doi:10.1111/codi.12878
Original article
Prognostic impact of hyponatraemia in patients with colorectal cancer J. S. Choi*, E. H. Bae*, S. K. Ma*, S. S. Kweon†‡ and S. W. Kim* *Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea, †Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea and ‡Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun-gun, Korea Received 9 July 2014; accepted 3 December 2014; Accepted Article online 19 December 2014
Abstract Aim Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated. Method We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3-year mortality, we categorized the patients as having normonatraemia (135– 147 mEq/l), or mild (130–134 mEq/l), moderate (125–129 mEq/l) or severe hyponatraemia (< 125 mEq/l). Results Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Coxproportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38–1.96; HR 2.24, 95% CI 1.69–2.98; HR 2.20, 95% CI 1.25–3.90, for patients
Introduction Although the incidence and mortality rates of colorectal cancer are quite variable between countries, globally it is one of the most common malignancies, having a diseasespecific mortality rate of almost 33% in the developed world [1–3]. Several prognostic indicators for patients with colorectal cancer, based on certain patient- and disease-related factors, have been identified in order to faciliCorrespondence to: Soo Wan Kim, MD, PhD, Department of Internal Medicine, Chonnam National University Medical School, 42 Jebongro, Gwangju 501-757, Korea. E-mail: [email protected]
with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long-term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved. Conclusion A substantial proportion of patients developed hyponatraemia during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer. Keywords Colorectal cancer, hyponatraemia, mortality What does this paper add to the literature? The prognostic value of hyponatraemia in patients with colorectal cancer has not been fully investigated. This study evaluates serum sodium levels in patients with colorectal cancer as a prognostic predictor of long-term mortality rates and demonstrated a prevalence in about one quarter of them.
tate optimal management [4–7]. These include the TNM staging system, serum carcinoembryonic antigen (CEA) levels and several molecular markers such as KRAS and BRAF mutations and microsatellite instability. Serum sodium is an easily obtained and routinely measured plasma electrolyte. Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, has been considered to be a marker of underlying disease severity and prognosis in various medical conditions including liver cirrhosis and congestive heart failure, and can also develop as a side effect of medication [8–12]. It is a common electrolyte disorder associated with tumourrelated conditions.
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
409
J. S. Choi et al.
Hyponatraemia in colorectal cancer
The incidence of hyponatraemia among cancer patients is high [13]. Furthermore, recent studies have indicated that hyponatraemia is associated with longer hospital stay and higher mortality in several types of cancer, but there are no reports on the incidence of hyponatraemia and the relation between hyponatraemia and prognosis for patients with colorectal cancer. In the present study we aimed to evaluate the incidence and severity of hyponatraemia during hospitalization, and to assess the prognostic impact of hyponatraemia in patients with colorectal cancer. The baseline, nadir and discharge serum sodium levels during hospitalization were determined, and the relationship between the presence of hyponatraemia and long-term mortality was assessed.
Method Study population
A retrospective evaluation was performed of patients with a diagnosis of colorectal cancer who had been admitted for at least 24 h to Chonnam National University Hwasun Hospital (CNUHH), Chonnam, Korea. CNUHH is a 700-bed teaching hospital and a tertiary referral centre for patients with cancer. Patients were classified according to the diagnostic C-code in the International Classification of Diseases, Tenth Revision codes. Between January 2004 and August 2010, 3466 patients presenting with colorectal cancer were admitted. Of these, we excluded 382 in whom the sodium level during hospitalization was not measured at least twice. An additional 140 patients were excluded because they met the following exclusion criteria including diagnosis of carcinoma in situ (n = 121) and an initial serum sodium level of ≥ 148 mEq/l (n = 19). The data obtained on the first admission were used for all analyses. Demographic, clinical and laboratory data were obtained from the hospital’s computerized database. This study was approved by the institutional review board of CNUHH. There was no need for consent given the retrospective nature of study. The study was performed in accordance with the Helsinki Declaration of 1975, as revised in 2000. Measurement of serum sodium level and clinical endpoint
Serial serum sodium levels during hospitalization were obtained from the patients’ medical records and reviewed by a trained study coordinator. Hyponatraemia was defined as a serum sodium level of < 135 mEq/l at
410
any point during hospitalization. For classification of the severity of hyponatraemia, serum sodium levels were categorized as normonatraemia (135–147 mEq/l), mild hyponatraemia (130–134 mEq/l), moderate hyponatraemia (125–129 mEq/l) and severe hyponatraemia (< 125 mEq/l). The primary end-point of the study was the 3-year mortality from the date of admission. Assessment of the survival status was obtained from the Gwangju Cancer Registry (GCR) and Jeonnam Cancer Registry (JCR). The purpose of and methods used to register patients with the GCR and JCR have been described previously [14]. Statistical analysis
Continuous variables with normal distributions were expressed as mean SD and were compared using one-way analysis of variance. Continuous variables with a skewed distribution were presented as median (with 25th and 75th percentiles) and were compared using the Kruskal–Wallis test. Pearson’s chi-squared test or Fisher’s exact test was used to evaluate the differences in categorical variables, which were expressed as numbers and percentages. The Kaplan–Meier method was used to estimate the 3-year mortality of all patients by severity and quartile of the serum sodium level, and comparisons between the groups were made using the log-rank test. Cox’s proportional regression analysis was used to compare the 3-year mortality values between each sodium level group. The hazard ratios (HRs) indicate the relative risk of death in each sodium level group compared with those in the lowest-risk sodium group (135–147 mEq/l). The confounders analysed included age, gender, TNM stage, comorbidities (hypertension, diabetes mellitus, congestive heart failure, chronic liver disease, chronic kidney disease and smoking status), previous therapy (surgery and chemotherapy) and laboratory variables [white blood cell (WBC) count, haemoglobin, serum creatinine, serum albumin, carcinoembryonic antigen (CEA) and blood glucose]. Increasingly adjusted models were established for the 3-year mortality rate to assess the relative confounding effect of certain factors. Subsequently, patients were categorized into four groups (persistent normonatraemia, resolved hyponatraemia, acquired hyponatraemia and persistent hyponatraemia) according to the change in serum sodium level during hospitalization between the initial and final measurement of serum sodium. The same variables as noted above were used for adjusted Cox proportional regression analysis. All statistical tests were two-tailed, and P-values < 0.05 were considered significant. Statistical analysis was performed using the Statistical Package for
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
J. S. Choi et al.
Hyponatraemia in colorectal cancer
hospitalization. The majority of patients presented with mild hyponatraemia (21.9%), with a lower incidence of moderate (4.9%) and severe (0.9%) hyponatraemia. The patients’ clinical characteristics, stratified by serum sodium level, are shown in Table 1. There were notable differences in the clinical characteristics according to the serum sodium level. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities and a more advanced TNM stage. Compared with patients with normonatraemia, hyponatraemic patients had a higher WBC count and elevated serum creatinine, CEA and blood glucose levels,
Social Sciences software, version 18.0 (SPSS; IBM, Armonk, New York, USA).
Results Baseline characteristics
A total of 2944 patients with colorectal cancer (mean age 63.4 11.4 years; 61.9% male) were included in the study. Hyponatraemia during hospitalization was evident in 814 (27.6%), patients, including 344 (11.7%) on admission and 470 (15.9%) at some point during
Table 1 Baseline characteristics of patients stratified by serum sodium level during hospitalization. Serum sodium level (mEq/l) 135–147 (n = 2130) Age (years) Male gender Past history Hypertension Diabetes mellitus Congestive heart failure Chronic liver disease Chronic kidney disease Smoking TNM stage (all) I II III IV TNM stage (colon cancer) I II III IV TNM stage (rectal cancer) I II III IV Previous therapy Surgery Chemotherapy Laboratory variables WBC (per mm3) Haemoglobin (g/dl) Serum creatinine (mg/dl) Serum albumin (g/dl) CEA (ng/ml) Blood glucose (mg/dl)
63 11 1305 (61.3%)
130–134 (n = 643) 65 11 413 (64.2%)
125–129 (n = 145) 67 11 92 (63.4%)
< 125 (n = 26) 65 14 12 (46.2%)
P-value < 0.001 0.193
726 338 86 70 133 722
(34.1%) (15.9%) (4.0%) (3.3%) (6.2%) (33.9%)
253 146 29 34 71 225
(39.3%) (22.7%) (4.5%) (5.3%) (11.0%) (35.0%)
72 34 12 18 30 60
(49.7%) (23.4%) (8.3%) (12.4%) (20.7%) (41.4%)
10 6 2 2 11 7
(38.5%) (23.1%) (7.7%) (7.7%) (42.3%) (26.9%)
< 0.001 < 0.001 0.087 < 0.001 < 0.001 < 0.001
438 704 719 269
(20.6%) (33.1%) (33.8%) (12.6%)
74 189 214 166
(11.5%) (29.4%) (33.3%) (25.8%)
15 41 41 48
(10.3%) (28.3%) (28.3%) (33.1%)
4 4 10 8
(15.4%) (15.4%) (38.5%) (30.8%)
< 0.001
264 513 485 178
(18.3%) (35.6%) (33.7%) (12.4%)
39 138 149 123
(8.7%) (30.7%) (33.2%) (27.4%)
10 33 26 33
(9.8%) (32.4%) (25.5%) (32.4%)
4 3 9 6
(18.2%) (13.6%) (40.9%) (27.3%)
< 0.001
174 191 234 91
(25.2%) (27.7%) (33.9%) (13.2%)
35 51 65 43
(18.0%) (26.3%) (33.5%) (22.2%)
5 8 15 15
(11.6%) (18.6%) (34.9%) (34.9%)
0 1 1 2
(0.0%) (25.0%) (25.0%) (50.0%)
< 0.001
18 (12.4%) 17 (11.7%)
5 (19.2%) 6 (23.1%)
< 0.001 < 0.001
10591 6055 11.2 2.1 1.16 1.11 3.22 0.66 6.9 (3.2,31.2) 138 68
13056 6542 10.7 2.4 1.62 2.06 3.20 0.76 7.9 (2.0, 44.7) 129 41
< 0.001 < 0.001 0.001 < 0.001 < 0.001 < 0.001
90 (4.2%) 92 (4.3%) 9350 3983 12.0 2.1 1.04 0.73 3.65 0.61 3.6 (2.1,8.2) 122 45
53 (8.2%) 57 (8.9%) 9423 4453 11.5 2.3 1.07 0.82 3.48 0.64 5.1 (2.5,14.7) 137 65
WBC, white blood cell; CEA, carcinoembryonic antigen. Values mean SD or median (interquartile range) or number (%).
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
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J. S. Choi et al.
Hyponatraemia in colorectal cancer
whereas haemoglobin and serum albumin levels were lower. Multivariate analysis of 3-year mortality according to serum sodium levels
Patients were followed up for a mean period of 4.08 2.43 years. Two hundred and sixty-three patients were lost to follow-up within 3 years. The duration of follow-up was right-censored at 3 years for Kaplan–Meier and Cox proportional regression analysis. A total of 794 (27.0%) patients died during the follow-up period. Kaplan–Meier curves for crude 3-year cumulative mortality categorized by severity and the quartile of serum sodium level are shown in Fig. 1. Table 2 shows unadjusted and adjusted Cox (a)
proportional regression analysis for 3-year mortality according to the serum sodium level. Unadjusted analysis showed a linear relationship between serum sodium level and 3-year mortality risk, and this relationship persisted even after adjustment for several confounders. In the fully adjusted model, compared with the normonatraemia group (135–147 mEq/l), the hyponatraemia group showed a higher mortality risk (HR 1.65, 95% CI 1.38–1.96; HR 2.24, 95% CI 1.69–2.98; HR 2.20, 95% CI 1.25–3.90, for patients with mild, moderate and severe hyponatraemia, respectively) resulting in a significant trend (P-value < 0.001). This finding was reconfirmed by a secondary analysis using the quartile of serum sodium level, although the level of statistical significance was border line for the second quartile group.
1.0
Cumulative survival
0.8
0.6
0.4
Serum sodium with 135–147 mEq/L Serum sodium with 130–134 mEq/L Serum sodium with 125–129 mEq/L Serum sodium with
Original article
Prognostic impact of hyponatraemia in patients with colorectal cancer J. S. Choi*, E. H. Bae*, S. K. Ma*, S. S. Kweon†‡ and S. W. Kim* *Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea, †Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea and ‡Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun-gun, Korea Received 9 July 2014; accepted 3 December 2014; Accepted Article online 19 December 2014
Abstract Aim Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated. Method We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3-year mortality, we categorized the patients as having normonatraemia (135– 147 mEq/l), or mild (130–134 mEq/l), moderate (125–129 mEq/l) or severe hyponatraemia (< 125 mEq/l). Results Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Coxproportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38–1.96; HR 2.24, 95% CI 1.69–2.98; HR 2.20, 95% CI 1.25–3.90, for patients
Introduction Although the incidence and mortality rates of colorectal cancer are quite variable between countries, globally it is one of the most common malignancies, having a diseasespecific mortality rate of almost 33% in the developed world [1–3]. Several prognostic indicators for patients with colorectal cancer, based on certain patient- and disease-related factors, have been identified in order to faciliCorrespondence to: Soo Wan Kim, MD, PhD, Department of Internal Medicine, Chonnam National University Medical School, 42 Jebongro, Gwangju 501-757, Korea. E-mail: [email protected]
with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long-term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved. Conclusion A substantial proportion of patients developed hyponatraemia during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer. Keywords Colorectal cancer, hyponatraemia, mortality What does this paper add to the literature? The prognostic value of hyponatraemia in patients with colorectal cancer has not been fully investigated. This study evaluates serum sodium levels in patients with colorectal cancer as a prognostic predictor of long-term mortality rates and demonstrated a prevalence in about one quarter of them.
tate optimal management [4–7]. These include the TNM staging system, serum carcinoembryonic antigen (CEA) levels and several molecular markers such as KRAS and BRAF mutations and microsatellite instability. Serum sodium is an easily obtained and routinely measured plasma electrolyte. Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, has been considered to be a marker of underlying disease severity and prognosis in various medical conditions including liver cirrhosis and congestive heart failure, and can also develop as a side effect of medication [8–12]. It is a common electrolyte disorder associated with tumourrelated conditions.
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
409
J. S. Choi et al.
Hyponatraemia in colorectal cancer
The incidence of hyponatraemia among cancer patients is high [13]. Furthermore, recent studies have indicated that hyponatraemia is associated with longer hospital stay and higher mortality in several types of cancer, but there are no reports on the incidence of hyponatraemia and the relation between hyponatraemia and prognosis for patients with colorectal cancer. In the present study we aimed to evaluate the incidence and severity of hyponatraemia during hospitalization, and to assess the prognostic impact of hyponatraemia in patients with colorectal cancer. The baseline, nadir and discharge serum sodium levels during hospitalization were determined, and the relationship between the presence of hyponatraemia and long-term mortality was assessed.
Method Study population
A retrospective evaluation was performed of patients with a diagnosis of colorectal cancer who had been admitted for at least 24 h to Chonnam National University Hwasun Hospital (CNUHH), Chonnam, Korea. CNUHH is a 700-bed teaching hospital and a tertiary referral centre for patients with cancer. Patients were classified according to the diagnostic C-code in the International Classification of Diseases, Tenth Revision codes. Between January 2004 and August 2010, 3466 patients presenting with colorectal cancer were admitted. Of these, we excluded 382 in whom the sodium level during hospitalization was not measured at least twice. An additional 140 patients were excluded because they met the following exclusion criteria including diagnosis of carcinoma in situ (n = 121) and an initial serum sodium level of ≥ 148 mEq/l (n = 19). The data obtained on the first admission were used for all analyses. Demographic, clinical and laboratory data were obtained from the hospital’s computerized database. This study was approved by the institutional review board of CNUHH. There was no need for consent given the retrospective nature of study. The study was performed in accordance with the Helsinki Declaration of 1975, as revised in 2000. Measurement of serum sodium level and clinical endpoint
Serial serum sodium levels during hospitalization were obtained from the patients’ medical records and reviewed by a trained study coordinator. Hyponatraemia was defined as a serum sodium level of < 135 mEq/l at
410
any point during hospitalization. For classification of the severity of hyponatraemia, serum sodium levels were categorized as normonatraemia (135–147 mEq/l), mild hyponatraemia (130–134 mEq/l), moderate hyponatraemia (125–129 mEq/l) and severe hyponatraemia (< 125 mEq/l). The primary end-point of the study was the 3-year mortality from the date of admission. Assessment of the survival status was obtained from the Gwangju Cancer Registry (GCR) and Jeonnam Cancer Registry (JCR). The purpose of and methods used to register patients with the GCR and JCR have been described previously [14]. Statistical analysis
Continuous variables with normal distributions were expressed as mean SD and were compared using one-way analysis of variance. Continuous variables with a skewed distribution were presented as median (with 25th and 75th percentiles) and were compared using the Kruskal–Wallis test. Pearson’s chi-squared test or Fisher’s exact test was used to evaluate the differences in categorical variables, which were expressed as numbers and percentages. The Kaplan–Meier method was used to estimate the 3-year mortality of all patients by severity and quartile of the serum sodium level, and comparisons between the groups were made using the log-rank test. Cox’s proportional regression analysis was used to compare the 3-year mortality values between each sodium level group. The hazard ratios (HRs) indicate the relative risk of death in each sodium level group compared with those in the lowest-risk sodium group (135–147 mEq/l). The confounders analysed included age, gender, TNM stage, comorbidities (hypertension, diabetes mellitus, congestive heart failure, chronic liver disease, chronic kidney disease and smoking status), previous therapy (surgery and chemotherapy) and laboratory variables [white blood cell (WBC) count, haemoglobin, serum creatinine, serum albumin, carcinoembryonic antigen (CEA) and blood glucose]. Increasingly adjusted models were established for the 3-year mortality rate to assess the relative confounding effect of certain factors. Subsequently, patients were categorized into four groups (persistent normonatraemia, resolved hyponatraemia, acquired hyponatraemia and persistent hyponatraemia) according to the change in serum sodium level during hospitalization between the initial and final measurement of serum sodium. The same variables as noted above were used for adjusted Cox proportional regression analysis. All statistical tests were two-tailed, and P-values < 0.05 were considered significant. Statistical analysis was performed using the Statistical Package for
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
J. S. Choi et al.
Hyponatraemia in colorectal cancer
hospitalization. The majority of patients presented with mild hyponatraemia (21.9%), with a lower incidence of moderate (4.9%) and severe (0.9%) hyponatraemia. The patients’ clinical characteristics, stratified by serum sodium level, are shown in Table 1. There were notable differences in the clinical characteristics according to the serum sodium level. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities and a more advanced TNM stage. Compared with patients with normonatraemia, hyponatraemic patients had a higher WBC count and elevated serum creatinine, CEA and blood glucose levels,
Social Sciences software, version 18.0 (SPSS; IBM, Armonk, New York, USA).
Results Baseline characteristics
A total of 2944 patients with colorectal cancer (mean age 63.4 11.4 years; 61.9% male) were included in the study. Hyponatraemia during hospitalization was evident in 814 (27.6%), patients, including 344 (11.7%) on admission and 470 (15.9%) at some point during
Table 1 Baseline characteristics of patients stratified by serum sodium level during hospitalization. Serum sodium level (mEq/l) 135–147 (n = 2130) Age (years) Male gender Past history Hypertension Diabetes mellitus Congestive heart failure Chronic liver disease Chronic kidney disease Smoking TNM stage (all) I II III IV TNM stage (colon cancer) I II III IV TNM stage (rectal cancer) I II III IV Previous therapy Surgery Chemotherapy Laboratory variables WBC (per mm3) Haemoglobin (g/dl) Serum creatinine (mg/dl) Serum albumin (g/dl) CEA (ng/ml) Blood glucose (mg/dl)
63 11 1305 (61.3%)
130–134 (n = 643) 65 11 413 (64.2%)
125–129 (n = 145) 67 11 92 (63.4%)
< 125 (n = 26) 65 14 12 (46.2%)
P-value < 0.001 0.193
726 338 86 70 133 722
(34.1%) (15.9%) (4.0%) (3.3%) (6.2%) (33.9%)
253 146 29 34 71 225
(39.3%) (22.7%) (4.5%) (5.3%) (11.0%) (35.0%)
72 34 12 18 30 60
(49.7%) (23.4%) (8.3%) (12.4%) (20.7%) (41.4%)
10 6 2 2 11 7
(38.5%) (23.1%) (7.7%) (7.7%) (42.3%) (26.9%)
< 0.001 < 0.001 0.087 < 0.001 < 0.001 < 0.001
438 704 719 269
(20.6%) (33.1%) (33.8%) (12.6%)
74 189 214 166
(11.5%) (29.4%) (33.3%) (25.8%)
15 41 41 48
(10.3%) (28.3%) (28.3%) (33.1%)
4 4 10 8
(15.4%) (15.4%) (38.5%) (30.8%)
< 0.001
264 513 485 178
(18.3%) (35.6%) (33.7%) (12.4%)
39 138 149 123
(8.7%) (30.7%) (33.2%) (27.4%)
10 33 26 33
(9.8%) (32.4%) (25.5%) (32.4%)
4 3 9 6
(18.2%) (13.6%) (40.9%) (27.3%)
< 0.001
174 191 234 91
(25.2%) (27.7%) (33.9%) (13.2%)
35 51 65 43
(18.0%) (26.3%) (33.5%) (22.2%)
5 8 15 15
(11.6%) (18.6%) (34.9%) (34.9%)
0 1 1 2
(0.0%) (25.0%) (25.0%) (50.0%)
< 0.001
18 (12.4%) 17 (11.7%)
5 (19.2%) 6 (23.1%)
< 0.001 < 0.001
10591 6055 11.2 2.1 1.16 1.11 3.22 0.66 6.9 (3.2,31.2) 138 68
13056 6542 10.7 2.4 1.62 2.06 3.20 0.76 7.9 (2.0, 44.7) 129 41
< 0.001 < 0.001 0.001 < 0.001 < 0.001 < 0.001
90 (4.2%) 92 (4.3%) 9350 3983 12.0 2.1 1.04 0.73 3.65 0.61 3.6 (2.1,8.2) 122 45
53 (8.2%) 57 (8.9%) 9423 4453 11.5 2.3 1.07 0.82 3.48 0.64 5.1 (2.5,14.7) 137 65
WBC, white blood cell; CEA, carcinoembryonic antigen. Values mean SD or median (interquartile range) or number (%).
Colorectal Disease ª 2014 The Association of Coloproctology of Great Britain and Ireland. 17, 409–416
411
J. S. Choi et al.
Hyponatraemia in colorectal cancer
whereas haemoglobin and serum albumin levels were lower. Multivariate analysis of 3-year mortality according to serum sodium levels
Patients were followed up for a mean period of 4.08 2.43 years. Two hundred and sixty-three patients were lost to follow-up within 3 years. The duration of follow-up was right-censored at 3 years for Kaplan–Meier and Cox proportional regression analysis. A total of 794 (27.0%) patients died during the follow-up period. Kaplan–Meier curves for crude 3-year cumulative mortality categorized by severity and the quartile of serum sodium level are shown in Fig. 1. Table 2 shows unadjusted and adjusted Cox (a)
proportional regression analysis for 3-year mortality according to the serum sodium level. Unadjusted analysis showed a linear relationship between serum sodium level and 3-year mortality risk, and this relationship persisted even after adjustment for several confounders. In the fully adjusted model, compared with the normonatraemia group (135–147 mEq/l), the hyponatraemia group showed a higher mortality risk (HR 1.65, 95% CI 1.38–1.96; HR 2.24, 95% CI 1.69–2.98; HR 2.20, 95% CI 1.25–3.90, for patients with mild, moderate and severe hyponatraemia, respectively) resulting in a significant trend (P-value < 0.001). This finding was reconfirmed by a secondary analysis using the quartile of serum sodium level, although the level of statistical significance was border line for the second quartile group.
1.0
Cumulative survival
0.8
0.6
0.4
Serum sodium with 135–147 mEq/L Serum sodium with 130–134 mEq/L Serum sodium with 125–129 mEq/L Serum sodium with
