Total number of cases was 110, all completed the follow up. Systematic analysis of all collected data revealed the following-
A. BASELINE CHARACTERISTICS: Incidence of complicated appendicitis among subjects undergoing appendectomy was found as following-
I) GENDER SPECIFIC:
Out of total 110 subjects of acute appendicitis, enrolled for the study, 66 subjects (60%) were male while the remaining 44 subjects (40%) were female. So, male: female ratio was 1.5:1. Overall occurrence of complicated (gangrenous/perforated on the basis of intra operative as well as histopathology report) appendicitis was 31.8% (35 out of them 15 were males and 20 females) and 68.2%(75 out of them 51 were males and 24 were females) subjects had appendicitis without complications. Complicated appendicitis was more (57.2%) in females than males (42.8%).But 45.45% of all females had complicated appendicitis while among males the rate of complication was 22.72%. 44% males and 25% femles had simple appendicitis while 12% male and 8% females had gangrenous appendicitis. Perforated appendicitis was found in 4% males and 7% females. [Table 1]
II) AGE SPECIFIC:
The overall mean age of all 110 subjects was 23.5 13.5 years (range 5 – 62 years). The mean age for males was 24.34 ± 12.70 years (range 5- 60years) and the mean age for females was 22.29 ±14.84years (range 6-62 years).Majority (almost 83%) of the cases belongs to first two decades (5-19 years) of life. But occurrence rate of complicated appendicitis was more at the extremes of ages. The ratio of complicated appendicitis among all study population were 43.75% (in <10 YRS age group), 70.96% (in 10-19 YRS age group), 25% (in 50-59 Yrs age) and 33% ( in age group more than 60 years).[TABLE 1]
B. RELATIONSHIP OF DIRECT BILIRUBIN AND INDIRECT BILIRUBIN WITH COMPLICATED APPENDICITIS:
Out of 110 subjects of acute appendicitis 41 subjects (37.27%) had hyperbilirubinemia (raised serum total bilirubin level > 1 mg/d).Out of 35 subjects diagnosed as complicated appendicitis 32 subjects (91.42%) had raised total bilirubin levels (> 1.0 mg/dL).while the remaining 03 subjects (8.58%) had normal levels (< 1.0 mg/dl).Among 75 subjects diagnosed as acute simple appendicitis 09 subjects (12%) had raised total bilirubin level (> 1.0 mg/dL), while the remaining 66 subjects (88%) had normal levels (< 1.0 mg/dL).
The mean TOTAL BILIRUBIN LEVEL for all subjects with acute uncomplicated appendicitis was 0.79 ±0.16 mg/dl (range being 0.45 -1.20 mg/dl) and that for complicated appendicitis was 1.39 ± 0.26 mg/dl ( range being 0.68-2.20 mg/dl) value was statistically significant p<0.05.Hence, it was seen that subjects with complicated (perforated/gangrenous) appendicitis had higher level of total bilirubin as compared to that of uncomplicated acute appendicitis.[TABLE 2]
The mean DIRECT BILIRUBIN for uncomplicated appendicitis subjects was 0.43 ± 0.10 mg/dl ( range being 0.20 - 0.70 mg/dl) and that for complicated appendicitis was 0.72 ± 0.13 mg/dl ( range being 0.38-1.10 mg/dl), which was statistically significant (p<0.05) rise of direct bilirubin with occurrence of complicated appendicitis.The mean INDIRECT BILIRUBIN for subjects with uncomplicated appendicitis was 0.36 ± 0.08 mg/dl ( range being 0.16-0.60 mg/dl) and that for complicated appendicitis was 0.66 ± 0.14 mg/dl ( range being 0.30-1.10 mg/dl), which was statistically significant (p<0.05) rise of direct bilirubin with occurrence of complicated appendicitis.
There was significant rise in both components of total bilirubin, direct as well as indirect bilirubin in subjects with complicated appendicitis, so it was Mixed Type Of Hyperbilirubinemia in gangrenous/perforated appendicitis. The sensitivity of Total serum bilirubin in predicting complicated appendicitis was found 91.43% (76.942% to 98.196%),where as the specificity of this test was 88.00%(78.439% to 94.363%). positive predictive value and negative predictive value were 78.03% and 95.65% respectively. Positive likelihood ratio and negative likelihood ratio were found to be 7.619 and 0.097 respectively taking prevalence of Complicated appendicitis be 31.80%.[TABLE 2]
After plotting the True Positive Rate (TPR)/sensitivity of Total Serum Bilirubin level against the False Positive Rate (FPR) of its detection of complicated appendicitis at various threshold settings a ROC (Receiver Operating Characteristic) curve was obtained which shows optimal criterion at Total Bilirubin Level 1.06 mg/dl where sensitivity was 91.43% and specificity was 97.33% at 95% confidence interval with 31.8% disease prevalence.[TABLE 2]
The prevalence of complicated appendicitis was found to be 31.8 % among all cases. So Area under the ROC curve (AUC) was 0.958 [Standard Error 0.0246 , 95% Confidence interval0.902 to 0.987, z statistic 18.614 ,Significance level P (Area=0.5) <0.0001] .[Table 3] shows criterion values and coordinates of the ROC curve. This ROC (Receiver operating characteristic) curve reveals diagnostic ability of Total Serum Biliruin level for complicated appendicitis, after taking into consideration of prevalence of complicated appendicitis among total cases .Optimal criterion was found at total bilirubin level 1.06 mg/dl.
So we can infer that, subjects with clinical features suggestive of appendicitis with higher values of serum total bilirubin, are more susceptible of having complicated appendicitis than those with normal or mildly elevated total bilirubin level.
COMPARISON OF PRE-OPERATIVE AND POST-OPERATIVE DAY 7 TOTAL BILIRUBIN LEVEL:
Serum total bilirubin level was checked in all study subjects irrespective of their final diagnosis on 7th Postoperative day to confirm that the hyperbilirubinemia was due to complicated appendicitis and it comes to normal range after appendectomy.It was seen that mean total bilirubin level was 1.39mg/dl in complicated appendicitis group(n=35) and 0.79mg/dl in uncomplicated appendicitis group. Both the group showed mean serum total bilirubin value 0.69mg/dl on 7th postoperative day. The preoperative mean total bilirubin of all the study subjects was 0.9841mg which came to a mean value of 0.6885mg/dl which was statistically significant(p<0.05).[Table 2]
C. RELATIONSHIP OF OTHER PATIENT RELATED PARAMETERS WITH COMPLICATED APPENDICITIS:
- ALVARADO SCORE:
The mean value for ALVARADO SCORE in Acute uncomplicated Appendicitis was 7.25 ± 0.71 (range 6-9) whereas for complicated appendicitis it is 8.5± 0.77 U/L (range 7-10 p value > 0.05) which is statistically significant. Only 5.33% subjects without complicated appendicitis had MANTRELS SCORE more than mean value for complicated appendicitis cases.So it was concluded that MANTRELS SCORE were significantly high in appendicular gangrenous change/perforation cases ,pre-operatively. And only 23% of all subjects with perforations(n=13)had SCORE below that mean value for complication at presentation. Score above mean value 7.66 had a sensitivity of 94.28% and specificity of 70.66% for complications.[TABLE 4]. Area Under Curve was 0.825 (range 0.741 to 0.891), Positive Likelihood Ratio = 3.214 Negative Likelihood Ratio = 0.081, Positive Predictive Value = 59.980% and Negative Predictive Value = 96.367% at 31.800% complicated appendicitis disease prevalence.
- DURATION OF PAIN:
This study revealed relationship between mean duration of pain and complicated appendicitis among the study population. The mean duration of pain was shorter for subjects with an acute uncomplicated appendicitis (9.0hours±5.12 range 6–12 hours) compared to those with a gangrenous/perforated appendix (20.2±1.49 hours, range 14–36 hours), it reached statistical significance (p<0.05).. The scattered plot diagram shows linear regression relationship between rise of total bilirubin level (0.0396 times) with increase of duration of pain(each hour).[Figure 2 ]
Gender wise distribution of pain duration:
This study showed among 66 men mean duration of pain was 11.78 hours ± 6.1 (range 6-36 hours) while it is 13.75 hours ±5.9( range 6-30 hours) among 44 females.[Figure 2]
40% of subjects with acute uncomplicated appendicitis and 71.42% of subjects with a gangrenous/perforated appendicitis presented with a fever. Statistical analysis revealed significant difference between two groups. And p value was<0.05.The mean temperature in acute uncomplicated appendicitis was 98.02 + 1.30 0F(range 97-100o F) whereas for complicated appendicitis it is 99± 1.49 0F (range 97-101o F ). Rise of temperature above mean value had sensitivity 71.43%( 53.69% to 85.36%) , specificity 60%( 48.04% to 71.15%) ,Positive Likelihood Ratio of 1.78 and Negative Likelihood Ratio of 0.476.[TABLE 5].
- RELATIONSHIP BETWEEN LIVER ENZYMES - ALKALINE PHOSPHATAGE (ALP), ASPARTATE AMINO TRANSFERASE (AST), ALANINE AMINO TRANSFERASE (ALT) AND C REACTIVE PROTEIN (CRP) WITH COMPLICATED APPENDICITIS:
The mean value for ALP in acute uncomplicated appendicitis was 126.04 ± 7.42 U/L (range 112-158 U/L) whereas for complicated appendicitis it was 125.85±5.01 U/L (range 120-146U/L p value > 0.05) which is not statistically significant. So it was concluded that ALP cannot differentiate between uncomplicated appendicitis and appendicular gangrenous change/perforation pre-operatively. And only 22.7% of all subjects (n=110) had MILDLY elevated serum ALP level at presentation.
The mean value for AST in acute uncomplicated appendicitis was 33.70 ± 2.99 U/L (range 26-39 U/L) whereas for complicated appendicitis it was 32.88± 3.38 U/L (range 26-39U/L p value > 0.05) which is not statistically significant. So it was concluded that AST cannot differentiate between uncomplicated appendicitis and appendicular gangrenous change/perforation pre-operatively. None (0%) of all subjects (n=110) had elevated serum AST level at presentation.
The mean value for ALT in acute uncomplicated appendicitis was 33.34 ± 2.71 U/L (range 27-40 U/L) whereas for complicated appendicitis it was 32.77±2.75 U/L (range 28-38U/L p value > 0.05) which is not statistically significant. So it was concluded that ALT cannot differentiate between uncomplicated appendicitis and appendicular gangrenous change/perforation pre-operatively. And only 0.9% of all subjects (n=110) had elevated serum ALT level at presentation.
So, this study showed isolated hyperbilirubinemia without much elevation in the liver enzymes. This isolated occurrence of hyperbilirubinemia was a significant predictor of gangrenous/perforated appendicitis.
90.7 % of all uncomplicated Appendicitis had normal CRP level(<0.6mg/dl) whereas only 14% of complicated appendicitis subjects had normal CRP level. Rest 86% of complicated appendicitis subjects had statistically significant rise of CRP(>0.6mg/dl) which was raised only 9.3% of uncomplicated appendicitis cases. So it was concluded that raised CRP level can differentiate between uncomplicated appendicitis and appendicular gangrenous change/perforation pre-operatively. [TABLE 6]
5. ULTRA SONOGRAPHICAL FINDINGS OF APPENDIX:
I. APPENDIX OUTER DIAMETER ON USG SCAN: The mean outer diameter of appendix of all study population was 7.6 mm. The mean appendix diameter on USG in uncomplicated Appendicitis was 6.64mm ± 0.69 (range 6-8mm) whereas for complicated appendicitis it was 9.71 mm ± 1.27 (range 7-12 mm, p value > 0.05) which was statistically significant. Sensitivity and specificity of increased appendix diameter on USG got sensitivity of 94.28% and specificity of 52.0%,Positive Likelihood Ratio 964, Negative Likelihood Ratio 0.110, Positive Predictive Value 47.805% and Negative Predictive Value 95.126%. [TABLE 7]. Scattered plot diagram showed one unit increase in appendix diameter was associated with 3.6% increase of total bilirubin level. So it was concluded that increased appendix diameter on USG was associated with appendicular gangrenous change/perforation pre-operatively.[Figure 3]
II. 93% of all uncomplicated Appendicitis had clear appendix lumen on USG whereas only 11.4% of complicated appendicitis subjects had clear lumen. Rest 88.6% of complicated appendicitis subjects had appendix lumen obstruction by fecolith, evident on pre-operative USG .But only 6.7% of uncomplicated appendicitis cases had luminal obstruction. So it was concluded that luminal obstruction on USG can predict appendicular gangrenous change/perforation pre-operatively.[TABLE 7]
III. Statistically significant (p<0.05) difference was found while assessing the cases, preoperatively on USG, for peri-appendix collection. No subjects with uncomplicated appendicitis (n=75) had any peri-appendix fluid collection. But among subjects with complicated appendicitis, 77.1% had pri-appendix fluid collection and only 22.9% had no collection as was evident on USG scan.
- MULTIVARIATE REGRESSION ANALYSIS OF DIFFERENT PARAMETERS WITH OCCURRENCE OF HYPERBILIRUBINEMIA:
Analysis of relationship of different patient related factors with occurrence of hyperbilirubinemia was done in this study.[Table 8] According to the analysis non significant variables with occurrence of hyperbilirubinemia are- Age <19 years=1.236(0.264-5.790),Gender-Female=0.462(0.124-1.714),duration of pain<9 hrs=0.955, Liver enzymes(viz. ALP,AST,ALT),C reactive Protein<0.6=1.783, Appendix outer diameter<8mm=1.620.The significant variable was complicated appendicitis=0.01(0.001-0.114).