The New Ropanasuri Journal of Surgery The New Ropanasuri Journal of Surgery
Volume 1 Number 1 Article 6
10-20-2016
Comparison of Japanese Classification with the TNM System in Comparison of Japanese Classification with the TNM System in the Assessment of Staging in Sigmoid and Rectal Cancer Patients the Assessment of Staging in Sigmoid and Rectal Cancer Patients at dr. Cipto Mangunkusumo and Fatmawati General Hospital: A at dr. Cipto Mangunkusumo and Fatmawati General Hospital: A Preliminary Study
Preliminary Study
Agi S. Putranto
Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, [email protected]
Yusak Kristianto
Training Program in Surgery, Department of Surgery, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital,
Grace Wangge
Department of Community Medicine, Faculty of Medicine, Universitas Indonesia
Follow this and additional works at: https://scholarhub.ui.ac.id/nrjs Recommended Citation
Recommended Citation
Putranto, Agi S.; Kristianto, Yusak; and Wangge, Grace (2016) "Comparison of Japanese Classification with the TNM System in the Assessment of Staging in Sigmoid and Rectal Cancer Patients at dr. Cipto Mangunkusumo and Fatmawati General Hospital: A Preliminary Study," The New Ropanasuri Journal of Surgery: Vol. 1 : No. 1 , Article 6.
DOI: 10.7454/nrjs.v1i1.6
Available at: https://scholarhub.ui.ac.id/nrjs/vol1/iss1/6
This Article is brought to you for free and open access by the Faculty of Medicine at UI Scholars Hub. It has been accepted for inclusion in The New Ropanasuri Journal of Surgery by an authorized editor of UI Scholars Hub.
New Ropanasuri Journal of Surgery 2016 Volume 1 No.1:19–22.
Comparison of Japanese Classification with the TNM System in the Assessment of Staging in Sigmoid and Rectal Cancer Patients at dr. Cipto Mangunkusumo and Fatmawati General
Hospital: A Preliminary Study
Agi S. Putranto,1 YusakKristianto,2 Grace Wangge.3
1) Division of Digestive Surgery, 2) Training Program in Surgery, Department of Surgery, Faculty of Medicine, Universitas Indonesia, dr. Cipto Mangunkusumo General Hospital, 3) Department of Community Medicine, Faculty of Medicine, Universitas Indonesia.
Email: [email protected] Received: 2/May/2016 Accepted: 20/Jul/2016 Published: 20/Oct/2016 http://www.nrjs.ui.ac.id DOI:10.7454/nrjs.v1i1.6
Abstract
Introduction. Lymph node metastasis of colorectal cancer is an independent prognostic factor and used as a guideline for adjuvant therapy.
Paralleled to this, TNM staging system has been used widely and nowadays referred to a gold standard of colorectal cancer staging. So far, such a system classifies the staging based on the numbers of positive lymph node involvement. Japanese classification was another kind of system do that categorize based on the distribution of lymph nodes involved (i.e. paracolic/rectal, intermediate, root of mesenteric artery).
Method. This was a preliminary study analyzed of 15 subjects with sigmoid and rectal cancer underwent surgery at dr. Cipto Mangunkusumo and Fatmawati General Hospital between September and October 2015. We studied the specimen for histopathological evaluation focused on the numbers of positive lymph nodes and the distribution of lymph node metastasis. Staging was carried out using both of TNM system and Japanese classification, and these variables were subjected to agreement analysis.
Results. We found more than twelve lymph nodes from each sample. Based on TNM staging system, there are seven subjects on stage II, three subjects with stage IIIb and five subjects with stage IIIc, meanwhile based on Japanese Classification, there were seven subjects with stage II, one subjects with stage IIIa and seven subjects with stage IIIb. Analysis of agreement between both of classifications resulted in coefficient Kappa of 49.3% (moderate category) with p-value of 0.04.
Conclusion. Our preliminary study showed that agreement between both of classifications to specify sigmoid and rectal staging is in moderate category. Japanese classification is feasible to be used. Agreement accuracy may be obtained with a bigger sample.
Keywords: Colorectal lymph node metastasis, TNM system, Japanese classification
Introduction
Clinical staging of colorectal cancer referred to an important factor in assessment of the prognosis. Metastasis to lymph nodes is important prognostic factor to survival and in assessment the candidates for appropriate treatment following surgery.1,2,3,4,5,6,7,8,9 Nowadays, a standard system widely used in the assessment is tumor nodule metastasis (TNM) system proposed by American Joint Conference on Cancer (AJCC) and TNM committee of the International Union Against Cancer (UICC). Such a system apply the numbers of positive lymph nodes spreading after assessing for at least 12 lymph nodes in an organ specimen after surgical removal.4,10,11,12 However, such a procedure encountering problem to find out the twelve lymph nodes of the criteria completely, although there were available techniques and were very helpful. The clinical dilemma enfacing as a complete of twelve lymph nodes is not obtainable, as the guideline for the planning of treatment following surgery, and to predict the prognosis as well.
The reported success to obtain the recommended twelve lymph nodes completely is as much as 20% of cases internationally. There are factors influencing such as patients’ factor, surgeon’s experience, and experience of the pathologist. Following a study run in 2005, Baxter and his coworkers reported in the journal of the National Cancer Institute their findings enrolled of 116.995 subjects of
colorectal cancer, he found only 37% subjects with complete twelve lymph nodes. It was concluded that the influencing factor was the experience of the surgeon and the pathologist.9
Japanese surgeon applies the assessment in a different approach. The assessment of clinical staging of colorectal is instituted through a system called Japanese classification, which assess the distribution of lymph nodes metastasis that may be found in pericolic, or intermediate, or near the base of inferior mesenteric artery.1 Should there is metastasis there, and then it is considered as a systemic disease (advanced stage) and certainly requires further postoperative management and attributed as poor prognosis.1 There were studies endorsed this concept of distribution of lymph nodes metastasis as an important prognostic variable, but somehow its application in clinical setting has not been established yet as there remains contoversies.1
Method
We run a cross sectional study to find out comparative result of the approach of metastasis distribution (i.e. Japanese classification) with positive lymph nodes concept (TNM system) in subjects with malignancy in sigmoid and rectum. Such a study is carried out in Department of Surgery of dr. Cipto Mangunkusumo and Fatmawati General Hospital in period of September to October 2015. All subjects diagnosed as sigmoid and rectal cancer who underwent
resection (both of laparotomy– or laparoscopic approach) with histopathology finding referred to adenocarcinoma were enrolled.
We exclude those who were irradiated preoperatively, and those with inappropriateness in setting up the margin, those with lymph nodes less than twelve found intraoperatively, and those with metastasis or synchronous cancer as well. The samples were obtained by the treatment, i.e. marking a location using silk suture and counting the number of lymph nodes in resected organ specimen postoperatively.
Further, the procedure continues to find out lymph nodes elsewhere until twelve nodes were completely achieved. The samples were subjected to histopathology evaluation to decide the staging in accordance to both of TNM system and Japanese classification.
These findings were analyzed using the appropriateness (coefficient Kappa) with table 3x3 on both of systems. The committee of ethic Faculty of Medicine Universitas Indonesia approved the study (733/UN2.F1/ETIK/2015, August 31, 2015).
Results
Out of enrolled 133 subjects, there were 16 of dropped out as we found incompleteness of chemotherapy. There were 52.6% subjects aged less than 50 years old and 56.4% were male. We found of 81.2% subjects with Karnofsky score >90, and 57.1% with SGA A, and 67.1% with normal BMI.
Tumor located in rectum found in 57.1% subjects, 21.1% in descending colon, and 14.3% in ascending colon. There were 72.1%
subjects of stage III with well differentiation type of 48.1% who diagnosed at the first presentation.
Low anterior resection was the most kind of surgery carried out of 33.1% subjects, followed by abdominoperineal resection of 18.8%, anterior resection and right hemicolectomy (each of 17.3%).
Table 1. Characteristic of subjects with colorectal cancer in the study.
Variables Data
TNM system
Category T
T1 T2 T3 T4a T4b
0 0 12
0 3
Category N
N0 N1a N1b N1c N2a N2b
7 1 0 0 4 3
Category M
M1a M1b
0 0 TNM stage II
TNM stage IIIa TNM stage IIIb TNM stage IIIc
7 0 3 5 Japanese classification
Category N
N0 N1 N2 N3
7 1 3 4 Stage II
Stage IIIa Stage IIIb
7 1 7
Table 2. Correlation between chemotherapy regimen and one year mortality rate TNM system
p value Stage II Stage IIIa–b Stage IIIc
Japanese classification
Stage II 7 0 0
0.04
Stage IIIa 0 1 1
Stage IIIb 0 4 2
There were seven subjects classified as stage II according to TNM system and Japanese classification. Then the appropriateness of both systems was 46.67%. One subject classified as stage IIIa (Japanese classification) and stage IIIa-b (TNM system). This showed that the
appropriateness of both systems was 6.7%. There were two subjects classified as stage IIIb (Japanese classification) and stage IIIc (TNM system). The appropriateness of both systems was 13.3 %. Thus, the overall appropriateness of both systems was 66.67 %. Following the
analysis, we found that Kappa of 49.3% with p value of 0.04. In contrast, there were four subjects classified as stage IIIa-b (TNM system) and stage IIIb (Japanese classification) was just showing the inappropriateness of the two systems. The inappropriateness also found in one subject who classified as stage IIIc (TNM system) and stage IIIa (Japanese classification).
Discussion
The median age of subject in the study is 55 years old; it was found slightly different to the literature which is 50 years old and lower than the median age reported in the US, which is 72 years old. About fifty five percent cancer found in the age ≥65 years of life.25 In the study, we found the samples dominated with male subjects and this was found parallel to the literature which is 55 per 100.000 population, as female is 41 per 100.000 population. However, the frequency of colorectal cancer in Indonesia is comparable between male and female and mostly found in younger age.25
The lymph nodes metastasis referred to an important prognostic factor in colorectal cancer particularly those with stage III.1,2,3,4,5,6,7,8,9
This lymph nodes metastasis is affected by the extend of dissected gut, lymph nodes dissection techniques, and specimen preservation.7
Nowadays, the lymph nodes metastasis is assessed by the number and the distribution of lymph nodes. TNM staging is the one which assessed by the number of positive lymph.4,10,11,12 But somehow, this kind of approach encountered the difficulties rather than Japanese classification. Such a difficulty found as this system also assess extend of tumor invasion that leading to varies of stage.2 Meanwhile, Japanese classification is proposed with the perspective of the distribution of lymph nodes that showing positive metastasis.
Furthermore, this distribution of lymph nodes metastasis referred to an independent prognostic factor to overall survival and disease free survival in subject with colorectal cancer. Metastasis in the base of artery (i.e. stage IIIb in Japanese classification) referred to a systemic disease and rolled as independent prognostic factor of survival.1,17,18 A study of Akagi and his coworkers concluded that the recurrence of stage IIIa was 24.10% whilst of stage IIIb was 40.80%. They found that from overall survival in five years point of view, stage IIIa was 71.40% and stage IIIb was 56%.7
Based on statistical analysis we found the appropriateness between the two systems was 66.67% and coefficient Kappa of 49.3% with significance (p value) of 0.04. This value of coefficient Kappa is interpreted as the appropriateness of the two systems referred to moderate agreement. This finding was realized that the minimal number of subject enrolled is an important issue.
It is realized also that the issue of appropriateness between the two systems has never been published, thus we could not compare this finding to any. We found the incidence of positive lymph nodes in the base of inferior mesenteric artery which, is between 0.3–8.7% in sigmoid and rectal cancer. These subjects were associated with poor differentiated tumor, advanced T category, perineural or lymphovascular invasion, and increased of preoperative CEA.1,17,18 In this study, there were four subjects with those mentioned condition, and classified as advanced stage III (IIIb/IIIc) according to TNM system and Japanese classification. Hence, the pursuit of positive lymph nodes should be carried out in every level (i.e.
paracolic, intermediate, and base of inferior mesenteric artery), that in fact has been carried out in the study.
A published study in Japan found that the prognosis of subject based on this distribution of metastasis of the lymph nodes found that the
five years life expectancy is 72.6% should the positive lymph nodes be found in paracolic/rectal (or, N1), and 51.2% in intermediate (or, N2), and 30% when located in the base of inferior mesenteric artery (or, N3).1 overall survival and disease free survival of subjects with stage III with positive lymph nodes in the base of inferior mesenteric artery is found not significant differed to subject with stage IV.
Unfortunately, we did not analyze this issue.
AJCC recommended to find twelve lymph nodes during curative treatment on colorectal surgery, as this finding refer to an important independent factor to overall survival. It is reported in the literature, that these twelve lymph nodes findings is not obtainable in about 50%
of subject.4,10,11,12 Fortunately, in the study a complete of twelve lymph nodes collection was accomplished completely. The succeeded finding of these lymph nodes of mesocolon and mesorectal region is carried out through collaborated works of the surgeon with the pathologist. In contrast, Japanese classification did not make the number of lymph nodes as an issue. Thus, any distributed metastasis of lymph nodes is enough to classify a stage of a subject with colorectal cancer.
So far, in our department as well as in Fatmawati General Hospital the TNM system remains used as the protocol in the assessment of staging in this malignancy and found stage IIIb and IIIc of TNM system dominated the colorectal cancer treated in both centers as most subjects presented in term of delayed case.
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