Evidence - Hemicolectomy right, open

  1. Literature summary

    Surgical therapy of colon cancer

    In the last 30 years progress in colon cancer therapy arose from an increasingly personalized approach to treatment, consistent implementation of oncological principles in surgery, more aggressive treatment protocols in metastatic disease, and the application of minimally invasive surgical techniques. In nonmetastatic colon cancer UICC II and III standardized treatment concepts in multinodal tumor therapy have increased the mean five-year survival rate from 65% to over 85% and reduced the mean locoregional recurrence rate from over 13% to less than 2%. [10]. In metastasized cancer, 20% of patients achieve a five-year survival rate of more than 40 % [19].

    Oncological principles in surgery

     En-bloc resection of the tumor-bearing segment of the colon with systematic locoregional lymphadenectomy is of decisive importance for the prognosis.  Systematic lymphadenectomy with a high yield of potentially metastatic lymph nodes is the basis for standardized classification of lymph node status, the resulting therapeutic recommendations and patient prognosis.

    In colon cancer centrad lymphatic metastasis spreads via the paracolic lymph nodes, which are affected in 70% of patients with nodal involvement, and via the intermedian lymph nodes to the lymph nodes along the primary artery. Longitudinal drainage along the sides of the tumor follows the paracolic lymph nodes with a maximum lateral spread of 10cm [25, 26]. The extent of the resection therefore depends on the region supplied by the primary arteries divided at their origins and should cover at least 10cm on both sides of the tumor. Being the last lymph node station, the primary lymph nodes are located centrally where the primary arteries arise from the main vessels.

    Due to the increasingly performed standardized en-bloc resection with systematic lymphadenectomy, and considering the established chemotherapy protocols, the overall prognosis in curative settings has improved in the last 20 years [16]. Retrospective trials have demonstrated a non-stage dependent correlation between the number of lymph nodes examined and the prognosis [8, 13].

    Outside of studies the concept of the sentinel lymph node has not proven its benefit as a staging tool in colon surgery [3, 4]. Even if the study data are ambiguous, as a quality criterion the current German S3 guideline"Colorectal carcinoma" recommends the excision and histological work-up of at least 12 lymph nodes [21].

    In addition to systematic lymphadenectomy, the concept of Complete Mesocolic Excision (CME) also aims at a maximum reduction in the number of local recurrences by increasing the radical extent and quality of resection. The technique was published by Hohenberger et al. in 2009 and is based on three core concepts [16, 24]:

    1. Dissection along the embryonic layers to protect both mesocolic fascial laminae of the resection area and avoid possible tumor cell seeding.
    2. Strict division of the respective primary vessels as close to their origins as possible results in the maximum number lymph nodes as well as maximum local radicality centrad.
    3. A sufficient length of the resected specimen maximizes the paracolic lymphadenectomy.

    Data from Denmark, Sweden and Germany show that in patients with colon cancer UICC stage I-III the CME technique correlates with better disease-free survival than in standard colon resection [5, 6, 18].

    Minimally invasive surgery

    In terms of indicators of oncological quality (R status, number of lymph nodes) and long-term results (tumor recurrence, survival), with surgeons of appropriate expertise single-center and multicenter RCTs (KOLOR, COST, CLASSIC-Trail) showed no difference between laparoscopic and open techniques in colon cancer surgery [7, 11, 14]. One benefit of minimally invasive surgery was a rather low short-term perioperative morbidity, while the overall morbidity and mortality remained unchanged [23]. According to the current German S3 guideline on "Colorectal carcinoma", laparoscopic resection of colon cancer may therefore be performed in appropriate cases, if the surgeon has suitable experience [21]. At present there is no evidence for the NOTES technique in colon cancer.

    Multimodal tumor therapy

    Numerous studies demonstrate the significance of medical tumor therapy in nonmetastatic colon cancer.  Adjuvant chemotherapy in UICC stage III correlates with a significant improvement of about 20 % in the prognosis of overall survival[22]. In stage II, since patients at risk (T4 tumor, perforated tumor, emergency surgery, number of studied/excised lymph nodes <12) have a significantly worse prognosis than same-stage patients without risk factors the former should be offered adjuvant chemotherapy [21]. In recent years the role of neoadjuvant chemotherapy in the treatment of locally advanced colon cancer has been studied. A randomized study in the UK on locally advanced colon cancer demonstrated that unlike adjuvant chemotherapy alone combined neoadjuvant/adjuvant chemotherapy (oxaliplatin, leucovorin and 5-FU) lowered the rate of R1 resection and resulted in significant downstaging. No tumor progression was observed while the neoadjuvant chemotherapy was ongoing [2, 12]. Studies have shown that computed tomography can identify the T-status of locally advanced colon cancer and thus select these patients for neoadjuvant chemotherapy or preoperatively assess their response to chemotherapy [1, 20]. However, long-term oncological results are still pending.

    Hepatic and pulmonary metastases

    In metastasis, the five-year survival rate is less than 10%. Under medical tumor treatment (combination of dual therapy and antibodies) and with the more aggressive indication for metastasis resection, about 20% of metastasized patients will profit from a five-year survival rate of up to 50% [15]. The combination of different chemotherapy protocols results in response rates of up to 60% and an R0 resection rate of up to 15% [9].

    Peritoneal metastasis

    If peritoneal metastases are already present in colon cancer, the indication for cytoreductive surgery followed by hyperthermal intraperitoneal chemotherapy (HIPEC) should be be considered. This combined treatment protocol has demonstrated a significant survival benefit in terms of prolonging median survival from 12.6 to 22.3 months [27]. The extent of peritoneal metastasis is determined with the Peritoneal Cancer Index (PCI). If the PCI score in patients without additional extraabdominal metastases is below 20, surgical cytoreduction with HIPEC can be performed in specialized centers - provided R0 resection is possible[21].

    Perioperative concept

    Most hospitals in Germany have implemented the ERAS concept ("enhanced recovery after surgery") of multimodal postoperative rehabilitation in gastrointestinal surgery, sometimes in modified form. The concept aims to quickly control the pathophysiologic changes caused by the surgical intervention, such as fatigue, bowel atony and insulin resistance. The concept includes early removal of gastric tubes and intrabdominal drains, early oral feeding, stimulation of bowel motility, effective analgesia (epi-/peridural) and early ambulation. Numerous studies have shown that the ERAS concept can significantly shorten the length of stay with a significantly lower complication rate [17].

  2. Ongoing trials on this topic

  3. References on this topic

    1: Arredondo J, González I, Baixauli J, Martá­nez P, Rodri­guez J, Pastor C, Ribelles MJ, Sola JJ, Hernández-Lizoain JL. Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy. J Gastrointest Oncol. 2014 Apr;5(2):104-11.

    2: Arredondo J, Pastor C, Baixauli J, Rodri­guez J, González I, Vigil C, Chopitea A, Hernández-Lizoáin JL. Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer. Colorectal Dis. 2013 May;15(5):552-7.

    3: Bembenek A. Current clinical status of sentinel lymph nodes in colon and proximal rectal cancer. Colorectal Dis. 2011 Nov;13 Suppl 7:63-6.

    4: Bembenek AE, Rosenberg R, Wagler E, Gretschel S, Sendler A, Siewert JR, Nährig J, Witzigmann H, Hauss J, Knorr C, Dimmler A, Gröne J, Buhr HJ, Haier J, Herbst H, Tepel J, Siphos B, Kleespies A, Koenigsrainer A, Stoecklein NH, Horstmann O, Grützmann R, Imdahl A, Svoboda D, Wittekind C, Schneider W, Wernecke KD, Schlag PM. Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial. Ann Surg. 2007 Jun;245(6):858-63.

    5: Bernhoff R, Martling A, Sjövall A, Granath F, Hohenberger W, Holm T. Improved  survival after an educational project on colon cancer management in the county of Stockholm–a population based cohort study. Eur J Surg Oncol. 2015 Nov;41(11):1479-84.

    6: Bertelsen CA, Neuenschwander AU, Jansen JE, Wilhelmsen M, Kirkegaard-Klitbo A, Tenma JR, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Iversen ER, Kristensen B, Gögenur I; Danish Colorectal Cancer Group.. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study. Lancet Oncol. 2015 Feb;16(2):161-8.

    7: Colon Cancer Laparoscopic or Open Resection Study Group., Buunen M, Veldkamp R, Hop WC, Kuhry E, Jeekel J, Haglind E, Pahlman L, Cuesta MA, Msika S, Morino M, Lacy A, Bonjer HJ. Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial. Lancet Oncol. 2009 Jan;10(1):44-52.

    8: Chen SL, Bilchik AJ. More extensive nodal dissection improves survival for stages I to III of colon cancer: a population-based study. Ann Surg. 2006 Oct;244(4):602-10.

    9: Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinó L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest.. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6.

    10: Fischer J, Hellmich G, Jackisch T, Puffer E, Zimmer J, Bleyl D, Kittner T, Witzigmann H, Stelzner S. Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades. Int J Colorectal Dis. 2015 Jun;30(6):797-806.

    11: Fleshman J, Sargent DJ, Green E, Anvari M, Stryker SJ, Beart RW Jr, Hellinger M, Flanagan R Jr, Peters W, Nelson H; Clinical Outcomes of Surgical Therapy Study Group.. Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial. Ann Surg. 2007 Oct;246(4):655-62; discussion 662-4.

    12: Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60.

    13: George S, Primrose J, Talbot R, Smith J, Mullee M, Bailey D, du Boulay C, Jordan H; Wessex Colorectal Cancer Audit Working Group.. Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer. 2006 Oct 9;95(7):841-7.

    14: Green BL, Marshall HC, Collinson F, Quirke P, Guillou P, Jayne DG, Brown JM. Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg. 2013 Jan;100(1):75-82.

    15: Heinrich S, Lang H. Neoadjuvant chemotherapy or primary surgery for colorectal liver metastases. Pro primary surgery. Chirurg. 2014 Jan;85(1):17-23.

    16: Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation–technical notes and outcome. Colorectal Dis. 2009 May;11(4):354-64; discussion 364-5.

    17: Kehlet H, Wilmore DW. Evidence-based surgical care and the evolution of fast-track surgery. Ann Surg. 2008 Aug;248(2):189-98.

    18: Merkel S, Weber K, Matzel KE, Agaimy A, Göhl J, Hohenberger W. Prognosis of patients with colonic carcinoma before, during and after implementation of complete mesocolic excision. Br J Surg. 2016 Aug;103(9):1220-9.

    19: Neumann UP, Seehofer D, Neuhaus P. The surgical treatment of hepatic metastases in colorectal carcinoma. Dtsch Arztebl Int. 2010 May;107(19):335-42.

    20: Norgaard A, Dam C, Jakobsen A, Plöen J, Lindebjerg J, Rafaelsen SR. Selection of colon cancer patients for neoadjuvant chemotherapy by preoperative CT scan. Scand J Gastroenterol. 2014 Feb;49(2):202-8.

    21: Pox C, Aretz S, Bischoff SC, Graeven U, Hass M, Heußner P, Hohenberger W, Holstege A, Hübner J, Kolligs F, Kreis M, Lux P, Ockenga J, Porschen R, Post S, Rahner N, Reinacher-Schick A, Riemann JF, Sauer R, Sieg A, Scheppach W, Schmitt W, Schmoll HJ, Schulmann K, Tannapfel A, Schmiegel W; Leitlinienprogramm Onkologie der AWMF.; Deutschen Krebsgesellschaft e.V.; Deutschen Krebshilfe e.V.. S3-guideline colorectal cancer version 1.0. Z Gastroenterol. 2013 Aug;51(8):753-854.

    22: Ragnhammar P, Hafström L, Nygren P, Glimelius B; SBU-group. Swedish Council of Technology Assessment in Health Care.. A systematic overview of chemotherapy effects in colorectal cancer. Acta Oncol. 2001;40(2-3):282-308.

    23: Schwenk W, Neudecker J, Raue W, Haase O, Müller JM. „Fast-track“ rehabilitation after rectal cancer resection. Int J Colorectal Dis. 2006 Sep;21(6):547-53.

    24: Sondenaa K, Quirke P, Hohenberger W, Sugihara K, Kobayashi H, Kessler H, Brown G, Tudyka V, D’Hoore A, Kennedy RH, West NP, Kim SH, Heald R, Storli KE, Nesbakken A, Moran B. The rationale behind complete mesocolic excision (CME) and a central vascular ligation for colon cancer in open and laparoscopic surgery: proceedings of a consensus conference. Int J Colorectal Dis. 2014 Apr;29(4):419-28.

    25: Tan KY, Kawamura YJ, Mizokami K, Sasaki J, Tsujinaka S, Maeda T, Nobuki M, Konishi F. Distribution of the first metastatic lymph node in colon cancer and its clinical significance. Colorectal Dis. 2010 Jan;12(1):44-7.

    26: Toyota S, Ohta H, Anazawa S. Rationale for extent of lymph node dissection for right colon cancer. Dis Colon Rectum. 1995 Jul;38(7):705-11.

    27: Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003 Oct 15;21(20):3737-43.

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Huang S, Ye J, Gao X, Huang X, Huang J, Lu L, Lu C, Li Y, Luo M, Xie M, Lin Y, Liang R. Progress of

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