Background
Due to proliferation and increased metabolism, cancer cells have high glucose requirements. The glucose uptake of cells is influenced by a group of membrane proteins denoted the glucose ...transporter family (Glut-1 to -12). Whereas increased expression and a negative correlation with survival have been described for Glut-1 in several types of cancer, the impact of other glucose transporters on tumor biology is widely unknown.
Methods
In this retrospective study, gastric cancer specimens of 150 patients who underwent total gastrectomy between 2005 and 2010 were stained for Glut-1, -3, -6, and -10 by immunohistochemistry. Expression of Glut-1, -3, -6, and 10 was correlated to prognosis as well as clinical and pathological parameters.
Results
Glut-1, Glut-3, Glut-6, and Glut-10 were expressed in 22.0, 66.0, 38.0, and 43.3 % of the analyzed samples. Whereas Glut-1, -6, and -10 did not show a correlation with prognosis, positive staining for Glut-3 was associated with higher UICC stage and inferior prognosis. The mean overall survival was 38.6 months for Glut-3 positive patients, as compared to 51.2 months for Glut-3 negative patients (
p
< 0.05). Coexpression of two or more of the analyzed glucose transporters was correlated to inferior prognosis. Glut-3 and UICC stage were significant prognostic factors in multivariate analysis.
Conclusions
All of the analyzed glucose transporters were expressed in a significant proportion of the gastric cancer samples. Glut-3 was associated with higher UICC stage and inferior prognosis. These findings are relevant to therapeutic approaches that target glucose metabolism as well as to imaging using radioactively labeled glucose.
Purpose
Therapeutic decisions in esophageal adenocarcinomas (EAC) restricted to mucosa (pT1a) or submucosa (pT1b) depend mainly on classic histomorphology-based criteria like tumor grading or ...lymphovascular invasion with limited success. There is a strong need for reliable pre-therapeutical biomarker-based evaluation also applicable on endoscopically obtained biopsies.
Methods
Patients who underwent esophagectomy due to EAC in a high volume center between 1999 and 2016 were included. Tissue microarrays (TMA) were retrospectively established from the formalin-fixed and paraffin-embedded material of the resected specimens and immunohistochemically stained using a monoclonal primary antibody specific for IMP3. IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong).
Results
371 EACs were interpretable for analysis. 109 patients (29%) had early invasive (pT1a/pT1b) and 262 patients (71%) locally advanced EAC (> pT2). 259 EACs (70%) revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. Early EAC had significantly lower IMP3 expression compared to advanced tumor stages (
p
< 0.0001). IMP3 positive pT1 EAC revealed higher levels of lymph node metastases (LNM) (
p
= 0.0001) and pT1b tumors showed higher rates of IMP3 positivity compared to pT1a (
p
= 0.007). Subdividing the submucosa in thirds, there was a significant trend for higher IMP3 expression with deeper tumor infiltration from pT1a to pT1b (sm3) (
p
= 0.0001). There was an association between IMP3 expression and shortened survival in pT1 EAC (
p
= 0.038).
Conclusions
IMP3 expression correlates with depth of tumor infiltration, rate of LNM and is associated with worse outcome. Thus, IMP3 might be useful for therapeutic decisions in early-invasive EAC.
Esophagogastric junction (EGJ) cancer is a solid tumor entity with rapidly increasing incidence in the Western countries. Given the high proportion of advanced cancers in the West, treatment ...strategies routinely employed include surgery and chemotherapy perioperatively, and chemoradiation in neoadjuvant settings. Neoadjuvant chemoradiation and perioperative chemotherapy are mostly performed in esophageal cancer that extends to the EGJ and gastric as well as EGJ cancers, respectively. Recent trials have tried to combine both strategies in a perioperative context, which might have beneficial outcomes, especially in patients with EGJ cancer. However, it is difficult to recruit patients for trials, exclusively for EGJ cancers; therefore, the results have to be carefully reviewed before establishing a standard protocol. Trastuzumab was the first drug for targeted therapy that was positively evaluated for this tumor entity, and there are several ongoing trials investigating more targeted drugs in order to customize effective therapies based on tissue characteristics. The current study reviews the multimodal treatment concept for EGJ cancers in the West and summarizes the latest reports.
A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this ...study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model.
An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart).
Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K
=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K
=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance.
Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.
The utility of 18-fluordesoxyglucose positron emission tomography (
F-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a ...rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based
F-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake.
Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX.
F-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake.
Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049).
This preclinical gastric cancer PDX based
F-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.
In the present study we review and discuss the current evidence and suggest how to proceed in the management of oligometastatic disease in upper gastrointestinal cancer.
An electronic search of the ...PubMed database for relevant articles was performed.
Both the search for 'oligometastasis', 'oligometastases', 'oligometastatic', 'oligometastatic disease' as well as 'esophageal' and 'esophageal cancer' and the search for 'oligometastasis', 'oligometastases', 'oligometastatic', 'oligometastatic disease' as well as 'gastric', 'gastric cancer', 'stomach', and 'stomach cancer' yielded very few studies. Most data need to be extrapolated in general studies on oligometastatic diseases of different origins. No randomized controlled trial could be found.
In the absence of data to formulate recommendations on how to proceed in the treatment of oligometastatic disease in upper gastrointestinal cancer, a more aggressive treatment of oligometastatic disease can be considered in patients whose tumors show a more favorable neoplastic behavior after the 'test of time'. The RENAISSANCE study will certainly deliver important data regarding this aspect.
Bleeding of an aberrant right subclavian artery following transthoracic en bloc esophagectomy and intrathoracic gastric reconstruction is a rare but severe complication in esophageal surgery. ...Preoperative diagnosis can be achieved by computed tomography or magnetic resonance angiography (MRA). Various treatment options are available; thus, the treatment can be challenging and should be adjusted to the severity of the symptoms. Bleeding of an aberrant right subclavian artery can result from perioperative vascular injury or various postoperative complications. We report about a case of a patient with esophageal cancer and an asymptomatic, simultaneously existing aberrant right subclavian artery. The patient underwent a successful conventional Ivor-Lewis esophageal resection without any life-threatening bleeding. Early detection and intraoperative identification was of major importance for successful surgery.
Introduction
In minimally invasive esophagectomy, a circular stapled anastomosis is common, but no evidence exists investigating the role of the specific localization of the anastomosis. The aim of ...this study is to evaluate the impact of an esophagogastrostomy on the anterior or posterior wall of the gastric conduit on the postoperative outcomes.
Material and methods
All oncologic minimally invasive Ivor Lewis procedures, performed between 2017 and 2022, were included in this study. The cohort was divided in two groups: a) intrathoracic esophagogastrostomy on the anterior gastric wall of the conduit (ANT,
n
= 285, 65%) and b) on the posterior gastric wall (POST,
n
= 154, 35%). Clinicopathological parameters and short-term outcomes were compared between both groups by retrieving data from the prospective database.
Results
Overall, 439 patients were included, baseline characteristics were similar in both groups, there was a higher proportion of squamous cell carcinoma in ANT (22.8% vs. 16.2%,
P
= 0.043). A higher rate of robotic-assisted procedures was observed in ANT (71.2% vs. 49.4%). Anastomotic leakage rate was similar in both groups (ANT 10.4% vs. POST 9.8%,
P
= 0.851). Overall complication rate and Clavien–Dindo > 3 complication rates were higher in POST compared to ANT: 53.2% vs. 40% (
P
= 0.008) and 36.9% vs. 25.7% (
P
= 0.014), respectively. The rate of delayed gastric emptying (20.1% vs. 7.4%,
P
< 0.001) and nosocomial pneumonia (22.1% vs. 14.8%,
P
= 0.05) was significantly higher in POST.
Conclusion
Patients undergoing minimally invasive Ivor Lewis esophagectomy with an intrathoracic circular stapled anastomosis may benefit from esophagogastrostomy on the anterior wall of the gastric conduit, in terms of lower rate of delayed gastric emptying.
A number of different surgical techniques for the treatment of cancer of the esophagus and the esophagogastric junction have been proposed. Guidelines generally recommend a transthoracic approach for ...esophageal cancer, including Siewert type I tumors. In tumors of the proximal esophageal third, transthoracic esophagectomy may be extended to a three‐field approach, including resection of cervical lymph nodes. However, the choice between transthoracic esophagectomy with intrathoracic anastomosis (Ivor Lewis esophagectomy) and the three‐incision approach with cervical esophago‐gastrostomy (McKeown esophagectomy) remains controversial, with guidelines varying among different countries. Furthermore, it is commonly accepted that Siewert type III tumors should be treated by extended total gastrectomy with transhiatal resection of the lower esophagus, whereas currently no consensus exists regarding the optimal surgical approach for the treatment of Siewert type II adenocarcinoma. Likewise, there is a major controversy regarding palliative and potentially curative treatment modalities in oligometastatic disease. This review deals with current surgical treatment standards for cancer of the esophagus and the eosphagogastric junction, including discussion of ongoing trials.
A number of different surgical techniques for the treatment of cancer of the esophagus and the esophagogastric junction have been proposed. This review deals with current surgical treatment standards for cancer of the esophagus and the eosphagogastric junction, including discussion of ongoing trials.
Background
Anastomotic leak after gastroesophageal surgery is a life-threatening complication. Self-expanding metal stent (SEMS) implantation or endoscopic vacuum therapy (EVT) have been established ...as alternatives to reoperation. This study compares the outcome of both interventions for anastomotic leak clinical management.
Methods
In this retrospective study, we identified all patients who received SEMS or EVT for anastomotic leaks after oncological gastroesophageal surgery between January 2007 and December 2016. Only patients with type II leaks according to the Esophagectomy Complications Consensus Group were included. Sealing rates, intervention-related complications, demographic characteristics, clinical history, leak characteristics, therapy duration, and in-hospital mortality were analyzed.
Results
One hundred eleven patients who received SEMS (
n
= 76) or EVT (
n
= 35) were identified and categorized by primary and final treatment. The overall closure rate in the final treatment analysis was 85.7% for EVT and 72.4% for SEMS (
p
= 0.152). ICU stay ranged from 0 to 60 days (median 6 days) for EVT and from 0 to 295 days (median 9 days) for SEMS (
p
= 0.704). EVT patients were hospitalized for 19–119 days (median 39 days) and SEMS patients for 13–296 days (median 37 days;
p
= 0.812). Demographic factors, comorbidities, and surgical parameters did not correlate with treatment or treatment success.
Conclusions
SEMS and EVT show comparable results for anastomotic leak management after oncologic gastroesophageal surgery. No superior outcome could be found for either one of the two treatments options.
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