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Number of Lymph Nodes in Primary Nodal Basin and a "Second Look" Protocol as Quality Indicators for Optimal Nodal Staging of Colon Cancer.

Regional lymph node (LN) metastasis is a strong negative prognostic factor in colorectal carcinoma. (1) The 5-year disease-free survival of patients with LN metastasis is reduced by up to 48%, depending on the T stage and the number of positive LNs, as compared to patients with node-negative cancer. (1) Moreover, nodal status is also a predictive factor for the efficacy of adjuvant chemotherapy that confers a definite survival benefit in stage III but not stage II carcinoma. (2,3) The 5-year disease-free survival in stage II colon cancer ranges from 64% to 79% depending on the T stage. (4) Potential causes for relapse in stage II colon cancer include peritoneal involvement, lymphovascular or perineural invasion, (5,6) and understaging of nodal disease status that leads to a patient being inappropriately denied adjuvant chemotherapy.

The critical importance of accurate LN staging has led previous studies to address the question of minimum number of LNs that need to be examined for optimal evaluation of nodal status. The recommended minimum number of LNs to be examined varies significantly across publications and ranges anywhere from 6 to 20. (7-13) Others have suggested that there is no minimum threshold that can accurately stage cancer for all patients and all LNs must be examined to ensure optimal nodal staging of colon cancer resections. (14,15) There are large population-based studies that do not show an association between increasing numbers of evaluated LNs and the proportion of LN-positive cancers. (16-19) The current American Joint Committee on Cancer (AJCC) guidelines suggest evaluation of 10 to 14 LNs in colorectal cancer resections as a minimum standard but encourage recovery of more LNs. (4) The Association of Directors of Anatomic and Surgical Pathology recommends that the mean number of LNs in a series of dissections should be approximately 12 to 15, (20) and the current College of American Pathologists colorectal cancer protocol recommends that specimens be reexamined if fewer than 12 LNs are identified. Unfortunately, none of the current guidelines emphasize the importance of the location from where most LNs should be examined and the numerical threshold continues to be the only quality indicator used in current practice.

The aim of our study was to evaluate distribution of positive LNs in colon cancer resections in the immediate vicinity and distant from the tumor site and to determine the proportion of cases that could be upstaged by instituting a "second look" protocol in all cases that were negative after the first search.

MATERIALS AND METHODS

Study Group

The study group consisted of 198 consecutive primary colon cancer resections evaluated prospectively during a 4-year period from 2010-2013. Two synchronous primaries were present in 3 of 198 resections. These synchronous carcinomas were evaluated and staged separately, thus bringing the total number of study tumors to 201. To evaluate the efficacy of the novel prospective "second look" protocol instituted during the study period, a series of 167 consecutive colon cancer resections performed during a 4-year period from 2006-2009 were used as a control group. One of these resections had 2 synchronous primaries, evaluated and staged separately, bringing the total number of tumors in the control group to 168. Recurrent colonic adenocarcinomas, rectal adenocarcinomas, and nonepithelial and metastatic tumors involving the colon were excluded from this study.

Prospective Lymph Node Evaluation Protocol

To determine the likelihood of finding positive LNs in the immediate vicinity of the tumor versus distant from the tumor mass, the LNs were examined separately from 2 distinct zones in each resection. The primary nodal basin (PNB) was defined as a segment of pericolonic soft tissue spanning the tumor plus an area 5 cm proximal and distal to the mucosal edge of the tumor mass. The secondary nodal basin (SNB) was defined as a segment of pericolonic soft tissue more than 5 cm away from the mucosal edge of the tumor (Figure 1). Lymph node searches were performed after overnight fixation in formalin either by a resident or a pathologist's assistant. No fat-clearing reagents were used in any case. Lymph nodes were retrieved separately from the PNB and the SNB and the number documented in the gross description. In all resections that were negative for nodal metastasis on initial LN examination, a second search was performed before rendering a final diagnosis. This added an additional day to turnaround time for signing out colon cancer resections that were pN0 after the first search. To avoid confirmatory bias, the second search was always performed by a pathology assistant not involved in the primary search ("second look" protocol). Before institution of this new "second look" protocol, second LN searches were performed only in cases where the minimum threshold of 12 LNs was not met on initial examination, and in these instances, the second search was performed by the same prosector who performed the first search. Although the number of positive LNs has prognostic significance, it has no bearing on the decision to offer or deny chemotherapy to these patients. In view of lack of significant treatment implications and lack of resources, a systematic second search in all cases, including those that were N+ after the first search, was considered to be of limited clinical use. In initially N+ cases, a second search was performed only in cases where the minimum 12 LN threshold was not met on initial examination as dictated by current guidelines. However, we did evaluate the effect of doing second searches in N+ cases by following the "second look" protocol in 30 N+ resections with more than 12 LNs after the first search. Colon cancer staging was performed according to the 7th edition of the AJCC cancer staging guidelines. (4)

Statistics

Student t test and Fisher exact test were used to assess significance of observed differences in continuous and categorical data, respectively.

RESULTS

Study Group

The study and control groups were similar in patient age (70 [+ or -] 14 and 75 [+ or -] 13 years, respectively), specimen length (27.5 [+ or -] 18.4 and 26.2 [+ or -] 15.7 cm, respectively), and tumor size (4.6 [+ or -] 2.6 and 4.9 [+ or -] 2.3 cm, respectively). The proportion of tumors involving the right versus left colon, tumors with superficial versus deep invasion (T1-2/T3-4), and tumors with negative versus positive LNs was also similar between the study and control groups (Table 1).

Lymph Node Yield Is Significantly Higher and Most Positive Nodes Are in the PNB

The specimen length of the resected specimen in a subset of cases was such that the entire specimen was part of the PNB. Therefore, SNB was present in only 68% (78 of 114) of the initially node-negative and in only 53% (46 of 87) of the node-positive specimens of the study group (Table 1). In the node-negative cases, an average of 20.9 [+ or -] 10.8 LNs were collected from the PNB and 8.5 [+ or -] 9.1 from the SNB (P < .001). The number of LNs from the PNB and SNB collected during the first and second LN searches is shown in Figure 2. Similarly, in node-positive cases, more LNs were found in the PNB (22.5 [+ or -] 10.3) than in the SNB (9.0 [+ or -] 9.5; P < .001). Overall, 10 or more LNs were harvested from the PNB in 86% (98 of 114) of initially node-negative cases and 90% (78 of 87) of the node-positive cases, and 15 or more LNs were examined from the PNB in 68% (78 of 114) of the initially node-negative cases and 80% (70 of 87) of the node-positive cases. These findings attest to the possibility of high LN yields from a focused examination of the PNB in colectomy specimens.

In node-positive resections (n = 87), positive LNs (range, 1-19) were found in the PNB in all cases. An SNB was present in 46 of 87 resections and positive SNB nodes were present in only 4 of 46 cases (9%) (range, 1-3; P < .001). This suggests that most LNs with metastatic adenocarcinoma in colon cancer resections are to be found within the PNB. Remarkably, in all 4 cases when positive LNs were found in the SNB, the PNB also showed LNs with metastatic tumor. Skip metastases, therefore, appear to be an uncommon occurrence in colon cancer and a focused PNB search should yield positive nodes, when present, in most cases. In a hypothetical scenario where LNs were to be collected only from the PNB, pN downstaging would have occurred from pN2b to N2a in only 1 of these 4 cases.

A Second LN Search Significantly Increases Number of LNs Examined

We analyzed LN yields separately for node-negative and node-positive colon cancer resections (Table 2). In the initially node-negative resections of the study group (n = 114), the LN yield after the first search was similar to the yield in node-negative resections of the control group (mean LN count, 18.2 [+ or -] 10.0 and 17.6 [+ or -] 7.0, respectively; P = .58). However, both of these LN counts were significantly lower than the final LN count of 26.6 [+ or -] 14.5 after a second search was performed in the study group in the initially node-negative cases (P < .001). Likewise, in the 30 node-positive cases of the study group in which a second LN search was performed, the LN yield after the first search was not significantly different from the yield in nodepositive control cases (20.0 [+ or -] 11.8 and 18.4 [+ or -] 8.4, respectively; P = .43) but was significantly lower than the final LN count (28.5 [+ or -] 15.0 after a second search was performed in the study group, P < .001). These results indicate that a second search by a different prosector significantly increases the number of LNs examined from both node-negative and node-positive colon cancer resections, and an average of 10 more LNs are found on a second search (Figure 2) without the use of any special fat-clearing agents.

A Second LN Search Upstages a Subset of Initially Node-Negative Cases

A second LN search was performed in the PNB of all initially node-negative cases (n = 114) and in 67 of 78 of available SNBs (Table 3). Five initially node-negative resections (4.4%) yielded 1 to 4 positive LNs on a second search. Positive LNs were present in the PNB in all 5 cases. This led to pN stage conversion from N0 to N1a in 3 cases, from N0 to N1b in 1 case, and from N0 to N2a in 1 case (Table 3). It is important to note that in all these 5 cases adequate numbers of LNs, according to the current AJCC guidelines, were already harvested during the first search (range, 10-27; mean, 17.6 [+ or -] 7.1) and these tumors would have been misclassified as pN0 had no second search been performed.

A second protocol search was also performed in 30 node-positive cases, and an SNB was present in 23 of 30 cases. Additional positive LNs were harvested in [+ or -] cases (20%) (range, 1-3 LNs), upstaging 4 cases from N1a to N1b, 1 case from N1b to N2a, and 1 case from N2a to N2b. All additional positive LNs found during the second search were from the PNB. These results once again emphasize the importance of a second LN search for accurate N staging in colon cancer resections and of a thorough PNB examination for increasing likelihood of finding positive LNs.

DISCUSSION

Lymph node yields in colon cancer resections correlate with modifiable factors, such as quality of surgery and of pathologic assessment, and with nonmodifiable factors, such as young age, high T stage, right-sided tumors, large tumor size, increased specimen length, microsatellite instability phenotype, and history of immunosuppressive therapy. (21-23) To improve the quality of pathologic assessment of LNs in colonic adenocarcinomas we used a novel protocol prospectively for examining LNs in colon cancer resections, separating LNs in close proximity to (PNB) and distant (SNB) from the tumor mass. We also performed a mandatory second search in all cases that were pN0 on the initial examination. Institution of this protocol resulted in improvement of several LN quality indicators, compared to our previous practice. First, the total yield of LNs increased significantly when 2 searches were performed, on average by 10 additional LNs. Moreover, our findings highlight the critical importance of a meticulous search of the PNB in colon cancer resections. More than two-thirds of the examined LNs were harvested from the PNB and most evaluated cases (88%, 176 of 201) regardless of the nodal status (N0 or N+) had 10 or more LNs harvested from the PNB. Lymph nodes with metastatic adenocarcinoma were found 10 times as often in the PNB than in the SNB. This is not surprising given the proximity of the PNB to the tumor mass, but reporting LN counts separately from PNB and SNB is not currently the standard of care where quality of LN examination is judged solely by number of LNs examined. In addition, all of the cases with positive nodes in the SNB also had positive nodes in the PNB. An attempt should certainly be made to evaluate all LNs removed during colon cancer resections, but a thorough focused search of the PNB is likely to correctly classify the N0 or N+ status for most patients. If only the PNB were evaluated in node-positive cases, the qualitative positive or negative node status would have been correctly determined in all cases, and only 1 of 46 cases would have been understaged as N2a rather than N2b. Taken together, our data indicate that most positive LNs are to be found within a 5-cm radius from the tumor edge and the number of LNs examined from this region is a superior quality indicator than total LN counts. Since LNs in the PNB have the highest risk of involvement by metastatic carcinoma, it is imperative to thoroughly sample these LNs. If the more distant LNs in the SNB are preferentially examined with undersampling of the PNB, colon cancer may be understaged and undertreated despite meeting current guidelines for minimum number of LNs to be examined in colon cancer resections.

Similar results have been reported previously by Cserni et al (24) and reinforced in a subsequent study. (25) In their original study, N0 or N+ nodal status was correctly determined in all 100 colorectal carcinoma resections when LNs were harvested within 3 cm from the tumor mass. In 97% of their specimens, positive LNs were located within [+ or -] cm from the tumor, similar to our findings. Additional support to the idea that evaluation of LNs in the immediate vicinity of colon cancer is particularly important comes from a study by Pusztaszeri et al (26) showing that 99.6% of 256 colon carcinomas had proper pN stage assigned when only LNs within 5 cm from the tumor were analyzed. However, our study differs from those cited above because we excluded rectal cancers and evaluated a homogenous group of colonic adenocarcinomas, compared our prospective data to previous practice, and used a second search protocol in all cases classified as N0 on initial examination. The second search protocol led to pN stage conversion in nearly 5% of cases, which is discussed in greater detail below. Overall, the accumulating evidence suggests that thorough evaluation of the PNB should be emphasized in future guidelines.

Another important finding of our study is the conversion of 5 of 114 initially N0 cases (4.4%) to N+ status by the second LN search protocol. All of these cases had adequate number of LNs on the initial search according to current guidelines and would have been staged as N0 if the second search had not been performed. The significance of this nodal status conversion cannot be emphasized enough since these patients may have been denied adjuvant chemotherapy if the N+ status was not classified correctly. The need for a routine second search may vary based on adjuvant chemotherapy protocols followed at different centers. If adjuvant therapy is routinely offered to patients with node-negative colon cancer with other high-risk features, such as perforation of visceral peritoneum or vascular invasion, then it is certainly reasonable to perform or forego a second search on the basis of presence or absence of these high-risk features.

Incomplete retrieval of LNs in the first search may be due to a combination of factors including time constraints, fatigue, and suboptimal pericolic tissue dissection. The second search also addresses another critical component of LN assessment in colon cancer resections and that is the thoroughness of LN sampling. There are data to suggest that most of the variation in the LN yields from colorectal adenocarcinoma resections can be accounted for by differences between prosectors. (27) It is impossible to know how many LNs have been left behind after a first search unless a second search is performed. For instance, if a surgeon removes 50 LNs during a resection and the pathologic examination yields 25 LNs after the first search, it may appear adequate by current guidelines but is, in fact, a suboptimal evaluation because half of all LNs removed were not examined. Our "second look" protocol by a different prosector offers a way to ensure standardization and high quality LN examination in colon cancer resections.

In the 16 months since completion of the study, we have examined data encompassing an additional 75 initially node-negative colon cancers and evaluated the impact of examining LNs from the PNB only. The number of LNs harvested from the PNB in the first and second searches during these 16 months has been similar to the performance characteristics during the study period (14.6 [+ or -] 8.0 versus 14.3 [+ or -] 9.5 and 6.2 [+ or -] 4.2 versus 5.6 [+ or -] 4.4, respectively). Moreover, 3 of 75 initially node-negative cases (4%) have converted to node-positive status after the second node search, supporting the consistency and value of the "second look" protocol. Positive LNs, in these 3 cases, were once again found in the PNB, similar to the node conversion cases during the study period. Similar findings were seen at Brigham and Women's Hospital in Boston, Massachusetts, by 2 of the authors (A.S. and M.G.D.). Fifty-five of 121 cases examined were pN0 after the first search and 2 of 55 initially node-negative cases (3.6%) converted to node-positive status after the second node search, supporting the consistency of the protocol results between different academic institutions (unpublished data). Interestingly, of the 8 cases with pN0 to pN+ conversion in our study, 3 were initially grossed by pathology assistants with 13, 15, and 21 years of experience and of the remaining 5 cases, 2 were grossed by postgraduate year (PGY) 1 residents, 2 by PGY2 residents, and 1 by a PGY3 resident. Although these data do not support a correlation between missed positive nodes and years of experience, it is difficult to draw firm conclusions given the small number of node conversion cases analyzed in the study.

Whether increasing numbers of evaluated LNs is associated with an increased proportion of node-positive cancers is debatable. Several single-institution and/or specific pT stage (pT3 and pT2) studies support the notion that increasing LN counts is associated with greater proportion of N+ cases. (9,10,14,15,18,28) However, several population-based or multicenter studies (16-19,29) have found no association between total node counts and percentage of N+ tumors. The reason for these conflicting results is likely multifactorial and may be related to differences in surgical technique, pathologic examination, methods of statistical analysis, and inclusion of completion colectomies for pT1 cancers initially detected in a polypectomy specimen. (30) Our study eliminates this variability by making comparisons prospectively within the same specimens. To our knowledge, ours is the first study to prospectively demonstrate the importance of a focused search of the PNB and to show that nearly 5% of colon cancers can be upstaged from N0 to N+ by instituting a "second look" protocol in initially node-negative cases. It should be noted that the second search is much easier to perform, since pericolonic fat is already sectioned. While sign-out for pN0 cases at our institution was delayed by just a day it is likely that the delay time will vary across institutions. Each laboratory must consider this aspect carefully in consultation with its surgical and oncology colleagues if it considers instituting a "second look" protocol.

In summary, the number of LNs examined from the PNB can be used as additional quality indicator in the future to determine the efficacy of LN examination in colon cancer resections. In addition, performing a second search before classifying a tumor as pN0 leads to identification of additional pN+ cases. The second node search protocol increases resource utilization and turnaround time, and these must be carefully balanced against the benefit of finding additional patients with node-positive colon cancer who are definite candidates for adjuvant chemotherapy. Laboratories where all prosectors consistently find 12 to 15 nodes in the PNB may certainly opt not to institute a "second look" protocol, whereas those that find a greater variability or consistently low PNB counts may be well served by following a "second look" protocol before signing out a case as pN0.

References

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(2.) Moertel CG, Fleming TR, Macdonald JS, et al. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol. 1995;13(12):2936-2943.

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(10.) Goldstein NS, Sanford W, Coffey M, Layfield LJ. Lymph node recovery from colorectal resection specimens removed for adenocarcinoma: trends over time and a recommendation for a minimum number of lymph nodes to be recovered. Am J Clin Pathol. 1996;106 (2):209-216.

(11.) Le Voyer TE, Sigurdson ER, Hanlon AL, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089.1 Clin Oncol. 2003;21(15):2912-2919.

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(14.) Cserni G, Vinh-Hung V, Burzykowski T. Is there a minimum number of lymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0 colorectal carcinomas? J Surg Oncol. 2002;81(2):63-69.

(15.) Goldstein NS. Lymph node recoveries from 2427 pT3 colorectal resection specimens spanning 45 years: recommendations for a minimum number of recovered lymph nodes based on predictive probabilities. Am J Surg Pathol. 2002;26(2):179-189.

(16.) Bui L, Rempel E, Reeson D, Simunovic M. Lymph node counts, rates of positive lymph nodes, and patient survival for colon cancer surgery in Ontario, Canada: a population-based study. J Surg Oncol. 2006;93(6):439-445.

(17.) Wong SL, Ji H, Hollenbeck BK, Morris AM, Baser O, Birkmeyer JD. Hospital lymph node examination rates and survival after resection for colon cancer. JAMA. 2007;298(18):2149-2154.

(18.) Parsons HM, Tuttle TM, Kuntz KM, Begun JW, McGovern PM, Virnig BA. Association between lymph node evaluation for colon cancer and node positivity over the past 20 years. JAMA. 2011;306(10):1089-1097.

(19.) Budde CN, Tsikitis VL, Deveney KE, Diggs BS, Lu KC, Herzig DO. Increasing the number of lymph nodes examined after colectomy does not improve colon cancer staging. J Am Coll Surg. 2014;218(5):1004-1011.

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(23.) Eveno C, Nemeth J, Soliman H, et al. Association between a high number of isolated lymph nodes in T1 to T4 N0M0 colorectal cancer and the microsatellite instability phenotype. Arch Surg. 2010;145(1):12-17.

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(28.) Baxter NN, Ricciardi R, Simunovic M, Urbach DR, Virnig BA. An evaluation of the relationship between lymph node number and staging in pT3 colon cancer using population-based data. Dis Colon Rectum. 2010;53(1):65-70.

(29.) Prandi M, Lionetto R, Bini A, et al. Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg. 2002;235(4):458-463.

(30.) Di Gregorio C, Benatti P, Losi L, et al. Incidence and survival of patients with Dukes' A (stages T1 and T2) colorectal carcinoma: a 15-year population-based study. Int J Colorectal Dis. 2005;20(2):147-154.

Mikhail Lisovsky, MD, PhD; Shannon N. Schutz, PA(ASCP); Michael G. Drage, MD, PhD; Xiaoying Liu, MD; Arief A. Suriawinata, MD; Amitabh Srivastava, MD

Accepted for publication April 22, 2016.

Published as an Early Online Release September 28, 2016.

From the Department of Pathology (Drs Lisovsky, Liu, and Suriawinata and Ms Schutz), Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and the Department of Pathology (Drs Drage and Srivastava), Brigham & Women's Hospital, Boston, Massachusetts.

The authors have no relevant financial interest in the products or companies described in this article.

Presented in part at the 101 st Annual Meeting of the United States and Canadian Academy of Pathology;March 2012; Vancouver, British Columbia, Canada.

Reprints: Amitabh Srivastava, MD, Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115 (email: Asrivastava@partners.org).

Please Note: Illustration(s) are not available due to copyright restrictions.

Caption: Figure 1. The primary and secondary nodal basins were defined as areas less than or more than 5 cm from the tumor edge, respectively. The entire specimen consisted of the primary nodal basin in some resections owing to the length of the resected colonic segment.
Table 1. Clinicopathologic Features of Cancers
Included in the Study

                           Study Group
                            (n = 201)

Patient age, y           70 [+ or -] 14

Tumor location,
No. (%)

  Cecum                      45 (22)

  Ascending                  58 (29)

  Hepatic flexure             6 (3)

  Transverse                 26 (13)

  Splenic flexure             5 (2)

  Descending                  9 (4)

  Sigmoid                    54 (27)

Specimen                27.5 [+ or -] 18.4
length, cm

Tumor size, cm          4.6 [+ or -] 2.6

T stage, No. (%)

  pT1                       18 (8.9)

  pT2                       28 (13.9)

  pT3                       89 (44.3)

  pT4                       66 (33.8)

N stage, No. (%)
  pN0                       114 (56.7)

PNB and SNB            PNB Only,   PNB and SNB,
Distribution            No. (%)      No. (%)

  Node-negative         36 (32)      78 (68)
  cases (n = 114)

  Node-positive         41 (47)      46 (53)
  cases (n = 87)

                         Control Group      P Value
                           (n = 168)

Patient age, y           75 [+ or -] 13      <.001

Tumor location,
No. (%)

  Cecum                     42 (25)           .54

  Ascending                 51 (30)           .82

  Hepatic flexure              0             >.99

  Transverse                16 (10)           .33

  Splenic flexure            5 (3)            .75

  Descending                 10 (6)           .49

  Sigmoid                   44 (26)           .91

Specimen               26.2 [+ or -] 15.7     .47
length, cm

Tumor size, cm          4.9 [+ or -] 2.3      .24

T stage, No. (%)

  pT1                       13 (7.7)          .71

  pT2                       12 (7.1)          .04

  pT3                      84 (50.0)          .30

  pT4                      59 (35.1)          .66

N stage, No. (%)
  pN0                      91 (54.2)

PNB and SNB                   N/A             N/A
Distribution

  Node-negative
  cases (n = 114)

  Node-positive
  cases (n = 87)

Abbreviations: N/A, not applicable; PNB, primary nodal
basin; SNB, secondary nodal basin.

Table 2. Lymph Node Yields in Node-Negative and
Node-Positive Tumor Resections

                                   Lymph Node         P Value

Node-negative cases

  Study group
    Initially node-negative    18.2 [+ or -] 10.0     .58 (a)
    cases, first search
    (n = 114)

    Initially node-negative    26.6 [+ or -] 14.5   <.001 (a,b)
    cases, second search
    (n = 114)

  Control group
    Node-negative cases        17.6 [+ or -] 7.0
    (n = 91)

Node-positive cases
  Study group
    Node-positive tumors,      20.0 [+ or -] 11.8     .43 (c)
    first search (n = 30)

    Node-positive tumors,      28.5 [+ or -] 15.9    <.001 (b)
    second search (n = 30)

    Node-positive tumors,      22.6 [+ or -] 14.9     .04 (d)
    routine search (n = 57)

  Control group
    Node-positive tumors       18.4 [+ or -] 8.4
    (n = 77)

(a) Versus node-negative cases of the control group.

(b) Versus the first search.

(c) Versus node-positive cases of the control group.

(d) Versus node-positive cases of the control group.

Table 3. Cases With Node Status Conversion From
N0 to N+ (a)

No. of LNs after the first search    10-27

No. of additional LNs after the      6-10
second search

Range of positive LNs per case       1-4
in the second search

Location of positive LNs found       Primary nodal basin
in the second search

Nodal stage after conversion         N1a (3 cases)
from N0                              N1b (1 case)
                                     N2a (1 case)

Extent of the primary tumor          T4, 3 patients
invasion (pT)                        T3, 2 patients

Lymphovascular invasion of           Present, 3 patients
the primary tumor                    Absent, 2 patients

Abbreviation: LNs, lymph nodes.

(a) Five of 114 cases (4.4%).

Figure 2. Distribution of lymph nodes retrieved from the primary
nodal basin (PNB) and secondary nodal basin (SNB) in NO cases in the
study after the first and second search.

      First Search   Second Search

PNB      14.6            6.2
SNB       4.5            4.1

Note: Table made from bar graph.
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Author:Lisovsky, Mikhail; Schutz, Shannon N.; Drage, Michael G.; Liu, Xiaoying; Suriawinata, Arief A.; Sriv
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Report
Date:Jan 1, 2017
Words:5218
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