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Pandemic Influenza A (H1N1) 2009 outbreak investigation in Nepal
Abstract
The World Health Organization, on 24 April 2009, announced a Public Health emergency of international concern caused by a new influenza virus Pandemic Influenza A 2009. The objective of this study was to analyze the basic epidemiology and distribution of Pandemic Influenza A 2009 in order to understand the course of Pandemic Influenza A 2009 in Nepal.
The analyses were based upon all confirmed and probable cases that consulted Avian Influenza Control Project and National Public Health Laboratory during 29 April 2009 to 21 September 2010.
Out of total 739 suspected samples collected, Pandemic Influenza A 2009 was detected in 210 cases in different districts of Nepal. The majority of cases were from the urban settlement of Kathmandu valley, Chitwan and Kaski and among age group 11-30 years. The clinical attack rate for Influenza like illness (ILI) was 28.48%. There was no significant difference between the clinical presentation of ILI and confirmed cases of Pandemic Influenza A 2009.
This study presented the investigation of outbreak that helped to inform the course of epidemic in affected population and therefore urge for public health interventions.
... However, H7N9 and other HPAI viruses were not detected [157]. Different studies reported pandemic H1N1 in Nepal [158,159]. [161]. Since the 2009 outbreak, the impacts have spilled across the country. ...
Avian/Bird flu is a viral disease of birds, caused by avian influenza virus (AIV). A highly pathogenic avian influenza (HPAI) H5N1 has breached the barrier of species to humans and other animals escalating the pandemic threat. If the H5N1 evolves to a human-to-human transmissible virus retaining its pathogenicity, it can trigger an influenza pandemic. H5N1 has a mortality rate of about 60%, varying with strains. Meaningful antigenic alteration in hemagglutinin (HA) and/or neuraminidase (NA) results in recurring pandemics. The HPAI H5N1 subtype alone has outreached more than 77 nations around the world since the first human case and death was reported in 1997. Wild and migratory birds are the AIV reservoirs. Poultry is primarily impacted by incidents and outbreaks of the disease. A wide range of serological and molecular methods have substantially aided in the identification of bird flu in humans. Candidate vaccines have been developed, yet are not ready for widespread use. Oseltamivir (brand name: Tamiflu) is the preferred drug for the management of human Influenza-like illness (ILI). Surveillance, mass awareness, and pandemic preparedness abiding WHO recommendations are of paramount importance for the prevention of bird flu outbreaks.
... Since then, Nepal has an increasing number of influenza positive cases with two major epidemics in year 2004 and 2009 [13,14]. The epidemic in 2009 was due to influenza A (H1N1) whose first case was seen in June 2009 among people returning from US [15,16]. In the very preliminary phase of diagnostic services of influenza virus in Nepal, we had very limited information about influenza infection and its types. ...
Background:
Influenza is a highly contagious viral respiratory infection caused by influenza viruses whose epidemic and pandemic have resulted in significant morbidity and mortality. The annual epidemic of influenza results in an estimated 3-5 million cases of severe illness and about 290000-650000 deaths globally. The vaccination program has been successful to control the epidemic however, it further needs improvement. This study was aimed to investigate the types of influenza viruses prevailing in Nepal during 2016 and, to match the recommended vaccine for use during the same season.
Methods:
A descriptive cross sectional study was carried out at National Public Health Laboratory, Kathmandu, Nepal for the period of one year (Jan-Dec 2016). A total of 1683 throat swab specimen was collected from patients of different age group referred to NPHL for influenza testing. The specimen was primarily stored at 4 °C and processed using ABI 7500 RT PCR system for the identification of influenza viruses.
Results:
Of the total 1683 patients suspected of having influenza infection, influenza viruses were isolated from 614 (36.5%) patients with male predominance. The highest number of infection was caused by influenza A/H3 strain (51.0%) followed by influenza B (40.4%) and influenza A (H1N1) pdm09 (8.6%). Two peaks of infection were observed during the year 2016. The widely available trivalent vaccine during the season did not match the prevailing strain because of the dominance of B/Yamagata lineage over B/Victoria lineage.
Conclusion:
We concluded that Nepal experiences semiannual cycle of influenza infection, firstly during the month of January-February and secondly during the month of July-August. The vaccine to be introduced in Nepal need to be decided by national authority based on prevailing influenza types to confer effective immunization.
... seroprevalence studies, epidemiological studies in different populations, mathematical models, etc. Other experiences in smaller groups of population provide additional results: 3.15% in a train in China [25], 4% in a primary school in China [26], 22% on a Peruvian Navy ship [27], 28.5% during an outbreak investigation in Nepal [28]. ...
The response to the emergence of the 2009 influenza A(H1N1) pandemic was the result of a decade of pandemic planning, largely centred on the threat of an avian influenza A(H5N1) pandemic. Based on a literature review, this study aims to define a set of new pandemic scenarios that could be used in case of a future influenza pandemic. A total of 338 documents were identified using a searching strategy based on seven combinations of keywords. Eighty-three of these documents provided useful information on the 13 virusrelated and health-system-related parameters initially considered for describing scenarios. Among these, four parameters were finally selected (clinical attack rate, case fatality rate, hospital admission rate, and intensive care admission rate) and four different levels of severity for each of them were set. The definition of six most likely scenarios results from the combination of four different levels of severity of the four final parameters (256 possible scenarios). Although it has some limitations, this approach allows for more flexible scenarios and hence it is far from the classic scenarios structure used for pandemic plans until 2009.
Introduction: On 2015, a cluster of chickenpox like symptoms was reported in Baidauly VDC of Nawalparasi, Nepal. This study aims to report the outbreak investigation and guide preventive and control measures.
Methods: This investigation was conducted in Baidauly VDC of Nawalparasi, Nepal where a large number of cases with infectious rashes with fever was reported. Data were collected using a semi-structured questionnaire comprising of socio-demographic characteristics and clinical features. A detailed clinical examination of the cases was also performed. The outbreak was described by time, place and person and the epidemiological curve drawn.
Results: A total of 55 cases from 27 households were affected by chickenpox. The outbreak continued for 45 days. The number of cases peaked (n=25) one month after detection of the primary case. The last case was reported after 15 days of the peak. The commonest age group affected was 5 to 15 years with a mean of 11.3 years (SD 8.9). The mean duration of rashes was 7.2 days (SD 1.7) which ranged from 3 days to 12 days. All the cases had rashes on head/face, trunk, arm and legs, and some had rashes inside the mouth (n=8) and palm (n=5). Almost 95% (n=52) cases experienced fever.
Conclusions: This study concluded that there was an outbreak of chickenpox. The signs and symptoms of the disease were due to chicken pox infection. Immediate preventive and control measures were recommended to halt the spread of the disease. Health education and awarness regarding the preventive measures of disease should be promoted.
Background:
High quality reporting of outbreak characteristics is fundamental to understand the behavior of various strains of influenza virus and the impact of outbreak management strategies. However, few studies have systematically evaluated the quality of outbreak reporting.
Objectives:
To conduct a systematic analysis and assessment for reporting quality of influenza outbreaks based on a modified version of the STROBE statement, and to examine characteristics associated with reporting quality.
Methods:
A literature search was conducted across three online databases (PubMed, Web of Science, MEDLINE) for reports of influenza outbreaks (pandemic H1N1, avian, seasonal). The quality of reports meeting our eligibility criteria was assessed using the Modified STROBE criteria and assigned a score out of 30. Mean differences (MD) and 95% confidence intervals (CI) were reported for comparisons of study characteristics.
Results:
Sixty-four outbreak reports were available for analyses. The average Modified STROBE score was 20/30. Peer reviewed articles were associated with a better quality of reporting (MD 2.79, 95% CI 0.79-4.78). Likewise, reports from authors affiliated with public health agencies were associated with better quality than those from academic institutions (MD 1.65, 95% CI -0.27 to 3.56).
Conclusions:
The development of explicit reporting guidelines specifically geared towards reporting of outbreak investigations proved to be useful. Providing information on patient characteristics, investigation details in introduction and results, as well as addressing limitations that could have biased the findings were frequently missing in the published reports. This article is protected by copyright. All rights reserved.
The serum level of gamma glutaryl transferase and alkaline phosphatase is raised in acute calculus cholecystitis and common bile duct stone. However, the rise in serum level of these enzymes in acute cholecystitis implies stone in the common bile duct is not well studied. Thus, it may lead to retained CBD stone on one side and unnecessary CBD exploration on the other during emergency laparoscopic cholecystectomy. The objective of the study is to predict presence of CBD stone by assessing serum level of gamma-glutamyltransferase (gamma-GT)and alkaline phosphatase.
A prospective study was designed which included 40 patients with clinically diagnosed and radiologically confirmed acute cholecystitis and 40 patients who had choledocholithiasis with or without cholangitis. Their serumgamma glutaryl transferase and alkaline phosphatase were analyzed.
Both acute cholecystitis and CBD pathology had significant increase in alkaline phosphatase (p-value: 0.05). However, in acute cholecystitis there was 1.69±0.118 fold increase and in CBD pathology there was 2.5±0.57 fold increase in alkaline phosphatase than normal.(130 IU /L). There was no statistically significant difference ingamma- GT in both acute cholecystitis and CBD pathology(p-value: 0.390). However it increases by 2.8±0.47fold in acute cholecystitis and by 2.2±0.16 in CBD pathology(p value: 0.627).
Although there is rise in serumγ-GT and alkaline phosphatase level in acute cholecystitis and CBD stone,only more than 2.5 fold rise in serum alkaline phosphatase level predicts CBD stone.
An outbreak of influenza was investigated between June 24 and July 30, 2009 in a residential school at Panchgani, Maharashtra, India. The objectives were to determine the aetiology, study the clinical features in the affected individuals and, important epidemiological and environmental factors. The nature of public health response and effectiveness of the control measures were also evaluated.
Real time reverse transcriptase polymerase chain reaction was performed on throat swabs collected from 82 suspected cases to determine the influenza types (A or B) and sub-types [pandemic (H1N1) 2009, as well as seasonal influenza H1N1, H3N2]. Haemagglutination inhibition assay was performed on serum samples collected from entire school population (N=415) to detect antibodies for pandemic (H1N1) 2009, seasonal H1N1, H3N2 and influenza B/Yamagata and B/Victoria lineages. Antibody titres>or=10 for pandemic (H1N1) 2009 and >or=20 for seasonal influenza A and B were considered as positive for these viruses.
Clinical attack rate for influenza-like illness was 71.1 per cent (295/415). The attack rate for pandemic (H1N1) 2009 cases was 42.4 per cent (176/415). Throat swabs were collected from 82 cases, of which pandemic (H1N1) 2009 virus was detected in 15 (18.3%), influenza type A in (6) 7.4 per cent and influenza type B only in one case. A serosurvey carried out showed haemagglutination inhibition antibodies to pandemic (H1N1) 2009 in 52 per cent (216) subjects in the school and 9 per cent (22) in the community.
Our findings confirmed an outbreak of pandemic (H1N1) 2009 due to local transmission among students in a residential school at Panchgani, Maharashtra, India.
Computed tomography detected the presence of dilated ducts in 15 of 18 cases with extrahepatic obstructive jaundice and demonstrated the obstructing lesion in 18 out of 25. The cause of the obstruction was detected in the absence of duct dilatation, and calculi which were radiolucent on conventional radiographs were demonstrated. Ulstrasound detected dilated ducts in eight of 10 cases, but demonstrated the cause of the obstruction in only one of 13 cases. Both techniques are capable of demonstrating dilated ducts in the majority of cases, but computed tomography is better at detecting the cause of the obstruction.
Grey-scale ultrasonography was performed without access to detailed clinical information in a prospective study of 55 jaundiced patients. Forty-one were eventually proved to have an extrahepatic obstructive cause, and 14 had intrahepatic "medical" disease. Satisfactory ultrasound images were obtained in 54 patients, and the bile duct calibre was correctly reported in 53 (96%). All 14 medical cases were correctly identified. Two patients with gallstones (one with a normal sized duct) were incorrectly classified as medical. A specific and correct disease diagnosis was given in five of the 14 medical cases (one metastases, four cirrhosis), and in 23 of the 41 obstructive cases (12/14 pancreatic cancer, 5/15 gallstones), 5/5 bile duct compression, 1/3 bile duct cancer. Ultrasonography is safe, cheap, and acceptable to patients. It should be the first imaging investigation in jaundiced patients, providing remarkable diagnostic accuracy and important guidance for further management.
The authors determined the most useful predictors of common bile duct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC).
Prospective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients.
Endoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent.
The identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment.
Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP/ES) can be associated with unforeseeable complications, especially when involving postprocedural pancreatitis. The aim of the study was to investigate risk factors for complications of ERCP/ES in a prospective multicentric study.
One hundred fifty variables were prospectively collected at time of ERCP/ES and before hospital discharge over 2 years, in consecutive patients undergoing the procedure in nine endoscopic units in the Lombardy region of Italy. More than 150 ERCPs were performed in each center per year by a single operator or by a team of no more than three endoscopists.
Two thousand four hundred sixty-two procedures were performed; 18 patients were discharged because the papilla of Vater was not reached (duodenal obstruction, previous gastrectomy, etc.). Two thousand four hundred forty-four procedures were considered in 2103 patients. Overall complications occurred in 121 patients (4.95% of cases): pancreatitis in 44 patients (1.8%), hemorrhage in 30 (1.13%), cholangitis in 14 (0.57%), perforation during ES in 14 (0.57%), and others in 14 (0.57%); deaths occurred in three patients (0.12%). In multivariate analysis, the following were significant risk factors: a) for pancreatitis, age (< or = 60 yr), use of precutting technique, and failed clearing of biliary stones, and b) for hemorrhage, precut sphincterotomy and obstruction of the orifice of the papilla of Vater.
The results of our study further contribute to the assessment of risk factors for complications related to ERCP/ES. It is crucial to identify high risk patients to reduce complications of the procedures.
The role of liver function tests (LFTs) in evaluating common bile duct (CBD) stones in patients with cholelithiasis has been studied widely. However, it is not clear whether these predictive models are useful in inflammatory gallstone disease.
A review was undertaken of 385 consecutive patients admitted as an emergency for acute calculous gallbladder disease. The diagnosis of calculous cholecystitis was confirmed by ultrasonography or histological confirmation of acute or chronic inflammation of the gallbladder. Patients with obvious jaundice, defined as a bilirubin level above 80 micromol/l, and gallstone pancreatitis were excluded.
Some 216 patients met the inclusion criteria, of whom 28 (13.0 per cent) were found to have CBD stones. LFT results were not significantly different in patients with chronic, acute or complicated acute cholecystitis. Using several cut-off levels, gamma-glutamyl transpeptidase (GGT) had the highest specificity, positive predictive value and negative predictive value, comparable to a scoring system that combined all LFTs. Bilirubin was the least specific and predictive. A cut-off point for GGT at 90 units/l produced a sensitivity of 86 per cent (24 of 28), specificity of 74.5 per cent (140 of 188), and positive and negative predictive values of 33 per cent (24 of 72) and 97.2 per cent (140 of 144) respectively. This represented a one in three chance of CBD stones when the GGT level was above 90 units/l and a one in 30 chance when the level was less than 90 units/l.
Selection criteria based on GGT can be used in acute calculous cholecystitis to identify high-risk patients who would benefit most from further imaging to exclude choledocholithiasis.
To assess the predictive ability of various indicators of common bile duct calculi, 457 patients undergoing cholecystectomy for gallstone disease were prospectively screened for the presence of 11 predefined criteria of possible choledocholithiasis. The predictive ability of the criteria, individually and in combinations, was determined. For all criteria, except a history of pancreatitis, a significantly increased incidence of choledocholithiasis was found. The number of positive criteria correlated positively with the frequency of common bile duct calculi. The negative predictive value and sensitivity of the total set of criteria were 98% and 89.5%, respectively. Following common duct exploration, the number of complications and the duration of postoperative hospitalization were significantly increased as compared with simple cholecystectomy. Peroperative cholangiography with cholecystectomy is recommended in all patients, with one or more criteria of possible choledocholithiasis. Routine peroperative cholangiography in patients with no positive criteria does not seem to be necessary.
This study of cholestatic jaundice suggests that gray scale ultrasonography should precede invasive techniques or surgery. The failure of ultrasound to demonstrate dilated ducts suggests intrahepatic cholestasis. Display of liver parenchyma by ultrasound provided the correct diagnosis of diffuse liver disease in 61% of the cases. Observation of a dilated biliary tree allowed differentiation between intrahepatic and extrahepatic obstruction, with an accuracy of 96.4%. One false positive (0.7%) occurred, and most false negatives were due to gallstones producing intermittent obstruction owing to a ball-valve effect.
Observations of normal biliary canaliculi suggest that physiological distention of intrahepatic biliary vessels does not occur. Long-standing obstruction of the biliary tree may result in permanent distention despite surgical relief, predisposing the patient to recurrent ascending cholangitis. This stresses the need for early diagnosis and prompt relief of extrahepatic biliary obstruction.
(Arch Intern Med 139:60-63, 1979)
Serum γ-glutamyl transpeptidase (GGT) activity correlates closely with the activities of alkaline phosphatase (ALP) and 5′-nucleotidase (5NT) in various forms of liver disease. Maximum elevations of all three enzyme activities are observed in diseases which particularly affect the biliary tract. Compared with the other two enzymes GGT is generally increased to a greater extent and is thus the most sensitive indicator of biliary-tract disease, while estimations of serum GGT are more reproducible than those of 5NT. However, a group of patients who had been treated with phenytoin and barbiturates were found to have elevated serum GGT activities without any other evidence of liver disease. The apparent effect of certain drugs on serum GGT activity indicates the need for caution in interpreting the results of this test.
A means of accurately predicting the presence of stones in the bile duct in patients undergoing laparoscopic cholecystectomy
for gallbladder stones is lacking. With the use of a three-stage analysis, a predictive score was developed from seven common
parameters. Initially the score was formulated by using data from a retrospective series of patients undergoing laparoscopic
cholecystectomy; the system was then tested prospectively over a l-year period in patients undergoing laparoscopic cholecystectomy
for gallbladder stones. This simple scoring system demonstrated an ability to predict bile duct stones with a sensitivity
in excess of 70%. The use of such a score may allow the development of preoperative strategies for treating patients undergoing
laparoscopic cholecystectomy.
The predictive value of the preoperative level of bilirubin, alkaline phosphatase and amylase as indicators of choledocholithiasis was determined by prospectively evaluating 304 consecutive patients undergoing cholecystectomy. Elevated levels of bilirubin and alkaline phosphatase are associated with an increased incidence of common duct stones, and the percentage incidence of stones increases with rising bilirubin and alkaline phosphatase levels. Alkaline phosphatase levels as great as 200 are associated with common duct stones in a low percentage of instances, being equivalent to that for unsuspected stones. Levels of 200 or greater are associated with a marked increase in the incidence of common duct stones. An elevated serum or urine amylase level, or both, is of little, if any, value as a predictor of common duct stones. Alkaline phosphatase appears to be a better indicator of common duct stones than does bilirubin, but neither bilirubin nor alkaline phosphatase in themselves are statistically significant indicators. Bilirubin and alkaline phosphatase in combination is a statistically significant predictor of common duct stones at all levels. The combination of a bilirubin level of greater than 3.0 and an alkaline phosphatase level of greater than 250 has a 76.2 per cent probability of an associated common duct stone. The quite important role of operative cholangiography in demonstrating unsuspected stones and in preventing unnecessary common duct explorations is reinforced.
Liver tests are utilized to determine the presence of biliary obstruction.
To examine our hypothesis that liver tests aid in elucidating whether patients have simple calculous cholecystitis (ACC) or choledocholithiasis (CDL).
We performed a retrospective study of patients admitted to two University of Texas Southwestern teaching hospitals with a clinical picture consistent with 'acute gallstone disease', i.e. cholecystitis +/- choledocolithiasis. The presence of ACC and CDL was based on defined clinical criteria.
The cohort consisted of 154 patients meeting specific entry criteria, primarily with right upper quadrant pain; 62 ACC, 79 both ACC and CDL and 13 CDL alone. Approximately 30% of patients with ACC had abnormal alkaline phosphatase (ALP) and/or bilirubin level and approximately 50% had abnormal aminotransferase levels. Among patients with ACC/CDL, 77% had abnormal ALP, 60% had abnormal bilirubin and 90% had abnormal aminotransferase levels. By multivariate analysis, increasing common bile duct size and an abnormal ALP and alanine aminotransferase (ALT) were excellent predictors of having ACC with CDL.
Liver test patterns can aid in elucidating CDL, including in ACC patients. Fundamentally, patients with CDL were more likely to have more abnormal liver tests, whether they had CDL only, or CDL and ACC. A dilated CBD, and abnormal ALP and ALT had modest sensitivity and high specificity for identification of patients with ACC and CDL.
Forty-seven patients with cholestatic jaundice were evaluated for extrahepatic biliary obstruction by ultrasonic cholangiography and the results verified by contrast cholangiography, celiotomy, or autopsy. Sonograms were evaluated both with ("official" reading) and without ("blind" reading) clinical information. By showing dilated bile ducts, sonography correctly diagnosed extrahepatic obstruction in 26 of 30 patients on "official" reading and 23 of 30 on "blind" reading. In all 17 patients without extrahepatic obstruction, sonography revealed the absence of dilated bile ducts. Among patients with extrahepatic obstruction, those with larger bile ducts had higher bilirubin concentrations, longer duration of jaundice, and were more reliably detected by sonography. In these patients, 94% with total bilirubin concentration greater than 10 mg/dl were detected by sonography, while 47% with total bilirubin concentration less than 10 mg/dl were detected. Although we recognize the limited sensitivity of sonography in early extrahepatic obstruction, we find it to be a valuable screening test in cholestatic jaundice.
The serum alkaline phosphatase was fractionated by polyacrylamide gel electrophoresis in 317 patients with elevated serum alkaline phosphatase activity. In 253 patients the source of the elevation was the isoenzyme of presumed liver origin, band L. In 87 of these patients, there was either no obvious liver disease or the alkaline phosphatase elevation was inappropriately high. In 19 of the 87, liver disease was further excluded by liver biopsy or by laparotomy. Because of this, biochemical studies were done to verify the hepatic origin of band L. Band L and alkaline phosphatase extracted from human liver migrated together on polyacrylamide gel electrophoresis before and after digestion with Vibrio cholerae neuraminidase. They had identical pH optima, sedimentation coefficients, Michaelis constants, and rates of inactivation at 55.5 degrees C. They had different rates of inactivation in 3 M urea. Over-all, the data indicate that band L is of liver origin, and that elevation of the hepatic alkaline phosphatase isoenzyme may be a nonspecific finding in certain patients.
This study reviews the results of transcystic common bile duct exploration (CBDE) for unsuspected stones found during laparoscopic cholecystectomy by a single surgeon in 150 consecutive patients. Fluoroscopic cholangiography was attempted in all but four patients. If the cholangiogram appeared to show common bile duct (CBD) stones, a 5 Fr, 8-mm ureteral stone basket was passed through the cystic duct into the duodenum, opened, and trolled through the CBD. Routine cholangiography was successful in 131 of 144 attempts (90%). An indication for CBDE was found by cholangiogram in seven patients (5%). Two cholangiograms were falsely positive. Stones were removed in five patients. Completion cholangiograms were normal in all patients. One patient developed mild pancreatitis but was discharged 2 days after laparoscopic cholecystectomy. The remainder were discharged on postoperative day 1. One patient was readmitted on postoperative day 2, possibly having passed a retained stone. Fluoroscopic CBDE was successful in clearing the CBD in all patients in this small series and deserves further evaluation.
Despite its relative safety (in comparison with surgery), and undoubted role in many clinical circumstances, biliary sphincterotomy is the most dangerous procedure routinely performed by endoscopists. Complications occur in about 10% of patients; 2 to 3% have a prolonged hospital stay, with a risk of dying. This document is an attempt to provide guidelines for prevention and management of complications, based on a workshop of selected experts, and a comprehensive review of the literature. We emphasize particularly the importance of specialist training, disinfection, drainage, and collaboration with surgical colleagues.
One hundred consecutive patients were prospectively studied to assess the clinical and biochemical features of symptomatic choledocholithiasis. Biochemical tests were performed during the three days following the onset of symptoms. Pain was the most frequent symptom of choledocholithiasis, observed in 75% of the patients, but rarely occurred alone (12%). Clinical symptoms were not different according to age. High serum gamma glutamyl transpeptidase and alkaline phosphatase were the most frequent biochemical abnormalities in patients with symptomatic choledocholithiasis: they were increased in 94 and 91% of cases, respectively. Only one patient had no biochemical abnormality. Serum transaminases could reach very high levels just as in hepatitis. Biochemical data did not differ regardless of whether the common bile duct was enlarged or not. Biochemical abnormalities had been studied over the first 10 days of spontaneous evolution in 25 patients while choledocholithiasis persisted: serum bilirubin and transaminases significantly decreased while serum gamma glutamyl transpeptidase, alkaline phosphatase, and amylase remained unchanged. These results indicate that, in patients with suggestive symptoms, choledocholithiasis is unlikely in the absence of biochemical abnormalities in the first three days following the onset of symptoms.
The role of clinical and biochemical criteria in predicting common bile duct (CBD) stones was analyzed in 76 patients with acute pancreatitis undergoing endoscopic retrograde cholangiopancreatography (ERCP) during the same hospital admission. Forty patients had ERCP within 72 hours; cholangiography was successful in 92%. Fifty patients had biliary pancreatitis; 25 patients had CBD stones and all were successfully removed by endoscopic sphincterotomy (ES). Twenty-six patients had nonbiliary pancreatitis. Two patients had complications from ERCP and/or ES; two patients died (no CBD stones) but ERCP was noncontributory. Significant differences were found between the biliary and nonbiliary disease groups with respect to age, and bilirubin. gamma-glutamyl transpeptidase, alkaline phosphatase, alanine transaminase, and amylase levels. The first four factors also discriminated between those patients with and without CBD stones. Logistic discriminant functions were estimated providing probabilities for the presence of CBD stones for each patient but were too cumbersome for clinical use. A simple scoring system was devised on the basis of cut-off levels: bilirubin greater than or equal to 40 mumol/L, gamma-glutamyl transpeptidase greater than or equal to 250 IU/L, alkaline phosphatase greater than or equal to 225 IU/L, and age greater than or equal to 70 years, indicating CBD stones. Bilirubin alone had a sensitivity and specificity of 80%; the specificity increased to 93% with all four factors. These results suggest that clinical and biochemical criteria and ERCP and/or ES may have important roles in the management of patients with suspected biliary pancreatitis.
A retrospective reviews of 195 consecutive patients who underwent elective cholecystectomy and operative cystic duct cholangiography (OCDC) were reviewed to establish criteria to correlate the preoperative laboratory data of liver chemistry tests and the actual biliary tract disease found in each patients. Patients who had a history of jaundice or other clinical indication for common bile duct exploration were excluded from this study. The patients were divided into four groups based on the results of the OCDC: I negative, II false positive, III false negative, and IV positive for choledocholithiasis. The results of the preoperative liver chemistry studies of the patients in each of the four groups were analyzed by the chi 2 method. The four liver chemistry tests were lactate dehydrogenase, SGOT, bilirubin, and alkaline phosphatase. When results of all preoperative liver chemistry tests were normal, there was no incidence of choledocholithiasis. As the number of chemistry test result elevations increased from one to four, the incidence of choledocholithiasis increased from 17% to 50% (p less than 0.001). Preoperative liver chemistry tests in selected patients undergoing elective cholecystectomy may provide a valuable indicator to the surgeon as to whether an OCDC should be performed at the time of surgery.
To assess the predictive ability of various indicators of common bile duct calculi, 457 patients undergoing cholecystectomy for gallstone disease were prospectively screened for the presence of 11 predefined criteria of possible choledocholithiasis. The predictive ability of the criteria, individually and in combinations, was determined. For all criteria, except a history of pancreatitis, a significantly increased incidence of choledocholithiasis was found. The number of positive criteria correlated positively with the frequency of common bile duct calculi. The negative predictive value and sensitivity of the total set of criteria were 98% and 89.5%, respectively. Following common duct exploration, the number of complications and the duration of postoperative hospitalization were significantly increased as compared with simple cholecystectomy. Peroperative cholangiography with cholecystectomy is recommended in all patients, with one or more criteria of possible choledocholithiasis. Routine peroperative cholangiography in patients with no positive criteria does not seem to be necessary.
Persistent choledochal stones, as well as negative choledochal explorations, lead to increased morbidity and expense in operations upon the biliary tract. In an attempt to establish more precise criteria for the presence of CBD stones, 1,000 consecutive cholecystectomies were studied and computer analyzed. Precise determination of the choledochal diameter and preoperative bilirubin levels permit a quite accurate estimate of the probable presence of a choledochal stone.
The ERCP report in the patient's chart was compared with findings on common duct exploration or cystic duct cholangiography in 72 patients and found to have a sensitivity of 90.4 percent, a specificity of 98 percent, and an accuracy of 95.8 percent. Factors having the potential to influence the accuracy of ERCP were errors in interpretation by the surgeon and the radiologist and the operative technique of cholecystectomy. Also, the interval between the performance of the procedure and operation was particularly important in the patient with multiple small gallstones or small common duct stones. Small gallstones may spontaneously pass from the gallbladder to the common duct, or small common duct stones may spontaneously pass into the duodenum; therefore, the longer the interval between ERCP and operation, the greater the likelihood of a discrepancy. At operation, gallstones may be squeezed into the common duct during manipulation of the gallbladder unless the cystic duct is obstructed before manipulation of the gallbladder. We found ERCP sufficiently accurate to make cystic duct cholangiography unnecessary in most patients with cholelithiasis having a preoperative ERCP examination.
A total of 103 consecutive patients with suspected biliary obstruction were studied using both computed tomography (CT) and ultrasound (US) to evaluate the relative accuracy of the methods. In 47 patients with confirmed obstruction, CT and US were comparable accurate in differentiating obstruction from nonobstruction. The precise level of obstruction was identified by CT in 88% and by US in 60%; the cause of obstruction was accurately predicted by CT in 70% and by US in 38%. Both methods detected useful additional information, such as cholelithiasis or retroperitoneal adenopathy. The authors use US as a screening examination; if there is doubt about the level and cause of sonographically demonstrated obstruction, CT has proved to be an accurate means of further evaluation.
A series of 500 cholecystectomies performed over a 7-year period was reviewed retrospectively. The reliability of preoperative clinical features such as jaundice and pancreatitis was assessed in determining the presence of choledocholithiasis, and was found to be of limited value. Investigations such as intravenous cholangiography and liver function tests were found also to be inaccurate in the detection of common duct stones as was the appearance of the duct at operation. The usefulness of the peroperative cholangiogram in the detection of common duct stones that would otherwise have been overlooked is emphasized. Common duct stones would have remained undetected in 25 per cent of patients with choledocholithiasis. Despite the use of routine peroperative cholangiography common duct stones were overlooked in 11.25 per cent of patients who underwent exploration.
Indications for intraoperative evaluation of the common bile duct during laparoscopic cholecystectomy are controversial, as is the goal of either anatomic definition or assessing for choledocholithiasis. One hundred twenty-five consecutive patients undergoing laparoscopic cholecystectomy underwent both intraoperative ultrasound and intraoperative cholangiography. Cholangiography required slightly more time to perform; it was more sensitive (92.8% vs 71.4%) but less specific (76.2% vs 100%) for choledocholithiasis than was ultrasound. Ultrasound was somewhat more difficult to perform, and, particularly in the setting of intraabdominal obesity, was often inadequate at providing clear visualization of the intrapancreatic common bile duct. It did not provide the same anatomic definition as an adequate cholangiogram. The overall incidence of choledocholithiasis was 11.2%.
Accurate preoperative prediction of choledocholithiasis is essential in order to minimize patient risk and curtail health care expenditures. This study was designed to identify independent risk factors for choledocholithiasis in patients who had undergone cholecystectomy for symptomatic cholelithiasis and to develop a predictive model based on those factors.
The charts of 1264 consecutive patients who had undergone cholecystectomy at one of three North Carolina hospitals between January 1, 1989 and December 31, 1991 were reviewed; 465 of these patients had confirmed presence or absence of choledocholithiasis by cholangiography and/or common bile duct exploration and were eligible for analysis. Candidate predictor variables included age and maximum preoperative values for each of the following: temperature, alkaline phosphatase, bilirubin, AST, amylase, white blood cell count, and common bile duct diameter. Model development and validation were conducted using standard data-splitting (60% "training," 40% "test") and logistic regression techniques.
Choledocholithiasis was confirmed in 115 (25%) of the 465 eligible patients. Univariate analysis identified bilirubin, common bile duct diameter, AST, temperature, alkaline phosphatase, and age as predictors. Multivariable analysis subsequently identified bilirubin, common bile duct diameter, AST, alkaline phosphatase, and age as independent predictors of choledocholithiasis. A final model containing these variables (except age, whose contribution to the model was small) accurately predicted choledocholithiasis (c-index = 0.76).
Accurate estimates of choledocholithiasis risk can be made using maximum preoperative bilirubin, common bile duct diameter, AST, and alkaline phosphatase values. Use of the model may help physicians select those patients with symptomatic cholelithiasis who would most likely benefit from further investigation to exclude choledocholithiasis.
The decision of whether or not to investigate for common bile duct stones before cholecystectomy utilizes clinical, laboratory, and radiologic information (indicators). There is tremendous individual variation among clinicians in the criteria used for making this decision. Our aim was to perform a meta-analysis of published data to estimate the performance characteristics of the most commonly used preoperative indicators of common bile duct stones.
Using predetermined exclusion criteria, we selected articles from a MEDLINE search and bibliographic review. Weighted averages were used to determine summary sensitivity, specificity, and positive and negative likelihood ratios for each indicator for stones.
From 2221 citations identified, 22 studies met inclusion criteria. The 10 indicators examined were reported in a common fashion in three or more articles, and could be assessed preoperatively. Seven exhibited a specificity greater than 90%. Indicators with positive likelihood ratios of 10 or above were cholangitis, preoperative jaundice, and ultrasound evidence of common bile duct stones. Positive likelihood ratios for dilated common bile duct on ultrasound, hyperbilirubinemia, and jaundice ranged from almost 4 to almost 7. Elevated levels of alkaline phosphatase, pancreatitis, cholecystitis, and hyperamylasemia exhibited positive likelihood ratios of less than 3.
This meta-analysis has identified indicators for duct stones and ranked them according to likelihood ratios. These findings can be applied as guidelines for whether to investigate for duct stones before cholecystectomy.
Although perioperative cholangiography is valuable and highly accurate in the detection of common bile duct (CBD) stones, its routine use is controversial, particularly in the era of the laparoscopic cholecystectomy because of its inherent disadvantages. The purposes of this retrospective and prospective study on cholelithiasis were to identify patients at low risk for CBD stones and to assess the validity of the low risk criteria.
For the first, retrospective study, 15 significant preoperative clinical, biochemical and sonographic variables were selected from 561 consecutive patients who underwent conventional cholecystectomy with routine intraoperative cholangiography (IOC) for cholelithiasis from January 1985 to December 1993, and independent risk factors predicting the presence of CBD stones were determined by multivariate logistic regression analysis. For the second, prospective study, from April 1994 to September 1995, a laparoscopic cholecystectomy (LC) was performed without perioperative cholangiography in 153 consecutive patients with the primary low risk criterion (sonographic CBD diameter < 10 mm) determined by the first study. All of the LC patients were followed-up for a median duration of 12 months (range 4 to 21 months).
In the first study, CBD stones were present in 95 (16.9%) patients. The most important independent predictor was a dilated CBD (> 10 mm). Three levels of risk were determined: (1) the low risk group (73.8% of the patients), in which the CBD was not dilated and the prevalence of CBD stones was 1.5% (6/408); the moderate risk group (7.8% of the patients), in which there was a dilated CBD with normal liver function tests and a prevalence of stones of 48.8% (21/43); and the high risk group (18.4%), in which there was a dilated CBD and abnormal liver function tests and a prevalence of stones of 66.7% (68/102). In the second study, two cases (1.4%) of symptomatic overlooked CBD stones were found on endoscopic retrograde cholangiography and retrieved by endoscopic sphincterotomy on postoperative days 18 and 20, respectively.
Preoperative assessment in cases of cholelithiasis can determine which patients are at low risk for having CBD stones, thereby avoiding unnecessary perioperative cholangiography. This selectivity is also valid in LC, since the incidence of symptomatic, overlooked CBD stones was very low.
Laparoscopic cholecystectomy (LC) has become the treatment of choice for elective cholecystectomy, but controversy persists over use of this approach in the treatment of acute cholecystitis. We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy (OC) in patients with acute cholecystitis.
63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The primary endpoints were hospital mortality and morbidity, length of hospital stay, and length of sick leave from work. Analysis was by intention to treat. Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography (LC group) or intraoperative cholangiography (OC group).
The two randomised groups were similar in demographic, physical, and clinical characteristics. 48% of the patients in the OC group and 59% in the LC group were older than 60 years. 13 patients in each group had gangrene or empyema, and one in each group had perforation of the gallbladder causing diffuse peritonitis. Five (16%) patients in the LC group required conversion to OC, in most because severe inflammation distorted the anatomy of Calot's triangle. There were no deaths or bile-duct lesions in either group, but the postoperative complication rate was significantly (p=0.0048) higher in the OC than in the LC group: seven (23%) patients had major and six (19%) minor complications after OC, whereas only one (3%) minor complication occurred after LC. The postoperative hospital stay was significantly shorter in the LC than the OC group (median 4 [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7).
Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality rate, and the morbidity rate seems to be even lower than that in OC. However, a moderately high conversion rate must be accepted.
There is a lack of multicenter prospective studies on complications of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP).
We studied 2769 consecutive patients undergoing ERCP at nine centers in the Triveneto region of Italy over a 2-year period. Six centers performed ERCP on less than 200 patients per year (small centers). General and ERCP-specific major complications were predefined. Data were collected at the time of ERCP, before discharge, and in cases of readmission within 30 days. ERCP was defined as therapeutic when endoscopic sphincterotomy (n = 1583), precut (n = 419), or drainage (n = 701) had been carried out, singularly or in combination.
One hundred eleven major complications (4.0%) were recorded: moderate-severe pancreatitis 36 (1.3%), cholangitis 24 (0.87%), hemorrhage 21 (0.76%), duodenal perforation 16 (0.58%), others 14 (0.51%). Among 942 diagnostic ERCPs there were 13 major complications (1.38%) and 2 deaths (0.21%), whereas among 1827 therapeutic ERCPs there were 98 major complications (5.4%) and 9 deaths (0.49%). The difference in the incidence of complications between diagnostic and therapeutic ERCPs was statistically significant (p < 0.0001). Small center and precut were recognized as independent risk factors for overall major complications of therapeutic ERCP, whereas the following risk factors were identified in relation to specific complications: (1) pancreatitis: age less than 70 years, pancreatic duct opacification, and nondilated common bile duct; (2) cholangitis: small center, jaundice; (3) hemorrhage: small center; and (4) retroperitoneal duodenal perforation: precut, intramural injection of contrast medium, and Billroth II gastrectomy.
Major complications are mostly associated with therapeutic procedures and low case volume. Present data support a policy of centralization of ERCP in referral centers. A more selected and safer use of precut may be expected to further limit the adverse events of ERCP.
This study assessed the effectiveness of laparoscopic ultrasound in detecting main biliary duct stones.
From November 1994 to August 1998, 600 patients treated by laparoscopic cholecystectomy were included in a prospective study, to compare intraoperative cholangiography and laparoscopic ultrasound. The biliary tree was successively explored by these two methods in the routine detection of common bile duct stones.
The feasibility of laparoscopic ultrasound was 100%. Cholangiography was performed only in 498 cases (83%). The time taken for laparoscopic ultrasound examination was significantly shorter (10.2 vs 17.9 min, P=0.0001). In this study, common bile duct stones were found in 54 cases (9%). For their detection, results were comparable to laparoscopic ultrasound and intraoperative cholangiography. For laparoscopic ultrasound, sensitivity was 80% and specificity 99%; and for cholangiography 75 and 98% respectively. Both examinations combined had a 100% sensitivity and specificity. Laparoscopic ultrasound failed to recognize the intrapancreatic part of the common bile duct in 78 cases (13%) and did not show anatomical anomalies detected by cholangiography. It did however detect other unsuspected intra-abdominal pathologies.
Laparoscopic ultrasound is safe, repeatable, and non-invasive, but a considerable learning curve is necessary to optimize its efficacy. Comparison of relative cost must be undertaken.
Magnetic resonance cholangiopancreatography (MRCP) is one of many newer noninvasive tests that can image the biliary tree.
To precisely estimate the overall sensitivity and specificity of MRCP in suspected biliary obstruction and to evaluate clinically important subgroups.
MEDLINE search (January 1987 to March 2003) for studies in English or French, bibliographies, and subject matter experts.
Studies were included if they allowed construction of 2x2 contingency tables of MRCP compared with a reasonable gold standard for at least 1 of the following: the presence, level, or cause of biliary obstruction.
Two independent observers graded study quality, which included consecutive enrollment, blinding, use of a single (versus composite) gold standard, and nonselective use of the gold standard. Logistic regression was used to examine the influence of publication year, quality score, proportion of patients having a "direct" gold standard, and clinical context on diagnostic performance.
Of 498 studies identified, 67 were included (4711 patients). Mixed-effect models were used to estimate the sensitivity and specificity, and quantitative receiver-operating characteristic analysis was performed. Magnetic resonance cholangiopancreatography had a high overall pooled sensitivity (95% [+/-1.96 SD: spread of SD, 75% to 99%]) and specificity (97% [spread of SD, 86% to 99%]). The procedure was less sensitive for stones (92%; odds ratio, 0.51 [CI, 0.35 to 0.75]) and malignant conditions (88%; odds ratio, 0.28 [CI, 0.18 to 0.44]) than for the presence of obstruction. In addition, diagnostic performance was higher in studies that were larger, did not use consecutive enrollment, and did not use gold standard assessment for some patients.
Magentic resonance cholangiopancreatography is a noninvasive imaging test with excellent overall sensitivity and specificity for demonstrating the level and presence of biliary obstruction; however, it seems less sensitive for detecting stones or differentiating malignant from benign obstruction.
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