Preoperative Staging and Defining Resectability

From a surgical perspective, the first objective in the management of suspected or confirmed pancreatic cancer is to determine the potential for resection. Routine exploratory laparotomy for the purpose of operatively determining resectability has been diminished by modern 3-D radiographic imaging, along with effective and sustainable nonoperative methods of palliation.

Careful correlation between preoperative CT findings and surgical results has better-defined CT criteria for resectability. The critical aspects that need be evaluated in a thorough radiographic assessment are the presence or absence of peritoneal or hepatic metastases; the potential involvement of the SMV and portal vein and the relationship of these vessels and their tributaries to the tumor; the relationship of the tumor to the SMA, celiac axis, hepatic artery, and gastroduodenal artery; and the presence of any aberrant vascular anatomy.

Unequivocal radiographic findings contraindicating resection include distant metastases, major venous thrombosis of the portal vein or SMV extending for several centimeters, and circumferential encasement of the SMA, celiac axis or proximal hepatic artery. Recent revisions of the National Comprehensive Cancer Network (NCCN) guidelines were an attempt to distinguish locally advanced unresectable tumors from potentially resectable tumors.22 Ambiguity exists in these guidelines because of the lack of clarity in defining clearly resectable situations from “borderline resectable” tumors and because of the subjective criteria used to define “borderline” tumors relative to locally advanced, unresectable lesions. The NCCN guidelines do offer a definition of what should be considered a radiographically resectable tumor. Patients without distant metastases and no evidence of tumor extension to the SMV and portal vein and clear fat planes around the celiac axis, the hepatic artery, and SMA should be categorized as having localized and resectable cancers.

More refined and objective criteria have been proposed by the M. D. Anderson Cancer Center Pancreas Cancer Group in an attempt to better define the term “borderline resectable” and to guide treatment decisions regarding the use of neoadjuvant therapy and the high likelihood of vein resection and reconstruction as a means to improve the rate of a complete and margin-negative resection.23 Radiographic findings of tumor abutment on the portal vein or SMV with or without venous deformity, and limited encasement of the mesenteric vein and portal vein (i.e., short segment occlusion with suitable vessel for anastomosis above and below) represent the extent of venous involvement that would categorize a tumor as borderline resectable.

Radiographic findings suggesting borderline arterial involvement as defined by M. D. Anderson Cancer Center include encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis and/or tumor abutment of the SMA involving < 180° of the artery circumference. In patients without clinically important major comorbidities, and in the absence of radiographic findings to suggest metastatic disease or locally advanced unresectable disease as outlined above, surgical resection should be considered feasible and likely to be achievable. Whether these resections would result in a higher-than-expected rate of margin-positive resections, and whether such resections would affect survival would best be determined by careful examination of outcomes relative to extent of vascular involvement using objective criteria to determine categorization of extent of disease.


Consensus Statement



1.

Tumors considered localized and resectable should demonstrate the following:

a.

No distant metastases.




b.

No radiographic evidence of SMV and portal vein abutment, distortion, tumor thrombus, or venous encasement.




c.

Clear fat planes around the celiac axis, hepatic artery, and SMA.











2.

Tumors considered borderline resectable include the following:

a.

No distant metastases.




b.

Venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction.




c.

Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis.




d.

Tumor abutment of the SMA not to exceed >180° of the circumference of the vessel wall.

Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement.

https://www.giejournal.org/article/S0016-5107(11)02166-3/pdf

EUS-guided FNA for diagnosis of solid pancreatic neoplasms: a meta-analysis

Development of minimally invasive biomarker assays for early detection and effective clinical management of pancreatic cancer is urgently needed to reduce high morbidity and mortality associated with this malignancy We hypothesized that if aberrantly expressing microRNAs (miRNA) in pancreatic adenocarcinoma tissues are detected in blood plasma, then plasma profiling of these miRNAs might serve as a minimally invasive early detection biomarker assay for this malignancy By using a modified protocol to isolate and quantify plasma miRNAs from heparin-treated blood, we show that miRNA profiling in plasma can differentiate pancreatic adenocarcinoma patients from healthy controls We have profiled four miRNAs, miR-21, miR-210, miR-155, and miR-196a, all implicated in the development of pancreatic cancer with either proven or predicted target genes involved in critical cancer-associated cellular pathways Of these, miR-155 has recently been identified as a candidate biomarker of early pancreatic neoplasia, whereas elevated expression of miR196a has been shown to parallel progression of disease The results revealed a sensitivity of 64% and a specificity of 89% with the analyses of plasma levels for this panel of four miRNAs The area under the receiver operating characteristic curve were estimated at 082 and 078 without and with leave-one-out cross-validation scheme, respectively These observations, although a "proof of principle" finding at this time, show the feasibility of developing plasma miRNA profiling as a sensitive and specific blood-based biomarker assay for pancreatic cancer that has the potential of translation to the clinic with additional improvements in the future

https://cancerpreventionresearch.aacrjournals.org/content/canprevres/2/9/807.full.pdf

MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease

The Art and Science of Cytopathology

Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses.

BACKGROUND

Although atypical or suspicious cytology may support a clinical diagnosis of a malignancy, it is often not sufficient for the implementation of therapy in patients with pancreatic carcinoma. Endoscopic ultrasound–guided fine-needle aspiration biopsy (EUS-FNAB) is a relatively new method for obtaining cytology samples, and one that may decrease the number of atypical/suspicious diagnoses. The goals of the current study were to prospectively evaluate the yield of EUS-FNAB in the diagnosis of patients presenting with solid pancreatic lesions and to evaluate the significance of atypical, suspicious, and false-negative aspirates.



METHODS

All patients who presented with a solid pancreatic lesion and underwent EUS-FNAB over a 13-month period were included in the current study. One endoscopist performed all EUS-FNABs. On-site evaluation of specimen adequacy by a cytopathologist was available for each case. Follow-up included histologic correlation (n = 21) and clinical and/or imaging follow-up (n = 80), including 38 patients who died of the disease.



RESULTS

EUS-FNABs were obtained from 101 patients (mean age, 62 ± 11.8 years; age range, 34–89 years). The male-to-female ratio was 2:1. Sixty-five percent of the lesions were located in the head of the pancreas, 12% were located in the uncinate, 17% were located in the body, and 6% were located in the tail. The mean size of the tumors was 3.3 cm (range, 1.3–7 cm). A median of 4 needle passes were performed (range, 1–11 needle passes). Sixty-two biopsies (61.4%) were interpreted as malignant on cytologic evaluation, 5 (5%) as suspicious for a malignancy, 6 (5.9%) as atypical/indeterminate, and 26 (25.7%) as benign processes. Of the 76 malignant lesions, 71 were adenocarcinomas, 3 were neuroendocrine tumors, 1 was a lymphoma, and 1 was a metastatic renal cell carcinoma. All except one of the suspicious/atypical aspirates were subsequently confirmed to be malignant. Agreement was complete for the atypical cases. Among the suspicious cases, 2 of the 5 were identified as carcinoma by one cytopathologist and as suspicious lesions by the other, yielding a 40% disagreement rate between the 2 cytopathologists. Therefore, for the 10 atypical or suspicious cases that later were confirmed to be malignant, the final diagnosis of malignant disease was not made due to scant cellularity that could be attributed to sampling error in 8 cases and to interpretative disagreement in 2 cases (20%). All four false-negative diagnoses were attributed to sampling error. Two percent of all biopsies were inadequate for interpretation. Of the 99 adequate specimens, 72 yielded true-positive results, 23 yielded true-negative results, and 4 yielded false-negative results. No false-positives were encountered. Therefore, the sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB for solid pancreatic masses were 94.7% (95% confidence interval [CI], 89.7–99.8%), 100%, 100%, and 85.2% (95% CI, 71.8–98.6%), respectively.



CONCLUSIONS

EUS-FNAB is a safe and highly accurate method for tissue diagnosis of patients with solid pancreatic lesions. Patients with suspicious and atypical EUS-FNAB aspirates deserve further clinical evaluation. Cancer (Cancer Cytopathol) 2003;99:285–92. © 2003 American Cancer Society.



DOI 10.1002/cncr.11643

Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma.

BACKGROUND

Endoscopic ultrasound (EUS) provides detailed imaging of both intramural and extramural structures within the abdomen and mediastinum. However, EUS is limited in its ability to differentiate an inflammatory/reactive process from a malignancy. Fine-needle aspiration biopsy (FNAB), coupled with EUS, allows for the sampling of the target lesion under ultrasound guidance in real time. To better evaluate the clinical utility and efficiency of EUS-FNAB, a retrospective analysis of the first 103 EUS-FNABs performed at our institute was undertaken.



METHODS

EUS-FNABs was performed in 80 patients with 103 lesions. Both air-dried and alcohol-fixed smears were prepared and stained with Diff-Quik (American Scientific Products, McGraw Park, IL) and Papanicolaou stains, respectively. In addition, ThinPrep slides (Cytyc, Boxborough, MA) and cell blocks, when additional material was available, were also prepared. Immunohistochemical stains were performed on cell blocks wherever required. Cytologic diagnoses were then correlated with the final diagnoses. The latter was based on histologic examination of biopsies/resected pathology materials (n = 54) and clinical follow up (n = 48). Follow-up information was not available for one lesion.



RESULTS

Of 103 EUS-FNABs, 42 FNABs were from the pancreas, 38 from the lymph nodes (10 mediastinal and 28 intraabdominal), 10 from the gastrointestinal tract, 7 from the liver, 4 from the adrenal gland, 1 from the biliary tract, and 1 from a retroperitoneal mass. The mean number of passes to obtain diagnostic materials was 3.3. Of 103 EUS-FNABs, 45, 9, 6, and 37 were reported as malignant, suspicious, atypical, and benign, respectively. Six FNABs were nondiagnostic. The authors did not encounter any false-positive cases. There were three false-negative cases (two pancreatic carcinomas and one gastrointestinal stromal tumor of the stomach). No complications were encountered. The sensitivity, specificity, and accuracy were 71%, 100%, and 81%, respectively. If the FNABs that were classified as suspicious were considered as malignant, the sensitivity, specificity, and accuracy were 86%, 100%, and 91%, respectively.



CONCLUSIONS

EUS-FNAB is a safe and accurate diagnostic procedure for the evaluation of intramural and extramural lesions of the gastrointestinal tract. In the majority of cases, it obviates the need for more invasive diagnostic procedures to obtain a tissue diagnosis. Cancer (Cancer Cytopathol) 2002. © 2002 American Cancer Society.



DOI 10.1002/cncr.10714

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10714

Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases.

BACKGROUND

Endoscopic ultrasound (EUS) is a powerful imaging modality to identify and determine the extent of a lesion. In addition, EUS is superior to a computed tomography scan in detecting lesions < 3 cm. The objective of the current study was to determine whether small lesions (≤ 25 mm) affected the specimen adequacy and the diagnostic accuracy for lesions aspirated under EUS guidance.



METHODS

In the current study, 209 consecutive EUS-guided fine-needle aspiration biopsy (EUS-FNAB) samples ≤ 25 mm (100 samples) or > 25 mm (109 samples) as determined by EUS were obtained from 151 patients with a mean age of 62 years (range, 39–94 years). A cytopathologist present in the endoscopy suite determined specimen adequacy. Yield of adequate samples for diagnosis, number of passes, and operating characteristics of EUS-FNAB for small (≤ 25 mm) and large lesions (>25 mm) were compared.



RESULTS

The overall yield of obtaining adequate samples for diagnosis was 96% (201 of 209). There was no difference noted with regard to the yield of obtaining samples (96% vs. 96%) from small or large lesions. A mean of 2.5 passes (range, 1–9 passes) was needed to obtain adequate samples from lesions ≤ 25 mm, whereas a mean of 4.5 passes (range, 1–11 passes) was needed to obtain adequate samples from lesions > 25 mm. The sensitivity (96% vs. 96%), specificity (100% vs. 100%), and diagnostic accuracy (98% vs. 97%) for EUS-FNAB were comparable whether the lesion was ≤ 25 mm or > 25 mm.



CONCLUSIONS

EUS-FNAB was a highly effective technique to obtain samples from small (≤ 25 mm) and large (> 25 mm) lesions without affecting the sensitivity, specificity, or diagnostic accuracy. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20451

Endoscopic ultrasound‐guided fine‐needle aspiration biopsy: A powerful tool to obtain samples from small lesions

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Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma.

Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases.

Endoscopic ultrasound‐guided fine‐needle aspiration biopsy: A powerful tool to obtain samples from small lesions