Introduction

Even though the incidence of colorectal cancer has been increasing over the last few years, the mortality rates have been decreasing gradually¹. Advances in diagnosis, treatment methods, and screening programs have affected survival outcomes positively². One of the most important factors affecting survival is the early diagnosis and treatment of complications. Many methods have been identified in predicting mortality and complications of colorectal cancer patients in the post-operative period³-¹¹. Biochemical parameters such as C-reactive protein (CRP), albumin levels, platelet count, neutrophil-lymphocyte ratios; pre-operative body mass index (BMI), stage of cancer, modified Glasgow Prognostic Score (mGPS); The American Society of Anesthesiologists (ASA) Score, and the age-adjusted Charlson comorbidity index (ACCI) which evaluate comorbidities, and sarcopenia scores, which assesses muscle quality, are the most used methods for the evaluation of mortality and morbidity. With the prediction and early diagnosis of complications, their treatment can be carried out in a shorter time. Thus, patients can be referred to adjuvant therapy right on time. And as a result, overall survival gets positively affected.

Sarcopenia is a syndrome that can lead to negative consequences such as physical disability, poor quality of life, and mortality due to the progressive loss of skeletal muscle mass and strength. It was first described by Rosenberg¹², and is usually prominent in the elderly and cancer patients. The easiest way to detect sarcopenia is through radiological methods. For this, the most frequently used muscle groups are the psoas muscle and abdominal wall muscles such as transversus abdominis, internal and external oblique muscles, and rectus abdominis. Skeletal muscle area in single-section images correlates well with total muscle volume, and an idea of the whole muscle mass can be obtained from these measurements¹³. In recent years, this method has been used more than others in evaluating morbidity, especially in cancer patients.

In our study, we aimed to determine the factors that predict early mortality and morbidity in patients who underwent laparoscopic right hemicolectomy and their superiority over each other. We aimed to evaluate stage of disease, obesity status, ASA score, ACCI, mGPS, and sarcopenia as predictive variables. Our primary outcome is to evaluate the relationship between our variables and complications and mortality. Our secondary outcome, on the other hand, is the analysis of our variables and other short-term results such as length of stay, operation time, and estimated blood loss.

Materials and methods

Our study was planned retrospectively in our institute´s surgical oncology department. The data of the patients were searched using the electronic patient file system of the hospital. Approval was obtained from our university´s ethics committee. Stages I, II, and III patients who underwent elective laparoscopic right hemicolectomy due to colon cancer between March 2010 and September 2022 were included in the study. Patients whose data could not be accessed and who underwent an additional surgical procedure and palliative surgery were excluded from the study. A total of 78 patients were included in the study after screening (Fig. 1).

Figure 1 Flow diagram of exclusion criteria. 

Demographic data of the patients such as age, gender, height, and weight, operative information such as tumor localization, type of surgery, operation time, estimated blood loss, and pathological results such as tumor diameter, tumor type, tumor progressions, lymph node involvement were evaluated in the study. CRP and albumin levels from biochemical data, as well as the comorbidity status of the patients, were recorded to be analyzed in our study. During the follow-up period, length of stay, complications, and mortality were assessed. The formula of dividing the weight (kg) by the square of the height (m²) was used when calculating the BMI of the patients. Obese patients were identified according to the obesity classification of the World Health Organization¹⁴. Stages were determined by the TNM staging specified in the eighth edition of the American Joint Committee on Cancer (AJCC)¹⁵. Stage I cancers were included in early-stage cancers, and Stages II and III cancers were included in advanced cancers. Comorbidities were scored according to ACCI¹⁶. The total score is the sum of the weighted scores for all variables. ACCI was assessed for all patients at baseline and patients were divided into three groups according to ACCI: 0-2, 3-4, and ≥ 5. One of the pre-operative indicators of systemic inflammation of the patients, mGPS, a measurement based on pre-operative serum albumin and CRP levels, was recorded. The calculation was made with the data in the last month before the operation. Patients with a CRP level of 10 mg/dl or less were determined as mGPS 0, those with a CRP level above 10 were determined as mGPS 1, and those with an albumin level above 35 g/L were determined as mGPS 2. mGPS 0 is low score and shows good prognosis, mGPS 1 is moderate and shows moderate prognosis, and mGPS 2 shows poor prognosis¹⁷. Complications were classified according to the Clavien-Dindo Classification¹⁸. Clavien-Dindo ≥ 3 was considered a major complication. Others were included in the mild complication category.

For the assessment of sarcopenia, the previously described scoring over psoas muscle volume was calculated¹⁹. If the patient had a contrast-enhanced computed tomography (CT) taken within the last month, it was included in the study. Sarcopenia calculations were made by a specialist radiologist using the picture archiving and communication system. No information was given to the radiologist about the patients. L3 vertebrae were detected in the axial section, and the right and left psoas muscle areas were measured from the upper border of the vertebrae in square centimeters (cm²) by freehand drawing method (Fig. 2). The first of these methods is the total psoas index (TPI). The total psoas area is used as a representation of total body muscle mass in the calculation²⁰. The TPA values obtained by the sum of the right psoas area and the left psoas area were divided by the square meter (m²) of the patient’s height and normalized according to the patients, and TPI was obtained. Another method is the Hounsfield Unit average calculation (HUAC). This method also measures the Hounsfield Unit (HU) values of the areas and the muscle density and in a way gives an idea about the quality of the muscle. While this value is low in muscles with more adipose tissue, HU values are higher in psoas muscles that are richer than muscle²¹. {[(Right psoas mean HU * Right psoas area)/TPA] + [(Left psoas mean HU * Left psoas area)/TPA]}/2 formula is used in the calculation²². For both genders, patients in the last quartile of calculated TPI and HUAC values were considered sarcopenic. Patients who were considered sarcopenic at either TPI or HUAC were considered sarcopenic in total.

Figure 2 Psoas area calculation by freehand drawing method. 

Results

78 patients were included in the study. The median age was 63. 37 (47.4%) of the patients were female. The demographic features of the patients are summarized in table 1. The median TPI value was 4.37 (3.24-5.11) in women and 4.84 (3.75-5.50) in men. The median HUAC value was 23.45 (20.94-27.23) in women and 25.01 (22.22-27.71) in men. No significant difference was found between the two genders for both parameters (p = 0.123, p = 403, respectively). According to TPI or HUAC, 35 (44.9%) patients were defined as sarcopenic. The patient outcomes are listed in table 2 based on sarcopenia status.

Discussion

Colorectal cancer-related mortality rates are gradually decreasing in the United States and many western countries²³. Early detection of the disease with screening programs, improved surgical techniques, and neoadjuvant and adjuvant treatments have significantly increased the survival time. However, mortality rates continue to increase, especially in Eastern Europe, and central and South American countries²⁴. Surgical resection is the only known curative treatment for colorectal cancer, which is still a major problem all over the world. Surgical resection, on the other hand, is not innocent. Mortality and complications may develop after colorectal cancer surgery, as in any surgery. While morbidity rates can reach up to 35% in colorectal cancer surgery, mortality rates have been reported between 1% and 16.4%²⁵. Predicting who may develop complications and recognizing and treating them earlier may positively affect survival outcomes.

Sarcopenia differs from cachexia, which is characterized by decreased BMI and weight loss in cancer patients and indicates muscle mass loss²⁶. It is an early diagnostic component and an indicator of nutritional status²⁷. Sarcopenia can also be observed in obese patients, as it is an indicator of muscle mass loss, not weight loss. Sarcopenia is very common in gastrointestinal system malignancies, as in many cancer types²⁸. The relationship between sarcopenia and oncological and clinical outcomes has been demonstrated in the previous studies²⁹-³². As reported, sarcopenia is associated with a prolonged length of stay, increased mortality, and complication rates³³. There are many studies that include negative medical results between colorectal cancers and sarcopenia³⁴-³⁶.

Another parameter used prognostically like sarcopenia is mGPS. It was first used by Forrest et al. to predict the prognosis of inoperable lung cancer³⁷. Although the ratio was used in the beginning, it was later modified and grouped¹⁷. Among the hemogram parameters, lymphocytes, monocytes, neutrophils, platelets, and red cell distribution width (RDW) and their ratios to each other are generally related to increased inflammatory processes. However, increased levels of CRP, which is itself an inflammatory marker, in the pre-operative period reflects an ongoing inflammatory reaction. It plays a role in the impairment of immune functions. Hypoalbuminemia is the indicator of impaired nutritional status and susceptibility to infection due to cancer. mGPS, calculated by the ratio of CRP and albumin level, is mostly preferred to predict long-term oncological outcomes and overall survival. However, in recent years, it has been reported that it may be associated with poor prognosis in the early postoperative period after colorectal cancer surgery³⁸.

In our analysis, we observed that sarcopenia, which we obtained from the measurements we made on the psoas muscle, was associated with complications. Early general complications are more common in sarcopenic patients. In addition, major complications were observed to be more frequent in sarcopenic patients. There was also an increased overall complication rate in sarcopenic patients in the multivariate analysis performed after adjusting for age, gender, ACCI, stage of disease, and mGPS. Therefore, care should be taken in terms of complications in laparoscopic right hemicolectomy operations to be performed in sarcopenic patients. However, sarcopenia has not been shown to influence predicting mortality. Instead of sarcopenia, mGPS should be used to evaluate mortality. mGPS is statistically significant in predicting mortality. There is an increased risk of mortality in patients with a high mGPS. While sarcopenia was superior in predicting complications, mGPS was found to be superior in predicting mortality.

No statistically significant relationship could be found between the stage of disease, obesity status, ACCI and ASA score, and complication and mortality, among the methods used in the literature for the evaluation of short and long-term outcomes. As is known, TNM staging is calculated by the extent of the tumor in the colon wall and lymph node, and the distant metastasis status. It is known that the long-term results of the disease are directly related to overall survival. We included Stages I, II, and III patients in our study. We found that staging was not associated with 30-day complications and mortality in our analysis. Another variable that we evaluated was obesity. In a study evaluating the relationship between long-term outcomes of colorectal cancer and BMI, no significant relationship was found between oncologic outcomes and BMI³. Since we know that cancer patients can be sarcopenic without being cachectic, we wanted to evaluate the obesity status in our study. However, we have seen that there is no relationship between short-term results and obesity status. Two of the calculations made with the comorbidities of the patients are the ASA score and ACCI. The ASA score is basically a scoring system used by anesthesiologists to determine surgical risk. ACCI, on the other hand, is a frequently used index in the literature to identify and classify comorbidities. Anemia, type 2 diabetes, hyperlipidemia, coronary artery disease, asthma, and chronic obstructive pulmonary diseases constituted most of the comorbidities in the patients included in the study. Wound healing could be impaired due to these diseases, and anastomotic leakage could increase. As a result, we would expect higher complication and mortality rates in those patients. However, we did not observe a relationship between ASA score and ACCI, which indicate comorbidity, and short-term results. We think that this is due to the fact that ASA score and ACCI are used for different purposes. Grouping and evaluating comorbidities as comorbidities that impair wound healing and those that do not impair wound healing, perhaps, would have enabled us to achieve more meaningful results. But this time, we would have evaluated the postoperative complications only on the basis of wound healing. Not evaluating cardiac, pulmonary, and all other complications would have been biased.

The secondary outcome of our study was to analyze our variables in terms of short-term outcomes other than complication and mortality. Cancer stage, obesity status, ASA score, and ACCI cannot be used predictively in the estimation of complications and mortality, as well as in the estimation of hospitalization time, operation time, and estimated blood loss. The relationship between sarcopenia, which is statistically significant in predicting complications, and mGPS, which we used to predict mortality, was first evaluated. Patients with a low mGPS and good prognosis have shorter hospital stays. In the study conducted by Xu et al., it was reported that mGPS could be used to predict long-term outcomes in colorectal cancers³⁹. We aimed to evaluate short-term outcomes in colorectal malignancies. We have demonstrated that mGPS can be used to predict mortality and hospital stay. Again, in the literature, it has been shown that mGPS is associated with the length of stay of colorectal cancer patients⁴⁰. When the relationship between sarcopenia and length of stay was evaluated, we observed that although it was not statistically significant, sarcopenic patients had a longer hospital stay.

As far as we know, it has not been evaluated before in the literature whether muscle loss, nutrition and inflammatory conditions of colorectal cancer patients will affect the operation time and intraoperative blood loss. Although van Wijk et al. previously reported that prolonged operation time is a risk factor for the development of sarcopenia⁴¹, we aimed to evaluate the opposite of this situation in our study. However, we did not show both the sarcopenia status and the statistical relationship of mGPS with the operation time. Likewise, there was no correlation between estimated blood loss and mGPS and sarcopenia status.

There were some limitations of our study. Firstly, our study is a single-centered retrospective study. For better results, multicentric, randomized controlled trials could be preferred. In our study, only mGPS, which contains CRP, was evaluated among the inflammatory parameters. CRP alone and other parameters used in the hemogram were not included in our study. We aimed to evaluate different parameters since there were many studies of this kind in the literature before. Another shortcoming is that only laparoscopic right hemicolectomy patients were included in the study. Our study does not provide any information about other colon and rectal cancer patients. In determining our patient group in this way, we aimed to include patients who were treated more homogeneously and with standard treatment. However, this resulted in a low number of patients, and we may have caused selection bias. In addition, 36 patients who underwent laparoscopic right hemicolectomy and met other inclusion criteria, but whose data could not be reached, were excluded from the study. In this context, further studies with larger volumes will be needed. Finally, only short-term results were discussed in our study. Since the majority of our patients consist of surgeries we have performed in recent years, long-term results can be evaluated in the later stages as long-term follow-up is completed.

Our study is illuminating in terms of predicting short-term outcomes after laparoscopic surgery in right colon cancers. It is a study in which multiple different variables such as stage of disease, obesity status, sarcopenia status, mGPS, ASA score, and ACCI are evaluated together, and short-term results are investigated. In this respect, it appears in the literature as a pioneering study. Our study has shown that the mGPS and sarcopenia can be used to estimate complications and mortality. Again, to the best of our knowledge, this is a rare study that evaluates the estimation of operative time and estimated blood loss from short-term outcomes for colon cancers. We believe that it will contribute positively to the literature with these aspects. These are the positive aspects of our work.

Conclusion

Sarcopenia status and mGPS are superior to other methods in predicting early outcomes. Sarcopenia can be used in the development of complications, and the mGPS can be used to predict mortality. While increased complications are observed in sarcopenic patients, mortality is higher in patients with high mGPS. However, randomized controlled studies are needed to obtain more reliable results and to eliminate the question marks.