новая папка / Operative Standards for Cancer Surgery Volume I 1st Edition

FIGURE 16-14 A,B: Intraoperative photograph of a locally advanced sigmoid colon cancer with bladder, ileum, and descending colon involvement.

FIGURE 16-15 En bloc multivisceral resection specimen including the sigmoid colon, rectum, terminal ileum, uterus, fallopian tubes and ovaries, and bladder.

En bloc resection that includes structures in which removal would result in low morbidity—the small bowel, ovary, or abdominal wall, for example—should be performed in almost all situations. Major resections likely to result in high morbidity, such as pelvic exenteration, nephrectomy, pancreaticoduodenectomy, or major nerve or vascular resection, should be preceded by careful surgical preparation and preoperative patient counseling. Multivisceral resection of advanced-stage colon cancer poses many challenges to the operating surgeon and may be associated with significant morbidity. There are situations in which aggressive multivisceral en bloc resection provides the only chance for cure.

Unfortunately, there are situations in which the surgery would be futile or result in unacceptably high morbidity; thus, the decision to proceed with resection should be based on a thorough preoperative evaluation and a discussion with the patient and the patient’s multidisciplinary care team. Proper planning includes review of imaging to determine the plan for both resection and reconstruction and assessment of patient’s functional status.

Morbidity rates following multivisceral resection range from 25% to 40% with 30-day mortality rates ranging from 4% to 9%.3,14,18 However, these data from singleinstitution reports reflect careful patient selection and treatment by experienced surgeons with coordinated multidisciplinary teams and recovery units. Thus, the patient’s comorbid factors and the surgeon’s experience should be considered in the management of these complex tumors. The need for thorough preoperative planning to reduce morbidity, including

contingency plans, cannot be overemphasized.19 A more detailed description of some specific situations of adjacent organ involvement is outlined in the sections below.

Duodenum and pancreas. Locally advanced cancer in the right colon may extend directly into the duodenum or pancreatic head or neck. The resection of such cancer may entail en bloc pancreaticoduodenectomy or partial duodenectomy. Fortunately, only a very small proportion of locally advanced T4 colon cancers involve the pancreas (1.7% to 8%) or duodenum (0.8% to 4%). Direct tumor infiltration (pT4b disease) of the duodenum or pancreatic head suspected on the basis of tumor adhesion is pathologically confirmed in 20% to 78% of patients, which demonstrates the variability in the presentation of such tumors and the difficulty in clinically assessing whether pathologic invasion is

present.3 Depending on the series, the risk for surgical morbidity is approximately 25% and that for surgical mortality is as high as 20%. In the setting of perforation or abscess, the surgical mortality rate is particularly high. Other adverse prognostic factors include nodal and distant metastasis; in the presence of such metastasis, the rate of early recurrence approaches 50% at a median time of 15 months. Regardless of the limited published evidence guiding surgery for colon cancer invading the duodenum and/or pancreas, the fundamental principles of

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oncologic resection should be maintained. The tumor should never be dissected off the duodenal wall or pancreas. In healthy, well-selected patients, partial duodenal wall resection can be performed by a surgeon who has the necessary skills and experience. Pancreaticoduodenectomy can be offered only if the need for it is recognized preoperatively, but the surgery should be preceded by proper counseling and multidisciplinary discussion that includes the consideration of neoadjuvant therapy. For symptomatic high-risk scenarios, temporizing adjuncts include gastrostomy, feeding jejunostomy, and ileostomy or gastrojejunostomy bypass.

Ureters and bladder. En bloc R0 resection is often appropriate for tumors invading urologic structures in the pelvis. The bladder is the most commonly involved organ among

patients with colorectal cancer, resected in 53% of cases in a large systematic literature review.18 In a recent series in which only bladder involvement was treated with limited

bladder wall resection, malignant adhesions increased the risk of local recurrence at the bladder tenfold.20 Thus, the importance of wide, complete, and en bloc resection should be emphasized. However, following composite resection of the urinary tract for colon cancer, up to one in four patients will have urologic complications and that many of these

patients (27%) will ultimately require surgical correction.21 Thus, a multidisciplinary approach to management of patients with colon cancer involving the urologic tract should be considered.

Uterus and ovaries. Female pelvic organs may be involved in both rightand leftsided colonic malignancies. Colon cancer involvement of the ovaries can occur via direct

extension, peritoneal dissemination, or hematogenous spread. Approximately 20% of multivisceral resections for colon cancer are associated with ovarian involvement.18 The

uterus and vagina may also become involved, although this is more commonly an issue in the setting of rectal cancer rather than colon cancer. Oophorectomy is advocated if there is clinical suspicion of ovarian involvement in the absence of disseminated peritoneal metastasis. Direct extension of the tumor into any female pelvic organs can be resected en bloc with curative intent and minimal morbidity.

The role of prophylactic oophorectomy in patients undergoing surgery for colorectal cancer has been a subject of some interest. The surgery can be performed with minimal morbidity, particularly among postmenopausal women. A survival benefit with prophylactic oophorectomy in patients with sporadic colorectal cancer has not been

demonstrated.22,23,24,25 Prophylactic oophorectomy should be considered and the indications preoperatively discussed for colon cancer patients who have hereditary

nonpolyposis colorectal cancer syndrome, as these patients are at risk for both occult synchronous and subsequent metachronous ovarian malignancy.26,27 Prophylactic

oophorectomy not only reduces the risk for ovarian cancer but has also been shown to be cost-effective.28

Abdominal wall and diaphragm. Abdominal wall invasion should be resected en bloc with negative margins. Preoperative planning for colorectal cancers invading the abdominal wall and/or diaphragm should include consultation with a reconstructive surgery team. Partial-thickness abdominal wall defects resulting from such resection may not require vascularized flap-based reconstruction but may be repaired primarily or

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with bioprosthetic or synthetic mesh replacement of the fascia. Full-thickness abdominal wall defects and/or those with skin involvement likely require reconstruction with a vascularized flap (Fig. 16-16). There are various options for temporary and definitive abdominal wall reconstruction. Concerns about the risk for subsequent hernia should not preclude aggressive resection. However, if the need for abdominal wall resection has not been preoperatively anticipated and immediate reconstructive options are unavailable, aborting the resection with planned subsequent return to surgery with a multidisciplinary surgical team should be considered. Diaphragm involvement is not a contraindication to en bloc resection, and primary or mesh (e.g., bioprosthetic) closure in patients with diaphragm involvement may be performed. Such an approach has been performed among

patients undergoing liver resection, and although associated with potentially increased morbidity, it does not increase operative mortality.29 However, the dissemination of cancer cells into the thoracic cavity either prior to exploration or

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due to iatrogenic tumor seeding will limit the utility of this effort. Avoiding injury to the phrenic nerve improves postoperative respiratory recovery.

FIGURE 16-16 A: En bloc multivisceral resection for locally advanced ascending colon cancer with abdominal wall and small bowel involvement and (B) subsequent photograph demonstrating the full defect and reconstruction with an anterolateral thigh pedicle flap.

5. REMOVAL OF LYMPHADENOPATHY BEYOND THE PRIMARY DISTRIBUTION

Recommendation: Clinically positive lymph nodes outside the primary field of resection that are identified at the time of resection should be biopsied or removed.

Type of Data: Retrospective observational studies.

Strength of Recommendation: Moderate.

Rationale

Lymphatic vessels course along the distribution of the mesenteric vessels. Drainage from the intestine courses toward the root of the mesentery, along the para-aortic nodes, and ultimately into the thoracic duct. Lymphatics in the cecum and proximal ascending colon most commonly drain along the ileocolic lymph nodes, which encircle the ileocolic vascular pedicle. Metastases from tumors of the ascending colon may be present in lymph nodes along the ileocolic, right, and middle colic arteries. Lymph drainage from the

transverse colon is primarily along the middle colic artery and then into the superior mesenteric lymph group.30

The inferior mesenteric lymph nodes, which are situated about the root of the inferior mesenteric artery, are afferent from peripheral nodes located along the marginal artery of Drummond and efferent to the lumbar nodal chain and superior mesenteric nodes.

Clinical Implications

In addition to the aforementioned primary routes of its lymphatic spread, colorectal cancer metastasis can also occur beyond the primary distribution and outside of the distribution of the primary resection along the following routes:

Para-aortic nodes. The para-aortic nodes are situated anterior to the lumbar vertebral bodies in proximity to the abdominal aorta. The para-aortic node group can be divided into three subgroups:

1.Preaortic group: These nodes drain the abdominal part of the gastrointestinal tract superior to the mid-rectum.

2.Retroaortic group: These nodes drain the lateral and preaortic regions.

3.Lateral group: These nodes, which drain the iliac regions, ovaries, and other pelvic organs, are located adjacent to the aorta and anterior to the spine. They extend laterally to the edge of the psoas major muscles and superiorly to the diaphragm.

Colorectal metastasis to the para-aortic nodes are uncommon but associated with poor prognosis. Metastases to the para-aortic lymph nodes most commonly occur in the preaortic or lateral groups, although multiple lymph nodes may be involved. The presence of para-aortic lymph node involvement signals the need for systemic chemotherapy and, when identified at surgery, should be removed for pathologic evaluation.

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Nodes within the small bowel mesentery (SBM). The root of the SBM is contiguous with the hepatoduodenal ligament around the superior mesenteric vein and the right side of the transverse mesocolon about the gastrocolic trunk. The inferior mesenteric vein runs along the left side of the root of the SBM. Colon cancer cells can spread to the SBM by direct extension, by extension along the neural plexus or neighboring ligaments, or by way of lymphatic channels. Much like that of para-aortic nodes, colorectal cancer involvement in this node group is associated with poorer prognosis, and the clinical significance of extended dissection into this distribution remains incompletely understood.

The lymphatic spread of colon cancer from the submucosal lymphatic channels through the epiand paracolic nodes to the intermediate nodes and then to nodes surrounding the superior mesenteric artery and/or para-aortic nodes was once considered to be an orderly and predictable process of tumor cell dissemination. Sentinel

lymphatic mapping studies have shown aberrant lymphatic drainage in approximately 4% of cases (range, 0% to 10%).31 However, these studies often do not specify the precise anatomical location(s) of the aberrant node(s). Aberrant lymphatic drainage beyond the relevant nodes in the central vascular pedicle may be identified as clinically abnormal lymph nodes by their size or other characteristics and should be resected for pathologic evaluation if it is safe to do so.

Intraoperative Assessment

The standard preoperative clinical evaluation of patients with nonmetastatic colon cancer includes CT of the chest, abdomen, and pelvis. During this evaluation, the patient should be carefully evaluated for enlarged lymph nodes along the superior mesenteric artery, superior mesenteric vein, and iliac vessels and about the abdominal aorta. Clinically suspicious lymph nodes (i.e., >1 cm) should be thoroughly evaluated and potentially resected at the time of operation (Fig. 16-17A,B). During the operation, the retroperitoneum and root of the mesentery should be carefully evaluated as part of routine exploration, and abnormal-appearing lymph nodes should be identified and resected for histologic evaluation.

FIGURE 16-17 Intraoperative photograph showing aortocaval adenopathy. Triangles point to lymph node. IVC, inferior vena cava.

P.296 The vast majority of lymph nodes in colon cancer patients are small (< 1 cm) and hardly visible or palpable at the time of operation. In fact, nearly 80% of nodal tumor metastases

are found in lymph nodes <5 mm in maximal dimension and are easily overlooked at the time of operation or pathologic evaluation.32,33,34,35 Nodes are generally considered to

be normal if they are smaller than 1 cm2. The consistency of nodes upon palpation may also be illustrative; for example, stony-hard nodes typically suggest cancer metastasis. Similarly, a group of mesenteric nodes that appear to be connected or move as a unit, called “matted” nodes, are consistent with lymphatic spread of disease.

Principles of Surgery for Lymphadenectomy

Traditionally, metastases in extraregional lymph node groups have been considered to be distant metastases. However, resection of isolated extraregional lymph node

metastasis is associated with improved survival analogous to resection of liver metastasis.36 At minimum, suspicious lymph nodes should be removed for diagnostic confirmation. There is insufficient data to support performing a more extended resection of the nodal basin (e.g., extended para-aortic lymph node dissection) versus targeted resection of involved lymph nodes. However, resection of isolated extraregional nodal metastasis is associated with improved survival, as has been observed following the resection of metastatic disease. Involvement of multiple lymph nodes outside of the primary distribution indicates disseminated disease, and excisional biopsy for histologic confirmation, but not routine radical lymph node dissection, should be performed when it is safe to do so. The patient should then be referred for systemic therapy.

REFERENCES

1.Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:583-596.

2.Chang GJ, Kaiser AM, Mills S, et al. Practice parameters for the management of colon cancer. Dis Colon Rectum 2012;55:831-843.

3.Gezen C, Kement M, Altuntas YE, et al. Results after multivisceral resections of locally advanced colorectal cancers: an analysis on clinical and pathological t4 tumors.

World J Surg Oncol 2012;10:39.

4.Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology 2010;257:674-684.

5.Grossmann I, Klaase JM, Avenarius JK, et al. The strengths and limitations of routine staging before treatment with abdominal CT in colorectal cancer. BMC Cancer

2011;11:433.

6.Devereux DF, Deckers PJ. Contributions of pathologic margins and Dukes’ stage to local recurrence in colorectal carcinoma. Am J Surg 1985;149:323-326.

7.Guillem JG, Wood WC, Moley JF, et al. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol 2006;24:4642-

4660.

8.de Vos tot Nederveen Cappel WH, Buskens E, van Duijvendijk P, et al. Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut 2003;52: 1752-1755.

9.Maeda T, Cannom RR, Beart RW Jr, et al. Decision model of segmental compared with total abdominal colectomy for colon cancer in hereditary nonpolyposis colorectal cancer. J Clin Oncol 2010;28:1175-1180.

10.Connell WR, Talbot IC, Harpaz N, et al. Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis. Gut 1994;35(10):1419-1423.

11.Ullman T, Croog V, Harpaz N, et al. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 2003;125(5):13111319.

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12.West NP, Hohenberger W, Weber K, et al. Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol 2010;28(2):272-278.

13.Hohenberger W, Weber K, Matzel K, et al. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation—technical notes and outcome. Colorectal Dis 2009;11(4):354-364.

14.Hoffmann M, Phillips C, Oevermann E, et al. Multivisceral and standard resections in colorectal cancer. Langenbecks Arch Surg 2012;397:75-84.

15.Benson AB III, Venook AP, Bekaii-Saab T, et al. Colon cancer, version 3.2014. J Natl Compr Canc Netw 2014;12(7):1028-1059.

16.Chen YG, Liu YL, Jiang SX, et al. Adhesion pattern and prognosis studies of T4N0M0 colorectal cancer following en bloc multivisceral resection: evaluation of T4 subclassification. Cell Biochem Biophys 2011;59:1-6.

17.Darakhshan A, Lin BP, Chan C, et al. Correlates and outcomes of tumor adherence in resected colonic and rectal cancers. Ann Surg 2008;247:650-658.

18.Mohan HM, Evans MD, Larkin JO, et al. Multivisceral resection in colorectal cancer: a systematic review. Ann Surg Oncol 2013;20:2929-2936.

19.Govindarajan A, Fraser N, Cranford V, et al. Predictors of multivisceral resection in patients with locally advanced colorectal cancer. Ann Surg Oncol 2008;15:1923-1930.

20.Luo HL, Tsai KL, Lin SE, et al. Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection. Int J Colorectal Dis 2013;28:631-635.

21.Stotland PK, Moozar K, Cardella JA, et al. Urologic complications of composite resection following combined modality treatment of colorectal cancer. Ann Surg Oncol

2009;16:2759-2764.

22.Banerjee S, Kapur S, Moran BJ. The role of prophylactic oophorectomy in women undergoing surgery for colorectal cancer. Colorectal Dis 2005;7:214-217.

23.Sielezneff I, Salle E, Antoine K, et al. Simultaneous bilateral oophorectomy does not improve prognosis of postmenopausal women undergoing colorectal resection for cancer. Dis Colon Rectum 1997;40:1299-1302.

24.Tentes A, Markakidis S, Mirelis C, et al. Oophorectomy during surgery for colorectal carcinoma. Tech Coloproctol 2004;8(suppl 1):s214-s216.

25.Young-Fadok TM, Wolff BG, Nivatvongs S, et al. Prophylactic oophorectomy in colorectal carcinoma: preliminary results of a randomized, prospective trial. Dis Colon Rectum 1998;41: 277-283; discussion 283-285.

26.Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006;354:261-269.

27.Lachiewicz MP, Kravochuck SE, O’Malley MM, et al. Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome. Gynecol Oncol 2014;132:434-437.

28.Yang KY, Caughey AB, Little SE, et al. A cost-effectiveness analysis of prophylactic surgery versus gynecologic surveillance for women from hereditary non-polyposis colorectal cancer (HNPCC) families. Fam Cancer 2011;10:535-543.

29.Li GZ, Sloane JL, Lidsky ME, et al. Simultaneous diaphragm and liver resection: a propensitymatched analysis of postoperative morbidity. J Am Coll Surg 2013;216:402-

30.Toyota S, Ohta H, Anazawa S. Rationale for extent of lymph node dissection for right colon cancer. Dis Colon Rectum 1995;38:705-711.

31.Stojadinovic A, Allen PJ, Protic M, et al. Colon sentinel lymph node mapping: practical surgical applications. J Am Coll Surg 2005;201:297-313.

32.Herrera-Ornelas L, Justiniano J, Castillo N, et al. Metastases in small lymph nodes from colon cancer. Arch Surg 1987;122:1253-1256.

33.Haboubi NY, Clark P, Kaftan SM, et al. The importance of combining xylene clearance and immunohistochemistry in the accurate staging of colorectal carcinoma. J R Soc Med 1992;85:386-388.

34.Rodriguez-Bigas MA, Maamoun S, Weber TK, et al. Clinical significance of colorectal cancer: metastases in lymph nodes < 5 mm in size. Ann Surg Oncol 1996;3:124-

130.

35.Ratto C, Sofo L, Ippoliti M, et al. Accurate lymph-node detection in colorectal specimens resected for cancer is of prognostic significance. Dis Colon Rectum 1999;42:143154; discussion 154-158.

36.Min BS, Kim NK, Sohn SK, et al. Isolated paraaortic lymph-node recurrence after the curative resection of colorectal carcinoma. J Surg Oncol 2008;97:136-140.

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Colon Resection: Key Question

In patients identified to have synchronous liver metastatic disease, does simultaneous curative resection (versus staged) affect survival, overall morbidity, or mortality?

INTRODUCTION

Synchronous colorectal cancer and liver metastasis presents an operative and decisionmaking challenge for both hepatobiliary and colorectal surgeons. Between 15% and 20% of patients presenting with colorectal cancer will harbor synchronous liver metastasis (SCRLM). Surgical resection is the only modality that potentially leads to cure, with 5-year

survival rates ranging from 25% to 60%; thus, when feasible, operative resection is paramount.1 Controversy, however, exists as to the timing of surgical resection (simultaneous versus staged) because of the potential impact on morbidity, mortality, and survival. The literature to date is composed of limited observational uncontrolled series with few metaanalyses and no randomized controlled trials. Therefore, the purpose of the review presented here is to examine the impact of timing of SCRLM on overall morbidity, mortality, and survival.

METHODOLOGY

An organized search of the MEDLINE database through PubMed was performed for the period between January 1990 and December 2013. Keyword combinations included a

database search in English for the following MeSH terms: (synchronous* OR simultaneous* OR combined OR concurrent) AND (staged OR “two-stage”) AND (colon OR colorectal OR rectal OR colectomy*) AND metastasis* AND (liver OR hepatectomy*). Directed searches of the embedded references from the primary articles also were performed. For studies that reported patients in more than one publication, only the most recent complete report was used. The final grade of recommendation was assigned

using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.2

The initial search yielded a total of 137 studies, of which the abstracts were reviewed. Studies to be included in our systematic review focused on observational studies of staged or simultaneous operations, comparative studies of staged versus simultaneous resection, and meta-analyses of staged versus simultaneous resection. Exclusion criteria included case reports and limited single-arm series, reviews, and trials that compared issues unrelated to the primary goal of this review. Through consensus of four reviewers, 105 studies were excluded, leaving 32 studies (29 observational studies and three meta-analysis manuscripts) to be reviewed in detail. Two individual members of the group reviewed each manuscript. Each article was then assessed for inclusion and assigned a strength of evidence. This recommendation was arrived at by reviewer consensus and based on the GRADE system (Table 16-1). A total of 18 observational series

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and three meta-analyses were included in the final analysis for this key question review. Figure 16-18 shows the CONSORT diagram summarizing study selection.

TABLE 16-1 Simultaneous versus Staged Morbidity and Mortality

DFS, disease-free survival; DSS, disease-specific survival; LOS, length of stay; LR, locoregional recurrence; NA, not applicable; NS, not significant; OR, overall recurrence; OS, overall survival; POT, predicted operative time.

The surgical resection techniques were defined as follows. Simultaneous resection was defined as concomitant resection of both the primary colorectal lesion and the synchronous liver metastasis. Staged resection was defined as resections that involved two separate operations, including traditional (e.g., colorectal resection followed by extirpation of the liver metastasis) and reverse (e.g., liver resection followed by colorectal surgery) strategies.

FIGURE 16-18 CONSORT diagram summarizing the literature search used for this review.

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FINDINGS

Morbidity and Mortality

Recommendation: Simultaneous resection is both safe and feasible. There is growing evidence that morbidity may be improved by simultaneous resection of colon cancer and liver metastasis in well-selected patients with fewer than three segments of liver disease.

Type of Data: retrospective observational studies and three separate meta-analyses.

Strength of Recommendation: strong recommendation based on consistent findings in multiple papers of limited quality.

Rationale

Since 2001, multiple single-arm series have demonstrated the feasibility of simultaneous resection in both colon and rectal cancer.3,4,5 These series, however, lack the methodology and strength of evidence to assure equal outcomes compared with a more traditional staged approach. Comparative series since 2007 have attempted to bridge this knowledge gap by addressing some of the selection bias that dominates current literature. Collectively, these series have attempted to define the impact of simultaneous resection on morbidity, mortality, and survival.

Traditionally, SCRLM resection has been avoided because of a long-held belief that the magnitude of the operation would prove excessive. In particular, concerns regarding complications and mortality, including concern about an anastomotic complication, insufficiency of the remaining liver segments, and intra-abdominal infection/abscess, have led

to this historical bias. Tanaka et al5 were one of the first groups to demonstrate that the extent of liver resection is a potential factor for increased morbidity and mortality. Several comparative studies have echoed this recommendation for caution when considering a simultaneous procedure. These series have stressed the importance of considering a

staged approach in patients who require more than three liver segments resected at the time of surgery.5,6,7,8,9,10

Other groups have reported equivalent morbidity outcomes when limited liver resection is performed.9,10,11,12,13,14,15,16,17,18,19,20 Nakajima et al6 successfully mitigated the potential risks by employing criteria by which to judge the feasibility of simultaneous resection. Differentiating operative approaches by predicting operative time (planned operative time (POT) < 6 hours = simultaneous resection, POT > 6 hours = staged resection) allowed for the identification of a cohort of patients who reliably had improved

outcomes when compared with outcomes of traditionally approached synchronous disease.6 More recent studies have improved matching, analysis, and patient selection in further attempts to address this fundamental concern. A number of series have actually demonstrated improved complication rates for those undergoing simultaneous surgical

resection.11,14,15,18,20 Three of these series demonstrated a decreased incidence of complications for all patients, as well as patients matched for extent of hepatic

resection.11,14,18 Specifically, the study by Capussotti et al11 controlled for the magnitude of liver resection by including only patients who had more than three liver segments P.306

resected. The authors reported an improved overall rate of total complications and an equivalent anastomotic leak rate for patients undergoing a simultaneous resection compared with a staged resection.

Only two of the 21 series demonstrated increased mortality after simultaneous resection.7,8 Reddy et al8 suggested that increased mortality was associated with major liver

resection. Likewise, Thelen et al7 demonstrated a high mortality rate among patients older than the age of 70 years and those who had more than a hemihepatectomy at the time of the simultaneous procedure. In general, however, the mortality rates reported by the majority of other series have not been significantly different for simultaneous and staged resection (Table 16-1).

Three meta-analyses have been published, one in 2010 and two in 2013.1,21,22 These three studies all included over 1,000 patients who underwent a simultaneous resection

and more than 2,000 operative procedures in total.1,21,22 All three studies demonstrated improved morbidity among patients who underwent a simultaneous approach to resection of synchronous disease. It must be stated that these series were based on retrospective data and therefore are considered to be overall lower quality levels of evidence. In general, these studies concluded that simultaneous resection was both safe and efficient with the potential for decreased morbidity in properly selected patients.

Beyond the issues of morbidity and mortality, many series have commented on other aspects of care that often affect both quality and cost. The majority of series to date have demonstrated shorter total length of stay (LOS) for patients treated with a simultaneous approach.8,11,12,13,14,15,16,17,20 In addition, two of the three meta-analyses reported that simultaneous resection resulted in shorter LOS.1,21

Survival

Recommendation: Overall survival and disease-free survival are not affected by timing of resection.

Type of Data: Retrospective observational studies and three separate meta-analyses.

Strength of Recommendation: Strong recommendation based on consistent findings in multiple papers of limited quality.

Rationale

Survival data are complicated by selection bias and the use of chemotherapy, which was rarely discussed in most of the published series (Table 16-2). In general, overall survival and disease-free survival rates have been shown to be similar after simultaneous versus staged resection in all series.6,7,12,16,17,20 A single series noted longer disease-free survival and progression-free survival items among patients treated with a delayed or staged operative approach.18 Overall survival rates, however, remained the same between groups in this series.18 In the 21 studies examined, 5-year survival rates ranged from 21% to 53%. All three meta-analyses found no difference in survival between a staged or simultaneous approach for synchronous disease1,21,22

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TABLE 16-2 Simultaneous versus Staged Survival

DFS, disease-free survival; DSS, disease-specific survival; HR, hazard ratio; LR, locoregional recurrence; NS, not significant; OR, overall recurrence; OS, overall survival; POT, predicted operative time; SCLM, synchronous colorectal liver metastases.

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Limitation

The main limitation of this review is the underlying primary data quality with a lack of well-controlled series with appropriate matching or complete statistical analyses. These observational series are therefore subject to significant selection bias that could lead to inappropriate conclusions. Moreover, the volume of data is heavily weighted toward simultaneous and traditionally staged operations, with limited data regarding other approaches such as the reverse-staged strategy. In addition, the use of neoadjuvant chemotherapy and the details of postoperative chemotherapy are largely omitted from most series. Finally, there seems little doubt that most published series are presented by centers of excellence, especially in liver surgery, which makes generalization of conclusions somewhat hazardous. In spite of the limitations mentioned, the majority of published data are consistent with less morbidity in well-selected patients undergoing simultaneous liver resection of three or fewer segments.

CONCLUSION

Simultaneous resection for patients identified with SCRLM appears to be both safe and feasible if performed by expert surgeons, especially for patients who require only a minor liver resection (≤3 segments). There is also good evidence that timing of the operation does not adversely affect overall survival or disease-free survival rates. Moreover, there is increasing evidence that overall morbidity and length of hospital stay may be lessened by a simultaneous approach. While studies of patients requiring a larger liver resection suggest that a simultaneous approach is feasible and safe, the data for such cases are more limited and do not allow for definitive recommendations. As such, for patients who require a major hepatic resection, the historical paradigm of a staged approach may be more prudent. An adequately powered randomizedcontrolled study in the setting of modern chemotherapy regimens would be needed to address this question more definitively.

Current evidence supports the feasibility and safety of simultaneous curative resection of colorectal cancer with liver metastasis. Simultaneous resection results in equivalent mortality and survival and potential improved morbidity in patients with fewer than three liver segments of disease.

REFERENCES

1. Yin Z, Liu C, Chen Y, et al. Timing of hepatectomy in resectable synchronous colorectal liver metastases (SCRLM): simultaneous or delayed? Hepatology

2013;57(6):2346-2357.

2.Terracciano L, Brozek J, Compalati E, et al. GRADE system: new paradigm. Curr Opin Allergy Clin Immunol 2010;10(4):377-383.

3.Lyass S, Zamir G, Matot I, et al. Combined colon and hepatic resection for synchronous colorectal liver metastases. J Surg Oncol 2001;78(1):17-21.

4.Boostrom SY, Vassiliki LT, Nagorney DM, et al. Synchronous rectal and hepatic resection of rectal metastatic disease. J Gastrointest Surg 2011;15(9):1583-1588.