not identified on CT and new synchronous tumours in two patients (8%). Patient management was altered in 10 patients (40%) as a direct result of PET-CT. No statistically significant association was observed between SUVmax and clinical outcome (p = 0.65).
Integrated PET-CT has a significant incremental value over conventional staging investigations mainly in the detection of distant metastases and synchronous tumours and frequently impacts on patient management.

View all citing articles on Scopus

View full text

Neoplasms of the esophagus and stomach

Abstract

Section snippets

Esophageal cancer

Gastric cancer

Gastrointest Endosc

Eur J Radiol

Surg Oncol

Ann Thorac Surg

Ann Thorac Surg

Clin Radiol

Clin Pos Imaging

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Am J Surg

Mol Imaging Biol

J Thorac Cardiovasc Surg

Cancer Statistics, 2004

CA Cancer J Clin

Neoadjuvant chemoradiation therapy in patients with surgically treated esophageal cancer

Acta Oncol

Positron emission tomography in the initial staging of esophageal cancer

Arch Surg

Endoscopic ultrasound and upper gastrointestinal disorders

J Clin Gastroenterol

Staging of esophageal cancer with FDG-PET

AJR

Positron emission tomography for staging oesophageal and gastroesophageal malignancy

Br J Cancer

Evaluation of 18F-FDG positron emission tomography in gastric and oesophageal carcinoma

Br J Radiol

Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma

J Clin Oncol

Evaluation of ¹⁸F-FDG positron emission tomography in gastric and oesophageal carcinoma