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Research ArticleOpen Access

Examination of Etiology and Laboratory Data in Involuntary Weight Loss: Does Prognostic Nutritional Index (PNI) Predict Malignancy? Volume 50- Issue 3

Mercan Tastemur1*, Cagla Ozdemir2, Seyma Tastemur3, Sanem Kayhan4 and Ibrahim Akdag4

  • 11University of Medical Sciences, Ministry of Health, Ankara City Hospital, Department of Geriatrics, Turkey
  • 22Ministry of Health, Kutahya Local Health Authority, Turkey
  • 33Ministry of Health, Sivas Numune Hospital, Turkey
  • 44Diskapi Yildirim Beyazit Research and Training Hospital, Turkey

Received: May 04, 2023;   Published: May 17, 2023

*Corresponding author: Mercan Tastemur, Geriatric Assistant, University of Medical Sciences, Ministry of Health, Ankara City Hospital, Department of Geriatrics, Ankara, Turkey

DOI: 10.26717/BJSTR.2023.50.007954

Abstract PDF

ABSTRACT

Background: Many examinations are performed to elucidate the etiology of involuntary weight loss and it is important not to miss any type of malignancy. In this study, we aimed to investigate the guiding feature of prognostic nutritional index (PNI) as a simple marker in determining the etiology of weight loss.

Methodology: 121 patients who were admitted to the internal medicine clinic due to their weight loss and hospitalized to investigate the etiology, were included in the study. “Multivariant Analysis” and “ROC Analysis” were performed to determine the factors affecting weight loss. The determining effect of PNI on etiology was evaluated.

Results: In 121 patients with weight loss, malignancy was detected in 30.5% of the etiology, while 69.5% of patients had chronic diseases or infectious diseases. PNI was found to be determinant in predicting malignancy (AUC: 741; 95% Cl 0.770-0.930; p <0.001). PNI optimal cut-off value for malignant diseases was determined as 33 (86% sensitivity, 50% specificity; youden index: 0.3642).

Conclusion: PNI is thought to be the guide in predicting malignancy in the etiology and in the examination plan in patients presenting with involuntary weight loss. In our study, low PNI was found to be an independent risk factor for malignancy.

Keywords: Involuntary Weight Loss; Malignancy; PNI

Abbreviations: ALP: Alkaline Phosphatase; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; CBC: Complete Blood Count; CRP: C- Reactive Protein; ESR: Erythrocyte Sedimentation Rate; FOBT: Fecal Occult Blood Test; HbA1C: Hemoglobin A1C; HCV: Hepatitis C Virus; HIV: Human Immunodeficiency Virus; LDH: Lactate Dehydrogenase; MPV: Mean Platelet Volume; N/L: Neutrophil / Lymphocyte; PNI: Prognostic Nutritional Index; TSH: Thyroid Stimulating Hormone; WBC: White Blood Cell

Background

Involuntary weight loss is defined as the loss of more than 5% of the body weight within 6-12 months, without the treatment of a chronic disease or not as a known result of a disease. It is associated with increased mortality rates, healthcare costs and workload [1-3].

There are many reasons for weight loss, but whein it is involuntary, it often indicates serious physiological or psychiatric disorders. Various studies investigating the causes of involuntary weight loss have revealed that malignancy is the most common cause and is found in 15% to 37% of patients. While non-malignant causes include gastrointestinal causes (15-37%), psychiatric disorders (10-23%), no cause can be found in 25% of them [4]. Given the broad differential diagnosis of involuntary weight loss, there is no single diagnostic approach for all patients. After the history and physical examination to reveal a possible diagnosis, basic laboratory examinations are performed.

Tests should include; electrolytes, glucose, hemoglobin A1C (HbA1C), calcium, kidney and liver function tests, thyroid stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), complete blood count (CBC), C-reactive protein (CRP), urinalysis, fecal occult blood test (FOBT), human immunodeficiency virus (HIV) and hepatitis C virüs (HCV) serology in risky patients and chest radiography, and age-appropriate cancer screening in patients with additional risk factors. Further evaluation should be based on the results of these initial tests. If no abnormality is detected at the initial assessment, the patient can be re-evaluated within one to six months [5,6]. When no reason is found, patients are followed up at frequent intervals. The important point here is that a life-threatening cause such as cancer is not missed [7].

Therefore, it is important to determine the parameters that can predict malignancy. Old age factor, presence of anemia, and high levels of ESR may be useful in demonstrating the association of involuntary weight loss with malignancy. In the presence of anemia and high ESR, the probability of involuntary weight loss due to malignancy is 64% in patients over 62 years of age, while the probability of malignancy in patients under 63 years of age is 9% in the presence of normal levels of hemoglobin and ESR. Various prediction scores have been developed that can predict malignancy in involuntary weight loss. One of them is the Hernandez Score. Independent predictive factors for malignancy in this scoring include being over 80 years of age, high alkaline phosphatase (ALP), lactate dehydrogenase (LDH), white blood cell (WBC) and low albumin levels [8,9].

PNI is a simple and comprehensive index that shows immunological and nutritional status calculated according to serum albumin levels and peripheral lymphocyte count. Albumin levels are affected by nutrition, kidney and liver function. Lymphocytes, on the other hand, provide insight into inflammatory and immune system activation [10]. PNI was first used by Buzby et al. in 1980, to evaluate the prognosis of patients undergoing gastrointestinal surgeryIt was revised by Onodera in 1984 [11]. It has also been used to predict prognosis in various malignancies, pulmonary embolism and cardiac diseases [12]. It has been shown to be associated with prognosis in many cancers such as esophagus, prostate, kidney, breast, lung, and colorectal. Numerous studies have been conducted that reveal its relationship with cardiac diseases. PNI is an effective indicator for evaluating the nutritional and immunological conditions of patients with cancer [13]. Albumin and CBC tests are required for every patient with involuntary weight loss. In this study, we aimed to demonstrate the role of PNI as a simple index in predicting malignancy in the etiology of involuntary weight loss.

Patients and Methods

Files of 4554 patients hospitalized in Ankara Dışkapı Yıldırım Beyazıt Training and Research Hospital Internal Medicine Clinic between January 2015 and June 2020, were retrospectively analyzed. 121 patients who applied to the internal medicine outpatient clinic with a complaint of weight loss and were hospitalized to investigate the etiology were included in the study. Patients aged 18 and over, who had an involuntary weight loss of more than 5% in the last 6-12 months were included in the study. The diagnosis of involuntary weight loss was made according to the diagnostic criteria. Weight loss was determined by the presence of 5% loss in those whose previous weight was known in the last 6-12 months, while in those whose weight could not be documented, it was confirmed by the abundance of clothes and belts or by confirmation from relatives [1,14,15].

Those who were under 18 years of age, who had voluntary weight loss, patients with a previously known diagnosis of malignancy, those who lost weight due to use of certain drugs, and those who did not want to participate in the study were excluded. Sociodemographic data and laboratory parameters of the patients were obtained by examining the files and system data of the patients. Patients with involuntary weight loss were divided into two groups as malignant and non-malignant groups, according to the etiological reasons. The non-malignant group consisted of endocrine, gastrointestinal, cardiopulmonary and infectious causes. The age and gender information of the patients were recorded. WBC counts, mean platelet volume (MPV), alanine aminotransferase (ALT), aspartate aminotransferase (AST), ESR, albumin, calcium, magnesium, phosphorus, CRP, vitamin D, Ferritin, LDH, uric acid levels were determined by laboratory tests.

Neutrophil / lymphocyte (N/L) ratio and PNI values were calculated. PNI was calculated using the following formula.

[11]. Sociodemographic and laboratory data of 121 patients were analyzed between malignant and nonmalignant two groups. Our study was approved by the Clinical Research Ethics Committee of University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital (Date:03.02.2020, Decision:81/13). The research was carried out in accordance with the Helsinki Declaration.

Statistical Analysis

Statistical analysis was performed using the SPSS version 21.0 (IBM®, Chicago, USA) package program. The conformity of the variables to the normal distribution was examined by using visual (histogram and probability charts) and analytical methods (Shapiro-Wilk test). Descriptive statistics were expressed as mean and standard deviation in normally distributed numerical data, and as number and percentage in nominal data. Normally distributed numerical variables were compared between two groups with the “Independent Samples T test” and between three groups with the “One way ANOVA test”. Numerical variables that did not show normal distribution were compared using the “Mann Whitney U test” between two groups and the “Kruskal Wallis test” between three groups. “Multivariant analysis” and “ROC analysis” were used to determine the factors affecting weight loss. In the statistical analyzes in the study, comparisons with a p value of less than 0.05 were considered statistically significant.

Results

121 patients with involuntary weight loss were included in the study. The mean age of all patients was 61.5 ± 14.3 years, 68.4 years for the malignant group and 58.4 years for the non-malignant group. Average weight loss was 10.5 (4-30) kg. While age, WBC count, platelet count, N/L ratio, CRP, ESR, ferritin, LDH, uric acid were higher; hemoglobin, albumin, vitamin D and PNI values were lower in the group with malignancy. These values were higher in the non-malignant group. The difference between the two groups in terms of laboratory data was statistically significant (p <0.05). The comparison of laboratory values between groups is given in (Table 1). In 121 patients with involuntary weight loss, malignancy was detected at a rate of 30.5%, and chronic diseases and infectious diseases were found at a rate of 69.5%. The most common malignancy was originating from the gastrointestinal system (3.6%). In the non-malignant disease group, the most common cause were endocrine system diseases (55%). Involuntary weight loss reasons are summarized in (Table 2). In the multivariant analysis, low PNI was found to be an independent risk factor for malignancy (OR: 1.196; 95% CI: 1.091-1.312; p <0.001) (Table 3). Other factors were age and LDH (p <0.05). PNI was found to be determinative for malignancy (AUC: 741; 95% Cl 0.770-0.930; p <0.001). The optimal cut-off value for malignant diseases was determined as 33 (86% sensitivity, 50% specificity; youden index: 0.3642) (Figure 1).

Table 1: Distribution of sociodemographic characteristics and laboratory parameters by malignancy.

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Note:

a) † İndependent Samples T-test.

b) †† Mann-Whitney U test.

Table 2: Causes of involuntary weight loss in 121 patients.

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Table 3: Regression analysis of determinants in malignity prediction.

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Note: Binary logistic regression.

Figure 1 Receiver-operating characteristic curves of PNI for malignant diseases.

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Discussion

Various factors have been proposed to predict malignancy in patients with involuntary weight loss. In fact, various scoring systems have been developed. However, more sensitive markers are needed for a predictive scoring based on the relationship between weight loss and malignancy. For this purpose, we aimed to evaluate the PNI value, which is the combination of nutrition and inflammation markers, in our study. In the literature, there is no study evaluating PNI in patients with involuntary weight loss. Our study is important in that it is the first study on this subject. Involuntary weight loss is a health problem that requires a large number of diagnostic tests, as it does not have a standardized guide. This situation causes increased workload and healthcare costs. The most important point here is that malignancy should not be ignored as an etiological cause. In our study for this purpose, we think that PNI is a guide as a simple marker in predicting malignancy in etiology.

There are many studies evaluating PNI in many cancers such as lymphoma, glioblastoma, stomach, colon and pancreas carcinomas. In a study by Xiao et al. comparing the B-cell lymphoma group and the healthy control group, they found that the PNI value in the lymphoma group was significantly lower than the healthy control group [16]. In a study by Karşıyakalı et al., it shows that PNI is a potential preoperative predictor of tumor and an independent risk factor for predicting tumor stage in patients with primary bladder cancer. Low PNI levels were found to be associated with high-stage disease [17]. In the study conducted by Xing-Wang Zhou et al. it was found that PNI> 44.4 is an independent prognostic parameter in evaluating the overall survival and the efficacy of adjuvant therapy in patients with glioblastoma [18]. Lower preoperative PNI values were significantly associated with more tumor growth, lymph node metastasis, lymphatic permeation and venous invasion in patients with gastric carcinoma. In addition, PNI value has been proven to be an independent prognostic indicator in gastric carcinoma [19]. In the meta-analysis in which Kaiyu Sun et al. examined the prognostic significance of PNI in cancer: fourteen studies with a total of 3,414 participants were analyzed. Low PNI has been associated with poor overall survival in cancer patients and the presence of postoperative complications. PNI has also been found to be associated with the depth of invasion and lymph node metastasis in gastric cancer [20].

In conclusion, PNI has been evaluated as a prognostic factor in many studies, especially in malignancies. In our study designed based on these studies, we evaluated PNI as a simple marker in predicting malignancy in the etiology of involuntary weight loss. We identified it as an independent predictive factor in patients with malignancies. We found the cut-off value of 33 in malignant patients. Various scoring systems have been developed to predict malignancy in the etiology of involuntary weight loss. Many laboratory parameters have been analyzed to reveal which of these are guiding. LDH, ESR, CRP, albumin and ALP are the most emphasized values. In cancer cachexia, there is no reduction in energy expenditure despite reduced calorie intake. There is a hypermetabolic condition characterized by an increase in biochemical processes such as gluconeogenesis, protein degradation, and lipolysis [21]. Therefore, laboratory parameters can be guiding.

In a study conducted by Metadilis et al. in which 101 patients with involuntary weight loss were evaluated, they showed that the possibility of malignancy is low, if physical examination and laboratory values such as CBC, CRP, AST, ALT are normal. On the other hand, in all 22 patients diagnosed with malignancy; an abnormality was found in at least one of the ALP, LDH albumin, ferritin tests, chest radiograph and abdominal ultrasound [22]. It has been shown that energy expenditure increases at rest in patients with lung cancer and is associated with higher CRP levels [23]. In our study, we found that these laboratory parameters were associated with malignancy, which supports the literature data [22,23]. Albumin was lower in malignant patients but was not detected as a predictive factor in multivariant analysis.

In the study by Xavier Bosch et al. in examined 2677 patients with involuntary weight loss, 37% non-malignant, 33% malignant and 16% psychosocial causes were found in the etiology. 14In our study, we found the most common non-malignant causes with a rate of 69.5% and malignant causes at a rate of 30.5%, in accordance with the literature. Unlike the literature, the most common non-malignant causes consist of endocrinological issues such as newly diagnosed diabetes, diabetes with irregular blood sugar and thyroid dysfunction [4,15]. Our main limitations were that our study was retrospective, the number of patients was small and it was a single-center study. In terms of revealing the factors that will enable us to predict malignancy in patients with involuntary weight loss, PNI can be a guide as a simple and inexpensive method that does not increase the cost and workload. In this study, we aimed to shed light on new studies in terms of usability in new scoring system. However, we think that prospective and multi-center studies are needed with larger patient groups.

Conclusion

PNI is an easily accessible and easily calculated parameter that has been used to predict prognosis in many diseases. In our study, we determined that this simple index is an independent predictor factor for malignancy in the etiology of involuntary weight loss. This simple test can save time, workload and healthcare costs to elucidate the etiology of involuntary weight loss, diagnose or rule out malignancy, one of the most important causes in the etiology.

Declarations

Availability of Data and Materials

All data are freely available for scientific purpose.

Competing Interests

The authors declare that they have no competing interests.

Funding

No funding sources for research.

Author Contributions

MT contributed to the conception, design of the work and the acquisition, analysis, interpretation of data, and the drafting and revision of the work, and final approval of the work. All authors had the data access and contributed to the article. Ethical Conduct of Research: Our study was approved by the Clinical Research Ethics Committee of University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital (Date:03.02.2020, Decision:81/13). The research was carried out in accordance with the Helsinki Declaration.

References

  1. Wong C J (2014) İnvolantary weight loss. Med Clin North Am 98(3): 625-643.
  2. Gaddey H L, Holder K (2014) Unintentional weight loss in older adults. Am Fam Physician 89(9): 718-722.
  3. Alibhai S M H, Greenwood C, Payette H (2005) An approach to the management of unintentional weight loss in elderly people. Can Med Assoc J 172(6): 773-780.
  4. Lankisch P, Gerzmann M, Gerzmann J F, Lehnick D (2001) Unintentional weight loss: diagnosis and prognosis. The first prospective follow-up study from a secondary referral centre. J Intern Med 249(1): 41-46.
  5. Bouras E P, Lange S M, Scolapio J S (2001) Rational approach to patients with unintentional weight loss. Mayo Clin Proc 76(9): 923-929.
  6. Vanderschueren S, Geens E, Knockaert D, Bobbaers H (2005) The diagnostic spectrum of unintentional weight loss. Eur J İntern Med 16(3): 160-164.
  7. Baicus C, Rimbas M, Baicus A, Caraiola S (2014) Cancer and involuntary weight loss: failure to validate a prediction score. Plos One 9(4): e95286.
  8. Baicus C, Ionescu R, Tanasescu C (2006) Does this patient have cancer? The assessment of age, anemia, and erythrocyte sedimentation rate in cancer as a cause of weight loss. A retrospective study based on a secondary care university hospital in Romania. Eur J Intern Med 17(1): 28-31.
  9. Hernández J L, Matorras P, Riancho J A, González Macías J (2003) Involuntary weight loss without specific symptoms: a clinical prediction score for malignant neoplasm. QJM 96(9): 649-655.
  10. Candeloro M, Di Nisio M, Balducci M, Genova S, Valeriani E, et al. (2020) Prognostic nutritional index in elderly patients hospitalized for acute heart failure. ESC Heart Fail 7(5): 2479-2484.
  11. T Onodera, N Goseki, G Kosaki (1984) Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi 85(9): 1001-1005.
  12. Mullen J L, Buzby G P, Matthews D C, Smale B F, Rosato E F (1980) Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support.Ann Surg 192(5): 604-613.
  13. Cheng Y L, Sung S H, Cheng H M, Hsu P F, Guo C Y, et al. (2017) Prognostic Nutritional Index and the Risk of Mortality in Patients With Acute Heart Failure. J Am Heart Assoc 6(6): e004876.
  14. Marton K I, Sox H C Jr, Krupp J R (1981) Involuntary weight loss: diagnostic and prognostic significance. Ann Intern Med 95(5): 568-574.
  15. Bosch X, Monclús E, Escoda O, Guerra García M, Moreno P, et al. (2017) Unintentional weight loss: Clinical characteristics and outcomes in a prospective cohort of 2677 patients. PLoS One 12(4): e0175125.
  16. Xiao L, Xiao S, Fan Z (2020) Clinical significance of prognostic nutritional index in predicting the efficacy in patients with B-cell lymphoma. Zhong Nan Da Xue Xue Bao Yi Xue Ban 45(2): 139-143.
  17. Karsiyakali N, Karabay E, Yucetas U (2020) Predictive value of prognostic nutritional index on tumor stage in patients with primary bladder cancer. Arch Esp Urol 73(2): 132-139.
  18. Zhou X W, Dong H, Yang Y, Luo J W, Wang X, et al. (2016) Significance of the prognostic nutritional index in patients with glioblastoma: A retrospective study.Clin Neurol Neurosurg 151: 86-91.
  19. Nozoe T, Ninomiya M, Maeda T, Matsukuma A, Nakashima H (2010) Prognostic nutritional index: a tool to predict the biological aggressiveness of gastric carcinoma. Surg Today 40(5): 440-443.
  20. Sun K, Chen S, Xu J, Li G, He Y (2014) The prognostic significance of the prognostic nutritional index in cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 140(9): 1537-1549.
  21. Fearon K C H, Glass D J, Guttridge D C (2012) Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab 16(2): 153-166.
  22. Metalidis C, Knockaert D C, Bobbaers H, Vanderschueren S (2008) Involuntary WEİGHT LOS. Does a negative baseline evalution provide adequate reassurance? Eur J Intern Med 19(5): 345-349.
  23. Staal van den Brekel A J, Schols A M, ten Velde G P, Buurman W A, Wouters E F (1994) Analysis of the energy balance in lung cancer patients. Cancer Res 54(24): 6430-6433.