Author Affiliations: Azienda Sanitaria Locale Roma H-Distretto 3, via Mario Calò, 5-00043 Ciampino, Rome, Italy (Peparini N); Department of Surgical Sciences, Sapienza University of Rome, viale del Policlinico 155, 00161 Rome, Italy (Caronna R and Chirletti P)

Corresponding Author: Nadia Peparini, MD, PhD, Azienda Sanitaria Locale Roma H-Distretto 3, via Mario Calò, 5-00043 Ciampino, Rome, Italy (Tel: +39-06-93275421; Fax: +39-06-79321150; Email: nadiapeparini@yahoo.it)

 

© 2015, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(15)60417-9

Published online September 17, 2015.

 

 

Contributors: PN conceived the study. PN and CR contributed to the acquisition of the data. PN, CR and CP contributed to the analysis and interpretation of the data. PN drafted the manuscript. PN, CR and CP critically revised the manuscript and gave final approval. PN is the guarantor.

Funding: None.

Ethical approval: Not needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

ABSTRACT: A correspondence between the "meso" of the rectum and of the pancreas has recently been reported. Here we highlight the differences between mesorectum and mesopancreas. Based on anatomical findings from a series of 89 consecutive pancreaticoduodenectomies and 71 consecutive total mesorectal excisions, we observed that in contrast to the mesorectum, the mesopancreas did not have well-defined anatomic boundaries and was continuous and connected through its components with the para-aortic area. In rectal cancer, tumor deposits and nodal involvement could be confined to the mesorectum (i.e., within the mesorectal fascia), whereas in pancreatic carcinoma, tumor deposits and nodal metastases occurred in the boundless mesopancreatic area. Total mesorectal excision was made en bloc with the rectum by dissecting along the mesorectal fascia; this was not the case for mesopancreatic excision since anatomical demarcation of the mesopancreas did not exist. Moreover, the growth pattern of pancreatic cancer showed greater dispersion, which was more prominent at the invasive front of the tumor and could potentially affect the status of the resection margin. These findings indicate that the mesorectum and mesopancreas are completely distinct from the pathological, surgical, and oncological standpoints.

 

(Hepatobiliary Pancreat Dis Int 2015;14:548-551)

 

KEY WORDS: pancreatic head carcinoma; surgical procedure; therapy; pancreatic cancer

The anatomy of the retropancreatic area is debated; the tissue has been described as a definite anatomical entity and termed mesopancreas^{[1, 2]} or retroportal lamina,^[3] possessing a triangular^[4] or rectangular^[3] shape and extending from the posterior surface of the head, neck, and uncinate process of the pancreas behind the superior mesenteric vein to the right^[2] or left side^[5] of the superior mesenteric artery (SMA) (considered as the limit of the mesopancreas^[3]), inferior vena cava, aortocaval groove, and aorta.^[5] Microscopically, retropancreatic tissues consist of areolar and adipose tissues, peripheral nerves, nerve plexuses, blood and lymphatic vessels or capillaries, and lymph nodes, with no fibrous sheath or fascia surrounding these structures.^[1-3]

 

In rectal cancer, the prevalence and the prognostic impact of the microscopic involvement of the circumferential resection margin (R1) are well-defined; however, in pancreatic carcinoma, the prevalence of the R1 resection margin is variable and its impact on outcome remains disputed. The recent adoption of standardized pathologic reporting protocols showed an increased R1 resection rate of 70%-80% and improved long-term survival by achieving a microscopically uninvolved margin status (R0). The so-called mesopancreatic resection margin is the most frequent site of R1 resection,^[2] and en bloc total mesopancreatic excision, by analogy with total mesorectal excision (TME), has been postulated to achieve an adequate retropancreatic margin clearance and thereby to decrease the prevalence of R1 resections.^{[4, 6]} However, in contrast to the clinically validated pathological assessment of TME specimens and definition of microscopic margin involvement in rectal cancer, there is currently no consensus on the pathological assessment of pancreaticoduodenectomy (PD) specimen resection margins or the definition of resection margin positivity in pancreatic cancer. To clarify these points, the present study examined differences between the mesorectum and mesopancreas.

 

 

We reviewed the operative reports of two previously reported case series: one comprising 89 subtotal stomach-preserving (i.e., pylorus-resecting) PDs,^[7] 54 of them were performed for pancreatic carcinoma; and another series of 71 TMEs with autonomic pelvic nerve-sparing for extraperitoneal rectal carcinoma.^[8] After PD, a Roux-en-Y reconstruction with anastomosis of the isolated Roux limb to the stomach and of the single Roux limb to both the pancreatic stump and hepatic duct was carried out in all patients. In 14 patients with pancreatic head carcinoma, a PD with extended (maximal) mesopancreatic resection was performed: early dissection of the 16a2 and 16b1 para-aortic areas was followed by the classical demolitive procedure approaching at last the SMA. Circumferential exposure of the SMA was carried out after division of the pancreas and removal of the retropancreatic (mesopancreatic) tissues from the portal and superior mesenteric vein.^[9] In nerve-sparing TMEs, the surgical procedure was anterior resection in 54 and abdominoperineal resection in 17 patients,^[8] depending on the distance of the tumor from the anal verge. The intra-operative anatomical findings of the retropancreatic and perirectal areas were analyzed.

 

 

Of the 71 patients who underwent TME (mean age: 61.1; range: 30-86 years), 51 were male and 20 female. No postoperative death occurred. After TME, a microscopic residual tumor (R1) was present in one patient at the distal resection margin, while macroscopic residual tumors (R2) were present in five patients because of unresectable distant metastasis. Pathological nodal involvement and/or distant metastasis (tumor-node-metastasis stage III/IV) was present in 38 (53.5%) patients. Of the 89 patients who underwent PD (mean age: 60.8 years; range: 35-85), 58 were male and 31 female. Their postoperative mortality rate was 2.2% (2/89). Of 54 patients who underwent PD for pancreatic carcinoma, 36 (66.7%) had regional lymph node involvement (pN1), whereas microscopic resection margin involvement (R1) was present in 2 patients (3.7%). Of 14 patients with carcinoma of the pancreatic head who were treated by PD with maximal mesopancreatic resection, 11 (78.6%) were pN1, and in one patient there was also para-aortic nodal involvement. There were no patients with resection margin involvement; however, no standardized protocol for pathological assessment of resection margin status was adopted at the time of surgery.

 

From the analysis of intraoperative findings of all TMEs and PDs, the following differences in surgical anatomy were observed between the mesorectum and mesopancreas.

1. A: The mesorectum occupies an anatomical area delimited by a distinct rectal fascia that envelops the rectum and mesorectal contents (i.e., adipose tissue, lymphoneurovascular structures, and lymph nodes of the rectum), separating them from pelvic autonomic nerves and plexuses that have an extrafascial course.

B: The so-called mesopancreas which lacks the well-defined boundaries of a single anatomic entity is not surrounded by any fascial structures but connected through its components (i.e., adipose tissue, blood and lymphatic vessels, lymph nodes, and extrapancreatic autonomic nerves and plexuses) with the para-aortic area.

2. A: During TME, the plane along the rectal fascia is a landmark for adequate surgical dissection. After surgery, the rectal fascia becomes a landmark for standardized pathological assessment of the completeness and quality of TME.

B: There are no landmarks either for adequate mesopancreatic resection during PD or for pathological assessment of the completeness of mesopancreatic resection after PD.

3. A: A circumferential resection margin results from en bloc surgical dissection of the rectum and mesorectum (TME) from the surrounding pelvic structures.

B: A mesopancreatic resection margin results from a necessary and maximal surgical dissection of the retropancreatic area (Fig. 1).

4. A: The prognostic impact of circumferential resection margin status and lateral clearance can be assessed with respect to the completeness of TME on the plane of the rectal fascia.

B: The prognostic impact of mesopancreatic resection margin status and tumor clearance cannot be assessed with respect to the completeness of the resection owing to the absence of an anatomic boundary for the mesopancreas.

 

 

From the histopathological standpoint, in rectal cancer, tumor deposits (TDs; i.e., macroscopic or microscopic nests or nodules found in the lymph drainage area of a primary carcinoma without evidence of residual lymph nodes in the nodules) as well as nodal involvement may be confined to the mesorectum, that is, within the mesorectal fascia, and circumferential resection margin status and lateral tumor clearance are assessed using the mesorectal fascia as a landmark for adequate surgery, i.e. TME. Consequently, complete excision of the mesorectum should be performed en bloc with the rectum by dissecting along the rectal fascia in the plane that separates this from the parietal pelvic fascia (the holy plane), thereby maintaining the integrity of the rectal fascia and mesorectal contents, and sparing the autonomic pelvic nerves and plexuses. In contrast, owing to the absence of a surrounding fascia and anatomic boundaries for the mesopancreas and the continuity between the mesopancreatic and para-aortic areas, in pancreatic carcinoma TDs and nodal metastases occur anywhere within the boundless mesopancreatic area. Moreover, mesopancreatic resection margin status and tumor clearance (i.e., the completeness of the resection) must be evaluated without the aid of landmarks of the completeness of the resection. Thus, even if mesopancreatic structures are removed with the PD specimen, an en bloc resection of the mesopancreas is not possible since mesopancreatic dissection must inevitably be performed through these structures, thereby disrupting their anatomic continuity regardless of the adopted surgical technique.^[9] Moreover, mesopancreatic excision cannot be considered total or complete because anatomic mesopancreatic limits, which can be included in the dissection field, do not exist. To minimize the rate of occurrence of R1 mesopancreatic resection margins, mesopancreatic excisions should be extended as far as possible by performing the dissection beyond the right side of the SMA to the left side and along the para-aortic area^[9] (Fig. 2) and removing the mesopancreatic nervous plexuses. Such extended mesopancreatic excision is not technically feasible en bloc.

 

Finally, it should be considered that the R1 mesopancreatic resection margin, as well as local recurrences after R0 surgery, may not be due to inadequate surgery and histopathological underestimation, but may instead result from tumor cells remaining at (R1) or behind (R0) the mesopancreatic resection margin as a consequence of epithelial-to-mesenchymal transition-related processes of tumor progression; for example, mesopancreatic TDs, tumor budding (i.e., the presence of dedifferentiated, isolated single cells or small clusters of up to five cells scattered in the stroma at the invasive tumor front), or a dispersed pattern of growth at the tumor periphery.^[10] From an oncological standpoint, the growth pattern of pancreatic cancer is more dispersed than the homogeneous and compact growth pattern of rectal cancer. This is more prominent towards the tumor periphery (i.e., the invasive front of the tumor), where the growth pattern may impact the resection margin status, suggesting that the limit of clearance (≤1 mm) adopted for the microscopic involvement of the circumferential margin in rectal cancer is insufficient in pancreatic cancer.^[10] Therefore, based on our findings, the "meso" of the pancreas and the "meso" of the rectum are distinct entities from the pathological, surgical, and oncological perspectives.

 

 

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