ROLE OF GLUTAMINE SUPPLEMENTATION ON IMPROVING THE NUTRITIONAL, FUNCTIONAL AND IMMUNOLOGICAL STATUS OF MALIGNANT OBSTRUCTIVE JAUNDICE PATIENTS AT A TERTIARY CARE CENTRE.

Gp. A mean BMI was 16.32+2.64 on admission and 16.37+3.42 on 42 nd day. In Gp.B mean BMI on admission was 18.15+1.27 which improved to 21.35+2.53 on 42 nd day.In Gp.A mean Karnofsky score was 55.60+20.02 on admission and 21.20+25.71 on 42 nd day.In Gp.B mean Karnofsky score on admission was 60.00+19.58 and 24.00+33.54 on 42 nd day.The mean IL-2 Level in Gp.A was 13.93+26.80 pg/ml on admission and 81.30+79.46 pg/ml on 42 nd day.The mean IL-2 Level in Gp.B was 9.07+26.93 pg/ml on admission which reduced to 8.27+15.21 pg/ml on 42 nd day.IL-6 Level in Gp.A was 79.43+96.83pg/ml on admission and173.10+217.94pg/ml on 42 nd day.IL-6 Level in Gp.B was 390.06+345.22 pg/ml on admission which reduced to 230.71+201.65pg/ml on 42 nd day.TNF- α Level in Gp.A was 59.53+ 56.63pg/ml on admission and 202.30+224.84pg/ml on 42 nd day. TNF- α Level in Gp.B was 95.33+ 72.21 pg/ml on admission which reduced to 67.80+52.35pg/ml on 42 nd day. Conclusion: Glutamine supplementation helps in improving the Nutritional status and reducing mortality of MOJ patients.


INTRODUCTION
Gallbladder cancer is the most common malignancy of the biliary tract. Women are affected three times more commonly than men, and the vast majority patients stricken with this disease are older than 40 years of age. Among the highest incidences in the world are in women from Chile (27/100,000), Poland IJBR 2 [3] [2011]213-221 www.ijbr.ssjournals.com (14/100,000), India (10/100,000), Japan (7/100,000), and Israel (5/100,000).Other high-risk areas include parts of Pakistan,Korea, Slovakia, Spain, Ecuador, and Colombia. 5 Patients with unresectable or metastatic GBC have a poor prognosis. [1] Due to its non specific clinical presentation, it is seldom diagnosed preoperatively except in advanced cases. 9 Cancer epidemiology articles often point out that cancer rates tend to be higher among males than females yet rarely is this theme the subject of investigation. 3 The aetiology of carcinoma gall bladder is poorly understood. Chronic cholecystitis and gallstones, choledochal cysts, female gender, age and exposure to carcinogens are some of the factors implicated in the causation of gall bladder cancer but a definite cause -effect relationship has yet to be established for any of these factors. 9 Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness.It plays a central role in nitrogen transport within the body, is a fuel for rapidly dividing cells, such as in the gut and immune system and has many other metabolic functions. Under normal physiological conditions , Glutamine Is synthesised in large amounts by the human body and is therefore considered non-essential. It has been hypothesized that glutamine may become a conditionally essential amino acid in patients with catabolic disease. 11

PATIENTS ELIGIBILITY CRITERIA
Fifty malignant obstructive jaundice patients in which endoscopic drainage was not possible (the obstruction was not negotiable by guide wire) were included in the study. Glutamine Non-

PATIENTS EXCLUSION CRITERIA:
Patients were excluded from the study when they presented with obstructive jaundice with bilirubin concentrations <5mg% and if Patients were unfit for ERCP/ surgery.

STUDY DESIGN
The study was designed so that all patients were attempted an ERCP and stent placement. The patients in which ERCP was not possible were taken in the study. A prospective, randomized, BMI: Was determined by using formula: mass (kg) / (height (m)) 2 .

Statistical Methods
Results are expressed as mean ± SD and proportion, as appropriate. Statistical differences between haematological, chemical, and cytokine data were analysed using the Wilcoxon rank sum test or two sample t-test adjusting for unequal variance, if required. Stata 11.1 was used to analyze the data. A p value <0.05 was considered to be significant.

Discussion
This study analyzed the effect of Glutamine supplementation on nutritional status ,functional status and immunological status of patients with obstruction of the biliary tract.The average age of the patients in Gp.A was was similar to that of patients in Gp. B i.e patients were between 45-60 years of age.In a study , it was observed that majority of patients with obstructive jaundices were in the range of 60 to 69 years old in male and 50 to 59 years in female. 4 In Gp.A, 55.56% patients were females and in Gp.B, 44.44% patients were female which shows that GB carcinoma has a female preponderance. Another study stated that the female-tomale ratio is 3:1. 2 In a study it was found that 44.36% were male and a female to male ratio was 1.25. 4 The average duration of jaundice was since last 125-140 days. A study stated the average duration of jaundice was 1.15 months i.e.45-46 days. 10 9 In a study, it was found that Cholecystolithiasis, is present in 70-90% of patients. 2 The risk of carcinoma gall bladder in patients with gall stones may be increased 4 to 7 times. 13 In another study, association of gall stones with carcinoma gall bladder has been found. 8 Significant difference was found in the improvement in BMI of the supplemented group.A showed that GBC influences the nutritional status of the patients. Fortythree percent of GBC patients were malnourished with low body mass index (BMI). 7 An elevated body mass index and multiparity are also correlated with an increased risk of developing gallbladder cancer. A Norwegian cohort study including over two million people and 1715 cases of gallbladder cancer showed a relative riskdeveloping gallbladder cancer of 2.53 for women aged 20-44 years patients with a body mass index greater than 30. 5 No significant improvement was seen in the functional status of both the group.This might be because of carcinoma being in very advanced stage.The levels S.Bilirubin levels (total), S.Bilirubin levels (direct),SGPT, SGOT and S.Alkaline Phosphatase levels increased on 42 nd day in Gp.A but the levels decreased significantly in the Glutamine supplemented group i.e. Gp.B.In a study, mean serum bilirubin level in patients with obstructive jaundice was 230+110 mmol/L, mean SGPT levels were 172 + 175 IU/L , mean SGOT levels were 205 +188 IU/L and mean S.Alkaline Phosphatase levels were 817+868 IU/L. 12 IL-2 is a cytokine whic is normally produced by the body during an immune response.The levels of IL-2 were increased in Gp.B but were significantly decreased in Gp.A after supplementation. IL-6 is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation.The IL-6 levels were also decreased significantly in the supplemented group than in the nonsupplemented group.TNF -alpha is a IJBR 2 [3] [2011]213-221 www.ijbr.ssjournals.com cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction.Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases, as well as cancer. The TNF-α levels were also decreased significantly in the supplemented group than in the nonsupplemented group. The mean TNF-α and CRP concentrations were significantly lower in the supplemental group than in the control group (P < 0.05), and the increase in TNF-α levels postoperative was significantly lower in the supplemental group than in the control group (41.02 ± 27.56 vs 160.09 ± 35.17, P < 0.05). 6 The mean survival of patients was higher in the Glutamine supplemented group. Patients with GB carcinoma have an overall mean survival rate of 6 months, and the 5-year survival rate is 5%. 2