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Mesopancreatic Stromal Clearance Defines Curative Resection of Pancreatic Head Cancer and Can Be Predicted Preoperatively by Radiologic Parameters

View Article: PubMed Central - PubMed

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability.

Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011.

Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status.

Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

No MeSH data available.


Related in: MedlinePlus

Conventional and histopathological margin status assessment. Example of a tissue slide from the mesopancreatic margin with brown immunohistochemical staining for Pan-Cytokeratin for better visualization of tumor cells. The tumor cells (TU) are surrounded by a dense fibrotic stroma (S) and invade the mesopancreatic fatty tissue (MF). The closest distance to the inked resection margin (R) is marked by a red arrow. Although no tumor cells are found directly at the resection margin, there is broad contact of the fibrotic stroma to the resection margin. Margin status in this case is negative by conventional R-status (R0, zero tumor cell distance rule), but positive by circumferential margin concept (CRM+, 1-mm tumor cell distance rule) and positive by stromal clearance concept (S+, zero stroma distance rule). For details see manuscript text.
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Figure 1: Conventional and histopathological margin status assessment. Example of a tissue slide from the mesopancreatic margin with brown immunohistochemical staining for Pan-Cytokeratin for better visualization of tumor cells. The tumor cells (TU) are surrounded by a dense fibrotic stroma (S) and invade the mesopancreatic fatty tissue (MF). The closest distance to the inked resection margin (R) is marked by a red arrow. Although no tumor cells are found directly at the resection margin, there is broad contact of the fibrotic stroma to the resection margin. Margin status in this case is negative by conventional R-status (R0, zero tumor cell distance rule), but positive by circumferential margin concept (CRM+, 1-mm tumor cell distance rule) and positive by stromal clearance concept (S+, zero stroma distance rule). For details see manuscript text.

Mentions: All macroscopic and microscopic reports were reviewed independently by 3 experienced pathologists. Reexamination of the H&E stained tissue slides from the tumor and resection margins was performed at 200 and 400-fold magnification. Each resection margin was considered separately. Conventional resection margin status (R-status) was considered positive (R+) when tumor cells were found directly at any margin (zero tumor cell distance rule, see Figure 1).


Mesopancreatic Stromal Clearance Defines Curative Resection of Pancreatic Head Cancer and Can Be Predicted Preoperatively by Radiologic Parameters
Conventional and histopathological margin status assessment. Example of a tissue slide from the mesopancreatic margin with brown immunohistochemical staining for Pan-Cytokeratin for better visualization of tumor cells. The tumor cells (TU) are surrounded by a dense fibrotic stroma (S) and invade the mesopancreatic fatty tissue (MF). The closest distance to the inked resection margin (R) is marked by a red arrow. Although no tumor cells are found directly at the resection margin, there is broad contact of the fibrotic stroma to the resection margin. Margin status in this case is negative by conventional R-status (R0, zero tumor cell distance rule), but positive by circumferential margin concept (CRM+, 1-mm tumor cell distance rule) and positive by stromal clearance concept (S+, zero stroma distance rule). For details see manuscript text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998270&req=5

Figure 1: Conventional and histopathological margin status assessment. Example of a tissue slide from the mesopancreatic margin with brown immunohistochemical staining for Pan-Cytokeratin for better visualization of tumor cells. The tumor cells (TU) are surrounded by a dense fibrotic stroma (S) and invade the mesopancreatic fatty tissue (MF). The closest distance to the inked resection margin (R) is marked by a red arrow. Although no tumor cells are found directly at the resection margin, there is broad contact of the fibrotic stroma to the resection margin. Margin status in this case is negative by conventional R-status (R0, zero tumor cell distance rule), but positive by circumferential margin concept (CRM+, 1-mm tumor cell distance rule) and positive by stromal clearance concept (S+, zero stroma distance rule). For details see manuscript text.
Mentions: All macroscopic and microscopic reports were reviewed independently by 3 experienced pathologists. Reexamination of the H&E stained tissue slides from the tumor and resection margins was performed at 200 and 400-fold magnification. Each resection margin was considered separately. Conventional resection margin status (R-status) was considered positive (R+) when tumor cells were found directly at any margin (zero tumor cell distance rule, see Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability.

Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011.

Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status.

Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

No MeSH data available.


Related in: MedlinePlus