A Study of Surgical Management of Intestinal Obstruction s1

“A COMPARATIVE STUDY OF MODIFIED ALVARADO SCORE AND ULTRASONOGRAPHY IN THE PRE-OPERATIVE DIAGNOSIS OF ACUTE APPENDICITIES”

Synopsis of the Dissertation

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

In partial fulfillment of the regulations for the Award of Degree of MASTER OF SURGERY-GENERAL SURGERY

Submitted by

Dr. AKSHAI. C.K., M.B.B.S. Post Graduate in General Surgery

Under the guidance of Dr. MAHIMANJAN SINGH MB.B.S., M.S., PROFESSOR Department of General Surgery SAH & R.C., B.G.NAGARA.

SRI ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,

B.G.NAGARA, NAGAMANGALA TALUK, MANDYA DISTRICT RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA ANNEXURE II PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE AND Dr. AKSHAI. C.K. ADDRESS NO. 33, NEW KALPATARU BHAVAN, A.I.M.S., B.G.NAGARA, MANDYA DISTRICT, KARNATAKA - 571448. SRI ADICHUNCHANAGIRI INSTITUTE 2. NAME OF THE INSTITUTION OF MEDICAL SCIENCES, B.G.NAGARA

3. COURSE OF THE STUDY & SUBJECT M.S. IN GENERAL SURGERY

4. DATE OF ADMISSION TO COURSE 1ST JULY 2011 “A COMPARATIVE STUDY OF 5. MODIFIED ALVARADO SCORE AND TITLE OF THE TOPIC ULTRASONOGRAPHY IN THE PRE- OPERATIVE DIAGNOSIS OF ACUTE APPENDICITIES” BRIEF RESUME OF THE INTENDED WORK APPENDIX – I 6. 6.1 NEED FOR THE STUDY APPENDIX – IA 6.2 REVIEW OF THE LITERATURE APPENDIX – IB 6.3 OBJECTIVES OF THE STUDY APPENDIX – IC MATERIALS AND METHODS APPENDIX – II 7. 7.1 SOURCE OF DATA APPENDIX – IIA

7.2 METHOD OF COLLECTION OF DATA- INCLUDING SAMPLING PROCEDURE IF APPENDIX – IIB ANY

7.3 DOES THE STUDY REQUIRE ANY YES INVESTIGATIONS OR INTERVENTIONS APPENDIX – IIC TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS; IF SO PLEASE DESCRIBE BRIEFLY

7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION APPENDIX – IID FOR THE ABOVE 8. LIST OF REFERENCES APPENDIX – III

9. SIGNATURE OF THE CANDIDATE

The study of scoring procedures for early and 10. REMARKS OF THE GUIDE accurate diagnosis of conditions like appendicitis would be apt and, the erroneous diagnosis and the treatment afflicted wrongly would grossly be prevented. The scoring is also cost effective. Hence, the study is recommended

11. NAME AND DESIGNATION OF {IN BLOCK LETTERS}

11.1 NAME & DESIGNATION OF Dr. MAHIMANJAN SINGH MBBS, MS GUIDE PROFESSOR DEPARTMENT OF GENERAL SURGERY, A.I.M.S, B.G.NAGARA

11.2 SIGNATURE OF GUIDE

11.3 CO-GUIDE (IF ANY) No

11.4 HEAD OF DEPARTMENT Dr. R. SRINATH MB.B.S., M.S., PROFESSOR AND HEAD DEPARTMENT OF GENERAL SURGERY, A.I.M.S, B.G.NAGARA.

11.2 SIGNATURE

12 12.1 REMARKS OF THE CHAIRMAN & The facilities required for the investigation will be PRINCIPAL made available by the college

Dr. SHIVARAMU. M.G., M.B.B.S., M.D. PRINCIPAL, AIMS, B.G. NAGARA.

12.2 SIGNATURE

APPENDIX - I

6. BRIEF RESUME OF INTENDED WORK

APPENDIX - IA

6.1 NEED FOR THE STUDY:

It has been claimed that diagnostic aids can dramatically reduce the number of appendicectomies in patients without appendicitis, the number of perforations, and the time spent in hospital. Unfortunately, no error-free diagnostic test exists for appendicitis.

Laboratory investigations (e.g. complete blood count, C-reactive protein and urinalysis) are often ordered during the initial evaluation, but are known to be imperfect indicators of appendicitis when used on their own. Decision making in cases of acute appendicitis may be difficult, radiological investigations are not of much help, though ultrasound, laparoscopy and

C.T scan may be helpful. Diagnostic accuracy regarding appendicitis also depends on the experience of surgeon, yet the need for supportive measures is always there. This has led practitioners in search of an alternate diagnostic tool to - a tool that will be accurate, reliable and valid. This search has led to renewed interest in clinical scoring systems. The Alvarado scoring system released in 1986 by Alvarado et al is reported to be relatively simple to apply and guarantee high efficacy. Alvarado score in this context is a cheap tool and an effective mean of stratifying patients according to the risk of acute appendicitis. It is based on history, clinical examination, and few laboratory investigations, which help to reduce negative appendicectomy rate and improved patient quality of care.

The aim of this study is to validate the user-friendly pre-operative diagnostic method based on prospectively collected data from patients admitted for suspected appendicitis incorporating the Modified Alvarado score and graded compression Ultrasonography. The

following study also will compare the accuracy of the two modalities and examines the value of using both modalities together.

APPENDIX - IIB

6.2 REVIEW OF LITERATURE

Appendicitis is the most common acute surgical condition of the abdomen.1 Approximately 7% of the population will have appendicitis in their lifetime, 2 with the peak incidence occurring between the ages of 10 and 30 years.3 Abdominal pain and anorexia are the predominant symptoms. The most important physical examination finding is right lower quadrant tenderness to palpation. A complete blood count and urinalysis are sometimes helpful in determining the diagnosis and supporting the presence or absence of appendicitis, while appendiceal computed tomographic scans and ultrasonography can be helpful in equivocal cases. Delay in diagnosing appendicitis increases the risk of perforation and complications. Complication and mortality rates are much higher in children and the elderly, probably because the greater omentum which is a policeman of the abdomen is short like a bib in children and has a less protective response in the elderly. Atypical presentation, expanded differential diagnosis and communication difficulty are some factors also responsible for the disproportionally high perforation rate in the elderly.3

Despite technologic advances, the diagnosis of appendicitis is still based primarily on the patient's history and the physical examination. Prompt diagnosis and surgical referral may reduce the risk of perforation and prevent complications.4 The mortality rate in nonperforated appendicitis is less than 1%, but it may be as high as 5% or more in young and elderly patients, in whom diagnosis may often be delayed, thus making perforation more likely.1

Pathogenesis

The appendix is a long diverticulum that extends from the inferior tip of the cecum.5 Its lining is interspersed with lymphoid follicles.3 Most of the time, the appendix has

an intraperitoneal location (either anterior or retrocecal) and, thus, may come in contact with the anterior parietal peritoneum when it is inflamed. Up to 30 percent of the time, the appendix may be "hidden" from the anterior peritoneum by being in a pelvic, retroileal or retrocolic (retroperitoneal retrocecal) position.6 The "hidden" position of the appendix notably changes the clinical manifestations of appendicitis.

Obstruction of the narrow appendiceal lumen initiates the clinical illness of acute appendicitis. Obstruction has multiple causes, including lymphoid hyperplasia of Peyers patches (related to viral illnesses, including upper respiratory infection, mononucleosis, gastroenteritis), fecoliths, parasites, foreign bodies, Crohn's disease, primary or metastatic cancer and carcinoid tumour. Lymphoid hyperplasia is more common in children and young adults, accounting for the increased incidence of appendicitis in these age groups.1,5

History and Physical Examination

Abdominal pain is the most common symptom of appendicitis.3 In multiple studies,3-5 specific characteristics of the abdominal pain and other associated symptoms have proved to be reliable indicators of acute appendicitis. A thorough review of the history of the abdominal pain and of the patient's recent genitourinary, gynecologic and pulmonary history should be obtained.

Anorexia, nausea and vomiting are symptoms that are commonly associated with acute appendicitis. The classic history of pain beginning in the periumbilical region and migrating to the right lower quadrant occurs in only 50 percent of patients.1 Duration of symptoms exceeding 24 to 36 hours is uncommon in nonperforated appendicitis.1

In a recent meta-analysis,7 likelihood ratios were calculated for many of these symptoms . A likelihood ratio is the amount by which the odds of a disease change with new information (e.g., physical examination findings, laboratory results).8 This change can be

positive or negative. Symptoms such as anorexia, nausea and vomiting commonly occur in acute appendicitis; however, the presence of these symptoms does not necessarily increase the likelihood of appendicitis nor does their absence decrease the likelihood of the diagnosis.

Moreover, other symptoms have more notable positive and negative likelihood ratios.

A careful, systematic examination of the abdomen is essential. While right lower quadrant tenderness to palpation is the most important physical examination finding, other signs may help confirm the diagnosis. The abdominal examination should begin with inspection followed by gentle palpation (beginning at a site distant from the pain), auscultation and, finally, abdominal percussion. The rebound tenderness that is associated with peritoneal irritation has been shown to be more accurately identified by percussion of the abdomen than by palpation with quick release.1

As previously noted, the location of the appendix varies. When the appendix is hidden from the anterior peritoneum, the usual symptoms and signs of acute appendicitis may not be present. Pain and tenderness can occur in a location other than the right lower quadrant.6 A retrocecal appendix in a retroperitoneal location may cause flank pain. In this case, stretching the iliopsoas muscle can elicit pain. The psoas sign is elicited in this manner: the patient lies on the left side while the examiner extends the patient's right thigh. In contrast, a patient with a pelvic appendix may show no abdominal signs, but the rectal examination may elicit tenderness in the cul-de-sac. In addition, an obturator sign (pain on passive internal rotation of the flexed right thigh) may be present in a patient with a pelvic appendix.3

The differential diagnosis of appendicitis is broad, but the patient's history and the remainder of the physical examination may clarify the diagnosis. Because many gynecologic conditions can mimic appendicitis, a pelvic examination should be performed on all women with abdominal pain. Given the breadth of the differential diagnosis, the pulmonary,

genitourinary and rectal examinations are equally important. Studies have shown, however, that the rectal examination provides useful information only when the diagnosis is unclear and, thus, can be reserved for use in such cases.5

Laboratory and Radiologic Evaluation

If the patient's history and the physical examination do not clarify the diagnosis, laboratory and radiologic evaluations may be helpful.

Laboratory Tests

The white blood cell (WBC) count is elevated (greater than 10,000 per mm3) in 80 percent of all cases of acute appendicitis.9 Unfortunately, the WBC is elevated in up to 70 percent of patients with other causes of right lower quadrant pain.10 Thus, an elevated WBC has a low predictive value. Serial WBC measurements (over 4 to 8 hours) in suspected cases may increase the specificity, as the WBC count often increases in acute appendicitis (except in cases of perforation, in which it may initially fall).5

In addition, 95 percent of patients have neutrophilia1 and, in the elderly, an elevated band count greater than 6 percent has been shown to have a high predictive value for appendicitis.9 In general, however, the WBC count and differential are only moderately helpful in confirming the diagnosis of appendicitis because of their low specificities.

A more recently suggested laboratory evaluation is determination of the C-reactive protein level. An elevated C-reactive protein level (greater than 0.8 mg per dL) is common in appendicitis, but studies disagree on its sensitivity and specificity.4,5 An elevated C-reactive protein level in combination with an elevated WBC count and neutrophilia are highly sensitive (97 to 100 percent). Therefore, if all three of these findings are absent, the chance of appendicitis is low.5

In patients with appendicitis, a urinalysis may demonstrate changes such as mild pyuria, proteinuria and hematuria,1 but the test serves more to exclude urinary tract causes of abdominal pain than to diagnose appendicitis.

Radiologic Evaluation

The options for radiologic evaluation of patients with suspected appendicitis have expanded in recent years, enhancing and sometimes replacing previously used radiologic studies.

Plain radiographs, while often revealing abnormalities in acute appendicitis, lack specificity and are more helpful in diagnosing other causes of abdominal pain. Likewise, barium enema is now used infrequently because of the advances in abdominal imaging.5

Ultrasonography and computed tomographic (CT) scans are helpful in evaluating patients with suspected appendicitis.11 Ultrasonography is appropriate in patients in whom the diagnosis is equivocal by history and physical examination. It is especially well suited in evaluating right lower quadrant or pelvic pain in pediatric and female patients. A normal appendix (6 mm or less in diameter) must be identified to rule out appendicitis. An inflamed appendix usually measures greater than 6 mm in diameter, is noncompressible and tender with focal compression. Other right lower quadrant conditions such as inflammatory bowel disease, cecal diverticulitis, Meckel's diverticulum, endometriosis and pelvic inflammatory disease can cause false-positive ultrasonography results.12

CT, specifically the technique of appendiceal CT, is more accurate than ultrasonography . Appendiceal CT consists of a focused, helical, appendiceal CT after a

Gastrografin-saline enema (with or without oral contrast) and can be performed and interpreted within one hour. Intravenous contrast is unnecessary.12 The accuracy of CT is due in part to its ability to identify a normal appendix better than ultrasonography.13 An inflamed

appendix is greater than 6 mm in diameter, but the CT also demonstrates periappendiceal inflammatory changes.14. If appendiceal CT is not available, standard abdominal/pelvic CT with contrast remains highly useful and may be more accurate than ultrasonography.12

Clinical Scoring Systems

Although imaging as a diagnostic aid for appendicitis has received the most attention over the past decade, there has been renewed interest in clinical scoring systems because of the variable performance of ultrasound and the important concern of malignancy risk with CT scans in children. Clinical scoring systems, a type of clinical decision rule, quantify the individual contributions that various components of the history, physical examination and simple tests make towards diagnosis, prognosis or likely response to treatment. They aim to help clinicians cope with the uncertainty of medical decision-making and help with efficiency by standardizing the collection and interpretation of clinical data. They are inexpensive, time- efficient diagnostic tools that have the potential to improve patient outcomes.

Methodologic Standards for the development and Validation of Clinical Decision Rules.

Methodologic standards for the development of clinical decision rules were originally described by Wasson et al.23 More recently, Steill and his colleagues assessed clinical decision rule articles in four major medical journals and proposed modifications to Wasson et al’s original methodologic standards24. They have identified eight criteria upon which to judge the adequacy of a clinical prediction rule.

1. The outcome assessed by the decision rule should be clinically important and clearly

defined. Clinically important outcomes should be objective and reproducible in other

settings. For example, confirmation of appendicitis by the presence of certain criteria on

histologic examination of the pathological specimen is an objective measure that can be

assessed in multiple settings, whereas a behavioural outcome such as admission to

hospital may be dependent of local factors and difficult to replicate. To avoid observation

bias, the outcome measure should be assessed without knowledge of the predictor

variables.

2. All potential predictor variables of the outcome should be clearly defined and collected in

a prospective fashion. Investigators should ensure that the physicians in their study have

been adequately trained to evaluate the patients and that the collection of data is

standardized. Clinical data is most reliable when collected prospectively and recorded on

a data collection form designed specifically for the decision rule study. Data collected

from a review of the medical record lacks precision and there are often large amounts of

missing information. This method of data collection is generally unacceptable other than

for the assessment of feasibility.

3. The assessment of the predictor variables must be reliable. This refers to the consistency

or reproducibility of the findings by the same clinician or by different clinicians. Decision

rules are highly dependent on the findings from the clinical examination; therefore, the

findings must be reliable in order for the rule to be dependable. Only predictor variables

with good agreement (beyond that expected by chance alone) should be considered for

inclusion in a decision rule.

4. The study subjects must be well described in terms of inclusion criteria, method of

selection, clinical and demographic characteristics and the study setting. Explicit

inclusion criteria allows the reader to understand what types of patients were studied and

therefore, to which patients the rule may be applicable. The method of patient selection

should be free of bias, so that the study subjects encompass a wide clinical and

demographic spectrum and are representative of all patients seen at the site with the

designated condition.

5. The authors should justify the number of subjects enrolled in the study. Of particular

importance is that the sample size must be appropriate for the statistical technique chosen.

There may be problems with over fitting the data if there are too few outcome events per

predictor variable. A commonly used “rule of thumb” is that there should be at least 10

patients with positive outcomes per independent variable in the prediction rule. For

example if a clinical decision rule for appendicitis was composed of 5 variables, there

should be at least 50 cases of appendicitis in the study population. Another important

consideration in choosing the sample size is the degree of precision desired around the

measure of accuracy.

6. The mathematical techniques used to derive a decision rule should be adequately

described and justified. Many techniques are available, from a simple 2x2 cross tabulation

of each predictor variable with the outcome to sophisticated multivariate analyses.

Univariate analyses are easy to perform but do not allow for the exploration of the

relationship of predictor variables with each other and with the outcome. Logistic

regression analysis predict the likelihood of a binary outcome (appendicitis or no

appendicitis) and tend to lead to decision rules with a higher overall accuracy of the

classification of patients but possibly less than optimal sensitivity (that is less than 100%

classification of abnormal patients). Chi-squared recursive partitioning is another method

of analysis. This method progressively divides the patients into a subpopulation that

includes only patients with a particular outcome. Rules derived by this method tend to be

very sensitive.

7. The decision rule must make good clinical sense, be easy to use and provide a course of

action. Decision rules should demonstrate content validity, which means that most

clinicians would consider the items in the rule to be clinically reasonable and would find

no obvious missing items. Ease of use depends on factors such as the length of time

needed to apply the rule and the simplicity of its interpretation. In the emergency

department, it is unlikely that physicians would embrace a rule that requires extensive

calculations or the use of a calculator. Steill and his colleagues believe that decision rules

are more likely to be used if they suggest a course of action rather than merely provide a

probability of outcome.

8. Lastly, the authors should present the accuracy of the rule based on the population from

which the decision rule was derived. Sensitivity, specificity, positive predictive value and

negative predictive value should be presented. Likelihood ratios can be presented if

information about the posttest probability of an outcome based on the decision rule would

be helpful. Receiver operator characteristic (ROC) curves give an overall estimate of the

accuracy of a rule, but are of limited clinical use because the posttest probability is not

provided.

Once a decision rule has been derived, McGinn and his colleagues stipulate that a rule should only be widely-adopted once they have been adequately tested in validation studies and their impact on clinical behaviour has been assessed25. Successful validation and impact studies move a prediction rule through a hierarchy of evidence (Level 4 to Level 1) and they recommend only implementing a rule into routine clinical practice once Level 1 evidence has been achieved.

At this point, there is sufficiently large confidence in its accuracy and in its ability to improve upon current practice. When rules are derived but not validated, or validated only in retrospective databases or by sample splitting within the original data set, they are of Level 4 evidence. Progression to Level 3 evidence occurs when the rule has been validated in a similar population or setting as the original derivation population. At this stage, clinicians may consider using the rule with caution if the patients in the study are similar to those in the development setting.

Level 2 evidence is attained when accuracy of the rule has been demonstrated in one large prospective study with a broad spectrum of patients and clinicians or in several smaller

settings that differ from one another. At this stage, the rule can be used with confidence in its accuracy.

Finally, Level 1 evidence is attained after an impact analysis has been done, demonstrating a change in clinician behaviour with beneficial consequences. This validation process is very important because many statistically derived rules or guidelines fail to perform well when tested in a new population. The reason for this poor performance may be statistical (overfitting or instability in the original derived model) or may be related to differences in prevalence of disease or difference in how the decision rule was applied.

Clinical Scoring Systems in the Diagnosis of Appendicitis

Many appendicitis scoring systems exist, however, until recently, most have not been applied routinely in clinical practice because of a failure to achieve diagnostic accuracy in repeated validation studies. 27-33

The most widely known appendicitis score was developed by Alvarado in 1986. 27The score, officially called the MANTRELS score, but also known as the Alvarado score, was developed by a retrospective record review of 277 patients hospitalized for abdominal pain suggestive of appendicitis from 1975 - 1976 in Philadelphia. The mean age of the study population was 25.3 years (range 4 - 80). Information about patient age, sex, duration of pain, symptoms, physical signs and the results of laboratory and pathology reports was abstracted from medical records. For each diagnostic indicant abstracted, the sensitivity, specificity, positive and negative predictive values and probability of disease based on a positive and negative test were calculated. A diagnostic weight was assigned to each indicant by adding the true-positive rate and true-negative rate for that item. Eight items with the highest diagnostic weights were retained after univariate association with the outcome (appendicitis)

was confirmed. The retained diagnostic indicants, the weights and score value are listed in the table below:

Diagnostic Indicant Diagnostic Weight Score Migration of Pain 0.72 1 Anorexia 0.63 1 Nausea +/- vomiting 0.66 1 Tenderness in RLQ 0.84 2 Rebound pain 0.59 1 Elevation temperature >37.7 c per oral 0.69 1 Leukocytosis > 10,000 0.83 2 Shift to left > 75% neutrophils 0.70 1 Total 10

The two components with the highest diagnostic weight (leukocytosis and tenderness in the right lower quadrant) were arbitrarily assigned a value of 2 while the remaining components were assigned a value of 1, such that the score would sum to 10.

In this cohort of 277 patients, the mean score for those with appendicitis (227 patients) was 7.71 (SD 1.53) and for those without appendicitis (50 patients) was 5.24 (SD

2.02). When a cut-point of 6 was retrospectively applied to Alvarado’s cohort, such that patients with scores ≤ 5 would be observed and patients with scores ≥ 6 would be taken to the operating room, there would have been 16 (5.8%) cases of missed appendicitis and 24 (8.7%) negative appendectomies. If the cut-point was changed to 5, such that patients with scores ≤ 4 would be observed and patients with scores ≥ 5 would be taken to the operating room, the number of missed cases of appendicitis would fall to 8 (2.9%) but the number of negative appendectomies would increase to 31 (11.2%). At this cut-point, the sensitivity of the score is

92% (95%CI: 89%, 96%), specificity 52% (95%CI: 38%, 65%), positive predictive value

90% (95%CI: 85%, 93%) and negative predictive value 62% (95%CI: 47%, 75%). The prevalence of appendicitis in this cohort was 82%. Alvarado concluded that scores of 5-6

were compatible with appendicitis, scores of 7-8 indicate probable appendicitis and scores of

9-10 indicate very probable appendicitis.

The Modified Alvarado’s Score

Symptoms: M = Migratory right iliac fossa pain 1 A = Anorexia 1 N = Nausea/vomiting 1 Signs: T = Tenderness right lower quadrant 2 R = Rebound tenderness right iliac fossa 1 E = Elevated Temperature 1 Investigation: Leucocytosis 2 Total score 9

The Alvarado score has been criticized for using the sum of the true-positive rate and true-negative rate to determine the diagnostic weight of each score item. Since Alvarado defined accuracy as the weighted average of the sensitivity and specificity using weights determined by the prevalence of appendicitis, it is problematic when the sensitivity and specificity of a score item are not equal, as the diagnostic weight is directly proportional to disease prevalence.34 In populations with high disease prevalence, items with high sensitivity are disproportionately rewarded with high diagnostic weights while in populations with low disease prevalence, items with high specificity receive higher diagnostic weights. Peter and

Hedges advocate that the likelihood ratio would be a better discriminator between those with and without disease and a clinical score using this method might be more generalizable to other populations. To the best of our knowledge, this proposal for an alternative methodology did not receive any further comments by other investigators and a score based on likelihood ratios was never formally created or validated. Despite this and other methodologic criticisms and the mixed results in the validation studies, the Alvarado score is the most widely used score in clinical practice.

Treatment

The standard for management of nonperforated appendicitis remains appendicectomy.

Because prompt treatment of appendicitis is important in preventing further morbidity and mortality, a margin of error in over-diagnosis is acceptable. Currently, the rate of negative appendectomies is approximately 20 percent.15 Some studies have investigated nonoperative management with parenteral antibiotic treatment, but 40 percent of these patients eventually required appendicectomy.3

Appendicectomy may be performed by laparotomy (usually through a limited right lower quadrant incision) or laparoscopy. Diagnostic laparoscopy may be helpful in equivocal cases or in women of childbearing age, while therapeutic laparoscopy may be preferred in certain subsets of patients (e.g., women, obese patients, athletes).16

While laparoscopic intervention has the advantages of decreased postoperative pain, earlier return to normal activity and better cosmetic results, its disadvantages include greater cost and longer operative time.4 Open appendicectomy may remain the primary approach to treatment until further cost and benefit analyses are conducted.

Complications

Appendiceal rupture accounts for a majority of the complications of appendicitis.

Factors that increase the rate of perforation are delayed presentation to medical care,17 age extremes (young and old)18 and hidden location of appendix.6 A brief period of in-hospital observation (less than six hours) in equivocal cases does not increase the perforation rate and may improve diagnostic accuracy.18

Diagnosis of a perforated appendix is usually easier (although immediately after rupture, the patient's symptoms may temporarily subside). The physical examination findings

are more obvious if peritonitis generalizes, with a more generalized right lower quadrant tenderness progressing to complete abdominal tenderness. An ill-defined mass may be felt in the right lower quadrant. Fever is more common with rupture, and the WBC count may elevate to 20,000 to 30,000 per mm3 with a prominent left shift.3

A periappendiceal abscess may be treated immediately by surgery or by non-operative management.4 Non-operative management consists of parenteral antibiotics with observation or CT-guided drainage, followed by interval appendectomy six weeks to three months later.1

Special Considerations

While appendicitis is uncommon in young children, it poses special difficulties in this age group. Young children are unable to relate a history, often have abdominal pain from other causes and may have more nonspecific signs and symptoms. These factors contribute to a perforation rate as high as 50 percent in this group.1

In pregnancy, the location of the appendix begins to shift significantly by the fourth to fifth months of gestation. Common symptoms of pregnancy may mimic appendicitis, and the leukocytosis of pregnancy renders the WBC count less useful. While the maternal mortality rate is low, the overall fetal mortality rate is 2 to 8.5 percent, rising to as high as 35 percent in perforation with generalized peritonitis. As in non-pregnant patients, appendicectomy is the standard for treatment.3

Elderly patients have the highest mortality rates. The usual signs and symptoms of appendicitis may be diminished, atypical or absent in the elderly, which leads to a higher rate of perforation. More frequent perforation combined with a higher incidence of other medical problems and less reserve to fight infection contributes to a mortality rate of up to 5 percent or more.1

Summary

Prompt diagnosis of appendicitis ensures timely treatment and prevents complications. The importance of diagnosing appendicitis early enough that perforation is avoided while minimizing the number of negative appendectomies that are performed is widely recognized. The diagnosis is a challenge. The search of the perfect diagnostic tool has been unsatisfactory.

Laboratory investigations are a helpful adjunct to diagnosis, but on their own perform poorly. Imaging with ultrasound performs very well in the hands of experienced operators however has important limitations, leading to misclassification of cases, when commonly found patient characteristics such as obesity, pain or an unusual location of the appendix are present. In teaching hospitals where residents often perform ultrasounds, especially after hours, the results from accuracy studies has not been consistent. The only highly sensitive and specific tool is CT scan, but because of its risk associated with lifetime risk of mortality from cancer, it cannot be used freely as a diagnostic aid. Clinical scoring systems have received a lot of attention in the literature because they are cost-effective, time-efficient tools that present no risk to the patient. They systematically quantify the individual contributions that various components make towards diagnosis, prognosis or likely response to treatment.

APPENDIX - IC

6.3 AIMS AND OBJECTIVES

General Objective

 To determine and compare the diagnostic accuracy of the Modified Alvarado Scoring

System and Ultrasonography in clinical practice for acute appendicitis at A.I.M.S.,

B.G.Nagara during the period of the study.

Specific Objectives

 To determine the sensitivity, specificity, positive predictive value, negative predictive

value and accuracy of the Modified Alvarado score.

 To determine the sensitivity, specificity, positive predictive value, negative predictive

value and accuracy of Ultrasonography in the diagnoses Acute Appendicitis.

APPENDIX - II

7. MATERIALS AND METHODS

APPENDIX - IIA

7.1 SOURCE OF DATA:

The material for the present study will be collected from the patients who present with

RIF pain with / without fever and vomiting, admitted to the Department of Surgery at Sri

Adichunchanagiri Hospital and Research Centre, B.G.Nagara, Mandya District, during the period of 18 months.

Sample Size: Minimum of 50 patients fulfilling the inclusion criteria

APPENDIX - IIB

7.2 METHOD OF DATA COLLECTION:

 This study is a longitudinal prospective study.

 A minimum of 50 cases of Acute Appendicitis

 Period of study is from December 2011 to June 2013.

 A Pre-structured Performa will be used to collect relevant data.

 Detailed history taking

 Complete clinical examination of the patient.

 Routine and Special Investigations including Ultrasound

 Application of the Modified Alvarado scoring system

 Performing surgery for the selected cases, noting per-operative findings and follow-up

of histological-pathological reports

INCLUSION CRITERIA :

 Patients aged between 12- 60 years of age of both gender admitted with the

provisional diagnosis of acute appendicitis.

EXCLUSION CRITERIA

 Patients below 12 years or above 60 years

 Patients managed conservatively

 Patients undergoing interval appendectomy

 Patients with RIF mass

 Patients with presentation of urological, gynecological or surgical problems other than

appendicitis

STATISTICAL ANALYSIS;

The collected data will be incorporated in a redesigned clinical proforma and then tabulated in a master chart of 50 patients

APPENDIX - IIC

7.3 Does the study require any investigations or interventions to be conducted on patients or other animals; if so describe briefly:

INVESTIGATIONS:

Routine Investigations like -

1. Blood

 Total count

 Differential count

 Hemoglobin

 ESR

 Bleeding time and Clotting time

 Random Blood Glucose

 Fasting and past-prandial Blood Glucose

 Blood Urea, Serum Creatinine

 HIV/ HbsAg

 Blood grouping and Rh typing

2. Urine routine- Urine Albumin, Sugar and Microscopy

3. Pus Culture and Sensitivity

Special Investigations like -

1. Ultrasonography - abdomen; pelvis

2. Plain radiographs – Chest X-Ray, Erect X-Ray abdomen.

3. CT Scan - abdomen

4. ECG

5. Tissue biopsy wherever applicable

No animal studies will be conducted in this study.

APPENDIX – II D

7.4 PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL

SECTION A “A COMPARATIVE STUDY OF MODIFIED ALVARADO SCORE AND a Title of the study ULTRASONOGRAPHY IN THE PRE- OPERATIVE DIAGNOSIS OF ACUTE APPENDICITIES”

Dr. AKSHAI. C.K. Principle investigator NO. 33, NEW KALPATARU BHAVAN, b (Name and Designation) A.I.M.S., B.G.NAGARA, MANDYA DISTRICT, KARNATAKA - 571448.

Dr. MAHIMANJAN SINGH Co-investigator MBBS, MS c PROFESSOR (Name and Designation) DEPARTMENT OF GENERAL SURGERY, A.I.M.S, B.G.NAGARA DEPARTMENT OF RADIODIOAGNOSIS Name of the Collaborating d AND DEPARTMENT OF PATHOLOGY Department/Institutions A.I.M.S., B.G.NAGARA Whether permission has been obtained from e the heads of the collaborating departments YES & Institution Section – B APPENDIX I Summary of the Project Section – C APPENDIX IC Objectives of the study Section – D APPENDIX IIB Methodology Where the proposed study will be A SAH & RC, B.G.NAGARA undertaken B Duration of the Project 18 MONTHS C Nature of the subjects: Does the study involve adult patients? YES Does the study involve Children? YES Does the study involve normal volunteers? NO Does the study involve Psychiatric patients? NO Does the study involve pregnant women? YES

D If the study involves health volunteers

I. Will they be institute students? NO II. Will they be institute employees? NO III. Will they be Paid? NO IV. If they are to be paid, how much per NA session?

E Is the study a part of multi central trial? NO

F If yes, who is the coordinator? (Name and Designation) NO

Has the trial been approved by the ethics NO Committee of the other centers?

If the study involves the use of drugs please NA indicate whether.

I. The drug is marketed in India for the NA indication in which it will be used in the study.

II. The drug is marketed in India but not for the indication in which it will be used in the NA study

III. The drug is only used for experimental use in humans. NA

IV. Clearance of the drugs controller of India NA has been obtained for:

 Use of the drug in healthy volunteers  Use of the drug in-patients for a new indication. NA  Phase one and two clinical trials  Experimental use in-patients and healthy volunteers.

G How do you propose to obtain the drug to be used in the study? - Gift from a drug company NA - Hospital supplies - Patients will be asked to purchase - Other sources (Explain) H Funding (If any) for the project please state - None - Amount NA - Source - To whom payable

Does any agency have a vested interest in the I NO out come of the Project?

Will data relating to subjects /controls be stored J NO in a computer? Will the data analysis be done by K - The researcher? YES - The funding agent NO L Will technical / nursing help be required form the staff of hospital. YES

If yes, will it interfere with their duties? but it will not interfere with their duties.

Will you recruit other staff for the duration of NO the study?

If Yes give details of I. Designation II. Qualification NA III. Number IV. Duration of Employment

M Will informed consent be taken? If yes NO Will it be written informed consent: NO Will it be oral consent? NO

Will it be taken from the subject themselves? NO Will it be from the legal guardian? If no, give NO reason:

N Describe design, Methodology and techniques APPENDIX II

Ethical clearance has been accorded.

Chairman, P.G Training Cum-Research Institute, A.I.M.S., B.G.Nagara. Date :

PS : NA – Not Applicable

APPENDIX – III

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