Definition and reporting of lymphadenectomy and complete mesocolic excision for radical right colectomy: a systematic review

Background Several procedures have been proposed to reduce the rates of recurrence in patients with right-sided colon cancer. Different procedures for a radical right colectomy (RRC), including extended D3 lymphadenectomy, complete mesocolic excision and central vascular ligation have been associated with survival benefits by some authors, but results are inconsistent. The aim of this study was to assess the variability in definition and reporting of RRC, which might be responsible for significant differences in outcome evaluation. Methods PRISMA-compliant systematic literature review to identify the definitions of RRC. Primary aims were to identify surgical steps and different nomenclature for RRC. Secondary aims were description of heterogeneity and overlap among different RRC techniques. Results Ninety-nine articles satisfied inclusion criteria. Eight surgical steps were identified and recorded as specific to RRC: Central arterial ligation was described in 100% of the included studies; preservation of mesocolic integrity in 73% and dissection along the SMV plane in 67%. Other surgical steps were inconstantly reported. Six differently named techniques for RRC have been identified. There were 35 definitions for the 6 techniques and 40% of these were used to identify more than one technique. Conclusions The only universally adopted surgical step for RRC is central arterial ligation. There is great heterogeneity and consistent overlap among definitions of all RRC techniques. This is likely to jeopardise the interpretation of the outcomes of studies on the topic. Consistent use of definitions and reporting of procedures are needed to obtain reliable conclusions in future trials. PROSPERO CRD42021241650. Supplementary Information The online version contains supplementary material available at 10.1007/s00464-022-09548-5.


Inclusion criteria and outcome definition
The type of studies eligible for inclusion were original articles (retrospective, prospective, randomised controlled trials [RCT]), systematic reviews and meta-analysis. The presence of a clear definition of the surgical technique in the methods section was considered a fundamental additional inclusion criterion.
Three authors (D.V., A.M.G. and L.S.) independently screened each record from full-text articles for eligibility and extracted the data, including quality analysis. Disagreement was resolved by discussion and consensus; if no agreement was reached, a fourth author was consulted (B.S.).
The primary aims were the identification of (a) the surgical steps for RRC, (b) the different nomenclatures adopted and (c) the number of reports and prevalence of each RRC step for a given technique. A surgical step for RRC was defined as a surgical manoeuvre mentioned by a given article as being exclusive to RRC as opposed to standard right colectomy. A nomenclature was defined as a particular name given to describe an RRC technique.
Secondary aims included the identification of definitions for each RRC nomenclature (each made up of a combination of the RRC steps previously identified) and the heterogeneity and overlaps in these definitions.
Heterogeneity was defined as the absolute number and percentage of different definitions for a given RRC nomenclature, which will be reported in a table. Overlap was defined as the percentage of definitions that were used to describe two or more different RRC nomenclatures.
A sub-analysis identified RRC steps in Western (including Australia, Russia and Turkey) vs Asian countries and in different time periods (2009-2015 vs 2016-2021) in an effort to detect geographical or temporal peculiarities/ tendencies. Data extraction and quality assessment (Fig. S1) Each article was carefully read and analysed independently by two authors (B.S. and L.S.) in an effort to identify surgical steps that authors attributed specifically to RRC as opposed to a minimal/standard right colectomy.
Study quality was assessed using Newcastle Ottawa Scale (NOS) for non-RCTs and the modified Jadad scale score for RCTs.
NOS is an assessment tool used to measure the quality of non-randomized studies included in systematic reviews [14]. Each article was assessed for 9 parameters, each awarding up to one point, with a maximum total score of 9 points. Modified Jadad scale score is used to assess the quality of RCT by evaluating three parameters each awarding one point with three point awarded for high-quality RCT [15].

Data synthesis (Fig. S1)
The techniques described in each article were listed based on the presence or absence of each of the steps previously identified. These data were grouped in an excel sheet.
Furthermore, the definition of each technique given by the original author was recorded to reveal overlapping of definitions and evaluate heterogeneity.
Descriptive statistics were produced from the dataset: categorical data were merged and are reported as numbers and/or percentages. There was no comparative statistical analysis.

Systematic search
The systematic search process is summarised in Fig. 1. The initial database search identified 2602 articles. After initial screening and exclusion of duplications and after full-text reading of the remaining articles, 99 eligible articles were included in the qualitative review. Table 1 summarizes year, journal, design and country of publication for each study as well as NOS or Jadad scale score . All studies were published between 2009 and 2021 and > 50% from 2018 onwards. The most common study type was retrospective (54%), while only 3% of the studies included were RCTs. Average NOS score was 7.8 and average modified Jadad scale score was 6.7.

Primary aim: RRC surgical steps
Eight surgical steps were identified and recorded as specific for RRC as opposed to standard right colectomy: (1) Central arterial ligation (at the root from the superior mesenteric artery (SMA)). Central arterial ligation was described in 100% of the included studies; preservation of mesocolic integrity in 73%; dissection along the SMV plane in 67%; dissection along the left border of the SMA in 11%; dissection of the GCTH in 45%; sub-pyloric lymph-nodes dissection in 18%; a complete Kocher's manoeuvre in 11% and an omentectomy in 39% of studies.

Primary aim: number of reports and prevalence of each surgical step for a given technique
(1) CME (n of studies = 48) All CMEs studies reported central arterial ligation but not all the papers clearly reported preservation of mesocolic integrity (83.3%) and SMV dissection (66.7%). GCTH dissection was associated in 35.4%, sub-pyloric lymph-nodes dissection in 20.8%, omentectomy in 41.7% and a full Kocher's manoeuvre in 12.5%.
(2) CME + CVL (n = 22) CME + CVL descriptions included preservation of mesocolic integrity in 83.3%, SMV dissection in 54.5% and SMA dissection in 9.1%. GCTH dissection was described in 40.9%, sub-pyloric nodes retrieval in 18.2%, omentectomy in 45.5% and a full Kocher's manoeuvre in 13.6%.  [41] 2019 Surgical Endoscopy Retrospective study China 7 Ho MLL et al. [42] 2019 Journal of Gastrointestinal Oncology Technical note China 8 Hohenberger W et al. [9] 2009 Colorectal Disease Prospective study Germany 9 Huang JL et al. [43] 2015 International Journal of surgery Retrospective study China 8 Kanemitsu Y et al. [44] 2013 Diseases of the Colon & Rectum Retrospective study Japan 9 Karachun A et al. [45] 2019 British Journal of Surgery Randomised controlled trial Russia 6* Kataoka K et al. [46] 2020 British Journal of Surgery Retrospective study Japan 8 Killeen s et al. [47] 2014 Colorectal Disease Systematic Review Ireland 8 Killeen S et al. [48] 2014 Techniques in Coloproctology Technical note USA Kim CW et al. [49] 2016 Medicine Observational study South Korea 7 Kim IY et al. [50] 2016 International Journal of Surgery Retrospective study South Korea 9 Kim NK et al. [51] 2016 Surgical Oncology Technical note South Korea 8 Kim JS et al. [52] 2021 Asian Journal of Surgery Retrospective study South Korea 7 Kobayashi H et al. [53] 2020 Clinics in Colon and Rectal Surgery Retrospective study Japan 9 Koc MA et al. [54] 2021 Medicine Retrospective study Turkey 7 Lan YT et al. [55] 2010 Annals of Surgical Oncology Retrospective study Taiwan 9 Larach JT et al. [56] 2021 ANZ Journal of Surgery Retrospective study Australia 7 Lee SD et al. [57] 2009 International Journal of Colorectal Disease Retrospective study South Korea 9 Liang JT et al. [60] 2015 Surgical Endoscopy Prospective study Taiwan 7 Livadaru C et al. [61] 2019 World Journal of Gastrointestinal Oncology Retrospective study Romania 7 Luglio G et al. [62] 2015 Annals of Medicine and Surgery Prospective study Italy 8 Melich G et al. [63] 2014 Canadian Journal of Surgery Retrospective study South Korea 7 Merkel S et al. [64] 2016 British Journal of Surgery Observational study Germany 9 Mori S et al. [65] 2015 Digestive Surgery Observational study Japan 7 Mori S et al. [66] 2014 Surgical Endoscopy Retrospective study Japan 7 Nagasaki T et al. [67] 2015 World Journal of Surgery Observational study Japan 8 Nakajima K et al. [68] 2014 Japanese Journal of Clinical Oncology Randomised controlled trial Japan 7* Olmi S et al. [69] 2020 Journal of the Society of Laparoscopic & Robotic Surgeons Retrospective study Italy 7 Olofsson F et al. [70] 2016 Colorectal Disease Retrospective study Sweden 8 Ouyang M et al. [71] 2019 Cancer Management and Research Retrospective study China 7 Ow ZGW et al. [72] 2020 European Journal of Surgical Oncology Systematic Review and Meta-Analysis Singapore 9 Ozben V et al. [73] 2018 Journal of Robotic Surgery Prospective study Turkey 7 Pedrazzani C et al. [74] 2018 Journal of Gastrointestinal Surgery Retrospective Study Italy Perrakis A et al. [75] 2018 Archives of Medical Science Retrospective study Greece 7 Petz W et al. [76] 2017 European Journal of Surgical Oncology Prospective study Italy 8 Pramateftakis MG et al. [77] 2010 Techniques in coloproctology Clinical study Greece 7 Prevost GA et al. [78] 2018 World Journal of Surgical Oncology Retrospective study Switzerland 8 Ramachandra C et al. [79] 2020 Indian Journal of Surgical Oncology Retrospective study India 7 Rinne JKA et al. [80] 2019 Journal of Gastrointestinal Surgery Retrospective study Finland 9 Sahara K et al. [81] 2020 Surgery Today Retrospective study Japan 7 Sammour T et al. [82] 2019 Colorectal Disease Retrospective study USA 8 Sheng QS et al. [83] 2017 Annals of Surgical Treatment and Research Retrospective study China 7 Shin JW et al. [84] 2014 Techniques in Coloproctology Retrospective study South Korea 9 Shin JK et al. [85] 2018 Surgical Endoscopy Retrospective study South Korea 8 Siani LM et al. [86] 2014 Scandinavian Journal of Surgery Retrospective study Italy 7 Siddiqi N et al. [87] 2020 Surgical Endoscopy Retrospective study UK 8 Spinoglio G et al. [88] 2016 Annals of Surgical Oncology Retrospective study Italy 8 Spinoglio G et al. [89] 2018 Annals of Surgical Oncology Retrospective study Italy 8 Storli KE et al. [90] 2013 Digestive Surgery Prospective study Norway 7 Storli KE et al. [91] 2014 Techniques in Coloproctology Prospective study Norway 9 Subbiah R et al. [92] 2015 International Journal of Colorectal Disease Retrospective study India 9 Takahashi H et al. [93] 2016 Surgery today Retrospective study Japan 7 Takemasa I et al. [94] 2013 Surgical Endoscopy Prospective study Japan 7 Thorsen Y et al. [95] 2016 Techniques in Coloproctology Prospective study Norway 8 Thorsen Y et al. [96] 2019 ScienceDirect Observational study Norway 7 Tominaga T et al. [97] 2021 International Journal of Clinical Oncology Observational study Japan 8 Wang Y et al. [98] 2017 World Journal of Surgical Oncology Observational study China 8 Wei M et al. [99] 2018 Medicine Observational study China 7 (3) CVL (n = 1) CVL only: this paper described central arterial ligation only.
(4) Modified CME (mCME, n = 5) mCME is a "modified technique" of CME that included preservation of mesocolic integrity, reported in 80% and SMV dissection in 60%. GCTH dissection was reported in 60% of the papers, sub-pyloric nodes retrieval in 20% and omentectomy in 40%. Dissection along the SMA or a full Kocher's manoeuvre was not reported. D3 studies included preservation of mesocolic integrity in 33.30%, dissection of the SMV in 83.3% and of the SMA in 38% of reports. Dissection of GCTH and subpyloric nodes were reported in 66.6% and 16.7%, respectively; omentectomy and a full Kocher's manoeuvre in 22.2% and in 5.5%, respectively.
Results of systematic analysis of surgical techniques are summarised in Table 2.

Secondary aim: heterogeneity in definitions
Thirty-five different definitions of RRC were identified ( Table 3). The definitions used in each study are reported in Table S2 [16 -113]. Among the forty-eight articles regarding CME, there were twenty-two different descriptions of the operation. The most common definitions (recurring in 16.67% of studies) were central arterial ligation and preservation of mesocolic integrity. CME + CVL featured fourteen different definitions in twenty-two studies, the most common of which (35.71%) included only central arterial ligation and conservation of mesocolic integrity. The modified version of CME (mCME) was defined in four different ways. D3 was described with eleven different techniques: the most common technique (22.22%) included CVL, mesocolic preservation, SMV dissection, gastrocolic and pyloric nodes dissections and omentectomy. D3 + CME featured five descriptions, in 40% of cases including CVL, mesocolic preservation, SMV, gastrocolic and pyloric nodes dissection.  [103] 2020 Journal of the Balkan Union of Oncology Retrospective study China 7 Xie D et al. [104] 2016 Annals of Surgical Oncology Observational study China 8 Yamamoto M et al. [105] 2019 Surgical Endoscopy Prospective study Japan 7 Yan D et al. [106] 2020 Journal of the Balkan Union of Oncology Retrospective study China 7 Yang Y et al. [107] 2019 Diseases of the Colon & Rectum Technical notes USA 7 Yi X et al. [108] 2019 Surgical Endoscopy Retrospective study China 7 Yozgatli TK et al. [109] 2019 Journal of Laparoendoscopic & Advanced Surgical Techniques Observational study Turkey 7 Zedan A et al. [110] 2021 International Surgery of Surgical Oncology Prospective study Egypt 8 Zhao LY et al. [111] 2014 World Journal of Gastroenterology Prospective study China 9 Zhao LY et al. [112] 2014 World Journal of Gastroenterology Retrospective study China 8 Zurleni T et al. [113] 2018 International Journal of Colorectal Disease Retrospective study Italy 9 *Jadad score 1 3

East vs West
All six RRC steps were used by both Easter and Western studies. Of note, omentectomy was more prevalent in Eastern studies (48% vs 30.6%) as was GCTH dissection (54% vs 36,7%), while sub-pyloric lymph-node dissection was more common in the West (14% vs 22,4%), and dissection along the left border of the SMA was almost three times more common in the west (6 vs 16,3%) (Fig. S2).

Discussion
The current systematic review identified significant variability in the reporting and definitions of RRC, despite the existence of standardised, systematic descriptions that have been produced over years. Up to 35 different combinations of the key components of a RRC were observed, with several studies inappropriately claiming to perform a given procedure according to the descriptions provided by the authors. Such variability raises several concerns, as it is difficult to address the actual benefits of extensive approaches when no agreed terminology and procedures are being adopted.
Since the detailed description of D3 lymphadenectomy advocated by Asian guidelines [114] and the report on CME with CVL by Hohenberger et al. [9] to perform a RRC, a vast myriad of articles with a combination of definitions of RRC have been published.
The lack of uniformity undermines the proper evaluation of the clear benefits of any technique over the others. It is interesting to note that the CME description by Hohenberger [9] clearly differs from any "standard" right hemicolectomy for right colon cancer, but some of the proposed techniques do not differ from a proper right colectomy for cancer. Even if some authors have suggested some benefits of extended lymphadenectomy [115], most agree that there is need for more prospective or randomised studies to identify this as necessary for RRC [116]. The discrepancies in available definitions used in the published studies make it difficult to draw conclusions.
This systematic review offers several contributions to the understanding of RRC. It identifies the fundamental surgical steps reported by every single study. Commonly used definitions of these steps can be found in Table 4. Some of these surgical steps are adopted quite uniformly by all the authors, while others seem not to be considered fundamental.
The main surgical steps commonly shared by the authors are two, central arterial ligation and preservation of the  It allows a significantly higher number of nodes to be excised compared to so-called low-tie of the organ's vessels. This technique indeed may provide rationale for superior oncological results (in terms of both local and distal control) [9] but certainly it is not a novel concept; high-tie of vascular structures being one of the pillars of oncologic surgery. The rationale to remove more lymph nodes is also suggested by reports on lymph node ratio (number of positive nodes divided by the total number of harvested nodes) that can be more prognostically relevant than the number of positive nodes per se [117]. Preservation of mesocolic integrity is predominantly mentioned in studies focussing on CME and it can be properly regarded as a "novel" manoeuvre; it follows a well-known anatomical dissection plane and encompasses the removal of all the lymphoadipose tissue lateral to the SMV. The embryologic fasciae that need to be respected during RRC with CME would be the fusion fascia of Toldt and the fusion fascia of Fredet [118][119][120].
Whether the integrity of the mesocolic fascia does represent a necessity to prevent local recurrence is far from being clarified. The proposers of CME should be credited for having raised attention towards the importance of a truly radical approach to right colon cancers [9] A retrospective study of surgical specimens reported longer survival for those patients with stage III colon cancer whose colon was excised with intact mesocolon, compared with patients who had received less than optimal surgery. The surgical technique is well defined and requires the surgeon (1) to remain within the mesocolic plane, (2) to perform central ligation of the tumour-feeding artery, and (3) to remove an appropriate length of large bowel on either side of the tumour [100]. A medial to lateral approach to dissection has been advocated with laparoscopy and a lateral to medial one in open surgery, but the direction of dissection was independent from extent of resection and never reported as specific to RRC.
According to Hohenberger et al. [9], the lymphoadipose tissue covering the SMV and the head of the pancreas should be removed in the event of potentially affected nodes at preoperative CT scan, or if these are detected intraoperatively at these sites. The removal of the lymphoadipose tissue along both lateral and medial sides of SMV and the GCTH defines a D3 lymphadenectomy [8,121,122].
For what concerns the other surgical steps variably associated to RRC, the consensus drops significantly, and they are reported by a minority of authors.
The dissection along the SMV between the ileocolic vein and the GCTH (Gillot's fat pad) [123] is based on data suggesting that 3% of right colon cancer metastasise to central lymph nodes, located anteriorly to the SMV [19,117,[128][129][130][131]. This may be important in the staging process (as up to 0.2-2% of patients harbour skip metastases in central nodes) and might probably ameliorate prognosis [117,128,129]. The SMV plane of dissection is an excellent surgical plane for dissection. Nevertheless, it can be considered dangerous due to the importance of the structure and because of the thin wall of the vein [132][133][134].
Authors reporting on the more extensive D3 lymphadenectomy most frequently mention dissection of the SMA. This procedure may result in autonomic dysfunction, due to consensual resection of nerve plexuses lying anterior to the SMA. Symptoms may include severe refractory diarrhoea [94,95].
Dissection of the GCTH requires the removal of lymphoadipose tissue covering the head of the pancreas and is usually employed by authors of D3 or in case of tumours of the hepatic flexure or proximal transverse colon. No study to date has specifically focussed on the advantages of this surgical step alone.
Dissection of sub-pyloric lymph nodes, complete Kocher manoeuvre and omentectomy are generally not considered integral part of RRC if not in a limited number of reports. Dissection of station six nodes could be theoretically useful in cancers of the hepatic flexure and proximal transverse colon [135]. As said, no benefit has been demonstrated and there is no consensus to its routine Table 4 Common definitions of the surgical steps identified for radical right colectomy Step Definition (1): Central arterial ligation Ligation at their roots of the ileocolic artery, the right colic artery (when present) and the right branch of the middle colic artery (for cancers of the caecum and ascending colon up to the right flexure) or the stem of the middle colic artery (cancers of the left side of the hepatic flexure or proximal transverse colon) (2): Preservation of mesocolic integrity Dissection along the embryological plane and complete excision of the mesocolon, conserving the integrity of its anterior and posterior sheaths (3) Dissection along the superior mesenteric vein (SMV) plane The dissection plane is offered by the anterior and lateral face of the SMV (4) Dissection along the left border of the superior mesenteric artery (SMA) The dissection plane offered by the SMA run below and laterally to the SMV. It requires a dissection of the left border of the SMV and the anterior surface of the aorta (5) Dissection of the gastrocolic trunk of Henle (GCTH) The GCTH has numerous and frequent anatomic variations. In most cases the right/middle colic vein can be dissected free and individually divided while preserving pancreaticoduodenal and gastroepiploic veins. Further lymph nodes are harvested at this level (6) Sub-pyloric lymph-nodes dissection Removal of lymphoadipose tissue around the origin of the gastroepiploic vessels. This manoeuvre usually includes sacrifice of these vascular structures (7) Complete Kocher's manoeuvre Complete mobilisation of the 1 st to 3 rd portions of the duodenum from their attachments to achieve 180° rotation of the duodenum and pancreatic head to access retropancreatic and caval lymph nodes (8) Omentectomy Resection of the greater omentum together with the surgical specimen application. A complete Kocher manoeuvre allows dissection of retro-duodenopancreatic nodes, but no rationale exists for their removal in colon cancer. The utility of omentectomy in colonic surgery has not been thoroughly investigated to date. Different authors with variable combinations of the main surgical steps, resulting in a great heterogeneity of definitions, have defined individual surgical techniques. In this systematic review, 36.36% of CME definitions were unique, while the rest overlapped with definitions used for CME + CVL (40.90%), D3 (22.72%), mCME (13.64%) and D3 + CME (13.64%).
Obviously, this variability in definition makes aggregation of results from these studies incorrect from a methodological point of view, such that meta-analyses would be of questionable scientific value. In fact, the current "CME" literature includes different surgical operations, which are mistakenly given the same name.
Of course, this introduces a further element of confusion in interpretation of the literature, making comparison among different RRC techniques virtually impossible and the twelve ongoing randomized trials possibly not completely confrontable. Of note, there have been proposals for standardised assessment and reporting of CME and D3 lymphadenectomy in RRC; a consistent utilisation of such approaches could ease the interpretation of prospective studies, allowing to objectively addressing whether extended approaches confer any survival benefit [136,137].
After more than 10 years of debate, it is apparent that a clarification on surgical technique has been long overdue: a globally agreed consensus on the precise surgical steps to be performed for each given procedure (herein defined RRC) is necessary and expectedly awaited. Ethical approval According to local IRB, ethical approval for systematic review is not required.
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