BMC Medical Informatics and Decision Making Computerized clinical documentation system in the pediatric intensive care unit
2001

James A Menke
Department of Pediatrics, Children's Hospital
The Ohio State University
ColumbusOHUSA

Cynthia W Broner firstname.lastname@example.com
Deborah Y Campbell firstname.lastname@example.com
Medical University of South Carolina
CharlestonSCUSA

Michelle Y Mckissick firstname.lastname@example.com
Department of Nursing
Children's Hospital
ColumbusOHUSA

Joy A Edwards-Beckett
BMC Medical Informatics and Decision Making Computerized clinical documentation system in the pediatric intensive care unit

BMC Medical Informatics and Decision Mak-ing
132001BioMed Central Research article *Corresponding author
Background:To determine whether a computerized clinical documentation system (CDS): 1) decreased time spent charting and increased time spent in patient care; 2) decreased medication errors; 3) improved clinical decision making; 4) improved quality of documentation; and/or 5) improved shift to shift nursing continuity.Methods: Before and after implementation of CDS, a time study involving nursing care, medication delivery, and normalization of serum calcium and potassium values was performed. In addition, an evaluation of completeness of documentation and a clinician survey of shift to shift reporting were also completed. This was a modified one group, pretest-posttest design.Results: With the CDS there was: improved legibility and completeness of documentation, data with better accessibility and accuracy, no change in time spent in direct patient care or charting by nursing staff. Incidental observations from the study included improved management functions of our nurse manager; improved JCAHO documentation compliance; timely access to clinical data (labs, vitals, etc); a decrease in time and resource use for audits; improved reimbursement because of the ability to reconstruct lost charts; limited human data entry by automatic data logging; eliminated costs of printing forms. CDS cost was reasonable.Conclusions: When compared to a paper chart, the CDS provided a more legible, compete, and accessible patient record without affecting time spent in direct patient care. The availability of the CDS improved shift to shift reporting. Other observations showed that the CDS improved management capabilities; helped physicians deliver care; improved reimbursement; limited data entry errors; and reduced costs.

Background

Computerized clinical documentation systems (CDS) provide for the documentation of patient care using com-puters. For example, the CDS records the vital signs directly from the cardio-respiratory monitors, while other documentation, such as nursing assessments are entered by the clinician. Reported benefits of computerized clinical systems in the adult care setting include: 1) nursing time savings [1,2]; 2) improved decisions and productivity of physicians [3,4] ; 3) decreased medication errors [5]; 4) decreased turn-around time for results [4]; 5) easier quality assurance process [6]. These potential benefits have not been studied well in the pediatric setting [7].

As part of the implementation of a CDS in our Pediatric Intensive Care Unit (PICU), we evaluated some effects of this system. The objectives of the study were to determine whether the CDS affected time spent by nursing in patient care; decreased medication errors; increased the speed of clinical decision making; improved the quality of documentation; and improved shift to shift continuity when compared to paper charting.

Computer software/hardware

The Eclipsys Continuum 2000 CDS (Eclipsys Corporation, Delray Beach, Fl.) was chosen for implementation in the PICU at Children's Hospital, Columbus, OH. At the time of the study, the PICU had 16 beds with an average daily census of 11.3, an average length of stay of 3.4 days and 1205 admissions for the year. Recently, we opened a new PICU with 35 beds with the Eclipsys as the CDS, but we haven't studied it yet in the larger unit. At the time of this study, the system used Sun SPARCstations (Sun Microsystems, Mountain View, CA) with a peer to peer network. There was an Eclipsys workstation at each bedside and 2 at the nursing station. There was built in redundancy for reliability with mirrored copies of individual patient data stored in 2 different Sun SPARCstations on the network. Since this study was completed, the system was upgraded to a client server architecture using either pc's or x-terms as the client .

The system was connected to the Hewlett Packard Component Monitoring System (Hewlett Packard, Palo Alto, CA) using Hewlett Packard's proprietary Careport interface. In addition, the Eclipsys system is connected through the hospital's interface engine using an HL7 interface to the hospital laboratory system and the hospital information system. The connections permit the automatic logging of data from the cardiorespiratory monitor to the ECLIPSYS System, and the automatic transfer of laboratory data to the Eclipsys system as soon as the laboratory personnel verify them as being accurate. Nursing, laboratory, and respiratory care staff used a graphical user interface to document care on the ECLIP-SYS System. The graphical interface allows for 'point and click' data entry, charting by exception, and text entry by keyboard. Each clinician has a unique electronic signature. All data entry is automatically included in an audit trail that maintains all versions of data as is changed or corrected. The clinical information is stored in a propri-etary database designed by ECLIPSYS for fast individual patient access. After discharge the patient's information is archived. During the hospitalization of a patient all non-textual information is sent to a relational database, which allows ad hoc and prewritten queries about the information in the database which cannot be obtained using the clinical database. These queries use Structured Query Language (SQL) and were the basis of the computerized chart audits.

Methods

Five aspects of care were studied during two three month time periods before and one three-month time period after the installation of the CDS as suggested by the statistician since we underwent a paper charting change at the time of this study. This is a modified one group, pretestposttest design. An independent observer performed a time/motion study to measure time spent charting and in direct patient care by the nursing staff. As a measure of medication error, we chose to evaluate delays in medication delivery since this system did not have order entry. A chart (paper or computer) audit was performed to determine the difference in time between scheduled and actual medication delivery. To assess the speed of clinical decision-making we audited charts (paper or computer) to determine the time it took for abnormal potassium and ionized calcium values to return to normal. The presumption was that if clinicians had better access to laboratory data, they would respond to abnormalities in a more timely fashion. This improved response would result in a more rapid return of abnormal values to normal.

We evaluated the completeness of nursing documentation by a review of nursing documentation. The specific questions addressed were: 1) did the nurses notes reflect the care plan; 2) were the care goals based on nursing diagnosis; 3) were the nursing care plans completed; 4) was a psychosocial assessment completed; 5) were safety precautions documented; 6) were the parent education sessions documented; 7) was the parent's response to the education reported; and 8) were nursing interventions evaluated

The last aspect of the study included an evaluation of shift to shift continuity. We wanted to compare the "paper" shift change with the "computer" shift change. The major difference was the replacement of multiple sources of paper info about the patient with a single computerized source of information about the patient available at the time of shift change. We accomplished this with a Likert scale questionnaire administered to nursing staff immediately following change of shift report. The questionnaire was designed to determine attitudes of the incoming nursing staff about shift report (a copy of the questionnaire is available upon request). Each question was rated on a scale of 1 to 5 with 5 expressing the most positive attitude towards the shift report experience. In addition, one question rated the time it took to complete the shift report.

All five assessments were completed for each time period. The data were analyzed using one way or two way ANOVA where appropriate.

Results

The nursing time study demonstrated no significant difference in nursing time devoted to direct patient care or charting between the pre-CDS and the CDS time periods ( Table 1). The medication delivery audit showed an apparent significant increase in delayed medication deliveries during the CDS time period ( Table 1). The laboratory normalization time data could not be analyzed because too many data concerning the time of reporting of results were missing from the paper chart audit. Data obtained from the CDS were 100% complete, however.

In all areas, nursing documentation was superior during the CDS time period both in content and legibility (Figure 1). The survey of shift-to-shift reporting showed significantly more positive reporting experiences during the CDS time period, with no increase in time required (Table 1).

Throughout the study, we attempted to document important incidental findings related to the implementation of the CDS. To this end, we made several observations during the course of the study that we thought important to report. The complete and legible computerized clinical documentation helped our nurse manager to increase her span of managerial control by providing better incident documentation, and enhanced her ability to develop employees with easier access to legible charting by individual nurses. During the CDS portion of our study, we had a JCAHO audit and noted that our documentation was in compliance because the CDS forced legible and complete documentation. Our clinicians (physicians, nurses and respiratory therapists) appreciated the automated calculations done by the CDS (shift and daily I&O) and the ability to compare physiological data graphically. Accessibility to the patient's chart improved since an individual chart could be viewed on any of the 18 computer workstations in the unit. This improved accessibility gave the clinicians the ability to chart concurrently while viewing clinical data (lab and vital signs) during resuscitations. According to the hospital's internal auditor, the hospital increased hospital reimbursement by about $300,000 during the first year because of the CDS's ability to recreate lost charting from the computer files. Automatic logging of information re-duced human data entry and the associated transcription errors. We eliminated the cost for standard nursing and respiratory forms. Finally, the cost of the system seemed reasonable. Using the figures at the time of the purchase, the cost of the hardware and the software, if expanded to all our critical care beds would be $24/patient day if amortized over 3 years.

Discussion

In the last five years, computerized clinical systems have become generally more available [8]. Evaluations of the usefulness and effectiveness of some these clinical systems have been reported, but most evaluations are in the adult care setting [7]. The evaluation of the implementation of the CDS in the PICU at Children's Hospital provides some insight into the use of computerized clinical systems in a pediatric critical care setting. Prior to the implementation of the CDS in our PICU, the only computer systems available was a stat lab report printer and access to the laboratory's departmental computer system using a very crude user interface.

A decrease in documentation time and consequently an increase in the time available to the nurse for direct patient care are described as a benefit of these computerized systems [9] In contrast, our experience demonstrated no increase in time devoted to direct patient care with the introduction of the CDS. One of the reasons for this lack of observed benefit might be our timing of the Posttest time period. We may still have been on the learning curve and this probably warrants further study. However, we did note that the documentation provided by the CDS was more complete and always legible; in addition, it took no longer to chart with the CDS as compared to the paper system. The content was more complete because the CDS, depending on the documentation, forced the clinician to document a certain way, guided the clinician, or made documentation easier for the clinician. Although we did not perform a measurement of accessibility, a single chart can be accessed simultaneously by all 18 workstations in the PICU. This is one of the major benefits of an effective clinical system [10]. The Eclipsys System handles record locking on a first com first served basis. A record cannot be updated by more than one person at a time. In addition, to access the system, one must logon using a unique ID and password. Each use of the system is provided and ID and password. Once logged on, the system presents a census list of patients from which the user can open any one chart at a time. Access time is almost instantaneous.

Another major benefit of computerized clinical documentation systems is a reduction of medication errors [5]. In our institution, we have 2 major sources of medication error -transcription errors and delivery time er-rors. We did not implement a physician order entry component (we are currently in the process of doing so), but chose to evaluate the effect of CDS on delays in delivery of medications. We noted a surprising increase in delayed delivery of medications during the CDS time period. However, after closer analysis and discussion with the nursing staff, it appeared the observed increase in delayed medications resulted from better data from the CDS. Times of delivery of medications are logged by the CDS automatically during the charting process. When using the paper system, nurses would commonly chart a medication that was delivered within 30 minutes of a scheduled time as being delivered on time. The more accurate CDS data led to the identification of a hitherto unrecognized problem of the paper system.

During analysis of chart audit of laboratory value normalization, we noted that the paper chart did not contain the information needed to complete the analysis in the majority of the cases. In contrast, every CDS chart contained all the necessary information. In addition, the audit of the paper chart required in excess of 40 hours to get a set of incomplete data, whereas the CDS audit required about 20 minutes, which included developing the SQL search statements required by the CDS. We learned that not only could we get more complete data from the CDS, but also we could do it in a fraction of the time when compared to the paper chart audit. Hence, both the medication and the laboratory audit were simpler using the CDS.

The evaluation of the end-of-shift reporting study suggests that use of the CDS resulted in more positive attitudes towards the change of shift reporting by the nurses. This is likely related in part to the more complete, readable and organized CDS chart. Having the chart available for the shift report may also have influenced the nurses. Moreover, shift change reporting did not take more time with the CDS.

The introduction of the CDS represented a major change in the way the clinicians cared for patients in the PICU at Children's Hospital. For most people change is hard and if not managed well may result in confrontation as occurred at the University of Virginia Medical Center when a computerized order entry system was implemented [11], [12]. While there were a number of institutional issues involved in the confrontation over the physician order system, the University of Virginia's system forced people to change the way they did their job [12]. Innovation may be easier if the individual perceives a 'personal' benefit that results from the change [13]. The 'personal' benefit must be of importance to the individual. In our situation, we found several "value added" benefits for the clinicians that included legibility, completeness, accessibility, and timeliness of information. Furthermore, there was no time cost of the change since the new CDS method of clinical documentation took no longer than the paper based system.

As the Post-test period progressed, unanticipated benefits became apparent. We found that the system allowed for improved management functions of the nurse manager, and 'forced' JCAHO documentation compliance. Our clinicians noted the automated calculations provided by the CDS and the graphic display of physiologic data to be helpful. Having the chart available in more than one location was noted to be helpful both in normal situations as well as during resuscitative efforts. The CDS reduced the time and resources need for audits while at the same time it increased hospital reimbursement. Automatic logging of information reduced human data entry and the associated transcription errors.

Conclusions

The computerized documentation system provided a more legible, complete patient record without increasing the time needed to document care. The CDS was more accessible and it improved shift to shift reporting. We speculate that the widespread use of computerized documentation systems giving better access to clinical data will improve clinician's ability to evaluate outcomes and improve care. This will take some degree of intentionality and an understanding of the data storage systems. Furthermore, the integration of clinical paths and automated variance analysis with the CDS will make the process of reducing variance in patient care much simpler. Finally, we believe the cost savings from having clinical data available in an organized fashion will more than pay for the CDS systems.

Abbreviations and glossary of computer terms

CDS -computerized clinical documentation system

Decision Support Database -a collection of information about the patients that the clinician's have decided to save in order to ask global questions about groups of patients.

Graphical User Interface -software on the computer that uses pictures/graphics and text to communicate with the user and allows the user to manipulate a pointing device (mouse) to move about the software and to enter information.

Interface Engine -A computer/software system that translates information between various computer networks.

JCAHO -Joint Commission on Accreditation of Healthcare Organizations

Network -a number of microcomputer workstations connected together using cables. The connections allow the computers to communicate with each other and a central computer running the network.

PICU -pediatric intensive care unit

Relational Database -a collection of information, which has been, structured such that it is relatively easy to ask questions about the data in the collection.

Structured Query Language (SQL) -a standard way of asking questions about information in a relational database.

Sun SPARCstation -a microcomputer based workstation that has strong graphic capabilities.

Figure 1
1Improvement in quality of documentation: A barchart comparing the completeness of nursing documentation for each time period and for each area of documentation.

Table 1 :
1Nursing Time Study Data, Medication Error Study Data, and Shift Change Survey DataSignificance when

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Competing interestsDeborah Y. Campbell, R.N. -at the time of this study Ms Campbell was an employee of Children's Hospital, subsequently she worked for Eclipsys
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Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings

Jo Tashiro
Shigeki Yamaguchi
Toshimasa Ishii
Asami Suzuki
Hiroka Kondo
Yohei Morita
Kiyoka Hara
Isamu Koyama
Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings
R E S E A R C H Open Access
Background: Cancer patients not admissible for adjuvant chemotherapy are generally at high risk of considerably inferior prognosis. The aim of this retrospective study was to evaluate poorer survival without administration of oral adjuvant chemotherapy of stage III colon cancer patients in clinical settings. Methods: Between April 2007 and September 2011, 259 patients with stage III colon cancer who underwent curative surgery were retrospectively assigned to the adjuvant chemotherapy group of 171 patients (66%) and the surgery alone group of 88 patients. Oral fluorouracil (5-FU) derivatives used in adjuvant chemotherapy, such as oral uracil and tegafur plus leucovorin (UFT/LV) or capecitabine, were the most commonly used. Results: The 3-year relapse-free survival (RFS) rates were 74.9% for all cases, 58.3% for the surgery alone group, and 83.4% for the adjuvant chemotherapy group (P = 0.0001). The chemotherapy group was associated with a dramatic improvement in survival for stage IIIB (surgery alone 57.7% versus adjuvant chemotherapy 83.9%; P = 0.0001) and stage IIIC (surgery alone 18.2% versus adjuvant chemotherapy 57.3%; P = 0.006) patients. There was a significant difference in the overall recurrence rate between groups (surgery alone 35.2% versus adjuvant chemotherapy 18.1%; P = 0.002). Multivariate analysis identified adjuvant therapy as an independent predictive factor of reduced recurrence (hazard ratio (HR): 3.231; P = 0.004) and improved RFS (HR: 2.653; P = 0.001). Conclusion: In clinical settings, adjuvant therapy was the only significant prognostic factor of survival. Since many patients prefer not to receive chemotherapy, it is critical to inform stage III colon cancer patients that chemotherapy raises their chances of survival by three-fold compared with curative surgery alone.

Background

Adjuvant chemotherapy after curative resection for stage III colon cancer patients has been widely recommended as a standard treatment to prolong disease-free survival (DFS) and overall survival (OS) since the early 1990s [1,2]. The National Surgical Adjuvant Breast and Bowel Project (NSABP) reported the results of a surgical adjuvant clinical trial (protocol C-03) that indicated significant extension of DSF and OS in stage II and III colon cancer patients who received fluorouracil (5-FU) plus leucovorin (LV) compared with patients who received semustine, vincristine, and 5-FU (protocol C-04) [3][4][5]. Furthermore, the NSABP protocol C-06 demonstrated that oral uracil and tegafur (UFT) plus LV (UFT/LV) were associated with DSF and OS rates similar to those obtained with a regimen of intravenous weekly bolus 5-FU plus LV (5-year DFS 67.0% versus 68.2%, 5-year OS 78.5% versus 78.7%) [6][7][8]. 5-FU significantly improves DFS and OS rates over surgery alone, with relative risk reductions of 30% and 26%, respectively [9].

The Xeloda® in Adjuvant Colon Cancer Therapy (X-ACT) trial was undertaken to compare the efficacy and tolerability of oral capecitabine with 5-FU/LV (intravenous bolus) as adjuvant therapy for patients with stage III colon cancer [10,11]. The 3-year relapse-free survival (RFS) rates were 65.5% with capecitabine and 61.9% with 5-FU/LV, for an absolute difference of 3.6% (95% CI, −0.9 to 8.1; P = 0.12). The 3-year OS rates were 81.3% with capecitabine and 77.6% with 5-FU/LV, giving an absolute difference of 3.7% (95% CI, −0.1 to 7.5; P = 0.05) between treatment groups. Since oral capecitabine offers equivalent clinical benefits in terms of efficacy, safety, convenience, and treatment cost, it can replace intravenous 5-FU/LV in the adjuvant treatment of stage III colon cancer.

Generally, patients not receiving adjuvant chemotherapy have considerably inferior prognosis. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) reported recurrence rates of 30.8% for stage III colon cancer [12]. The present retrospective study evaluated the prognosis of stage III colon cancer patients excluded from adjuvant chemotherapy because they were older patients, had a high risk of severe comorbidities, or simply refused to receive treatment.

The limitations of the study are that it has retrospective clinical observations, a lack of patient randomization, and a dependence on the information available in the patient files. Which is more benefit or more harm associated with various treatment strategies is decided depending on the situation of each patients in clinical settings. Therefore, the aim of this study was to demonstrate the poor prognosis without oral adjuvant chemotherapy for stage III colon cancer patients in clinical settings.

Patients and methods

Patient selection criteria

Between April 2007 and September 2011, 259 patients with stage III colon cancer who underwent curative surgery were retrospectively assigned to the adjuvant chemotherapy group (n = 171) or the surgery alone group (n = 88). The database contained detailed information on patient characteristics, operative findings, histology, laboratory findings, and adjuvant therapies. The follow-up survival data were collected retrospectively through medical record analyses. The exclusion criteria were as follows: rectal cancer; malignancy other than colon cancer; and patients who did not receive adjuvant chemotherapy or did not have any information about the chemotherapy. Cancer was staged using the American Joint Committee on Cancer (AJCC) 7th edition TNM classification: colon and rectum [13].

Chemotherapy adjuvant regimens

All patients started receiving adjuvant ≥8 weeks after curative surgery. They were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, to have signed informed consent, and be aged between 20 and 80 years old. The JSCCR recommends four adjuvant therapy regimens for stage III colorectal cancer: intravenous 5-FU/LV, UFT/LV, capecitabine, or FOLFOX (5-FU/LV plus oxaliplatin). In Japan, given the expected benefits and possible risks of toxicity, a consensus has not been reached as to whether adjuvant regimens containing oxaliplatin should be given to stage III patients. Several oral 5-FU derivatives are available, such as oral UFT/LV or capecitabine, and they are preferred for their convenience. Consequently, these were the most commonly used regimens in this study [14].

The UFT regimen is a preparation of tegafur-uracil in a molar ratio of 1:4. Tegafur is the 5-FU prodrug converted to 5-FU in the liver. LV is used to modulate 5-FU biochemically, and has been widely adopted for the treatment of advanced colorectal cancer [8,15]. The 5week cycles of chemotherapy consisted of 4 weeks of oral UFT/LV, followed by 1 week of rest, and were repeated for ≥6 months. The UFT was administered at a dose of 300 mg/m 2 /day, and LV was administered at a dose of 75 mg/day. The daily doses of UFT/LV were divided into three doses administered every 8 h with water. Patients were instructed to avoid food from 1 h before to 1 h after each dose. Capecitabine is an oral fluoropyrimidine that generates 5-FU preferentially in tumor tissue through a three-step enzymatic cascade [16]. The adjuvant was administered at a dose of 1.250 mg/m 2 twice a day for 14 days, followed by 7 days of rest. Standard care included a total of eight cycles. The amount of drug received was based on reported pill counts and patient declarations at the end of each cycle.

Follow-up protocol

The patients were scheduled for follow-up visits every 3 months during the first 3 years, every 6 months during the next 2 years, and annually thereafter. Each visit included a physical examination and computed tomography (CT) scans of the chest, abdomen, and pelvis. Colonoscopies were performed during the first, third, and fifth year of follow-up. The median follow-up period was 41 months (range: 3 to 73 months).

Data analysis

Statistical analysis was performed using SPSS version 21.0 software (SPSS Inc., Chicago, IL, USA). The chisquared test or Fisher's exact probability test were used to compare recurrence rates. Logistic regression analysis was conducted on the parameters found to be significantly associated with recurrence by chi-squared tests or Fisher's exact probability test (P <0.05) to identify the independent factors of recurrence. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Stepwise forward Cox regression model was conducted for parameters found to be significantly associated with survival by the log-rank test (P <0.05) in order to identify the independent factors of survival. Values of P <0.05 were considered significant in all analyses. This analysis was conducted using the intention-to-treat theory.

Results

Patient characteristics

The two groups were similar with respect to gender, tumor location, depth of invasion, tumor differentiation and lymphovascular invasion, and TNM subclassification (IIIA/IIIB/IIIC) (Table 1). However, mean age was significantly higher in the surgery alone group (63.4 versus 75.4 years; P <0.0001). The causes for adjuvant chemotherapy rejection were older patients (>80 years), high risk of severe comorbidities or postoperative complication, and self-judgment of refusal.

Prevalence of each adjuvant regimen

The UFT/LV regimen was performed in 104 patients (61%), capecitabine in 59 patients (34%), and other types in eight patients (5%; S1 and single-agent of UFT). The overall compliance was 77%, as 40 patients discontinued the therapy without evidence of a protocol event. The most common symptoms of drug toxicity were severe nausea and diarrhea (3.5%); the risks of severe hepatitis, neutropenia, and hand foot syndrome (5%) only with capecitabine. The completion rate of adjuvant chemotherapy was significantly less in patients with UFT/LV (72%) than with capecitabine (83%; P <0.0001).

Survival analysis

The Kaplan-Meier estimates of 3-year OS and 3-year RFS survival are presented in Figure 1 and Figure 2, respectively. When the two groups were compared, the adjuvant chemotherapy was associated with a significant improvement in 3-year OS (surgery alone: 81.7% versus adjuvant chemotherapy: 93.5%; P <0.001) and RFS (surgery alone: 58.3% versus adjuvant chemotherapy: 83.4%; P <0.001). Furthermore, chemotherapy did not affect the 3-year OS of stage IIIA and IIIC patients, and the 3-year RFS of stage IIIA patients.

Univariate and multivariate analyses were conducted for each clinicopathological factor ( Table 2). Based on univariate analysis, advanced age was associated with poorer survival, whereas adjuvant chemotherapy was associated with improved survival. Multivariate analysis was performed to identify independent predictors of survival. Chemotherapy was the only significant prognostic factor of improved survival (hazard ratio (HR): 0.379; 95% confidence interval (CI), 0.214 to 0.670; P = 0.001), aside from oncological factors (depth of tumor invasion and TNM stage).

Cancer recurrence occurred in 62 patients (recurrence rate (rec rate), 23.9%) during the follow-up period. The risk of recurrence during the first 3 years was two-fold higher for surgery alone (rec rate, 35%) than with adjuvant chemotherapy (rec rate, 18%). The overall median  Multivariate analysis was performed to identify independent predictive factors of recurrence (Table 3). Chemotherapy was the only significant predictive factor of recurrence (HR, 3.076; 95% CI, 1.422 to 6.653; P = 0.004) apart from oncological factors (depth of tumor invasion and TNM stage).

Discussion

Recently, practice-based research (studies based on medical care) which got rid of the distance of a clinician and the researcher tends to be regarded as important [17]. It is a valuable study method that provides information from daily clinical situations. The present study provides the survival outcome of stage III colon cancer patients. We report that patients treated only by curative surgery for various reasons had considerably inferior prognosis than those receiving both surgery and chemotherapy.

Oncologists are aware of this, but tend to disregard factors affecting the efficacy of adjuvant chemotherapy, such as age, comorbidity, and postoperative patient conditions. Cohort studies including these parameters would provide a more comprehensive analysis of cancer treatment outcome. For patients intolerant to anticancer drugs, cancer recurrence and prognosis due to aggravation of serious comorbidity are important factors influencing survival. The survival rates we present for surgery alone are more realistic because they account for the patients who refused chemotherapy for economic, social, or philosophical reasons.

The 3-year RFS rate of the surgery alone group was significantly lower than for the chemotherapy group. In addition, chemotherapy was associated with a two-fold  lower cancer recurrence rate during the first 3 years for stage III colorectal cancer patients, with 18% and 35%, respectively. Both stage IIIB and IIIC patients benefited from chemotherapy with a dramatic improvement in survival rate over surgery alone. Multivariate analysis only identified chemotherapy as an independent predictive factor for improvements in prognosis and reduction in cancer recurrence. Therefore, patients unable or unwilling to receive chemotherapy have a poor oncological prognosis. It is critical to provide this information to the patients unable to receive adjuvant chemotherapy for stage IIIB and IIIC. When recurrence occurs in stage IIIB and IIIC colon cancer patients, the oncologic surgeon who makes the decision of surgery alone treatment will provide the best supportive care. The present study emphasizes the needless of chemotherapy in cases of stage IIIA colon cancer. Whereas both groups had an excellent outcome, chemotherapy after surgery raised the 3-year RFS from 87.4% to 100%. While the sample sizes were too small to reach statistical significance, it is likely that chemotherapy could be omitted for certain types of stage IIIA colon cancer with low risk of recurrence, such as node positive T1/T2 patients. Adjuvant administration must be decided based on the status of each patient with stage IIIA colon cancer. While the benefits of 100% 3-year RFS is important for patients, it must be weighed against the adverse effects.

We must determine how to improve the treatment of patients with poor performance status, severe comorbidities, and older patients who are not normally eligible for chemotherapy [18]. The older age patient group is commonly overlooked in clinical trials and, as a result, is often undertreated despite the proven efficacy of adjuvant therapy [19,20]. The X-ACT trial added to the growing volume of evidence suggesting that age alone should not be a barrier to the use of adjuvant chemotherapy in colon cancer [21,22]. On the other hand, performance status should be the governing factor. In addition, it is important to remember that renal impairment is more common in older patients, and is associated with an increased risk of toxicity with UFT/LV or capecitabine. Renal function should therefore be assessed before the onset of chemotherapy. The most appropriate type of chemotherapy requires a risk-benefit assessment of each adjuvant regimen available based on age, disease stage, performance status, comorbidities, and patient preference. For cancer patients hospitalized for severe comorbidities, an immunity activation agent (that is, polysaccharide-K) may be added to singleagent UFT, but the impact on recurrence has not been determined [23].

Conclusion

Although other reports have documented treatment outcomes in stage III colon cancer, the present study analyzed a rare subset of colon cancer patients (stage IIIA, IIIB, and IIIC) treated only with oral adjuvant chemotherapy at a single institution. Receiving adjuvant chemotherapy was the only prognostic factor for an improved treatment outcome in a clinical setting. Patients that are uncertain about the benefits of adjuvant chemotherapy should be informed of the poor survival rates for stage IIIB and IIIC colon cancer, as well as the excellent survival rates for stage IIIA colon cancer without adjuvant chemotherapy. Unfortunately, stage IIIB and IIIC colon cancer patients who cannot undergo adjuvant chemotherapy because of severe comorbidities, an advanced age, or by choice, need to be informed of the inferior prognosis without treatment.

Figure 2
2Kaplan-Meier estimates of 3-year overall survival (OS) of all cases, and patients with stage IIIA, IIIB, and IIIC colon cancer. Survival analysis compares the surgery alone group and chemotherapy group.

Abbreviations 5 -
5FU: Fluorouracil; AJCC: American Joint Committee on Cancer; ASA: American Society of Anesthesiologists physical status classification system; CEA: Carcinoembryonic antigen; CI: Confidence interval; CT: Computed tomography; DFS: Disease-free survival; ECOG: Eastern Cooperative Oncology Group; HR: Hazard ratio; JSCCR: Japanese Society for Cancer of the Colon and Rectum; LV: Leucovorin; NSABP: National Surgical Adjuvant Breast and Bowel Project; OS: Overall survival; rec rate: Recurrence rate; RFS: Relapse-free survival; TNM: Tumor, node, metastasis; UFT: Uracil and tegafur; X-ACT: Xeloda in Adjuvant Colon Cancer Therapy.

Table 1
1Comparison of patient characteristics stratified according to receipt of adjuvant chemotherapy and rejected reasons of adjuvant chemotherapy Figure 1 Kaplan-Meier estimates of 3-year relapse-free survival (RFS) of all cases, and patients with stage IIIA, IIIB, and IIIC colon cancer. Survival analysis compares the surgery alone group and chemotherapy group.Variable
Surgery
(n = 88)

Adjuvant
chemotherapy (n = 171)

P value

Gender
0.78

Female
38
77

Male
50
79

Age (years, mean)
75.4
63.4
<0.0001

Comorbidity
60 (68%)
82 (47%)
0.002

ASA (grade ≥3)
27 (30%)
2 (1%)
<0.0001

Location

Right side of colon
36
62
0.47

Left side of colon
52
109

Colon
77
136
0.11

Rectosigmoid
11
35

Serum CEA

≥5
36 (41%)
73 (43%)
0.78

≥10
19 (22%)
43 (25%)
0.53

Postoperative hospital
stay (mean)

10.8
8.9
0.08

Histological type

Differentiated
79
156
0.7

Undifferentiated
9
15

Lymphovascular
invasion (≥2, 3)

26 (30%)
46 (27%)
0.65

Tumor depth

T1/T2/T3/T4
13/5/52/18
9/15/113/34
0.06

Lymph node
metastasis

N1 (1 to 3)
65
131
0.33

N2 (4≤)
2 3
4 0

Lymph node
number (≥12)

81 (92%)
161 (94%)
0.52

TNM stage

IIIA/IIIB/IIIC
16/60/11
22/127/22
0.380

Rejected reasons of
adjuvant chemotherapy

Older person
(>80 years)

37 (42%)

Self-judgment
29 (33%)

Severe
comorbidities

16 (18%)

Postoperative
complications

6 (7%)

ASA, American Society of Anesthesiologists physical status classification
system; CEA, carcinoembryonic antigen; TNM, tumor, node, metastasis.

Table 2
2Univariate and multivariate regression analysis for relapse-free survival (RFS) of stage III colon cancerVariable
Comparison
Univariate
Multivariate

P value
HR
95% CI
P value

Gender
Female versus male
0.24

Age
0.001
1.01
0.986 to 1.043
0.324

Comorbidity
No versus yes
0.745

ASA (grade ≥3)
No versus yes
0.008
1.000
0.505 to 1.98
0.999

Location
Right versus left side of colon
0.306

Colon versus rectosigmoid
0.406

Serum CEA
<5 versus ≥5
0.074
0.84
0.519 to 1.366
0.49

Operation
Laparoscopic versus open surgery
0.082
1.01
0.597 to 1.700
0.98

Tumor depth
T1, 2 versus T3, 4
0.002
0.26
0.089 to 0.733
0.01

Lymph node metastasis
N1 (1 to 3) versus N2 (4<)
0.004
0.71
0.387 to 1.301
0.27

TNM stage
IIIA, B versus IIIC
<0.0001
0.4
0.204 to 0.797
0.01

Adjuvant chemotherapy
No versus yes
<0.0001
2.65
1.48 to 4.756
0.001

ASA, American Society of Anesthesiologists physical status classification system; CEA, carcinoembryonic antigen; CI, confidence interval; HR, hazard ratio;
TNM, tumor, node, metastasis.

Table 3
3Multivariate regression analysis for cancer recurrence of stage III colon cancerVariable
Comparison
Multivariate

HR
95% CI
P value

Age
1
0.968 to 1.036
0.941

Comorbidity
No versus yes
0.96
0.490 to 1.864
0.895

ASA (grade ≥3)
No versus yes
1.34
0.452 to 3.994
0.595

Location
Right versus left side of colon
1.08
0.561 to 2.089
0.81

Serum CEA
<5 versus ≥5
0.61
0.316 to 1.167
0.135

Operation
Laparoscopic versus open surgery
1.08
0.503 to 2.301
0.85

Morbidity
No versus yes
0.64
0.189 to 2.154
0.47

Tumor depth
T1, 2 versus T3, 4
0.17
0.037 to 0.801
0.03

Lymph node metastasis
N1 (1 to 3) versus N2 (4<)
0.56
0.244 to 1.268
0.16

TNM stage
IIIA, B versus IIIC
0.29
0.106 to 0.785
0.02

Adjuvant chemotherapy
No versus yes
3.23
1.458 to 7.159
0.004

CEA, carcinoembryonic antigen; CI, confidence interval; HR, hazard ratio.

http://www.wjso.com/content/12/1/145
AcknowledgementsThis study was not funded by an outside source.Competing interestsThe authors declare that they have no competing interests.Authors' contributions JT acted as guarantor of the integrity of the study, conceived the study concept, designed the study, defined the intellectual content, performed the literature research, undertook clinical and experimental studies, performed data acquisition, data analysis, and statistical analysis, and prepared and edited the manuscript. SY reviewed the manuscript. All authors read and approved the final manuscript.
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Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution. Tashiro, World Journal of Surgical Oncology. 12145Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings. Submit your manuscript at www.biomedcentral.com/submitCite this article as: Tashiro et al.: Inferior oncological prognosis of surgery without oral chemotherapy for stage III colon cancer in clinical settings. World Journal of Surgical Oncology 2014 12:145. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit