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Article: Stelzner, S, Hohenberger, W, Weber, K et al. (3 more authors) (2016) Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread. International Journal of Colorectal Disease, 31 (2). pp. 377-384. ISSN 0179-1958 https://doi.org/10.1007/s00384-015-2434-0

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[email protected] https://eprints.whiterose.ac.uk/ International Journal of Colorectal Disease Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread --Manuscript Draft--

Manuscript Number: Full Title: Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread Article Type: Original Article Keywords: Complete mesocolic excision; transverse mesocolon; gastrocolic trunk; superior mesenteric ; superior mesenteric Corresponding Author: Sigmar Stelzner, M.D. Krankenhaus Dresden-Friedrichstadt Dresden, GERMANY Corresponding Author Secondary Information: Corresponding Author's Institution: Krankenhaus Dresden-Friedrichstadt Corresponding Author's Secondary Institution: First Author: Sigmar Stelzner, M.D. First Author Secondary Information: Order of Authors: Sigmar Stelzner, M.D. Werner Hohenberger, M.D., Ph.D. Klaus Weber, M.D. Nicholas P. West, M.D. Helmut Witzigmann, M.D., Ph.D. Thilo Wedel, M.D., Ph.D. Order of Authors Secondary Information: Funding Information: Abstract: Purpose: Although lymph node metastases to pancreatic and gastroepiploic lymph node stations in transverse colon cancer have been described, the mode of lymphatic spread in this area remains unclear. This study was undertaken to describe possible pathways of aberrant lymphatic spread in the complex anatomic area of the proximal superior mesenteric artery and vein, the , and the lower pancreatic border. Methods: Abdominal specimens obtained from four cadaveric donors were dissected according to the principles of complete mesocolic excision. The vascular architecture of the transverse colon was scrutinized in search of possible pathways of lymphatic spread to the pancreatic and gastroepiploic lymph nodes. Results: Vascular connections between the transverse colon and the greater omentum at the level of both the hepatic and the splenic flexure could be identified. In addition, small vessels running from the transverse mesocolon to the lower pancreatic border in the area between the and the inferior mesenteric vein were demonstrated. Moreover, venous contributaries to the gastrocolic trunk could be exposed to highlight its surgical importance as a guiding structure for complete mesocolic excision. Conclusion: The technical feasibility to clearly separate embryologic compartments by predefined tissue planes in complete mesocolic excision was confirmed. However, the vicinity of all three endodermal intestinal segments (, midgut, and hindgut) obviously gives way to vascular connections that might serve as potential pathways for lymphatic metastatic spread of transverse colon cancer.

Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Additional Information: Question Response 1. Was this manuscript been published no previously or under consideration in whole or in part somewhere else? 2. Was this manuscript in its present form yes has been read and approved to submission to "International Journal of colorectal disease" for publication by all participated authors? 3. Acknowledgments: The authors thank Stefanie Gundlach, Merle Winkler, Bettina Facompré and Clemens Franke for their support in the anatomical dissections, histologic work-up and processing of the figures. 4. Conflict of interest or financial NPW is supported by Yorkshire Cancer Research, UK and the Pathological Society of disclosure: Great Britain and Ireland. All authors declare no conflicts of interest. 5. Do you certify that this research is yes entirely original? 6. Which of the following government none agencies provided funding for your research? Suggested Reviewers: Nikos Gouvas, M.D. Consultant Surgeon, "Konstandopouleion Hospital" of Athens, Greece [email protected] Mr. Gouvas is an interantionally recognized expert colorectal surgeon who has published on complete mesocolic excision. Ayhan M. Kuzu, M.D. Consultant General Surgeon and Anatomist, Genral Surgery [email protected] Prof. Kuzu has published many articles on modern anatomy of the colon and and is an internationally renowend expert in the field.

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Anatomy of the transverse colon revisited with respect to complete mesocolic 1 2 excision and possible pathways of aberrant lymphatic tumor spread 3 4 5 6 Authors: 7 8 Sigmar Stelzner (1), Werner Hohenberger (2), Klaus Weber (2), Nicholas P. West (3), Helmut 9 10 Witzigmann (1), Thilo Wedel (4) 11 12 Affiliations: 13 14 (1) Department of General and Visceral Surgery, Dresden-Friedrichstadt General Hospital, 15 16 Dresden, Germany 17 18 (2) Department of Surgery, University Hospital Erlangen, Friedrich-Alexander University 19 20 Erlangen-Nürnberg, Erlangen, Germany 21 22 (3) Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of 23 24 Leeds, Leeds, United Kingdom 25 26 (4) Department of Anatomy, Center of Clinical Anatomy, Christian Albrechts University of 27 28 Kiel, Kiel, Germany 29 30 31 32 Correspondence: 33 34 Sigmar Stelzner, MD 35 Department of General and Visceral Surgery 36 Dresden-Friedrichstadt General Hospital 37 Friedrichstr. 41 38 39 01067 Dresden 40 Germany 41 Tel.: ++49 / 351 / 480 11 42 42 Fax: ++49 / 351 / 480 11 49 43 E-Mail: [email protected] 44 45 46 Acknowledgments 47 48 The authors thank Stefanie Gundlach and Merle Winkler for their support in the anatomical 49 50 dissections and photographing of the macroscopic specimens, Bettina Facompré for her 51 support in the histologic work-up of the microscopic specimens, and Clemens Franke for his 52 53 assistance in the processing of the figures. 54 55 56 57 58 59 60 1 61 62 63 64 65 Abstract 1 2 3 Purpose: Although lymph node metastases to pancreatic and gastroepiploic lymph node 4 5 stations in transverse colon cancer have been described, the mode of lymphatic spread in 6 7 this area remains unclear. This study was undertaken to describe possible pathways of 8 9 aberrant lymphatic spread in the complex anatomic area of the proximal superior mesenteric 10 11 12 artery and vein, the greater omentum, and the lower pancreatic border. 13 14 Methods: Abdominal specimens obtained from four cadaveric donors were dissected 15 16 17 according to the principles of complete mesocolic excision. The vascular architecture of the 18 19 transverse colon was scrutinized in search of possible pathways of lymphatic spread to the 20 21 pancreatic and gastroepiploic lymph nodes. 22 23 24 Results: Vascular connections between the transverse colon and the greater omentum at the 25 26 level of both the hepatic and the splenic flexure could be identified. In addition, small vessels 27 28 running from the transverse mesocolon to the lower pancreatic border in the area between 29 30 the middle colic artery and the inferior mesenteric vein were demonstrated. Moreover, 31 32 33 venous contributaries to the gastrocolic trunk could be exposed to highlight its surgical 34 35 importance as a guiding structure for complete mesocolic excision. 36 37 38 Conclusion: The technical feasibility to clearly separate embryologic compartments by 39 40 predefined tissue planes in complete mesocolic excision was confirmed. However, the 41 42 vicinity of all three endodermal intestinal segments (foregut, midgut, and hindgut) obviously 43 44 gives way to vascular connections that might serve as potential pathways for lymphatic 45 46 47 metastatic spread of transverse colon cancer. 48 49 50 51 52 Key words: 53 54 55 Complete mesocolic excision, transverse mesocolon, gastrocolic trunk, superior mesenteric 56 57 vein, superior mesenteric artery, anatomy 58 59 60 2 61 62 63 64 65 Introduction 1 2 3 Complete mesocolic excision (CME) describes the mobilisation and separation of the colon 4 5 together with the entire regional mesocolon and supplying vessels as a contiguous and 6 7 coherent embryologically defined compartment from the surrounding tissues in combination 8 9 with a central vascular tie [1,2]. It represents the consequent extension of the philosophy of 10 11 12 total mesorectal excision (TME) and of cancer-arresting capabilities of both the mesorectal 13 14 and mesocolic fascia respectively to the entire large bowel [3-5]. Arterial blood supply, 15 16 venous and lymphatic drainage take place within the boundaries of the mesocolon; and it is 17 18 presumed that there are no compartment-crossing vessels that could potentially pave the 19 20 way to cancer spread outwith the main route along the colic [6]. It has been proven 21 22 23 that CME results in a higher lymph node yield, a larger area of removed, a greater 24 25 distance between the tumor and the central vascular tie and ultimately in better patient 26 27 outcome [7-10]. 28 29 30 The transverse colon, however, exhibits embryologic and anatomic peculiarities that result 31 32 from its central position between the foregut and midgut. Although its proximal two thirds 33 34 correspond to the end of the midgut and its distal third to the beginning of the hindgut, it is in 35 36 37 an intimate relationship with the proximal superior mesenteric vessels and with foregut 38 39 structures such as the greater omentum, the , and the lesser sac. On the one hand, 40 41 this peculiar topographic relationship gives rise to the possibility of aberrant lymphatic 42 43 spread; on the other hand, the venous drainage is especially variable and closely related to 44 45 46 pancreatic and omental . If the surgeon is not aware of the latter, some troublesome 47 48 bleeding may occur during surgery. 49 50 51 Thus, we performed a macroscopic dissection study in human cadaveric donors to search for 52 53 possible vascular connections between derivatives of the fore-, mid- and hindgut in order to 54 55 provide a morphologic basis for cancer spread outside the main drainage routes. 56 57 Furthermore, we aimed to scrutinize the peculiar anatomical features of the venous drainage 58 59 60 3 61 62 63 64 65 into the superior mesenteric vein at the triangle between the right transverse mesocolon, the 1 2 pancreas and the greater omentum. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 61 62 63 64 65 Materials and Methods 1 2 3 Macroscopic studies 4 5 Gross anatomical dissections were undertaken on four formalin-fixed specimens obtained 6 7 8 from cadaveric donors (body donation programme, Institute of Anatomy, University of Kiel, 9 10 Germany), which exhibited no evident disease of the intra-abdominal organs. The greater 11 12 omentum and the colon/mesocolon were released from the parietal fascia along areolar 13 14 tissue planes as far as possible. Care was taken to preserve even tiny vessels that possibly 15 16 17 crossed these areolar planes. 18 19 Furthermore, the tributaries to the superior mesenteric vein just below the pancreatic head 20 21 22 and neck were meticulously dissected to describe their course in relation to the surgical 23 24 technique of CME. Dissection then followed the posterior leaf of the lesser sac that was 25 26 carefully detached from the anterior aspect of the transverse mesocolon to get access to the 27 28 lower border of the pancreas. The relation of the mesocolon to the pancreas left of the 29 30 superior mesenteric vessels and to the was demonstrated. Finally, findings 31 32 33 obtained from the dissection studies were verified during surgical operations performed for 34 35 transverse colon cancer or cancer at either the hepatic or the splenic flexure. All steps of the 36 37 dissection studies were photographically documented using a high resolution digital colour 38 39 camera. The dissected specimens were preserved for reference purposes and instructional 40 41 42 skills laboratory workshops. 43 44 Microscopic studies 45 46 47 Tissues were harvested from sites of the transverse mesocolon where vascular structures 48 49 could be identified by diaphanoscopy running from the transverse colon towards the lower 50 51 52 border of the pancreas. Specimens (approximately 2 cm x 2 cm) were dehydrated in 53 54 increasing series of alcohol, embedded in paraffin wax and cut perpendicular to the surface 55 56 of the transverse mesocolon. The mesocolic cross-sections were stained with haematoxylin 57 58 59 60 5 61 62 63 64 65 & eosin and Masson´s trichrome /orcein to characterize the vascular structures at histological 1 2 level. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 6 61 62 63 64 65 Results 1 2 3 Macroscopic findings 4 5 Separation of embryological planes was proven to be feasible in formalin-fixed specimens. 6 7 8 The mesocolic package could easily be mobilized from the parietal fascia on either side, the 9 10 duodenum and the pancreatic head (Fig. 1). Separation of the greater omentum from the 11 12 transverse colon was also possible along a preformed embryological plane. The area of the 13 14 greater omentum attached to the wall of the transverse colon was almost free of adipose 15 16 17 tissue and could be released from the bowel wall and the anterior aspect of the transverse 18 19 mesocolon. Thus, the lesser sac remained initially unopened reflecting its embryological 20 21 origin from the dorsal mesogastrium. The tissue that could be dissected off the transverse 22 23 mesocolon represents the two posterior leafs of the dorsal mesogastrium. In the region of 24 25 both the hepatic and splenic flexures small blood vessels were identified that connected the 26 27 28 greater omentum with the bowel wall (Fig. 2). 29 30 At the lower border of the pancreatic body and proximal tail, the transverse mesocolon 31 32 33 consisted only of a thin tissue sheet that was attached to the retroperitoneum along an 34 35 insertion line running from the inferior mesenteric vein towards the superior aspect of the 36 37 duodenojejunal flexure and the tissue bridge over the superior mesenteric vessels. Within 38 39 this mesocolic sheet, several small vessels could be readily observed by diaphanoscopy 40 41 42 extending between the transverse colon and the lower pancreatic border (Fig. 3). Whereas 43 44 some vessels established direct connections between the transverse colon and the 45 46 pancreas, other vessels originated either from the pancreatic side or from the bowel side 47 48 without any obvious communications. 49 50 51 The main arterial blood supply of the transverse colon was provided by a single middle colic 52 53 artery in all specimens. Further ramifications were variable. In two specimens, the middle 54 55 56 colic artery divided into two branches only few centimeters from the origin of the superior 57 58 mesenteric artery that ran parallel to each other towards the bowel before forming an arcade 59 60 7 61 62 63 64 65 close to the bowel wall to supply the transverse colon. An additional branch originated from 1 2 the proximal part of the middle colic artery to form the (Fig. 3, 4). In the other 3 4 two specimens, the middle colic artery divided in an obtuse angle with a branch running to 5 6 7 each of the two flexures without a separate branch for the right colon (Fig. 5). 8 9 Venous drainage of the middle and left transverse colon was carried out by the middle colic 10 11 12 vein that peripherally followed the middle colic artery but took a different course centrally and 13 14 drained directly into the superior mesenteric vein in all specimens. On the right side, two 15 16 veins of about the same diameter, namely the and the superior right colic 17 18 vein, merged in three specimens and received tributaries from the right gastroepiploic and 19 20 pancreaticoduodenal veins forming the gastrocolic trunk (Fig. 5, 6). This venous trunk 21 22 23 entered directly into the superior mesenteric vein. Thus, centrally the course of the veins was 24 25 completely independent from the course of the arteries (compare Fig. 4, 5, 6). In the fourth 26 27 specimen, the right colic vein was missing and venous drainage of the right side of the 28 29 transverse colon was realized by the superior right colic vein only. The connection of the 30 31 32 right-sided colic veins to the gastroepiploic and pancreaticoduodenal veins marked the end 33 34 of the embryologic tissue interfaces. From this confluence point towards the superior 35 36 mesenteric vein the venous vessels were embedded in . 37 38 39 On the left side, separation of the descending mesocolon from the parietal fascia was as 40 41 feasible as on the right side, again without any evidence of vessels crossing the 42 43 embryological interface. This observation could be confirmed intraoperatively during 44 45 46 mobilisation of the and the splenic flexure for CME (Fig. 7). Only around 47 48 the inferior mesenteric artery, a continuous tissue connection to the para-aortal tissue and 49 50 similarly, but to a lesser extent, around the inferior mesenteric vein to the retropancreatic 51 52 tissue was encountered. Between these two connections, the mesocolon medial to the 53 54 55 inferior mesenteric vein consisted only of a thin connective tissue layer covered by 56 57 that spread over the lateral aspect of the first jejunal sling and the parietal fascia. 58 59 60 8 61 62 63 64 65 Microscopic findings 1 2 3 Cross-sections of the transverse mesocolon were covered on either side by a serosal 4 5 mesothelial lining supported by a subserosal connective tissue layer. Embryologically, the 6 7 serosal layer of the anterior aspect belongs to the posterior leaf of the greater omentum. The 8 9 mesocolic matrix was primarily composed of lobular adipose tissue and loosely arranged 10 11 12 connective tissue septa. Those vascular structures previously identified by diaphanoscopy at 13 14 the macroscopic level connecting the transverse colon and the pancreatic border could be 15 16 readily confirmed at the microscopic level. Based on their histological peculiarities, the 17 18 vascular structures consisted of arteries, veins and lymphatic vessels (Fig. 8, 9a, 9b). 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 9 61 62 63 64 65 Discussion 1 2 3 The emergence of the superior mesenteric vessels between the pancreas and the duodenum 4 5 represents the embryological pivot of intestinal rotation. This intestinal rotation shapes the 6 7 peculiar architecture of colonic anatomy with its frame-like position around the small bowel 8 9 and its adhesions between the mesocolic parts and the structures sited posterior to it [11]. 10 11 12 The transverse colon is situated in the centre of abdominal anatomy; the right and middle 13 14 third deriving from the midgut, and the left third from the hindgut. Moreover, it is covered by 15 16 the greater omentum and thus stays in direct connection to the embryological foregut. 17 18 19 The caecum, and hepatic flexure including the corresponding mesocolon 20 21 can easily be separated from the parietal fascia, the duodenum and the pancreatic head 22 23 within an embryological interface [12]. It is possible to gently open this interface that reveals 24 25 thin areolar tissue without breaching the fascial layers on either side [13]. In this plane we 26 27 28 were not able to demonstrate vascular connections crossing the interface. It is reasonable to 29 30 presume that an intact covering on the mesocolon, the mesocolic fascia, serves as a tumor- 31 32 arresting barrier in the same way as it was demonstrated for the mesorectal fascia [3,5]. It is 33 34 one of the cornerstones of CME to respect the integrity of this embryological envelope [1,7]. 35 36 37 If surgical dissection follows this plane, an accidental injury to the ureter is not possible as it 38 39 belongs to a different embryological compartment. 40 41 42 The only connection of the right mesocolic package to the retroperitoneal structures is 43 44 represented by the tissue along the superior mesenteric vessels that consists of nerves, 45 46 lymphatics, and adipose tissue extending from just below the neck of the pancreas 47 48 proximally towards the ileocolic vessels distally. This part of the superior mesenteric vessels 49 50 51 is by some authors called the "surgical trunk" [14-16]. However, the close relationship of the 52 53 various embryologically defined components of the viscera entails that vascular architecture, 54 55 especially venous drainage, is complex and variable [14,17,18]. 56 57 58 59 60 10 61 62 63 64 65 Based on these considerations it is mandatory for right-sided CME to meticulously identify 1 2 the specific course of the veins in this area, which differ substantially from that of the arteries. 3 4 Although commonly not mirrored in anatomical textbooks, it has been described by several 5 6 7 authors that the colic vein draining the region of the hepatic flexure, called the superior right 8 9 colic vein, joins with the right gastroepiploic vein to form a short venous trunk that ends in 10 11 the superior mesenteric vein [13,14, 19,20]. This trunk was first described as the gastrocolic 12 13 vein by Henle in 1868 [21]. Many variants of this venous confluence have been found. Quite 14 15 commonly, an anterior pancreaticoduodenal vein contributes to Henle s trunk as does the 16 ’ 17 18 right colic vein and rarely even the [14,18,19,22]. There is still a debate on 19 20 whether this pancreaticoduodenal vein belongs to the anterior-inferior or to the anterior- 21 22 superior arcade [23,24]. We could demonstrate that due to the aforementioned variability, 23 24 more than one pancreaticoduodenal vein may run into this venous trunk. This peculiar 25 26 27 confluence of veins from the foregut and midgut explains the bleeding episodes frequently 28 29 observed during dissection in this area despite the identification of the confluence of the 30 31 superior right colic vein and the right gastroepiploic vein. Hohenberger et al. have raised the 32 33 awareness of this critical region ("bleeding point") in the surgical community and 34 35 36 standardized dissection of these veins as guiding structures that lead to the superior 37 38 mesenteric vein in right-sided CME [1]. 39 40 41 The arterial blood supply of the transverse colon is also variable when compared to a highly 42 43 constant ileocolic artery for the right-sided colon and a similarly constant left colic artery for 44 45 the left-sided colon [25]. The right colic artery originates directly from the superior mesenteric 46 47 artery in only 15 to 40 % [26,27]. In about 45 %, it derives from the middle colic artery as a 48 49 distinct branch (as observed in our cases), or the right branch of the middle colic artery 50 51 52 directly supplies the right colon. Rarely, the right colic artery originates from the ileocolic 53 54 artery [27]. The middle colic artery divides into a right and a left branch in approximately 60 55 56 %. In the remaining 40 %, an independent left branch is described. Very rarely it originates 57 58 from the inferior mesenteric artery or from a dorsal pancreatic artery [27]. These variants 59 60 11 61 62 63 64 65 may then give way to aberrant lymphatic tumor spread. Of note is that surgical dissection of 1 2 the left-sided embryological planes has been part of total mesorectal excision and therefore 3 4 more widely practiced compared to the complete mobilization of the right-sided 5 6 7 embryological planes. This observation may partly explain the better outcomes for left-sided 8 9 colon cancer when compared to right-sided tumors [28-30]. 10 11 12 The transverse colon is in close topographic contact to foregut structures, e.g. to the greater 13 14 omentum including the gastrocolic , and the pancreas. Although separation of the 15 16 greater omentum from the transverse colon and mesocolon was possible, we found small 17 18 vessels in the region of both the hepatic and splenic flexure that crossed between these fore- 19 20 and midgut derivates. These vascular connections could serve as tracks for blood vessel and 21 22 23 lymphatic tumor spread to lymph nodes within the greater omentum and along the 24 25 gastroepiploic vessels. Perrakis et al. gave clinical proof of this hypothesis in a recent series 26 27 of 45 patients with carcinoma of the transverse colon or the colonic flexures. They 28 29 encountered lymph node metastases in four (9 %) of these patients at the gastroepiloic 30 31 32 arcade [31]. In another series of 98 patients including cancers of the distal ascending colon, 33 34 four patients (4 %) with gastroepiploic or infrapyloric lymph node metastases could be 35 36 identified [32]. Apart from vascular tumor spread, direct infiltration of the greater omentum 37 38 ("per continuitatem") encompasses an additional possibility of metastatic omental and 39 40 41 gastroepiploic lymph node disease. These observations provide the rationale to resect the 42 43 greater omentum if it is in direct anatomical contact with the cancer-bearing segment of the 44 45 colon. Omentectomy must include the corresponding and the feeding 46 47 gastroepiploic vessels. The safety margins should parallel the extent of colonic resection. 48 49 50 Furthermore, we found small vascular structures within the transverse mesocolon composed 51 52 of arteries, veins and lymphatic vessels running between the transverse colon and the lower 53 54 55 pancreatic border. These vessels crossed the transverse mesocolon in the region between 56 57 the middle colic artery and the inferior mesenteric vein, and established connections between 58 59 the transverse colon and foregut derivatives (pancreas). Again, this anatomical peculiarity 60 12 61 62 63 64 65 may explain the clinical observation by Perrakis et al. who demonstrated lymph node 1 2 metastases in infrapancreatic lymph nodes in five (11%) out of the aforementioned 45 3 4 patients [31]. Based on these considerations, mobilisation and dissection of the transverse 5 6 7 mesocolon for transverse colon cancer should therefore follow the lower border of the 8 9 pancreatic compartment and meticulously separate the entire transverse mesocolon in order 10 11 not to leave behind residual mesocolic tissue. This step of dissection routinely includes 12 13 lymph nodes at the lower pancreatic border that may accompany the described small vessels 14 15 in the transverse mesocolon towards the pancreas but are often hardly recognizable. For 16 17 18 pathologic work-up, this region of the specimen needs to be marked in order to allow the 19 20 identification of the topographic localization in case of lymph node metastases. 21 22 23 Studies that have analyzed putative lymphatic connections of the transverse mesocolon to 24 25 the pancreatic lymph nodes are rare. Hirono et al. used the indocyanine green fluorescence 26 27 imaging method to describe the lymphatic drainage of the pancreas. They could identify a 28 29 connection to lymphatic tissue around the middle colic artery via the superior mesenteric 30 31 32 artery [33]. Toyota et al. found metastatic infrapyloric lymph nodes in four of 53 (7.5 %) right- 33 34 sided transverse and in one of 188 (0.5 %) ascending colon cancers [15]. Morikawa et al. 35 36 could demonstrate that involvement of central lymph nodes along the main vascular trunk 37 38 only occurred in pT3 and pT4 tumors [34]. From these reports it can be deduced that 39 40 41 involved lymph nodes in the pancreatic area occur in up to 10 % of transverse colon 42 43 carcinoma, are more common in advanced cases and may rarely be found even without any 44 45 other lymph node stations involved. 46 47 48 Conclusion 49 50 51 We have been able to generate evidence to support the concept of CME by gross anatomic 52 53 dissection studies highlighting the embryologically distinct colonic/mesocolonic compartment 54 55 similar to the descriptions of the mesorectal compartment. Anatomic peculiarities of the 56 57 veins draining the right colon into the superior mesenteric vein, together with veins from the 58 59 60 13 61 62 63 64 65 and pancreas, were described and must be respected during surgical dissection. 1 2 Finally, small blood and lymphatic vessels between the transverse colon/mesocolon and the 3 4 greater omentum as well as the pancreas could be identified as possible routes of additional 5 6 7 lymphatic tumor spread, emphasizing complete removal of omental and mesocolic tissues. 8 9 10 11 12 Disclosures 13 14 15 NPW is supported by Yorkshire Cancer Research, UK and the Pathological Society of Great 16 17 Britain and Ireland. All authors declare no conflicts of interest. 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 14 61 62 63 64 65 Figures legends 1 2 Figure 1: 3 4 Separation of the right-sided mesocolic package from the parietal fascia and duodenum with 5 6 mobilisation of the hepatic flexure. Note the smooth surface of both the ascending 7 8 mesocolon and the underlying parietal fascia. GB – gall bladder. 9 10 11 12 Figure 2: 13 14 Small vessel (red indicator) crossing from the left transverse colon to the greater omentum at 15 16 the level of the gastrocolic ligament. 17 18 19 20 21 22 Figure 3: 23 24 25 Diaphanoscopy of the transverse mesocolon reveals small vessels (arrow heads) between 26 the bowel wall and the inferior pancreatic border. SMV – superior mesenteric vein; MCA – 27 28 middle colic artery (right and left branch); RCA – right colic artery (deriving from the middle 29 30 colic artery). 31 32 33 34 Figure 4: 35 36 Proximal superior mesenteric artery (SMA) and its branches comprising the middle colic 37 38 artery (MCA, red vessel loop), right colic artery (RCA) deriving from the middle colic artery, 39 40 inferior pancreaticodurdenal artery (IPDA), and jejunal arteries (JA). RGEA – right 41 gastroepiploic artery (red indicator). Tributaries of the gastrocolic trunk are highlighted by the 42 43 blue indicator (for details see figure 6). 44 45 46 47 Figure 5: 48 49 50 Proximal superior mesenteric artery (SMA) and vein (SMV) with the transverse mesocolon 51 flipped upwards. The middle colic artery (MCA) divides into two main branches which run 52 53 along the transverse colon on either side. The gastrocolic trunk (white star) is formed by the 54 55 tripod of the right gastroepiploic vein (RGEV), the superior right colic vein (SRCV) and a 56 pancreaticoduodenal vein (PCV) and receives the right colic vein only shortly before it drains 57 58 59 60 15 61 62 63 64 65 into the SMV. The middle colic vein (MCV) drains directly into the SMV forming a trunk with 1 2 two (JV). 3 4 5 6 Figure 6: 7 8 Tributaries of the gastrocolic trunk (white star) comprise the right colic vein (RCV), superior 9 10 right colic vein (SRCV), pancreaticoduodenal veins (PDV), and right gastroepiploic vein 11 (RGEV) highlighted by blue indicators. The middle colic vein (MCV) directly drains into the 12 13 superior mesenteric vein (SMV). 14 15 16 17 18 Figure 7: 19 20 Intraoperative view of the left upper abdominal quadrant during CME for transverse colon 21 cancer. The splenic flexure has been mobilised following the embryological planes. The 22 23 greater omentum was removed from the greater curvature. The is seen at the 24 25 duodenojejunal flexure. Note the smooth surface of the parietal fascia after complete removal 26 of the left-sided mesocolic package. 27 28 29 30 31 Figure 8: 32 33 Transverse mesocolon with serosal coverings. The upper serosal layer is elevated by 34 35 forceps to expose the adipose tissue harbored within the transverse mesocolon. The 36 histologic section displayed in figure 8 corresponds to the interrupted black line. MCA 37 – 38 middle colic artery 39 40 41 42 43 Figure 9: 44 45 Histological cross-section of the transverse mesocolon. Overview magnification (a) and 46 higher magnification of insert (b). Between the two continuous serosal layers (arrowheads) 47 48 extends adipose tissue and connective tissue septa with embedded vascular structures. The 49 50 insert displays the characteristic features of arteries (A), veins (V) and lymphatic (L) vessels. 51 Masson´s trichrome /orcein. 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Morikawa E, Yasutomi M, Shindou K, Matsuda T, Mori N, Hida J, Kubo R, Kitaoka M, 12 13 Nakamura M, Fujimoto K, Inofusa H, Hatta M, Izumoto G (1994) Distribution of 14 metastatic lymph nodes in colorectal cancer by the modified clearing method. Dis 15 Colon Rectum 37:219-223 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 19 61 62 63 64 65 Figure1 Click here to download Figure we_2014_301.tif Figure2 Click here to download Figure we_2014_302.tif Figure3 Click here to download Figure we_2014_303.tif Figure4 Click here to download Figure we_2014_304.tif Figure5 Click here to download Figure we_2015_34.tif Figure6 Click here to download Figure we_2014_305.tif Figure7 Click here to download Figure we_2014_306.tif Figure8 Click here to download Figure we_2014_307.tif Figure9 Click here to download Figure we_2015_33.tif