Radial EUS versus linear EUS in evaluation of mediastinal lymph nodes in lung cancer staging: a prospective double blind trial

Abstracts

Study on contrast enhanced EUS in differential diagnosis of pancreatic tumor Qi Zhu Background/Aims: To investigate the feasibility of contrast-enhanced EUS of the pancreas and to describe the characteristics of enhancement of the normal pancreas and the pancreas affected by inflammatory or focal disease. Methods: Between March and December 2007, 18 patients with suspect or identification of chronic pancreatitis and focal lesion on conventional ultrasound or CT /MRI imaging; and 5 patients with normal pancreas were included in the study. After baseline EUS examination, 2.5 ml SonoVue (Bracco, Italy) was administered intravenously in 20s, then contrast-enhanced EUS was performed at low MI and the whole process was recorded. The final diagnosis was achieved by cytology / histopathology obtained from biopsy, and the characteristics of enhancement was analyzed. Results: Adequate recordings could be obtained in all 23 patients. Based on cytology/histology results, the investigated pancreatic diseases were classified as chronic pancreatitis(n Z 2), pancreatic carcinoma(nZ13) and pancreatic insulinoma(nZ3). 5 patients with normal pancreas revealed a relatively homogeneous punctiform or claviform enhancement pattern, while 2 patients with chronic pancreatitis revealed inhomogeneous claviform or plaquelike pattern. In addition, 13 patients with focal pancreatic carcinoma revealed a inhomogeneous punctiform or claviform pattern , while 3 patients with focal insulinoma revealed a holo-plaquelike pattern. Besides, different enhancement phase and intensity were identified in different disease. Conclusions: The preliminary study indicated that contrast-enhanced EUS is a safe and feasible imaging modality in the differential diagnosis of pancreatic diseases. It improves the NPV of EUS-FNA and help to diagnose without EUS-FNA.

(mucinous) cystic lesions using EUS diagnosis, aspirate appearance, cytology, fluid amylase and tumour markers. Methods: Retrospective review of consecutive patients referred for EUS-FNA of suspected neoplastic pancreatic cysts between June 2003 and December 2007. All aspirates were sent for cytology and if sufficient for amylase, CEA and CA19-9 assays. The terms viscid and mucoid were classified as indicating a mucinous aspirate all other terms e.g. thin and serous were classified as non mucinous. All suspected pseudocysts at the time of referral were excluded. Only patients with a definitive diagnosis were included in this study. Criterion for a final diagnosis was based on positive histology or cytology or follow up of greater than 12 months with typical clinical course for pseudocysts. Results: 173 EUS with FNA were performed in 149 patients. The average age was 64 years (19-94). A final diagnosis was reached in 95 patients. 61 patients had malignant or premalignant lesions; Adenocarcinoma nZ14, Mucinous Cystadenocarcinoma nZ 14, IPMN nZ15, Mucinous Cystadenomas nZ10 and other malignant lesions nZ8 (unclassified mucinous malignancyZ 6, pseudopapillary tumorZ1, and GISTZ1). 34 patients had benign disease; Pseudocyst nZ19 and Serous CystadenomasZ6, Neuroendocrine Tumour nZ4 and other benign lesions nZ5. A Receiver Operating Characteristic (ROC) curve was calculated for CEA, CA199 and amylase. A cutoff CEA O84 had a sensitivity of 72% and specificity of 82% with an AUC of 0.83 (p O 0.001). Descriptive statistics for each test are shown in table below. In addition the performance of a combination of all tests was assessed (a positive result in any 1 test counting as a positive combined test). Table 1. EUS n Z 112 Cytology n Z 111 CEAO84 ng/mL n Z 64 Fluid appearance n Z 95 Combined (EUSþ/ Cytologyþ/ Fluid app.þ/ CEA)

Preliminary study on EUS guided oncolytic adenovirus implantation in patients of non-operative pancreatic cancer Qi Zhu Objective: To observe the safety and clinical therapeutic effection of oncolytic adenovirus(H101) implantation under EUS guidance combined with gemcitabine in patients of advanced pancreatic cancer. Method: H101 were deliveried locally into 3 sites of the lesion under EUS guidance with the dose of 1.510^12 vp on d1, Gemcitabine was given on d2, d9, d16. 1 month was a circle. A total of 2 circles were given. Tumor volume before and W2, M1, M2 after treatment were assessed by Helical CT scanning and perfusion imaging including blood flow(BF), blood volume(BV), mean transit time (MTT) and permeability surface (PS) were evaluated before and W2, M1 after treatment. Besides, Clinical index including KPS, pain score, CA19 -9 etc were evaluated. Adverse events as well as complications were observed and recorded. Results: 6 patients with clinical assessed unresectable advanced pancreatic cancer were enrolled. All patients completed the two circles of treatment. Tumor volume was decreased slightly in 5 cases 2 months after treatment, but without statistical difference(P Z 0.078). Perfusion imaging shows that MMT was significant increased 2 weeks after the treatment (P Z 0.049). There were no obvious difference of BF, BV and PS. Main clinical outcomes including increase of KPS in 2 patients, obviously decrease of pain score in 3 patients. 3 patients were dead 2.5, 2.5, 3 months after treatment respectively. 3 patients were still alived. Major adverse effects were fever, flu-like symptom, nausea, vomiting, abdominal pain, leucopenia etc. but were graded as 1～2. Conclusion:EUS guided oncolytic adenovirus implantation on advanced pancreatic cancer is potentially feasible and safe, and with combined gemcitabine, it revealed the efficacy to improve the clinical symptoms, shrinking the tumor volume and destroy the angiogenesis of the tumor.

The performance of linear EUS, fluid visual viscosity assessment, fluid cytology and fluid tumour markers in the diagnosis of pancreatic cystic lesions in a single tertiary referral centre K. Oppong, K. Elamin, M. Nayar, P. Matthews, S. Ramakrishnan, P. Matthews, D. Manas, B. Jaques, S. White, R. Charnley Aim: To assess the clinical utility of EUS and FNA in our tertiary referral centre in correctly differentiating benign (non-mucinous) and malignant/premalignant

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Accuracy

Sensitivity

Specificity

PPV

NPV

75 75 77 76 80

77 65 72 75 94

69 93 82 78 55

88 94 84 85 79

51 60 70 65 85

Conclusion: EUS diagnosis, cytology, CEA, and fluid appearance performed moderately well in discriminating between benign and premalignant/malignant cysts. However the combination of the tests provided a high sensitivity and NPV. This is the first study to demonstrate that a combination of all the examined parameters in EUS FNA is better than the best individual component.

Radial EUS versus linear EUS in evaluation of mediastinal lymph nodes in lung cancer staging: a prospective double blind trial Laith H. Jamil, Kanwar R. S. Gill, Seth Gross, Julia Crook, Timothy Woodward, Massimo Raimondo, Michael B. Wallace Purpose: Endosonography has recently being used for mediastinal lymph node (MLN) evaluation during staging of lung cancer. The radial endoscopic ultrasound (R-EUS) provides high quality cross sectional images, but cannot guide fine needle aspiration (FNA). Linear EUS (L-EUS) has the ability to guide FNA but has a limited field of view. Use of both endoscopes may improve lymph node detection but is less efficient. In this study, we evaluated the accuracy of radial and linear EUS endoscopes alone and in combination for the detection of mediastinal lymph nodes. Methods: Patients suspected of having lung cancer underwent back to back REUS and L-EUS evaluation by 1 of 3 experienced endosonographers. Patients were blindly randomized to which procedure would be performed first. If an FNA was required, it would be performed after completing both R-EUS and LEUS examination. Examinations were recorded in the following order; Liver, Celiac axis, Left Adrenal, and Mediastinal/Esophageal pull through. Recorded procedures were then to be reviewed by 2 different experienced endosonographers; neither of whom had performed the procedure. Both were blinded to the original findings and the alternate procedure results. IRB approval was obtained. Results: To date, a total of 9 patients (study ongoing) underwent evaluation for suspected lung cancer. A total of 13 abnormal MLNs were noted on both procedures. There was agreement on 5/13 (38%) in regards to location (table 1). Both R-EUS and L-EUS identified a malignant appearing celiac LN. L-EUS picked up a malignant appearing liver lesion. Both R-EUS and L-EUS found 4 malignant appearing MLNs that were not seen by the other examination. There were 8 benign appearing MLNs. There was poor agreement on the location of any benign MLNs (Table 2). There was an adrenal adenoma that was seen on R-EUS only. In total, there was an agreement on the presence of MLNs in 5/21 (24%). Limitations: Small number of patients, Malignant and benign appearing and location decision was based on the endosonographers interpretation recorded imaging of the MLN.

Volume 69, No. 2 : 2009 GASTROINTESTINAL ENDOSCOPY S265

Abstracts

Conclusion: Based on reviewing recorded REUS and L-EUS for MLNs, there is poor agreement in number and location of benign and malignant appearing MLNs. Patients undergoing lung cancer staging should undergo both procedures for proper staging evaluation.

Table 1. Number of malignant appearing mediastinal lymph nodes, according to location, as seen by R-EUS and L-EUS Linear EUS Station 8 & 9 Station 8 & 9 Radial EUS Station 7 Station 4R &5 Not seen

Station 7

Station 4R & 5

1

Not seen

Table 1. Comparison of T Staging by R-EUS and L-EUS T staging by L-EUS T staging by R-EUS T4 T 1-3 No tumor

T4

T 1-3

No Tumor

I 2

2 5 1

2

Total 13 patients. Number represents number of patients for each T stage by corresponding procedure. There was an agreement in 8 of 13 patients (62%).

2 4

1 1

1

Table 2. Agreement of lymph node staging evaluation by R-EUS and L-EUS N staging by L-EUS

3

There was an agreement in 5 of 13 lymph nodes.

N staging by R-EUS N0 N1

Table 2. Number of benign appearing mediastinal lymph nodes, according to location, as seen by R-EUS and L-EUS

N0

N1

7 1

3 2

Numbers represent number of patients corresponding to N stage. There was an agreement in 9 of 13 patients (70%).

Linear EUS Station 8 & 9 Station 8 & 9 Radial EUS Station 7 Station 4R &5 Not seen

Station 7

Station 4R & 5

Not seen 1 4

1

2

There was no agreement between R-EUS and L-EUS as to location of these lymph nodes.

Radial versus linear EUS in evaluation of suspected pancreatic cancer: is it sufficient to use linear eus alone? Laith H. Jamil, Kanwar R. S. Gill, Seth Gross, Julia Crook, Massimo Raimondo, Timothy Woodward, Michael B Wallace Purpose: Endosonography is widely used for diagnosis and staging of pancreatic cancer. The radial endoscopic ultrasound (R-EUS) provides high quality cross sectional images, but cannot guide fine needle aspiration (FNA). Linear EUS (LEUS) has the ability to guide FNA but has a limited field of view. Use of both endoscopes may improve pancreatic cancer staging, but is less efficient. In this study, we evaluated the accuracy of R-EUS and L-EUS endoscopes alone and in combination for the detection and staging of pancreatic malignancies. Methods: Patients suspected of having a pancreatic mass underwent R-EUS and LEUS evaluation by 1 of 3 experienced endosonographers. Patients were randomized to which procedure was performed first. If an FNA was required, it was performed after completing both examinations. Examinations were recorded in a standardized order; (pancreas body-from stomach, pancreatic head-from duodenal bulb, pancreas uncinate-from 3rd duodenum, liver, and mediastinum). Offline reviews of recorded procedures were then performed by 2 EUS endoscopists, neither of whom had performed the procedure, and were blinded to the findings of the original exam and alternative endoscope. IRB approval was obtained. Results: To date a total of 14 patients (study ongoing) underwent EUS for suspected pancreatic malignancy. One patient was excluded because of defective recording. T staging agreed in 8/13 (62%) (Table 1). In the other 5 cases, R and L each labeled 2 separate patients as T4, while L and R labeled them as T2 and T3 respectively. In one patient, the radial did not identify a T2 lesion. N staging agreed in 9/13 (70%) (Table 2). In M staging, R identified 1 M stage, which was not seen by L exam. Limitations: Small number of patients, TNM staging was based on recorded procedures, and not real time. Conclusion: Based on reviewing recorded R and L EUS, there is poor agreement in TNM staging between R and L EUS. Patients suspected of having a pancreatic tumor should undergo both procedures for proper staging evaluation.

S266 GASTROINTESTINAL ENDOSCOPY Volume 69, No. 2 : 2009

Restaging and assessment of resectability of locally advanced pancreatic cancer by EUS after neoadjuvant therapy Jon Walker, Uzair Chaudhary, Nestor Esnaola, Joseph Romagnuolo, Robert Hawes, Brenda Hoffman Background: Despite the extensive use of endoscopic ultrasound (EUS) as a staging modality for pancreatic cancer, a review of the literature reveals a paucity of reports of EUS in restaging after neoadjuvant chemotherapy and/or radiation. The purpose of the present study was to evaluate EUS as a restaging modality in patients with locally advanced pancreatic cancer without distant metastases (typically stage II-III) receiving a novel neoadjuvant chemotherapeutic protocol. Methods: Study patients received initial CT and EUS examinations for diagnosis and staging, followed by neoadjuvant chemotherapy consisting of gemcitabine, oxaliplatin, cetuximab per protocol and subsequent restaging CT and EUS examinations within one month following therapy. If sufficient radiologic response was attained to make the tumor resectable, surgical resection was performed and the CT/EUS stages were compared to resected surgical pathology. Results: Twenty-six patients were included in the present study to date. After completion of the neoadjuvant chemotherapy protocol, 7 patients showed sufficient radiologic improvement on CT and/or EUS to allow for attempted surgical resection. Initial diagnostic pre-treatment EUS in all 7 chemoresponsive patients demonstrated no greater than stage IIB. During exploratory laparotomy, all patients were deemed operable, and Whipple resections were performed. Post-treatment, EUS T staging was correct in 3 of these 7 patients. Incorrect T staging was primarily due to microscopic peripancreatic (non-vascular) invasion. EUS N staging was correct in 3 of 7 patients, all due to understaging. Of these three false negative N0 staging cases, nodal malignancy was diagnosed microscopically. CT scan correctly T restaged 3 and N restaged 2 of the 7 patients, respectively. In patients failing to respond to neoadjuvant chemotherapy (N Z 8), 4 of 8 were noted to be Stage III on EUS and all were T3 or T4. EUS and CT staging were in agreement in 5 cases and were in agreement on Stage III or IV in 4 of 4 cases. Conclusions: Preliminary evidence suggests that a restaging EUS can be an effective modality for determining surgical resectability in patients with locally advanced pancreatic cancer of stage IIB or less. EUS and CT showed agreement in their findings of stage III disease, suggesting that EUS may be of limited additional benefit for more advanced but not metastatic adenocarcinoma.

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