Clinical judgment and harmonic ultrasonography in the diagnosis of acute appendicitis: Experience with a modified score-aided diagnosis.

Clinical judgment and harmonic ultrasonography in the diagnosis of acute appendicitis:

Experience with a modified score-aided diagnosis.

Ossama M Zakaria,a MD; Tamer A Sultan,b MD

a) Division of Pediatric Surgery, Department of Surgery, Suez Canal University, Egypt.

b) Division of Pediatric Surgery, Department of Surgery, Menoufyia University, Egypt.

Co"espondence: e-mail: ossamaz2004@yahoo.com

Abstract

Background: Appendicitis is the most common surgical emergency in children, yet diagnosis of equivocal presentations continues to challenge clinicians.

Aim: The objective of this study was to investigate the hypothesis  that the use of a modified clinical  practice and harmonic ultrasonographic grading scores (MCPGS)  may improve the accuracy in diagnosing acute appendicitis in the pediatric population.

Patients & methods: Main outcome measures: Sensitivity,  specificity, and accuracy ofthe

modified scoring system. Five hundred and thirty patients presented with suspected diagnosis of acute appendicitis during the period from December 2000 to December 2009 were enrolled in this study. They were classified into 2 equal groups.

Group I (n=265): Included  children who presented with suspected diagnosis of acute

appendicitis. To these children a special clinical practice guideline system (CPGS) incorporating clinical judgment and results of gray scale US was applied),2

Group II (n=265): Included a similar group of children with equivocal diagnosis of acute

appendicitis (AA), to whom a modified clinical practice guideline system (MCPGS) was applied.

Statistical analyses were carried out using Z test for comparing 2 sample proportions and student's t-test to compare the two quantitative data in both groups.Sensitivity and specificity for the 2 scoring systems were calculated using Epi-Info software.

Results: The Number of appendectomies declined from 200 (75.5%) in group I to 187 (70.6%)

in group II (P>0.05).

Specificity was significantly  higher when applying MCPGS (90.69%) in group II compared to 70.47% in group I when CPGS was applied (P<0.01). Furthermore, the PPV was significantly higher in group II (95.72%) than in group I (82.88%) (P <0.01).

Conclusions: MCPGS tends  to reduce the numbers of avoidable and unnecessary appendectomies in suspected  cases of pediatric  acute appendicitis that may help in saving hospital resources.

Key  words:  Acute appendicitis, children, Harmonic ultrasound scan, CPGS,  MCPGS.

Introduction:

Certainty of clinical diagnosis is the most challenging task  in  clinical practice. It is relatively straight forward to  look  up the treatment  once a correct diagnosis has been made. A single perfect diagnostic test for acute appendicitis does not exist.1,3

Despite the  number  of algorithms and diagnostic tests available, about 200/o of patients with   appendicitis are   misdiagnosed.3-9

Presence of normal appendix ranges from

5-25% out  of suspected cases  of acute appendicitis.5,10-13 Negative appendectomies were  thought to be relatively harmless; nevertheless, they  result  in  considerable unnecessary clinical  and economic costs.t4

Even  despite the uncertainty of diagnosis, appendicitis demands prompt treatment in order not to be neglected and misdiagnosed leading to progression of the disease with its associated morbidity and mortality that may include the risk of perforation which happens in approximately one third of the cases.5, 15,16

Inan attempt to improve diagnosis, attention has turned to radiological imaging. The use of ultrasound scan (US) has been advocated  as the readily available simple and fast imaging modality particularly in  thin  patients and children. A normal appendix is not frequently observed using gray-scale US, 17-18 however, on the other  hand, Harmonic imaging  (HI) increases  the contrast  and spatial resolution resulting in artifact-free images, and has been shown  to significantly improve  abdominal ultrasonography. However, only a handful of reports exist  regarding its  application in pediatric patients. Most  of  them  do  not encompass its use in acute appendicities.t9

This work aimed to investigate and assess the hypothesis that the use of a modified clinical practice, judgment and harmonic ultrasonography as a modified score-aided diagnosis; MCPGS may improve the accuracy in diagnosing acute appendicitis in children with equivocal pictures of acute appendicitis and to compare these  results  with  those  of previously published data   of  CPGS),2

Patients and methods:

The study was carried out during the period from December 2000 to December 2009.Cases

of suspected pediatric acute appendicitis were included in the study. The first 265 cases were referred  to as Groupl to whom the clinical judgment and ultraosongraphy score  aided CGPS was applied.1 This was a modification of previously published scoring  methods2,3 including certain subjective clinical parameters measured as 1 point  such  as fever  of  38, anorexia  and vomiting,  tachycardia  of more than  120  beats/minute. Abdominal pain parameters were also measured with special emphasis on guarding or rigidity, positive per­ rectal  examinations, however, a  positive rebound tenderness was given 3 points in this score  method   as  well  as  other clinical, laboratory and harmonic  US measurements Table(l);   Results for this group are already published.I  The next 265 cases were referred to as Groupll to whom the proposed usage of harmonic ultrasonography clinical judgment and practice as a modified score aided system MCPGS was applied.

Groupll (n=265): consisted of a similar

group of children in whom our modified score aided system  MCPGS with  twenty five variables including harmonic ultrasound (US) examination and a marker  of inflammatory response was assessed in multivariate analysis using the finding  of AA at operation as the end point were enrolled in this study Table(2). Exclusion criteria  included  those who were proved to have other causes of acute abdominal pain rather than acute appendicitis. Children were equally distributed regarding sex and age into 2 equal groups.

illtrasonography was performed using linear and curved transducers with  ultrasound frequencies ranging between 2.5 and 7.5 MHz, commercially available US systems (Sonoace XP8; Medison, Korea). The examination was performed with  both  conventional and harmonic imaging US. Scanning  parameters were optimized for each method, and all images were obtained with the use of the same focal zone. An external  video with cine playback mode was used to obtain identical images in two standard planes, longitudinal and transverse scans.  Images  were  obtained with  the two methods in random sequence to facilitate their masking for the observers. Harmonic images were acquired at a transmitting  frequency of

2.0 MHz and a receiving hannonic bandwidth of 4.0 MHz. Conventional US images were obtained at a frequency of3.5 MHz, which is a frequency used commonly at abdominal imaging in  adults. The  harmonic and conventional US modes were switched  by means of a toggle switch on1he scanner control panel Figure(l). In both groups the rationale of active watchful waiting  in suspected appendicitis was a prudent and safe strategy with the use of at least one time repetition of conventional US or Harmonic US in groups I

and n,respectively with no increase in the risk of perforation.

All appendices were routinely sent for histopathological examination.

Collected data were statistically analyzed using  X2 test.  Continuous variables  were analyzed  using Z test and student's  t-test.

.05were considered statistically significant Sensitivity and specificity were calculated for the CPGS. Kappa test was used to verify the specificity.  All calculations were performed using SAS version 8.2.

(A)                                             (B)

Figure (1): Acute appendicitis by conventional US

(A) Longitudinal scan showing a peristaltic non compressible blind ended tubular structure with distinct thickened wall/ayers and diameter > 6mm

(B) Transverse scan showing target sign appearance.

-&iiihl!fiil!ffNtiiDWfl:tJ

Table (1): Clinical  Practice Guideline  Scoring  System  (CPGS) 1.

Clinical data

Investigations Laboratory

- Reliefby                  No                     Yes antispasmodic

- Bowel Habit              Yes                     No alteration

-Rebound                 Yes (3)                  No tenderness

- Guarding or               Yes                     No rigidity

- +veP.R.                   Yes                     No examination

Total  score

Focused

abdominal

u.s.     - +ve fmdings in           No                     Yes

female Adnxae

- +ve fmdings in           No                     Yes liver, Gall

bladder,

billiary passages

- +ve fmdings               No                     Yes kidneys

-Free fluid                   Yes                     No

Interpretation of results:

21- 15 =Highly suggestive of appendicitis.

14- 8 = Patient needs  repeated  evaluation for conclusive result.

7- 0 = The diagnosis of acute appendicitis in not likely.

-  II              (

Table (2):Modified clinical practice and harmonic ultrasonographic grading score (MCPGS).

1                    0

Clinical data  General           -Fever                                                       Yes                No

Abdominal -HR.                                                >120/min. <120/min

-Vomiting                                                   Yes                No

Abd.pain

-Localized                                                  Yes                No

- History of similar - attacks                  No                  Yes

-Character                                            Constant Intermittent

-Severity                                                     Intolerable Tolerable

-Course                                                       Progressive Regressive

-Relief by antispasmodic                      No                  Yes

- Bowel Habit alteration                         Yes                No

Laboratory

-tenderness                                                Yes                No

- Guarding or rigidity                                Yes                No

Focused        -+ve P.R.                                                    Yes                No

Investigations  abdominal  Associated intra- abdomin,. Disease  No                    Yes

u.s.

-High WBCs                                              Yes                No

- Elevated  CRP                                        Yes                No

-Urine analysis (Findings ofUTI)          No                  Yes

-Aperistaltic non- Compressible                                                                     Yes                                                                     No blind ended  tubular structure

-Distinct thickened appendicial                                                                      Yes                                                                      No wall layers

- Outer  diameter> 6mm

-Target sign appearance

Total   score                                -Appendicolith(s)                                 Yes                No

-Periappendiceal                                                                   Yes                                                                   No fluid collection

- Echogenic Prominent pericecal fat  Yes                 No

- +ve fmdings in female

Adnexae                                                   No                  Yes

Interpretation of results:

15- 25 =Highly suggestive of appendicitis.

8 -   14 = Patient needs repeated evaluation for conclusive result.

0 -   7 = The diagnosis of acute appendicitis in not likely.

Table (3): Sensitivity, specificity, PPV and NPV for Group IL

Sensitivity= 100%                  Specificity= 90.69% PPV = 95.72%      NPV                                  = 100%

The Number of appendectomies declined from 200 (75.5%) in group I to 187 (70.6%) in group

II (P>0.05).

Results:

Our study included 530 children of whom

280 were males and 250 were females, with a male to female ratio of 1.12:1. Our patients aged between  one year and 17 with a mean age of 12.6 ±1.4 (mean± S.D.). No significant differences were observed  between  the two groups as regard  age and sex distribution.

In group I, traditional clinical judgment and grey  scale US score aided CPGS  were performed. 200 patients (75.5%) underwent appendectomy, of them 35 appendices (17.5%) were normal at histopathological evaluation. The  remaining 65  patients (24.5%) were discharged from the Pediatric Surgical Facility as not having appendicitis. Yet, out of those

65, 3 children (4.6%), (2 males and I female) were  re-admitted. Ultrasonography was repeated suggesting acute appendicitis. They underwent appendectomy with  positive pathological results. A total of  203 appendectomies (76.6) were performed in this group.

In group  II,  I87  patients (70.6%) have

undergone appendectomy, of them 90 patients (48.1%) showed an MCPGS score between I5 and 22, those patients were kept with no oral feeding (NPO), intravenous fluid infusion (IV fluid) of appropriate type and amount according to  patient's age before undergoing appendectomy.

Only 8 out of the total appendectomies (4.3%) were  normal at histopathological evaluation.

The remaining 97 patients (36.6%) initially showed  MCPGS of  8-I4. On  repeated evaluation every 2 hours for a maximum of 6

times and repetition  of harmonic US during the repeated evaluation for at least one time, their score progressed to 15 or more [61 patients (62.9%) with a MCPGS of I5-I7, II patients (Il.3%) with MCPGS of 18, and 25 patients (25.8%) with  MCPGS  of  I9].  During the observation period, these patients were kept with  nothing to be taken  orally (NPO), intravenous (IV) fluids were administered as appropriate. No antibiotics were given in order not  to alter  the clinical picture. However, antibiotics were started once the diagnosis was confirmed. No  false  negative cases  were recorded when using MCPGS.

On the other hand, 78 children (29.4%) did not undergo appendectomy, 48 of them (61.5%) showed MCPGS of 8 or less at the initial examination. They   were  referred to  the Pediatric Medical Care  with  no  need  for surgical interventions. Thirty patients (38.5%) showed MCPGS between 9 and 14 declining with repeated examinations until their score became definitely 8 or less, they were managed medically.

Specificity ofMCPGS was higher than that of CPGS, this may be attributed to the use of harmonic US in this modified scoring system that seems to be significantly  superior to the conventional grey scale US 90.69% in group! Table(3) compared to a specificity of70.47% in  group  II  (Z=5.999, P<O.OI).   Also  the Positive Predictive Value for group II (95.72%) was significantly higher than that of group! (Z=4.727, P<O.OI). Applying Kappa analysis on that data of Table(l) revealed  the Kappa Measure  for Agreement to be 0.929 (93%), Confidence intervals (88.I-97.7),

(MCPGS vs.  Histopathology), Z Kappa=15.1, P value ofO.OOOl. These results show the high specificity of our fmding in the MCPGS group.

Discussion:

Acute appendicitis traditionally has been a

clinical diagnosis and remains so to this day. The diagnosis can be difficult to make in many children who may present with atypical symptoms or an equivocal physical examination.18

In our current study, the newly advocated score aided guideline system (MCPGS) based on clinical judgment, laboratory investigations for inflammatory response and harmonic US studies (Hn in association with the strategy of active watchful waiting performing repeated clinical examinations as well as at least one time repetition of Harmonic US before the decision-making process.    It was  highly accurate in the diagnosis of acute appendicitis in children. The specificity of the MCPGS was

90.69% compared to a specificity of70.47% in the children  to whom CPGS and active watchful waiting strategy was applied. In addition, we observed a statistically significant decrease in the negative appendectomy rate in groupll compared with those in groupl. The decrease in negative appendectomies occurred without a rise in the perforation rate. In fact, the perforation rate was lower under the MCPGS, although this change  was not significant.

The inclusion and exclusion criteria of group formation in our study aimed at avoiding any selection bias as regards the patient's age and sex, attending hospital staff, investigatory facilities whether laboratory or radiological and the pediatric surgical  team. Our study aimed at avoiding the selection bias mentioned before in similar scoring system.19 Screening ultrasound scanning for pediatric appendicitis has suboptimal accuracy, particularly in obese children with a low likelihood of appendicitis who should not routinely undergo ultrasound scanning.However, when followed by a second ultrasound scanning or a clinical reassessment, it offers  high diagnostic  accuracy  in lean

children.20

Targeted abdominal examination as well as hannonic ultrasound scan HI constituted around

75% of our MCPGS scoring system with the aim of increasing its specificity without affecting the system sensitivity.

Results showed the superiority ofharmonic imaging  over  conventional US for lesion visibility, with  harmonic imaging  being preferred over conventional US for 65% of cases. The fmdings were clearer and better defmed with harmonic imaging which thereby improved the detection of subtle lesions. Harmonic imaging theoretically improved signal-to-noise ratios by reducing noise from side lobe artifact in the near field and echo detection  from multiple  scattering  events.

This reduced noise was most likely responsible for the superiority of harmonic imaging over  conventional US in the visualization of the findings and improved the confidence of diagnosis for most cases. Harmonic imaging was  superior to conventional US in the visualization of lesions containing highly reflective tissues such as fat, calcium and air. It is therefore recommended to be used in obese patients. Better definition of  the  posterior acoustic shadows in calcifications and  appendicolith(s).21-28

In our study the negative appendectomy rate in groups I and II was 17.5 and 4.3%, respectively. Contrary to our results of group I some did show a negative appendectomy rate of 5.5% by applying somewhat similar scoring system.19 The reason for such difference may be their use of CT scanning in their system. However,  the difference in the negative appendectomy rate does not support the use of such an expensive sophisticated and hazardous radiological tool to children. CT scanning is not always available in all centers limiting its incorporation in clinical practice guideline scoring system. A recently published study of a practice guideline found that CT scan did not improve the accuracy of diagnosis in patients with suspected appenecistis.29 Their guideline  did not specifically address  the appropriate use of CT scan. Our study results ofMCPGS, however, did show a great decline in the rate of negative appendectomies. This goes with data of some authors who showed that an imaging protocol using US followed by CT in their patients with equivocal presentations  improved the  accuracy of

this and other studies recommending ultrasound as the imaging  modality of choice  in most patients. In addition the recommendation of MCPGS was not limited to imaging alone. Most clinical practice guidelines encourage, but  do not  require complaints with recommendations)!Measuring complaints can be challenging because  guidelines can include numerous recommendations and because patients do not, especially children do not always match preconceived scenarios.32

Although many  barriers limit physician acceptance of guidelines, 33the compliance with  our  MCPGS  is consistent with  other developed practice guidelines.2,3,6-9,34 A considerable portion of the improvement seen in our study could be because of the utilization and accuracy of suitable imaging. Practice guidelines and clinical  pathways  have been implemented for many conditions, 26 including acute appendecitis)6,30,35  Analysis of such guidelines  can focus on any combination of patient outcome, resource utilization or complaints with  recommendation.16,34-36

Although most appendicitis  guideline and pathways focus on decreasing postoperative treatment cost, a few concentrate on diagnosis itself. One such pathway in a pediatric hospital achieved a significant reduction in the number oflaboratory tests and X-rays without adversely affecting the  incidence of  negative appendectomies or perforation.34 However, in our   proposed  MCPGS we  included the minimum necessary laboratory investigations to measure the inflammatory response and time and  effort saving harmonic abdominal ultrasound scan  in  order  to  decrease the probabilities of misdiagnosing acute abdominal pain due to other reasons as acute appendicitis.

In our current study both groups underwent the active  watchful waiting strategy. This excludes that the decision-making process did result strictly from the MCPGS scale, and was not  rather based  on  the  repeated clinical reevaluation that was adopted also on PGCS. This exactly shows that our proposed score is superior to  the  real  life  common clinical practice.

ultrasonographic grading score (MCPGS) with the rationale of active  watchful  waiting in suspected appendicitis with  at least one time repetition of Harmonic US was a prudent and safe strategy.It may improve the accuracy of diagnosing acute appendicitis in the pediatric population as it is superior  to the real  life common  clinical  practice. It leads to fewer negative appendectomies compared with those children to whom it was not applied or other scoring  systems  were  applied  as the CPGS with  the same  strategy of active  watchful waiting and repeated US, without a significant change in the  perforation rate.  Moreover, inpatient observation for serial examinations was reduced significantly. Guidelines such as this  can  have  considerable impact  on  the diagnosis of acute appendicitis in children. A larger cohort  is  necessary to  validate our findings.

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