Comparison of clinical severity between group A, group B, and group C*.
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Cholelithiasis represents a very frequent health problem. The prevalence of cholelithiasis is higher in the developed regions such as Europe and North America in comparison to the developing regions of the world (Africa, Middle East, China, India, Far East). On average, gallstone disease affects 10–15% of the adulthood population in the age of majority [1, 2]. The cost of gallstone disease has high social, administrative, and economic impact as interference with work activities, home care, hospital admission, and so on. Mortality rate for gallstone disease reaches 0.6%, thanks to the reduction of more than 50% over the last 60 years [3]. Gallstone disease in its evolution involves acute cholecystitis and some risks of complications such as gallstone-related pancreatitis and cancer [4, 5]. Moreover, cholecystectomy morbidity encompasses various and diversified pathological conditions especially in severe inflammatory circumstances. We underline the problems connected with insufficient preoperative evaluation. Complications can be divided in intraoperative and postoperative. Intraoperative morbidity includes bile duct injury, gallbladder perforation, bleeding, and bowel perforation. Postoperative complications consist of infection and dehiscence of surgical incision, subhepatic abscess, residual choledocolithiasis, postcholecistectomy syndrome, umbilical hernia. Currently, cholecystectomy morbidity rate reaches 8.7–9.5% with up 15% in so-called difficult cholecystectomy. Among these complications is in evidence the bile duct injury which causes great impact on patient outcomes and requires usually complex and various procedures of repair: endoscopy, surgery, operative biliary radiology [6].
Various etiological conditions and risk factors can cause gallstone disease. We can underline the gender, age, obesity, fast weight loss, alcohol use, diabetes, pregnancy, hypertriglyceridemia, and so on. The study of pathogenesis of gallstones can identify all etiological factors. The majority of gallstones are non-pigmented stones which are composed of cholesterol (75% of cases). The cholesterol is retained in solution by an unsteady balance among levels of phospholipids, bile acids, and cholesterol (Admirand’s triangle) [7]. This balance can be disrupted by several factors: cholesterol supersaturation in bile, crystal nucleating factors because cholesterol supersaturates tends to precipitate and crystallize, impairment of gallbladder functions as motility, absorbtion, secretion, finally impaired enterohepatic circulation of bile acids that changes the balance of Admirand’s triangle. In summary, cholesterol stones are caused by cholesterol iperproduction, large cholesterol-phospholipid vesicles, crystal precipitation (cholesterol monohydrate crystal) [8]; moreover, by calcium nucleation, and other nucleating factors as mucin glycoproteins, immunoglobulins, and so on. In addition, impairment of gallbladder functions plays a significant role: decrease of motility with stasis as in prolonged fasting and parenteral nutrition, diabetic disease, long-term somatostatin therapy, alteration of absorptive, secretive activity with increase of water reabsorption. Finally, the reduction of intestinal reabsorption of bile acids in the entero-hepatic circulation is also in evidence. Crystallizations of cholesterol within bile form biliary sludge and biliary sludge can be considered a common precursor of the gallstones. Pigmented stones consist of calcium-bilirubinate. These stones are due to solubilization of unconjugated bilirubin with precipitation. There are two types: black and brown. Black stones reach about 15–20% of global biliary stones. They are caused and occur in several diseases: hemolytic disorders (increased red blood cell destruction), liver diseases, cirrhosis (abnormal metabolism of hemoglobin), distal ileal resection (reabsorption of bile salts), and long-term total parenteral nutrition (TPN). Commonly these stones form in gallbladder. Brown stones, on the contrary, are found in biliary ducts as primary common bile duct (CBD) stones. These stones are associated with infection in bile ducts. Bacteria (Escherichia coli, Klebsiella frequently) produce bacterial beta-glucuronidase; consequently deconjugated bilirubin, not hydrosoluble, forms calcium bilirubinate. Biliary infections are commonly associated with biliary ducts stenosis, ampullary stenosis, abnormal sphincter of Oddi, sclerosing cholangitis, cirrhosis.
Symptoms or complications of gallstones can develop in 1–2% of the patients for years [9]. Clinical presentation of cholelithiasis can be various: in the majority of cases (60–80%) lithiasis stay on long asymptomatic or for the patient’s whole life and its detection could be incidental. Symptoms of different degree, mild or severe for advanced complications occur in the 20–40% of patients. Acute cholecystitis is the very frequent surgical entity that occurs in 15–20% of patients with symptomatic disease. Cholecystitis could be caused by obstruction of the cystic duct by a gallstone with the same pathogenesis of biliary colic. The obstacle of bile outflow from gallbladder causes its wall distention and wall inflammation. This pathological condition may develop in different ways. In the severe cases (10–18%), the prolonged and complete obstruction causes extension of parietal flogosis resulting in disturbance of blood perfusion and necrosis. In the favorable cases, which are the majority, the stone moves, obstruction resolves, and inflammation may regress. In the acute cholecystitis, bacterial superinfection can occur in 50% of cases with positive bile culture (Escherichia coli, Klebsiella, Enterobacter, etc.) [10]. We can believe that acute cholecystitis starts as inflammatory disease without bacterial infection. Recently more complex pathogenesis has been hypothesized in acute cholecystitis. Acute cholecystitis should be produced with the addition of irritating factors of gallbladder mucosa to the blockage of the cystic duct. Lysolecithin has been used in experimental setting as irritant; but lysolecithin comes by catalyzation from lecithin, normal constituent of bile, by phospholipase A. Trauma of impacted gallstone may cause the release of this enzyme [11]. Moreover, lysolecithin was found in the gallbladder with acute inflammation [12]. Gallbladder flogosis should be worsened by further inflammatory mediators such as prostaglandins, which play an important role in functional activity of gallbladder (motility, fluid absorption, etc.) [13]. In summary, prolonged obstruction of gallbladder neck leads the increase of intraluminal pressure, with venous congestion, impaired blood supply, and lymphatic drainage. Damage of gallbladder wall (edema, intramural haemorrhage) and secondary bacterial infection complete the pathological features. Acalculous cholecystitis is acute inflammatory disease associated with right upper abdominal quadrant pain, leucocitosis, thickened wall without gallstones (ultrasonography (US) findings). Most frequently, it happens in patients with severe disease such as severe burns, trauma, major surgery, long-term TPN; frequently cholecys`titis can develop with high morbidity and mortality [14]. In the acute acalculous, cholecystitis probably can play a role of the bile stasis (fasting, narcosis) causing distension of wall, impaired blood supply, necrosis. Increased viscosity by dehydration and intestinal dynamic occlusion produces sludge formation and bacterial overgrowth in the gallbladder. US shows gallbladder wall thickening, sludge, pericholecystic fluid.
Gallstones disease can present and develop in the wide clinical range. Asymptomatic disease can be detected incidentally. The absence of symptoms is linked to the mobility of stones that will not obstruct the cystic duct. The presence of gallstones, although asymptomatic for a prolonged time, can develop in symptomatic disease with various clinical entities. Most simple and frequent presentation is biliary colic characterized by abdominal pain localized in right upper abdominal quadrant, nausea, vomiting, frequently irradiating to the right shoulder. Usually the colic lasts a few hours. Asymptomatic patients can develop symptomatic disease in 20–30% of cases in the long term (20 years). The clinical developments of gallstone disease encompass several presentations: biliary colic, acute cholecystitis (with various degree of severity such as gangrene, emphysematous cholecystitis, perforation, cholecystoenteric fistula, gallstone ileus), choledocolithiasis, cholangitis, biliary pancreatitis, gallbladder carcinoma. The significant clinical problem is the surgical indication of cholecystectomy for patients with asymptomatic gallstone. The overall likelihood of clinical appearance for asymptomatic patients should be about 30% but we have to insert it and evaluate it in specific conditions: demographic, pathophysiological, and clinical. Another relevant information for the surgical indication choice is the incidence of postoperative morbidity of cholecystectomy. From the literature, overall morbidity (minor and major) of cholecystectomy in the laparoscopic era for uncomplicated gallstone disease in patients without comorbidity is very low: overall complication rate is 1.5% and the mortality rate is less than 0.1% [15]. In summary, surgical treatment is the first choice in the patients with symptoms, cholecystitis, and gallbladder stone-related complications. Moreover, nowadays, the surgical indication for patients completely asymptomatic is debatable and not well defined. We can identify several clinical-pathological conditions without clear and evident clinical appearance in which laparoscopic cholecystectomy should be indicated: patients with mild clinical appearance such as intense discomfort in the right upper quadrant, nausea vomiting, biliary colic because considerable risk for developing complications, young patients because high likelihood to develop in later years symptoms or/and complications, patients with pigmented stones caused by hemolytic disorders (increased red blood cells destruction) because the risks linked to this pathology in case of gallstone-related complications, patients with clearly established gallbladder dysfunction that frequently develops symptomatic disease (25–30% of cases) [16], patient with large stones (>2 cm) for high risk to develop cholecystitis, patients with porcelain gallbladder (calcifications in the wall) because of the risk of gallbladder cancer (5–10%).
\nPatients with mild symptomatic gallstone disease such as recurrent biliary colic or mild postprandial discomfort can develop in about 20% of cases acute cholecystitis. This pathological evolution commonly is connected with obstruction by stones of gallbladder neck or cystic duct. The time duration of the obstructive condition (short or long time) can lead to decrease and resolution of inflammatory process or, on the contrary, to wall distension, impaired blood supply, ischemia, necrosis of gallbladder (severe cases 15–20%). In about 50% of cases, commonly in the prolonged impairment of bile outflow from the gallbladder, bacterial infection adds to flogistic process. In acute cholecystitis, patients complain of severe pain in abdominal right upper quadrant and overall the clinical presentation is overlappable to biliary colic but the characteristic pain is on the contrary prolonged greater than 4–6 hours. Usually fever, nausea, anorexia, and vomiting join and the pain should be referred to right shoulder or back. Frequently the patients refer previous episodes of biliary colic, or fatty food ingestion few hours before the onset of colic. Clinical observation shows the suffering patient with fever, tachycardia, nausea, emesis, anorexia, and inhibition or diminution of the respiratory movement of right upper quadrant and epigastric area of abdominal wall. On physical examination can be seen right upper quadrant tenderness of varying degree and positive Murphy’s sign with increased discomfort and/or inspiratory arrest while, palpating right upper quadrant, the patient is invited to make deep inspiration. A positive sign shows sensitivity of 97% and specificity of 93% [17]. In some cases (about 30%), acute cholecystitis can develop discrete extension of inflammation outside gallbladder wall causing local peritonitis with involvement of omentum and adjacent organs that forms a flogistic mass, palpable in upper right quadrant. Leukocytosis is an almost constant laboratory finding characterized by the white cell count increase, connected with the severity of the disease.
Cholelithiasis is the most frequent cause of acute pancreatitis. Clinical diagnostic difficulties may arise in the context of acute biliary pancreatitis. The major clinical problem is to distinguish clinical forms of hyperamylasemia, associated with severe abdominal pain, physical signs of upper abdominal tenderness and guarding based on acute biliary tract disease (acute cholecystitis, cholangitis, etc.) from acute biliary pancreatitis with evident pancreatic involvement. In the context of acute biliary pancreatitis may merge acute abdominal diseases different to each other; but they have in common hyperamylasemia and acute/severe upper abdominal pain and abdominal wall guarding. The correct diagnosis and distinction between moderate or severe acute biliary pancreatitis with hyperamylasemia, evident pancreatic involvement, severe upper abdominal pain/abdominal wall guarding, and acute biliary tract disease (cholecystitis, cholangitis, etc.) with hyperamylasemia, severe upper abdominal pain, abdominal wall guarding, minimal, or mild pancreatitis, allows to follow different therapeutic program overall in regard to timing of surgery [18]. Our aim is to define clinical and laboratory differentiation between these two clinical manifestation regarding the choice of therapeutic program. The presentation of consistent and appropriate experience should clarify some diagnostic difficulties, within the acute biliary pancreatitis, between two clinical-pathological forms different but confusable. We have evaluated 42 patients admitted in our Institution in the period September 2012/September 2014. The admission diagnosis was acute pancreatitis, based on first basic clinical and laboratory evaluation. Demographic features: male 26, female 16, mean age 64 years (range: 89–27 years). Signs and symptoms of 42 patients at the admission are reported in (Figure 1).
Frequency (%) of signs and symptoms in patients with diagnosis of acute pancreatitis.
In the first phase of the study, the patients have been divided by etiology of acute pancreatitis. The majority of cases (30 pts. 71%—Group A) shows biliary etiology, based on the detection with imaging study (US) of biliary lithiasis. In seven patients (Group B—16.6%), the clinical-anamnestic criteria show the alcoholic etiology (prolonged alcohol abuse). The other five patients (Group C—11.9%) have been classified as acute pancreatitis patients with unknown etiology. The patients subdivided following the etiological criteria (Groups A, B, C) have been evaluated regarding to severity of disease with Ranson criteria, pancreatic involvement with CT severity index (Balthazar), and finally likelihood of biliary etiology with Blamey criteria using clinical and laboratory data (age, sex, amylase, alkaline phosphatase, ALT) [19–22]. The important section of this study concerns the biliary pancreatitis. Within 30 patients with initial diagnosis of acute biliary pancreatitis (Group A), we have identified two subgroup: the first subgroup A1 that encompasses 18 patients with acute biliary pancreatitis with moderate/severe pancreatic involvement and the subgroup A2 that includes 12 patients with acute biliary disease and minimal pancreatic involvement based on transient hyperamylasemia. The aim of this subdivision and comparison is to identify, by laboratory and imaging study, two different clinical forms of acute pancreatitis: the pancreatic pattern (A1) and the biliary pattern (A2). The patients have been subdivided in three groups following the etiology criteria: biliary (Group A), alcoholic (Group B), and undefined pancreatitis (Group C). First, we can evaluate if there are differences among the groups of patients regarding clinical severity (Ranson score), degree of pancreatic involvement (CT severity index-Balthazar), and finally the likelihood of biliary etiology (Blamey score). The evaluation of clinical severity (Ranson score) between the group A (biliary) and group B (alcoholic) shows no differences with Student’s t-test: t = 0.1375 < t0.05 = 1.6896. Because of the low number of cases in our groups, we have also employed the Kolmogorov-Smirnov test for the comparison of clinical severity (Table 1).
Group Aa versus Group Bb | D = 0.205 < D0.05 = 0.554 |
Group A versus Group Cc | D = 0.634 < D0.05 = 0.640 |
Group B versus Group C | D = 0.429 < D0.05 = 0.800 |
Comparison of clinical severity between group A, group B, and group C*.
*Kolmogorov-Smirnov test.
aGroup A: biliary.
bGroup B: alcoholic.
cGroup C: undefined.
The results of the severity disease comparison (CT severity index) show that there are not statistically significant differences between group A versus group B and between group B versus group C. The comparison between group A versus group C shows also no differences (empirical p value < theoretical p value) even if in the group C there are mild pancreatitis and in group A there are severe pancreatitis. The comparison among the three groups of degree of pancreatic and extrapancreatic damage (CT severity index-Balthazar) demonstrates that, even in this area, there are not statistically significant differences (Table 2).
Group Aa versus Group Bb | t = 0.4345 < t0.05 = 1.609 |
Group A versus Group Cc | t = 0.2884 < t0.05 = 1.6939 |
Group B versus Group C | t = 0.2006 < t0.05 = 1.8595 |
Comparison of CT severity index between group A, group B, and group C*.
*Student’s t-test.
aGroup A: biliary.
bGroup B: alcoholic.
cGroup C: undefined.
Finally the evaluation of the predictive accuracy of biliary etiology based on clinical data (Blamey score) among the three groups did not provide effective results for the early definition of the biliary etiology because of no statistical differences (Table 3).
Group Aa versus Group Bb | t = 0.0568 < t0.05 = 1.6896 |
Group A versus Group Cc | t = 0.9195 < t0.05 = 1.6924 |
Group B versus Group C | t = 0.8594 < t0.05 = 1.8125 |
Comparison of Blamey score between group A, group B, and group C*.
*Student’s t-test.
aGroup A: biliary.
bGroup B: alcoholic.
cGroup C: undefined.
To identify the two subgroups A1 (pancreatic pattern) and A2 (biliary pattern) within the group A (acute biliary pancreatitis) have been used clinical features, laboratory, instrumental tests (imaging), therapeutical procedures employed. We have verified if there are statistically significant differences between group A1 and group A2 with respect to leukocytosis, amylasemia, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, clinical severity score (Ranson), modified CT severity index (Balthazar). The purpose of the study is to identify clinical or instrumental criteria for detection of pancreatic pattern versus biliary pattern in acute biliary pancreatitis. In the statistical evaluation, leukocytosis, amylasemia, and alkaline phosphatase did not show differences between the two groups. On the contrary, there are differences for bilirubin, AST, and ALT. The results of comparison, among subgroups A1 and A2, of clinical severity score (Ranson) and modified CT severity index (Balthazar) are different with statistical significance with Student’s t-test but not following Kolmogorov-Smirnov test (Table 4).
Student’s t-test | Kolmogorov-Smirnov test | |
---|---|---|
White blood cells | t = 0.2918 < t0.05 = 1.7011 | D = 0.22 < D0.05 = 0.500 |
Amylasemia | t = 0.8754 < t0.05 = 1.7011 | D = 0.203 < D0.05 = 0.500 |
Bilirubin | t = 2.0192 < t0.05 = 1.7011 | D = 0.72 < D0.05 = 0.500 |
AST | t = 2.1664 < t0.05 = 1.7011 | D = 0.67 < D0.05 = 0.500 |
ALT | t = 8.7062 < t0.05 = 1.7011 | D = 0.78 < D0.05 = 0.500 |
Phosphatase | t = 0.6253 < t0.05 = 1.7011 | D = 0.39 < D0.05 = 0.500 |
Ranson’s score | t = 1.8477 < t0.05 = 1.7011 | D = 0.363 < D0.05 = 0.500 |
Balthazar’s index | t = 1.8585 < t0.05 = 1.7011 | D = 0.416 < D0.05 = 0.500 |
Comparison within acute biliary pancreatitis between subgroup A1 and A2 with Student’s t-test and Kolmogorov-Smirnov test.
Finally, we have compared the results of clinical severity score and modified CT severity index respectively within the subgroup A1 (Figure 2) and subgroup A2 (Figure 3).
Correspondence between Ranson’s score (X) and Balthazar’s index (Y) in the A1 subgroup in acute biliary pancreatitis.
Correspondence between Ranson’s score (X) and Balthazar’s index (Y) in the A2 subgroup in acute biliary pancreatitis.
In the subgroup A1 (pancreatic pattern), the results of two scores are overlappable (covariance = 0.000177 > 0). Otherwise in the subgroup A2, the data of the two scores are discordant. The results of this section of our study allow several considerations. First, we can identify in the group A (acute biliary pancreatitis) two subgroups: A1 (pancreatic pattern) and A2 (biliary pattern). In the subgroup A2, the pancreatic involvement (valued with modified CT severity index) was mild (pancreatic edema); on the contrary, in the subgroup A1, the pancreatic damage was moderate/severe or severe (Grade C2, D3); the difference between the two groups is statistically significant with Student’s t-test not with Kolmogorof-Smirnov test. The clinical severity (Ranson score) was comparable in both groups and of middle level. The comparison of bilirubin, AST, ALT shows impairment significant in the subgroup A2; not significant the differences for amylasemia, leukocytosis, and alkaline phosphatase. The therapeutic program followed the indication of clinical evaluation. The first approach is based on medical treatment: fluid-electrolyte replacement, control of pain, nutrition, control of papillary flow and, if necessary removal of persistent papillary obstacle. Patients (18) with pancreatic pattern (subgroup A1), after initial medical treatment, followed by improvement of general conditions and pancreatic involvement, have been treated 7–10 days after onset of disease with cholecystectomy (13 pts.). In five patients with cholestatic index and persistent CBD dilation was planned magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic sphincterotomy prior the cholecystectomy, delayed for few days but in the same hospital stay. All cholecystectomies were performed with laparoscopic approach. On the other hand, patients (12) with biliary pattern (subgroup A2) because severe damage of general condition, imminent risk of developing severe sepsis, clinical/instrumental evidence of biliary inflammatory disease within acute biliary pancreatitis, underwent emergency surgery (48 hours from onset). The intraoperative findings were acute cholecystitis (6), within two cases choledocolithiasis and cholangitis, in six cases gangrenous cholecystitis. In these patients was present pancreatic edematous impairment. The conversion rate of these procedures was 16.6% (2/12). In both subgroups, postoperative morbidity was Grade I and Grade II according to Clavien-Dindo criteria. In the subgroup A2, mortality rate was 8.3% (1/12) [23]. We can conclude that it seems possible to identify two types of acute biliary pancreatitis for which the therapeutic approach should be different. The pancreatic pattern characterized by preeminent pancreatic involvement requiring conservative treatment following the severity and evolution of pancreatitis; not delayed cholecystectomy, control, and treatment of papillary obstacle if present, prolonged control of pancreatic and peripancreatic fluid-necrotic collections, and so on. The biliary pattern is characterized by persistent, severe acute biliary tract disease, accompanied by mild or moderate acute biliary pancreatitis. This clinical-pathological condition should undergo urgent surgical intervention to treat the septic-inflammatory disease (acute cholecystitis, cholangitis, etc.).
Acute cholecystitis can develop some inflammatory complications that give rise to severe pathological conditions, gangrenous cholecystitis, gallbladder empyema, emphysematous cholecystitis, perforation of gallbladder, cholecystoenteric fistula, and gallstone ileus. These complications are life-threatening with risk of severe sepsis and septic shock evolution, peritonitis, and so on; it is mandatory urgent surgical procedure. Gangrenous cholecystitis is a very dangerous complication because of the difficulty of preoperative detection. Gangrene is the development of wall phlogosis, impaired blood supply, wall ischemia, gangrene; the final development of this complication can be the perforation. Gangrene is not frequent complication and perforation can occur in 5–10% of these patients. Gangrene as complication of acute cholecystitis occurs frequently in patients with compromised clinical conditions: diabetes, trauma, severe burns, prolonged TPN and stay in intensive care unit, cardiac surgery. Frequently perforation is localized in a circumscribed peritonitis, characterized by pericholecystic abscess limited with omentum and surrounding organs. Free perforation causes generalized peritonitis, accompanied by severe impairment of clinical course such as abdominal wall guarding, fever, increase of leukocytosis, start of severe sepsis and septic shock. Gallbladder empyema results as pus collection in the gallbladder because of bacterial overgrow. Obviously, the septic site can initiate severe sepsis and septic shock. The clinical picture is severe with abdominal pain in upper right quadrant, leukocytosis, fever, and tachycardia. Initial medical treatment with broad-spectrum antibiotics must be followed by urgent cholecystectomy. In the emphysematous cholecystitis is added the superinfection of gas-forming organisms (Clostridium Welchii, Escherichia coli, Klebsiella, etc.) [24]. This complication is uncommon and usually develops in males, old and diabetics patients. The most frequent evolution of gallbladder wall emphysema (75% of cases) is gangrene and perforation. Clinical course develops severe sepsis and septic shock. Imagine exams (CT scan) show gas in the gallbladder wall. Emergency surgery should be the correct treatment.
\nCholecystoenteric fistula can be due to dual pathogenesis: long-standing pressure necrosis by large stones and flogistic adhesion of gallbladder wall with adjacent hallow organs, followed by pathological communication. Most frequent communications are with duodenum (70–85%) and right flexure of the colon (15–20%) [25]. Cholecystoduodenal fistula allows the passage into the small intestine of gallstones, usually of large size that cause decubital effect. The stone progress in small intestine and in the narrowest part, frequently ileum, stops and determines mechanical obstruction, that is gallstone ileus (about 15% of patients with cholecystoenteric fistula). Clinical course of gallstone ileus develops as common intestinal obstruction. In the past decades, this clinical condition appeared in the characteristic way: acute cholecystitis treated with medical therapy, in 7–10 days improvement of signs and symptoms (decompression of the gallbladder because the fistula forms), in the following several days appearance of clinical features of intestinal obstruction (gallstone ileus). In the therapeutic program, the first step is the resolution of intestinal obstruction by enterotomy and stone removal. The treatment of cholecystoduodenal fistula should be performed in the same time or delayed for impaired general conditions of patients.
\nIn the uncomplicated cholecystitis, usually there are no increase of serum total and direct bilirubin and alkaline phosphatase (cholestasis indexes). If the signs of cholestasis occur, may be due to choledocolithiasis, cholangitis, or the Mirizzi syndrome. There are two types of Mirizzi syndrome: in type I, a large stone blocked in the cystic duct and in the Hartmann’s pouch of gallbladder compresses the common bile duct but without fistula between gallbladder and common hepatic duct. In the type II, due to necrosis of wall of common hepatic duct, there is a fistula with various degrees of defect of hepatic duct wall and presence of stone in hepatic duct. The first type can be treated with “partial” cholecystectomy and repair of bile duct with T-tube. The type II requires more complex procedure with complex dissection and hepaticojejunostomy. On the other hand, there are patients, in course of acute cholecystitis, with mild increase of amylase, AST, ALT, bilirubin caused by papillary passage of sludge, pus, and cholesterol crystals [26]. Moreover in several cases because transient papillary obstruction during transpapillary passage of small stones, can occur elevation of serum transaminase levels (AST, ALT), so called “gallstone hepatitis” [27].
Plain radiography is not very useful to confirm the diagnosis of acute cholecystitis. In few cases, it may detect biliary disease such as biliary stones (only 10–15% of stones contain calcium enough to be radiopaque), gallbladder wall calcified, pneumobilia; but unfortunately, these findings are not diagnostic for acute cholecystitis. The role of plain radiography remains crucial in any acute abdomen to rule out some pathological condition such as perforated hollow organs (pneumoperitoneum), and intestinal obstruction (air fluid levels).
Transabdominal US should be employed as completion of clinical examination in patients with abdominal pain. It is very important to define accurately the reliable data that the US can provide in different diseases that can cause an acute abdomen. The US can detect gallstones (acoustic shadowing behind to the stones) with sensitivity of 84% and specificity of 99% [28–30]. We have to remember some features that US can highlight such as mobile gallstones in the gallbladder, polyps, small stones attached to the wall, very small stones without acoustic shadow, and the fluid absence around the gallstones that make difficult their detection. Finally, there are also some false negative exams with US that range from 5 to 15% in acute cholecystitis [31, 32]. More crucial for the diagnosis of acute cholecystitis are the gallbladder wall edema or pneumatosis (“double wall sign”) and wall thickening; both features of inflammation condition. US can detect bile duct dilation and also the site of obstacle if present. The US can add some information about pericholecystic fluid collection or inflammatory mass in upper right abdominal quadrant but the complete definition of these findings should be obtained by CT scan.
CT scan has limited role in the diagnostic confirmation of uncomplicated acute cholecystitis because the same information and sensitivity of US (presence of gallstones, gallbladder wall thickening, dilation of CBD). On the contrary, CT scan is crucial in the diagnostic definition of complications such as pericholecystic fluid, gallbladder empyema, emphysematous gangrene, perforation, limited peritonitis with inflammatory mass, intrahepatic and extrahepatic bile duct dilation, choledocolithiasis, concomitant pancreatitis, hepatic lesions.
Magnetic resonance imaging (MRI) as CT scan is of little help in the diagnosis of simple acute cholecystitis. On the other hand, MRI is very sensitive in detecting the morphology of biliary tract, gallstones, and bile duct stones. Moreover, it is a noninvasive technique in the study of intra- and extrahepatic biliary ducts [33, 34]. Cholescintigraphy, noninvasive test, allows anatomic and functional evaluation of liver, gallbladder, bile duct. This nuclear medicine exam uses intravenous injection of hepatic 2, 6-dimetyl-imidodiacetic acid (HIDA) that is rapidly excreted in the bile. Cholescintigraphy allows the functional evaluation of hepatic ability to extract the radionuclide, the flow into the biliary ducts and gallbladder and finally the passage into the duodenum within 30–60 min. In the acute cholecystitis, cystic duct obstruction by stones prevents to visualize the gallbladder; also, stones in the common bile duct or papillary obstacle prevent the passage of radionuclide into the duodenum. The sensitivity and specificity of HIDA test in detecting acute cholecystitis reach 90–95% [35]. In our experience, we do not have used this exam that nowadays is less frequently used.
The first approach in patients with acute cholecystitis includes fluid resuscitation, analgesia, suspension of oral intake, nasogastric tube, broad-spectrum antibiotics. This therapeutic scheme, while widely shared, may subject to small variations in timing of each therapeutic measures and in the choice of the antibiotic. Should be discussed the use of nasogastric tube if it can be employed widely at the onset of the disease or selectively in case of nausea, vomiting, abdominal distention. Control of abdominal pain is an essential therapeutic target. For this purpose, nonsteroidal anti-inflammatory drugs are widely used for analgesia. These drugs inhibit the activity of cyclooxygenase 1 and 2 (COX-1 and COX-2) with critical reduction of prostaglandins formation. Prostaglandin E2 plays protective role on epithelial cells of gallbladder by secreting mucin; its reduction decreases this mucin production and consequently the distention of gallbladder wall. The therapy with a single broad-spectrum antibiotic can be correct for mild or moderate acute cholecystitis. In the severe cases should be used more selective antibiotics such as imipenem/cilastatine, third-generation cephalosporine and metronidazole. Bacteria present in acute cholecystitis are frequently Escherichia coli, Enterococcus, Klebsiella, and so on. In the treatment of acute cholecystitis, cholecystectomy plays the central role as standard management. This statement seems seemingly plain and without controversies. There are in the literature several points of wide discussion in which we will report also our experience. The timing of the intervention is very important topic: the choice between early and delayed cholecystectomy with various operative outcomes. The first item to make is to define “early intervention.” Within acute cholecystitis, there are several clinical pathological conditions that are the evolution of the inflammatory/septic process, from mild to severe, life-threatening forms. The reasonable options, always in urgent approach, can vary from emergency to intervention within 24–48–72 hours (early procedures). Another consideration adds uncertainty in the choice of timing of intervention because the dissection difficulties of inflamed operative site, with the possible increase of intraoperative morbidity that can be very severe in both approaches, laparoscopic and open [36].
\nIn our experience about cholecystectomy morbidity, in the group which includes also the acute cholecystitis, we have compared the outcomes in two following periods: first period 2006–2008 and second period 2009–2011. Total morbidity in the second following period was markedly reduced from 18.5 to 9.96% (p = 0.009). With regard to morbidity by incomplete preoperative evaluation and surgical error, we have defined some criteria to increase the control and prevention: acceptable general anesthesia, clear visibility of surgical site, optimal exposition of the hepatic hilum and its structure, control of possible anatomical variations, finally convertion to open cholecystectomy if necessary [37]. Employing, since 2002, of antegrade dissection in laparoscopic cholecystectomy as standard technique allows reduction in intervention time (mean operative time 40 min) and decrease of the conversion rate (from 3.4 to 0.8%) in the comparison with common retrograde approach [38]. Minor postoperative morbidities as wound infections can be prevented following correct criteria of medications. In our experience, topical antibiotic application may reduce surgical wound infection in umbilical site after laparoscopic cholecystectomy [39]. Concerning the subhepatic collections, in our opinion, the common use of subhepatic drainage after cholecystectomy for acute cholecystitis enables the correct drainage of serous and/or serohematic secretions usually present in the first days in inflamed surgical site.
\nThere are in the literature several reviews regarding the timing of early or delayed cholecystectomy and the comparison of its operative morbidity. Tokyo guidelines suggest a therapeutic program for acute cholecystitis based on precocious severity assessment as guide for treatment choices. Mild acute cholecystitis should undergo early laparoscopic cholecystectomy, within 72 hours from onset with possible improvement of other medical problems. For moderate forms also should be performed early cholecystectomy with laparoscopic or open approach (conversion to open following difficult dissection). Severe acute cholecystitis can show, in addition, damage of general conditions (organ dysfunction) which needs to treat. For these clinical-pathological conditions, urgent surgery is necessary: the type of surgical procedures is connected with pathological findings such as gangrenous or perforated cholecystitis, local or generalized peritonitis, involvement of adjacent organs. The urgent procedures vary from cholecystecyomy to cholecystostomy, percutaneous gallbladder drainage, and so on. The revision of Tokyo guidelines [40] confirms the first choice of laparoscopic early cholecystectomy but without the exact definition of time of precocious intervention. We can underline that in the Tokyo guidelines is reported also the elective cholecystectomy, in all degree of severity, after improvement of the acute inflammatory process [41–43]. Nevertheless, another confirmation of the validity of early cholecystectomy, within 24 hours, regarding minor morbidity and lower cost, has been presented by Gutt CN [44]. More selective criteria have been used in order to bind the study of patients with acute cholecystitis excluding very severe forms (need of intensive care admission, urgent cholecystostomy, etc.) by Canadian Researchers. They employed a population-based analysis (20,000 patients—period 2004–2011) for comparison of operative outcomes of early and delayed cholecystectomy [45].
\nThis study showed, in the comparison of delayed cholecystectomy, that early cholecystectomy in the treatment of acute cholecystitis was associated with a lower risk of major bile duct injury, of operative mortality, of postoperative (30 days) mortality (respectively 1.36 and 0.46%) and finally a shorter hospital stay. It is also demonstrated almost same conversion rate between early and delayed laparoscopic cholecystectomy. Obviously early cholecystectomy put in a safe place for risk of recurrent gallstone disease. Similar results have been reported from other studies: early laparoscopic cholecystectomy (performed within 48 hours) is associated to better postoperative outcomes with lower morbidity and hospital stay [46, 47]. A very interesting French study evaluated the choice for optimal timing for early cholecystectomy [48]. Patients with acute cholecystitis from the French National Health Care database have been studied: 42,452 patient—507 hospitals—period 2010–2013. The exam of the literature shows the therapeutic indication of early laparoscopic cholecystectomy as standard procedure for acute cholecystitis. Nevertheless, with exception for urgent surgery indications (sometimes with various procedures) in case of very severe cholecystitis as perforated, gangrenous forms with local or generalized peritonitis, the time of “early surgery” is not well defined. Polo et al. in this study show that the optimal time for laparoscopic cholecystectomy in acute cholecystitis is between the first and third day after hospital admission. In this time interval is recorded lower risk of mortality and lower morbidity: common bile duct injury, reoperation rate, postoperative sepsis, conversion rate, and finally minor length of hospital stay and cost. The definition of best time for surgical procedure always has an element of uncertainty because it is very difficult to report the onset of the symptoms and is instead reported the hospital admission. To assess the significance of this inaccuracy is very difficult. Moreover, this study report also not negligible morbidity and mortality (range from 0.8 to 1.4%) for the patients treated within the first 24 hours. This particular result, in our opinion, proves the need, also in the program of early cholecystectomy, of a brief time interval for supportive therapy, and resuscitation to improve the general condition in patients with severe cholecystitis and septic complications. It is evident in the recent literature that the first, preferred choice for acute cholecystitis is the laparoscopic approach with conversion rate ranging from 10 to 15%. The first choice of the open approach should be limited to peritonitis, perforated chilecystitis but always as personal choice, that cannot be standardized. In the setting of the therapy of acute cholecystitis, we can propose the presentation of a series of consistent clinical cases, observed and treated in our Institution in the period September 2014–September 2016, to show our treatment program. In the chosen period, we have treated 42 patients with acute cholecystitis. Demographic data are the following: male 45.2% (19/42), female 54.7% (23/42), mean age 59.6% (range: 20–87 years). Furthermore, we have recorded the pathological features of the patients (Table 5).
Acute cholecystitis | 26 |
Severe cholecystitis | 16 |
Hydrope | (2/16) |
Emphysematous | (3/16) |
Gangrene/perforation | (7/16) |
Patients | 42 |
Pathological features in acute cholecystitis (September 2014–September 2016).
Therapeutic program in severe cholecystitis with complications, characterized by severe morbidity and mortality, demands ready surgical intervention. In our patients with severe acute cholecystitis (38%), prompt surgery was performed few hours after hospital admission; two patients needed preoperative intensive care and they were treated within 24 hours. The patients with acute cholecystitis were treated with laparoscopic early cholecystectomy performed within 72 hours (range: few hours–72 hours) based on the needs of preoperative treatments related to comorbidities. All these interventions start with laparoscopic approach and the conversion rate was 21% (9/42). Postoperative outcomes were characterized by minor morbidity, no mortality and the postoperative hospital stay was in mean 4.2 days (range: 2–14).
\nLaparoscopic cholecystectomy for acute cholecystitis, because of the inflammation and severe pathological involvement in the operative site, can be in most cases a “difficult cholecystectomy.” Our experience and other from the literature have shown that laparoscopic difficult cholecystectomies for acute cholecystitis are safe and effective and are associated with lower incidence of minor and major postoperative complications, moreover with several advantages as less respiratory infections, shorter postoperative course, and shorter hospital stay. Laparoscopic approach decreases some complications of laparotomy as infections, dehiscence, and laparocele [49–51].
\nThere is an impending risk of lesions of common bile duct during cholecystectomy for acute cholecystitis. The adoption of an operating procedure that puts at minor risk biliary duct lesions should be proposed. Gallbladder antegrade dissection is an operative procedure employed also in the past for open cholecystectomy. This well-known type of dissection has been proposed in the laparoscopic approach. Several data from the literature demonstrate the frequent use of this operative procedure in difficult cholecystectomy because of acute flogosis and the decrease in conversion rate to open with antegrade dissection [52, 53].
\nIn our study, we have compared postoperative results of two groups of patients submitted to antegrade dissection and retrograde dissection in laparoscopic approach [54]. This study shows that antegrade dissection in laparoscopy for acute cholecystitis with phlogosis of Calot’s triangle is safer procedure in comparison to retrograde approach, seems to reduce the operative time, and should significantly decrease the risk of intraoperative complications such as common bile duct injury and hemorrhages. In our opinion, confirmed by more recent experience, antegrade dissection may be proposed as a standard procedure of cholecystectomy and not only for interventions in the acute cholecystitis [38].
\nMoreover, there are some specific problems related to urgent cholecystectomy in cirrhotic patients. Cholelithiasis in cirrhotics occurs twice as often in the general population with a reported incidence of 9–13% versus 5% in non-cirrhotic patients [55]. Major incidence of cholelithiasis is due to several factors with various pathogenesis: hypersplenism, increased level of estrogen, increased intravascular hemolysis, reduction in gallbladder emptying, and motility. In our experience, published some years ago [56], this epidemiologic characteristic was confirmed. In this study, we have evaluated 65 cirrhotic patients with symptomatic gallstone disease treated with laparoscopic cholecystectomy in the decade 2002–2012. This group of patients has been compared with 81 non-cirrhotic patients with symptomatic gallstone disease, no significant morbidity and no significant differences in demographic data, and underwent laparoscopic cholecystectomy in the period October 2011–May 2012. Within the group of non-cirrhotic patients, the incidence of acute cholecystitis was 13.5% (11/81) and there are not further complications; on the contrary, in the cirrhotic group, the incidence of acute cholecystitis reached 27.6% (18/65) with several complications such as 1 cholangitis, 2 gallbladder hydrops, 2 gallbladder empyema, 3 gangrenous cholecystitis. The cohort of cirrhotics evaluated by Child-Pough classification shows 43 patients in A score (66.2%), 19 in B score (29.2%), and three patients in C score, medically treated preoperatively and reclassified in B8 score. Cirrhotic patients have undergone cholecystectomy: six with open approach as first choice, 59 with laparoscopic procedure with conversion rate 20.3%. The comparison of the results between the two cohorts of patients has been evaluated (Table 6).
VLC (47) | Open (6) | Converted (12) | ||
---|---|---|---|---|
Operative time (minutes) | 88.9 | 141 | 149 | 85 |
Hospitalization (days) | 4.8 | 9.1 | 8.1 | 3.2 |
Conversion rate | 20.34% | - | - | 3 (3.7%) |
Mortality | - | - | - | - |
Blood transfusion in peri-operative time | 2 (4.2%) | 1 (16.6%) | 2 (16.6%) | - |
Blood products transfusion in peri-operative time | 7 (14.9%) | 1 (16.6%) | 4 (33.3%) | - |
Hemoperitoneum | 1 (2.12%) | - | - | - |
Reintervention | 1 (2.12%) | - | - | - |
Pleural effusion | - | - | 2 (16.6%) | - |
Pulmonary condensation | - | - | 1 (8.33%) | - |
Trombocytopenia | - | - | 1 (8.33%) | - |
Atrial fibrillation | - | - | 1 (8.33%) | - |
Incisional hernia on umbilical port site | 4 (8.51%) | - | - | 2 (2.46%) |
Peri- and postoperative morbidity outcomes in cirrhotics (65) and in control group (81).
In this experience, laparoscopic cholecystectomy morbidity in cirrhotic patients is slightly increased compared to non-cirrhotics. Moreover, postoperative morbidity in cirrhotic patients is minor on the whole with laparoscopic approach than open procedure. Cholecystectomy in cirrhotic patients is associated with non-negligible rate of morbidity and mortality. The more frequent complications are blood loss, postoperative liver failure, and sepsis [57, 58]. Postoperative liver failure is due to the anesthetic agent’s action, which decrease hepatic arterial blood flow (the ability of cirrhotic patients to compensate for this ischemia is impaired) [59]. Diminished Kupffer cell function leads to reduced clearance of the enteric organisms, endotoxinemia, and risk of infection in cirrhotic patients. The increased risk of bleeding is related to reduced prothrombin time, thrombocytopenia, and portal ipertension. Finally, patients can have a gallbladder with a significant intrahepatic component due to atrophy of the right hepatic lobe and a hypertrophic left lobe with more difficulties for intervention [55, 60–62].
\nThe last evolution in the surgical treatment of acute cholecystitis is the robotic approach. On the whole, the main advantages of robotic surgery can be realized in some phases of complex laparoscopic procedures requiring high dexterity and best visualization. In this perspective, robotic approach for cholelithiasis and later for acute cholecystitis should be the start of valuable learning curve for robotic advanced skills in general surgery. Our experience in the field of gallbladder lithiasis confirms the safe feasibility of robotic approach that requires the use of standardized procedures. The obvious purpose of this approach, however, in the cholecystectomy, is the improvement of the technical skills in advanced and more complex robotic assisted surgical procedures [63]. The comparison of the results of laparoscopic versus robotic cholecystectomy proves the complete equivalence between both the procedures regarding of safety and feasibility in all types of gallbladder’s pathology. In particular, acute cholecystitis can be treated with robotic-assisted approach showing postoperative overlapping outcomes with symptomatic gallstones disease [64]. On the contrary, the data from a study based on the literature search with randomized controlled trials and population-based analyses shows that the advantages of current use of robotic surgery in cholecystectomy are not provable [65].
Acute cholecystitis encompasses clinical forms with various degree of severity and several cases (8–10%) present pathological findings that can make the operative site a surgical challenge, very difficult to treat. Indeed the laparoscopic approach, worldwide more common choice in the treatment of acute cholecystitis, presents significant conversion rate to open procedure (10–15%). Furthermore, besides more common clinical, laboratory, and instrumental features of acute cholecystitis, there are some diagnostic pitfalls, such as the biliary pattern that should be distinguished from the pancreatic pattern in the field of acute biliary pancreatitis. The treatment is focused on early laparoscopic cholecystectomy well defined usually within 24–72 hours. Nevertheless, severe, complicated acute cholecystitis can require urgent surgical intervention. Finally should be evaluated some particular components of a complex clinical problem such as laparoscopic antegrade dissection in acute cholecystitis to allow minor risk of biliary duct lesions, the control of the specific problems related to urgent cholecystectomy in cirrhotic patients, and finally the possible future increased use of robotic approach in the treatment of acute cholecystitis.
Thanks to improved storage capacities, databases in various fields such as banking have grown up to a rich level. Most of the strategic sales and marketing decisions are taken by processing these data. For example, strategies such as cross-sell, up-sell, or risk management are being created as a result of processing the customer data. Because of the increasing number of customers and the need for a higher processing capacity, it has made it more difficult to identify the customer requirements in a rapid and accurate way and to present solution recommendations. Innovative data mining applications and techniques are required to solve this issue [1].
The market basket analysis is one of the data mining methods applied to identify the pattern which is found in product ownership data of customers. Thanks to this analysis, a pattern among the products frequently bought together by the customers can be established. The obtained pattern plays an active role in developing cross-sell and up-sell strategies.
Market basket analysis consists of two main processes. These are clustering and association processes, respectively. The clustering process involves grouping of similar customers in terms of clusters. Thus, those customers which should be examined in the same category will be identified. During the association process, commonness in buying behavior of customers through a selected cluster is being identified, assuming that clustered customers having similar characteristics would demonstrate similar buying behaviors.
As the banking databases have grown up to a very high volume, the association process has become a very costly process in terms of time and memory consumption. In order to improve the time and memory performance, sampling process should be included in the previous phase of association.
In this regard, a sample which involves less observations in comparison to the whole data is used. We use the term “space” to refer the whole data set. In case the representation capability of the obtained sampling is high, loss of data is minimized, and the association process is realized through the sample instead of the space itself. Thus, less data shall be processed, and association rules (ARs) shall be obtained faster by consuming less memory.
As the subject of this book chapter was focused onto the banking data, customer segmentation conducted by the bank data was accepted as the clustering. As a result of the segmentation, clusters created by similar customers were used as input of sampling.
In this chapter, sample creation methods, techniques to find ideal sampling size, the space representing capability of these samples generated by these techniques, and association rules discovered through these samples were examined, respectively. Association rules obtained from both the space and sample were used to verify the sampling process. Besides, the spared amount in terms of time consumption was calculated.
This book chapter was organized as follows: Section 2 explains the studies toward deriving association rules through the space and sampling. Section 3 explains the parameters required to obtain association rules and the Apriori algorithm. Section 4 contains parameters to create the sample, sample creation methods, and the techniques used to calculate the sample size. Section 5 examines association rules obtained from the space and the sample and the results showing the representation capability of the sample for the respective space and the results showing rewards in terms of time consumption. Section 6 gives an overview and concludes the chapter.
In association rule mining, first the item sets, which are found together frequently, are found, and then the rules are obtained from these item sets.
Association algorithms are classified according to characteristics of the obtained item sets. In early studies Agrawal-Imielinski-Swami (AIS) algorithm which was allowed to find wide item sets was used, and then algorithms were found such as Apriori, which were used frequently now and which were able to process the bigger data sets faster [2].
The mutual usage of association discovery and sample creation methods is not a new approach. Sample creation studies toward association detection have begun with papers demonstrating mathematically that it was possible to create a sample which maintained the characteristics of the space. The following studies involved several techniques calculating the optimal number of observations [3, 4, 5, 6, 7].
At the beginning of the sample size detection studies, the data to be sampled were not considered; they have tried to determine the sample size using parameters not depending on the data such as margin of error, minimum support, and minimum confidence [3]. In current studies, formulas (using variables such as maximal process length or Vapnik-Chervonenkis (VC) size of the data cluster) considering the data characteristics have appeared [4, 5, 6, 7]. There exists a number of studies focusing on how the management of metadata of big data sets are provided in a distributed computing setting [8, 9, 10, 11]. Moreover, there exists a number of studies that are conducted in the field of information systems for managing distributed data storage platforms [12, 13, 14, 15, 16]. Unlike these studies, this chapter focuses on extracting meaningful information, i.e. association rules, from the big data sets. Initial results of the experimental studies, covered in this chapter, were reported in a previous study [17]. Sections 3 and 4 give detailed information on association detection and sample creation methods, respectively, and explain the techniques used in this study.
In data mining, it is used to determine the pattern found among the association algorithms and observations [2, 18, 19]. In case any organization’s transaction database is discussed, an analogy can be established between the observations and customers and between areas where a pattern is tried to be found and the bought products. Patterns obtained by association algorithms are processed to obtain association rules.
Association rules may be defined as follows: let us call each subset of products within the database an “itemset,” and let us call each set of products purchased together by the customer a “transaction.” The support count of any itemset is defined as the number of transactions associated with the items in the set within the database. The support indicates the ratio of support count to the number of transactions within the database. The itemset which meets the minimum support requirement is called the frequent itemset (FI).
For example, if a database with 10 transactions contains product A in 3 different transactions, then the product A’s support count is 3, and its support is 0.3. In case the minimum support is defined by a value lower than 0.3, then the product A will be classified as FI.
There are several algorithms deriving FI using the transactions within the database [2, 18]. In this chapter, Apriori algorithm was preferred due its ability of deriving all itemsets within the space. This algorithm derives primarily candidate itemsets starting with one-element itemset from the database. Those providing minimum support from candidate itemsets are filtered and recorded as FI. New candidate itemsets are created from the FI obtained in the previous step by increasing the number of elements. In each step, the candidate itemsets are passed through a minimum support test, and the algorithm continues until no FI with k-elements can be generated.
Among the elements of the FI obtained from the database, it is possible to derive association rules in A- > B format. Then, AR’s support gets equal to AUB itemset support. The confidence is defined as the ratio of AUB itemset support to the A itemset support. AR should meet the minimum confidence requirement specified by the customer [2].
Assuming that A - > B rule has a support of s and the confidence of c, we can derive that the itemsets A and B in the whole database are associated with a probability of s and a customer owning the itemset A might be an owner of the itemset B with a probability of c.
To find out all ARs within the database, a rule mining algorithm is applied to each FI obtained. Candidate rule combinations are created for rule mining among all subsets of a selected FI in A - > B format. Those providing minimal confidence from candidate rules are filtered and recorded as association rule.
Sample creation is the process of creating a subset containing the characteristics of a data set. The subset created through sampling is expected to represent the data set (space). In traditional statistical methods, the similarity of two data sets is measured by either χ2 test or Kolmogorov–Smirnov (K-S) test.
In this study, these tests were utilized, in order to measure the similarity of the created sample in comparison with its space. A comparison was conducted through p values (the probability p of finding the space characteristics) of the statistics resulting from both tests. In case the obtained p value exceeds 0.05, it can be deducted that “the sample is similar to the space with a probability of at least 95%.”
Sample creation is discussed under two topics, i.e., sample creation methods and sample size determination techniques. Sample creation methods are explained in Chapter 4.1 and sample size determination techniques explained in Chapter 4.2.
When creating samples from the space, it is possible to use several sample creation methods. These methods are classified according to the selection of observations from the space. The main sample creation methods are as follows:
The observations within the space are selected without following a specific routine. The selection probability of each observation is equal.
Systematic sampling: The observations within the space are numbered. Sampling interval is created by dividing the space size to the observation size. A random number is selected. The observation sample at this number from each interval is included.
This is used where the observations within the space can be divided into groups. The samples are created maintaining the ratio between the number of observations of groups within the space and the total number of observations. The selection probability of each observation in the same stratus is equal.
This is used where the observations within the space can be divided into groups. After the groups are determined, they are selected using the simple random sampling method. All observations within selected groups are included into the sample.
This is used where the observations within the space can be divided into groups. After the groups are determined, groups are selected by the simple random sampling method. Unlike cluster sampling, observations to be selected from groups are determined by the simple random sampling method.
Among the mentioned methods, the simple random sampling method stands up by its high speed. As the methods, which require creation of groups within the space and sorting of observations, need a pre-analysis, their time consumption is more than the simple random sampling method.
The expected parameter in sample creation methods is the size of the sample to be created. When the optimal sample size is calculated, a number which will not decrease its space representing capability should be found. Under association detection algorithms, it is important to derive all FIs and ARs within the space from the sample. In this study, techniques specialized on association detection algorithms have been examined from those developed for sample size determination [3, 4, 5, 7]. Sample size determination techniques are divided into two groups to minimize the FI and AR loss.
When the association algorithms will be run using the same parameters, support and confidence values calculated from the sample appear to be different than their counterparts calculated from the space. This margin of error is measured using two different methods. When calculating absolute margin of error, the absolute value of the difference between values from the space and the sample is considered. The relative margin of error is calculated by dividing absolute margin of error into the value within the space. In Table 1, the lines containing “absolute” at the “type of technique” column aim at reducing absolute margin of error, while those containing “relative” aim to minimize relative margin of error.
Sample size calculation techniques are provided.
Minimal sample size can be determined in terms of accuracy ε, probability of error δ, minimum support Θ, minimum confidence γ, d-index value of the space v, maximal process length of the space ∆, and the constant c. In formulas, the value η is calculated depending on variables Θ, γ, and ε; and the value p is calculated depending on values η and Θ.
All examined techniques are shown in Table 1 with suggested formulas and type of formula. The values found through the techniques determine the minimum number of transactions required for sample creation. The number of transactions which are equal to the values found is selected from the space by the preferred sample creation method.
Sample size determination techniques determine the minimum number of transactions required for sample creation. The number of transactions which are equal to the values found is selected from the space by the preferred sample creation method.
The complexity of the space is calculated theoretically using the Vapnik-Chervonenkis size [20]. Assuming that the transactions within the database are sorted according to their number of elements and that the “number of transactions” and “number of elements” are plotted on the coordinate system, the d-index value would correspond to the edge length of the largest square.
In this study, we use a d-index algorithm, which does not seek a sorting requirement among the transactions, and it calculates v (d-index value), by initializing with 1 and by increasing it. All transactions within the database should be scanned to find the value. Where a number of transactions are large and the item number within each transaction is less, such as banking data, the length of transactions becomes decisive in determining the d-index value. In d-index algorithm, the transactions within the database were sorted in descending order of item numbers, and the value v was calculated decreasingly beginning from the maximal transaction length. Here, it is not necessary to scan all transactions.
The tests were performed on product ownership data of banking customers. Statistical studies’ code development was performed on the widely used R programming language.
When tests were performed, the steps below were followed:
Determine the sample size utilizing various techniques
Create three different samples for each technique using the simple random sampling method
Compare the representability of the space for the obtained sample examination with χ2 and K-S tests
Use the Apriori algorithm included in the arules package of R language, and determine the FI and AR through the space and sample
Calculate the absolute error in support and trust values, and compare the results with those obtained from the space
Compare the duration of obtaining AR and the duration of sample creation. Generate AR from the sample
Theoretically, it is expected that the samples in various sizes obtained from FI and AR results are tuned with the results from the space, that there is a correspondence between representability and absolute error, and that the duration of transactions made on the sample and the memory consumption reduce.
To accelerate the test processes, instead of 143 products of the bank, 10 different product groups were determined, and the association between those groups was examined. The utilized banking data is a matrix including 1,048,575 customers and an ownership status of customers about 10 different product groups. The lines represent customers and the columns represent product groups. In case the customer owns a product, the intersection of that line-column indicates 1, otherwise 0. In these tests the following parameters were used: accuracy ε = 0.04, probability of error δ = 0.07, minimal support value Θ = 0.02, and minimum confidence γ = 0.06, 0.1, and 0.14.
Table 2 shows varying sample sizes corresponding to varying minimum confidence values. Because γ was not used as a parameter in formulas Toivonen, Chakaravarthy FI-absolute, Chakaravarthy AR-absolute, Riondato FI-absolute, and Riondato FI-relative, there are no variations in calculated sizes.
Calculated sample sizes based on varying minimum trust values are provided.
Techniques where the calculated size is larger than the space were not used at the sample creation step.
When Table 2 was examined in detail, it is obvious that the sizes obtained from the techniques Chakaravarthy FI-absolute, Chakaravarthy AR-absolute, Riondato FI-relative, and Riondato AR-relative are larger than the space (1,048,575). As the aim was to reduce the data set, these techniques were not examined in the following tests. In order to minimize the error due to simple random sampling method, three samples were created for each of the Zaki, Toivonen, Riondato FI-absolute, and Riondato AR-absolute techniques.
Table 3 shows average p values calculated from χ2 and K-S tests. As the similarity significance between the space and sample was accepted as 95%, it is expected that p values are higher than 0.05. The results indicate that values were obtained to prove an adequate statistical similarity between the space and all obtained samples. An instability is obvious regarding p values of Toivonen where the sample size does not vary. We consider this instability results from the small sample size provided by this technique.
p values calculated from χ2 and K-S tests were provided based on minimum trust values.
All the techniques were found to be similar to the space.
FIs and their corresponding ARs were determined from the samples created using Apriori algorithm. To measure the similarities of FIs and ARs, absolute error was calculated through support and trust values. Zaki and Toivonen techniques were inadequate to determine all FIs and ARs existing in the space for the value γ = 0.1. Because a loss of rule was undesirable, we have observed that these two techniques were not suitable to sample creation and time consumption tests were not examined. By calculating the error by substituting incomplete values with 0, the results on Table 4 were obtained. As expected, where absolute support error was high, an also high-confidence error was found.
Average support and trust absolute error generated based on varying minimum trust values are provided.
Techniques where AR loss was experienced were not tested in terms of running time.
In a comparative review of Tables 3 and 4, no relation was detected between support and confidence errors by the results obtained from χ2 and K-S tests. We have noticed that traditional statistical measurements were inadequate in measuring the representability of the sample which was created for association mining.
In Table 5, durations until creation of AR are provided for the space and created samples. While the duration from sample creation until obtaining the AR was provided for the space, the time required for sample size determination, total average time required for sample creation, and obtaining the AR by simple random sampling method were provided for the samples. As expected, the time performance of all techniques for each value γ was found better than the space. Even more benefits are expected by using actually 143 different products instead of 10 product groups in these tests.
The time until rule mining based on varying minimum trust values γ was given in seconds.
Techniques where AR loss was experienced were not tested in terms of running time.
FI and AR results of the samples were compared to those generated from the space. Within the space, the mostly encountered depository (D) product has a ratio of 94%, credit card (CC) product has 11%, and installment loan (IL) product has 8%. These products are found together within the space by a ratio of 2.3%. In spite of this low support value, three different rules with high confidence were derived. “CC, IL → D” rule was derived, and eventually, it was observed that 92% of people who have bought CC and IL also have bought D. According to another derived rule “IL, D -> CC,” it was discovered that 31% of people who bought CC and D also bought IL. It was also found through another rule CC, D - > IL that 28% of people who bought IL and D also bought CC. These rules could not be derived from the techniques Zaki and Toivonen, and information loss was experienced. Therefore, these techniques are not suitable on sample creation for association mining. As expected, when sample size increased, the obtained absolute error in results decreased.
The utilized banking data contains information about customers and the product groups of their owned products. In other words, instead of products owned by customers, banking product groups were used. This was preferred to reduce the data set sparsity and to accelerate the test speeds. So, it was observed that even tests on the space did not take longer than 2 seconds. Whenever the advantages in terms of duration seem to be in the order of seconds, tests to be conducted with a data set containing more products (or product groups) will show decisive advantages.
Because AR mining process through the space takes a long time, we have aimed at determining a smaller sized sample representing the space and AR mining through that sample. For this purpose, in this book chapter, we have investigated for techniques which provide an ideal sample size specialized on association mining.
The samples were created using the simple random sampling method, and three different samples were obtained per technique. We have tried to prevent a potential noise in our results by creating multiple samples.
The similarity of samples to the space was measured by the χ2 test and K-S test. It was obvious that after both tests the obtained values for association mining were inadequate in measuring the representability of samples. In those tests, no relationship was found among support and confidence error values. We consider that the probability of tests giving biased outputs and the inadequacy of suggested sample sizes in measuring were the reasons for having these results.
The results indicate that the duration of AR generation within the space was compared to the total time of sample size determination, sample creation, and AR generation through the sample. It was observed that each technique was better performing in terms of space results. Riondato FI-absolute and Riondato AR-absolute techniques have given good results based on calculated absolute error values. When smaller sample size and less time consumption criteria were considered, Riondato FI-absolute technique becomes favorable.
In future studies, the data set shall be renewed in this regard, and other sample methods will also be applied. Besides, results which might be related to a single data set shall be extended with tests to be performed on another data set, and the results shall be cross-checked.
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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