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Background
The gallbladder is located below the edge of the liver.The bile, produced within the liver, may be stored within the gallbladder, released in response to fat within the duodenum, or first portion of the small intestine. This bile assists in the digestion of fat. For a variety of reasons, gallstones may accumulate within the gallbladder, a condition known as chronic cholelithasis. In this condition, pain in the right upper quadrant may occur, often increased after fatty meals.
Chronic cholelithiasis is usually accompanied with chronic cholecystitis. The wall of the gallbladder may become thickened and fibrotic, which may prevent the gallbladder from contracting and expanding normally. Acute cholecystitis may precede the chronic condition and may result from cholelithiasis. In long standing cases, the gallbladder wall may calcify, sometimes called a porcelain gallbladder.
An abdominal ultrasound is the procedure of choice for the diagnosis of chronic gallbladder disease. If the ultrasonogram is nondiagnostic, oral cholecystography may still be used to evaluate a patient with suspected gallbladder disease. If a double dose of the oral contrast agent fails to cause gallbladder opacification, cholelithiasis and chronic cholecystitis are almost certainly present. Cholescintigraphy is used for the diagnosis of an acute cholecystitis and is not helpful in diagnosing chronic cholelithiasis or chronic cholecystitis.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE/PREVALENCE
Surgical treatment of gallstones: changes in a defined population during a 20-year period.Persson GE, Ros AG, Thulin AJ.
Department of Surgery, Ryhov Hospital, Jonkoping, Sweden.
Eur J Surg 2002;168(1):13-7 Abstract quote OBJECTIVE: To study developments in routine gallstone surgery in a defined population over a 20-year period with regard to incidence of operations, implementation of new methods, postoperative complications, and postoperative duration of hospital stay. DESIGN: Retrospective study of medical records.
SETTING: County hospital, Sweden.
SUBJECTS: All patients who were residents of Jonkoping during one of the three-year periods 1976-1978, 1986-1988, or 1996-1998 and had their first surgical treatment, either cholecystectomy/choledochotomy or therapeutic endoscopy for gallstone disease.
RESULTS: The overall annual incidence of operations for gallstones decreased from 2.01 to 1.13/1000 inhabitants between the first and second period (p < 0.001). This is explained by a significant reduction in the number of elective operations while the number of urgent operations increased between the first and second periods from 0.39 to 0.53/1000 (p < 0.05) and continued to increase and reached 0.75/1000 during the third period (p < 0.001). New methods were introduced for the treatment of gallstones that gradually made this type of operation more varied and complex in routine practice. The postoperative hospital stay decreased from 7.0 days during the 1970s to 3.9 days during the 1990s. Postoperative morbidity was unchanged.
CONCLUSIONS: The decreasing rate of gallstone surgery noted between the 1970s and 1980s did not continue through the 1990s. Urgent surgery for gallstone disease has gradually become more common and now predominates over elective surgery in routine practice. The introduction of less traumatic surgical techniques contributed to the significant decrease in hospital stay after gallstone surgery. However, morbidity has not decreased and the diversification of surgical techniques used for treatment of gallstones requires continuous evaluation in routine practice.
Laparoscopic cholecystectomy: an analysis on 114,005 cases of United States series.Vecchio R, MacFadyen BV, Latteri S.
Department of Surgery, University of Catania, Italy.
Int Surg 1998 Jul-Sep;83(3):215-9 Abstract quote 114,005 cases from 40 United States series of laparoscopic cholecystectomies (LC) were reviewed. Indications, conversion rates, rates of intra-operative cholangiography (IOC), and incidence of bile duct stone and iatrogenic bile duct injuries were assessed. Indications included acute cholecystitis in 11.6% and gallstone pancreatitis in 2.1% of reported cases.
Conversion rate was to be primarily related to inflammation. Unsuspected bile duct stones were detected intra-operatively in 7.8% of cases. 561 major bile duct injuries (BDI) and 401 bile leaks (BL) were recorded and acute or chronic inflammation was their most important potential predisposing factor. In series with a high rate of IOC performed during LC, BDJ and BL were slightly lower and lesions recognized intra-operatively were much higher than in series with low rate of IOC.
BDJ occurred in the first 50 patients of the surgeon's experience in about 91% of the cases.
AGE SEX
Gallbladder pathologies and cholelithiasis.Zahrani IH, Mansoor I.
Department of Histopathology, King Abdulaziz University Hospital, PO Box 6615, Jeddah 21452, Kingdom of Saudi Arabia.
Saudi Med J 2001 Oct;22(10):885-9 Abstract quote OBJECTIVE: Cholecystectomy, mostly due to cholelithiasis is one of the most common surgical procedures utilizing a significant amount of healthcare resources. As there are a huge number of cases, for example approximately 300 cases per year in our region, outlines this commonly encountered lesion should be recorded. Also, in an attempt to delineate the outline of the pattern, age and sex distribution of gallbladder diseases in the whole Kingdom, a comparative analysis is also included in this study with 7 other studies published from different parts of the Kingdom.
METHODS: Our study consisted of 740 consecutive gallbladder cholecyctectomies mostly for cholelithiasis received in a time frame of 3.5 years (for example between January 1997 through to May 2000) by the Department of Histopathology retrieved from the records of the laboratory. The outline of main gallbladder pathologies was tabulated. The number of gallbladders received with stones was also calculated. Age and sex distribution for gallbladder pathology and gallstones was also tabulated.
RESULTS: There were 131 males (18%) and 609 (82%) females, with a female ratio male 4.6:1. Benign lesions comprised 99% (mean age 36), mostly chronic cholecyctitis (97%) and acute cholecystitis which constituted 15 cases only (2%), malignant lesions comprised only 7 cases for example 1% of all lesions (mean age 65).
CONCLUSION: Gallbladder pathologies are very common and similar results have been obtained from other studies by comparative analysis. The mean cholecystectomy rates in the Kingdom totalled approximately 10%, mean age for all cholecystectomy diseases in both sexes equalled 37.05. The mean age for males was 42.26, females 37.25 and their ratio was 44.5:1.
GEOGRAPHY
Cholecystitis: the Ethiopian experience, a report of 712 operated cases from one of the referral hospitals.Bekele Z, Tegegn K.
Ras Desta Damtew Memorial Hospital, P.O. BOX 1032, Addis Ababa, Ethiopia.
Ethiop Med J 2002 Jul;40(3):209-16 Abstract quote This is a prospective study conducted from September 1991 to September 2000. Seven-hundred and twelve patients operated for acute and chronic cholecystitis were studied. The male to female ratios for elective and emergency admissions were 1:5 and 1:2.4, respectively. The mean age was 42.7 years. Acute cholecystitis accounted for 10.6% of the 712 cases. There were a total of 666 (93.5%) calculus and 46 (6.5%) acalculus cases. Empyema was seen in 77 (10.8%) patients and hydrops of the gallbladder in 35 (4.9%).
Iatrogenic Common Bile Duct (CBD) injury was found to be more of a problem of the contracted gallbladder. In this study severe complications like gangrenous gallbladder, perforated gallbladder, suppurative cholangitis and subhepatic abscess were found more in males than in females.
Calculus cholecystitis was found to be a common disease in Ethiopia, and that its features and prevalence as well as sex predilection compare well with reports from other areas. However the findings in this report were found to be different from the reports of the rest of the African Continent.
DISEASE ASSOCIATIONS CHARACTERIZATION SCLEROSING CHOLANGITIS
Diffuse lymphoplasmacytic acalculous cholecystitis: a distinctive form of chronic cholecystitis associated with primary sclerosing cholangitis.Jessurun J, Bolio-Solis A, Manivel JC.
Department of Laboratory Medicine and Pathology, Fairview-University Medical Center and University of Minnesota, Minneapolis 55455, USA.
Hum Pathol 1998 May;29(5):512-7 Abstract quote Inflammation of the gallbladder is known to occur in patients with primary sclerosing cholangitis (PSC). However, the histological features of this form of cholecystitis have not been adequately defined.
The aim of this study was to compare the inflammatory lesions of PSC-associated cholecystitis with those present in other cholecystopathies. The cases consisted of 11 gallbladders from patients with PSC who underwent liver transplantation.
As controls, gallbladders from liver transplant patients with primary biliary cirrhosis (n = 4) and other chronic nonbiliary hepatopathies (n = 8), and 13 cholecystectomies from patients with chronic cholecystitis with (n = 10) and without (n = 3) lithiasis, were studied. The following histological features were tabulated on coded slides: presence, depth of involvement, and distribution of the inflammatory infiltrate, predominant cell type, presence of lymphoid aggregates, epithelial damage, metaplastic changes (pyloric or intestinal), fibrosis, smooth muscle hypertrophy, and presence of Rokitansky-Aschoff sinuses.
At variance with the wide range of histological abnormalities present in other forms of chronic cholecystitis, most PSC-related cholecystitis showed a diffuse infiltrate (6 of 11) rich in plasma cells (6 of 11) predominantly confined to the lamina propria (9 of 11). The combination of these three features was present exclusively in PSC (5 of 11 PSC cholecystitis compared with 0 of 25 controls; P = .001). In conclusion, this study suggests that a characteristic form of cholecystitis may develop in patients with PSC.
SCLEROSING PANCREATITIS
Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis.Abraham SC, Cruz-Correa M, Argani P, Furth EE, Hruban RH, Boitnott JK.
Am J Surg Pathol 2003 Apr;27(4):441-51 Abstract quote Lymphoplasmacytic sclerosing pancreatitis (LPSP) represents a distinctive form of chronic pancreatitis characterized by diffuse fibroinflammatory infiltrates that can involve both the pancreatic ducts and acinar parenchyma. Several cases of inflammatory infiltrates within the gallbladder have been reported in association with LPSP, but the spectrum of gallbladder pathology in patients with LPSP has not been systematically reviewed. Many patients with LPSP have distal CBD fibrosis, strictures, and inflammation, features that overlap somewhat with primary sclerosing cholangitis (PSC).
In PSC, a pattern of gallbladder pathology termed "diffuse acalculous lymphoplasmacytic chronic cholecystitis" has been previously described as showing a triad of diffuse, mucosal-based, plasma cell-rich inflammatory infiltrates.
We studied 20 gallbladders from patients with LPSP and compared them with 20 gallbladders in PSC, 20 gallbladders with chronic cholelithiasis, and 10 gallbladders from patients with benign (non-LPSP) pancreatic disease. The following features were evaluated: degree and composition of mucosal inflammation and deep (mural) inflammation, lymphoid nodules, metaplasia, dysplasia/neoplasia, fibrosis, muscular hypertrophy, Rokitansky-Aschoff sinuses, and cholesterolosis.
The majority (60%) of gallbladders in LPSP contained moderate or marked inflammatory infiltrates and lymphoid nodules, frequencies similar to PSC but significantly higher than in chronic cholelithiasis and benign non-LPSP pancreatic disease. LPSP gallbladders received the highest scores for deep inflammation of all groups, and 35% of LPSP gallbladders showed transmural chronic cholecystitis. Overall, "diffuse lymphoplasmacytic chronic cholecystitis" was present in 50% of PSC cases and 25% of LPSP cases, but in only 5% of chronic cholelithiasis and none of non-LPSP benign pancreatic disease. Mucosal inflammation in LPSP gallbladders correlated significantly with the presence of inflammation in the extrapancreatic portion of the CBD.
These findings suggest that inflammatory pathology of the gallbladder is frequently associated with LPSP and that it is part of the spectrum of biliary tract disease in these patients, rather than a simple reflection of the pancreatitis itself.
SICKLE CELL ANEMIA
Cholecystectomy in Jamaican children with homozygous sickle-cell disease.Duncan ND, McDonald AH, Mitchell DI.
Department of Surgery, Radiology, Anaesthesia and Intensive Care, University Hospital of the West Indies, Kingston 7, Jamaica.
Trop Doct 2000 Oct;30(4):214-6 Abstract quote Twenty-seven children aged 18 years and under with homozygous sickle-cell disease had open cholecystectomy for symptomatic gallstones over the 12-year period 1985-1997.
Emergency procedures (done during period of acute exacerbation of symptoms) were performed on 16 patients. Four with haemoglobin levels greater than 1 g/dl below their steady state received a simple blood transfusion preoperatively designed to raise haemoglobin levels to 10 g/dl. All had acute or acute on chronic cholecystitis based on histological examination of gallbladder specimens. Twelve had common bile duct stones.
In two patients calculi were missed intraoperatively but these subsequently passed into the duodenum after a period saline irrigation via an in-situ t-tube. Six developed the acute chest syndrome (aetiology not determined) and this progressed to multi system failure and death in one.
This high level of postoperative mobility and mortality may in part be due to the high proportion of emergency procedures.
PATHOGENESIS CHARACTERIZATION DNA DAMAGE
Immunohistochemical detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in human chronic cholecystitis.Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Onoda N, Satake K.
Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Histopathology 2002 Jun;40(6):531-5 Abstract quote AIMS: Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings.
METHODS AND RESULTS: 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index.
CONCLUSIONS: Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.
HELICOBACTER
Lack of association between Helicobacter sp colonization and gallstone disease.Mendez-Sanchez N, Pichardo R, Gonzalez J, Sanchez H, Moreno M, Barquera F, Estevez HO, Uribe M.
Department of Gastroenterology, Medica Sur Clinic & Foundation, Mexico City, Mexico.
J Clin Gastroenterol 2001 Feb;32(2):138-41 Abstract quote Recently, Helicobacter sp has been identified in resected gallbladder tissue and in collected bile from Chilean patients with chronic cholecystitis. Therefore, it an association between bile Helicobacter sp and gallbladder cancer has been proposed. Interestingly, both Helicobacter colonization and gallstone disease (GD) happen very frequently in Chile. However, whether there is an association between Helicobacter colonization and GD has not been completely studied. The aim of this study was to determine the incidence of Helicobacter in human gallbladder tissues with GD.
The study included 95 Mexican patients undergoing cholecystectomy. Collected gallbladder specimens were assessed to identify Helicobacter sp using histology, immunohistochemistry, and polymerase chain reaction (PCR) analysis using Helicobacter-specific 16-S ribosomal RNA primers. Of the 95 specimens examined in detail, all had stones as follows: 56 (59%) had chronic cholecystitis; 7 (7.4%), acute cholecystitis: 15 (16%), both chronic and acute cholecystitis, 10 (9.5%), cholesterolosis, and 7 (7.4%), lymphoid hyperplasia. Specimens were considered positive for Helicobacter when histology was positive. Only 1 of the 95 specimens was positive for Helicobacter by immunohistochemistry analysis; 1 of 32 cases, by PCR.
These results suggest a low incidence of Helicobacter in the gallbladder epithelium of Mexican patients with GD. However, we can not discard the existence of uncommon Helicobacter sp in gallbladder epithelium and its association with gallstone pathogenesis. Additionally, this study suggests no apparent association between GD and Helicobacter colonization in a Mexican population.
MICROSATELLITE INSTABILITY Microsatellite Instability in Chronic Cholecystitis Is Indicative of an Early Stage in Gallbladder Carcinogenesis
Nobuyuki Yanagisawa, MD, Tetuo Mikami, MD, Kazuya Yamashita, PhD, and Isao Okayasu, MDAm J Clin Pathol 2003;120:413-417 Abstract quote
The study of microsatellite instability (MSI) in cases of severe chronic cholecystitis and gallbladder carcinomas, to cast light on its significance for tumorigenesis, revealed MSI in 9 (30%) of 30 cases of cholecystitis and 7 (41%) of 17 carcinomas, respectively. In addition, 5 (33%) of 15 samples of background mucosa of carcinoma were positive.
Respective figures for loss of heterozygosity were 3 (10%) of 30 cases of cholecystitis, 6 (35%) of 17 carcinomas, and 1 (7%) of 15 samples of adjacent nonneoplastic mucosa. No correlation was observed among MSI state, immunohistochemical hMLH1 or hMSH2 expression, and any clinicopathologic factors.
MSI was observed not only in gallbladder tumors but also in severe chronic cholecystitis and background mucosa, suggesting that it may have an important role in early-stage gallbladder carcinogenesis.VASOACTIVE INTESTINAL PEPTIDE
Hyperplastic innervation of vasoactive intestinal peptide in human gallbladder with cholelithiasis.Gonda T, Akiyoshi H, Ichihara K.
Department of Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Histol Histopathol 1995 Jul;10(3):669-72 Abstract quote The vasoactive intestinal peptide (VIP) immunoreactive nerve fibres in the gallbladder from 14 human patients with cholelithiasis was examined by immunohistochemical method. In the chronic cholecystitis, hyperplastic VIP immunoreactive nerves were observed around the hypertrophied muscle bundles, Rokitansky Aschoff Sinus and in the mucosal layer.
However, in the acute cholecystitis and gangrenous cholecystitis, reduction or disappearance of VIP nerve fibres was observed. These reductions or disappearances of VIP immunoreactive nerves may secondly result from severe tissue damage.
These results suggest that hyperplastic VIP nerves cause gallbladder relaxation, stasis and mucosal fluid unbalance, which may closely correlate to gallstone formation.
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC
Chronic acalculous biliary disease: cholecystokinin cholescintigraphy is useful in formulating treatment strategy and predicting success after cholecystectomy.Poynter MT, Saba AK, Evans RA, Johnson WM, Hasl DM.
Department of Surgery, Good Samaritan Hospital, Cincinnati, Ohio 45220, USA.
Am Surg 2002 Apr;68(4):382-4 Abstract quote Patients with symptoms consistent with biliary colic who do not demonstrate calculi on routine sonography present a diagnostic dilemma for clinicians.
For those patients in whom other disease entities have been excluded and in whom the history and physical examination exemplify classic signs and symptoms of biliary disease we show in this study that cholecystokinin cholescintigraphy with calculation of gallbladder ejection fraction is a predictor of pathology as well as subsequent symptom relief after cholecystectomy. The spectrum of pathology that makes up chronic acalculous biliary disease lacks a distinct definition, yet this review shows that cholecystokinin cholescintigraphy offers the surgeon the means to better counsel his or her patient with regard to surgical indications, options, and benefits.
We reviewed 26 patients who had no gallstones detectable, had gallbladder ejection fraction <35 per cent, and were status postlaparoscopic cholecystectomy for suspected chronic acalculous biliary disease.
Our results show histopathologic evidence of chronic cholecystitis in 100 per cent, and 92 per cent of the patients had improvement of symptoms and satisfaction with the operation to the point that they would undergo the surgery again without reservation.
Laparoscopic cholecystectomy without cholangiography: a study of 151 consecutive cases.Schroder TM, Linko KY.
Helsingin Laserklinikka, Finland.
Eur J Surg 1995 Jun;161(6):421-4 Abstract quote OBJECTIVE: To evaluate the safety of laparoscopic cholecystectomy without operative cholangiography.
DESIGN: Open study.
SETTING: Outpatient and private hospitals, Finland.
SUBJECTS: 151 Patients (of whom all but the first 10 were consecutive) with symptomatic gallstones, or chronic or acute cholecystitis.
INTERVENTIONS: Laparoscopic cholecystectomy and (in three patients) preoperative endoscopic retrograde cholangiography (ERC).
MAIN OUTCOME MEASURES: Conversion to open operation and morbidity.
RESULTS: Only 2 patients (2%) required conversion to open cholecystectomy (one bled and in one the anatomy was difficult) and 4 (3%) developed complications (bleeding, n = 2, bile collection, and subcutaneous emphysema as a result of malfunction of the carbon dioxide insufflator). Three patients underwent ERC after operation and two were found to have common duct stones. Both had been noted to have large cystic ducts at operation.
CONCLUSION: Laparoscopic cholecystectomy can be done safely by experienced surgeons without operative cholangiography.
Significance of wall thickness in symptomatic gallbladder disease.Sariego J, Matsumoto T, Kerstein M.
Department of Surgery, Hahnemann University, Philadelphia, Pa.
Arch Surg 1992 Oct;127(10):1216-8 Abstract quote One hundred cases of patients who underwent urgent cholecystectomy after presenting with symptoms of acute or subacute gallbladder disease were retrospectively reviewed. Sixty patients had pathologically proved acute cholecystitis, and 40 had chronic cholecystitis alone. One patient had an incidental gallbladder carcinoma, and four had global gangrene of the gallbladder.
Focal ischemia, transmural hemorrhage, or focal necrosis (indicating more severe disease) was present in 19 patients. Fifty-four percent of patients had thin-walled gallbladders. Among patients with more severe acute disease, 56% had thin walls. Conversely, 24% of thin-walled gallbladders and 22% of thick-walled gallbladders had evidence of focal necrosis or gangrene.
We conclude that gallbladder wall thickness, although demonstrable on preoperative ultrasound examination in all patients, does not correlate directly with severity of disease or pathologic findings.
LABORATORY
Hyperbilirubinemia without common bile duct abnormalities and hyperamylasemia without pancreatitis in patients with gallbladder disease.Kurzweil SM, Shapiro MJ, Andrus CH, Wittgen CM, Herrmann VM, Kaminski DL.
Department of Surgery, St Louis University School of Medicine, Mo.
Arch Surg 1994 Aug;129(8):829-33 Abstract quote OBJECTIVE: To determine the incidence of jaundice and hyperamylasemia in the absence of common bile duct abnormalities or clinical pancreatitis in patients undergoing cholecystectomy.
DESIGN: A continuous, prospective analysis of a consecutive case series was performed on all patients undergoing cholecystectomy.
SETTING: An urban, tertiary care university hospital.
PATIENTS: Adult patients with gallbladder disease.
INTERVENTION: All patients underwent cholecystectomy.
MAIN OUTCOME MEASURES: The presence or absence of common bile duct abnormalities was evaluated by cholangiography, and pancreatitis was identified by clinical signs, imaging studies, and direct visual inspection during cholecystectomy.
RESULTS: All patients (N = 1746) undergoing cholecystectomy were prospectively categorized as having chronic calculous (n = 1410), acute calculous (n = 217), chronic acalculous (n = 70), or acute acalculous (n = 49) gallbladder disease. It was uncommon for patients with chronic calculous cholecystitis to have an elevated bilirubin level with no choledocholithiasis and a normal common bile duct or to have hyperamylasemia without pancreatitis. Twenty-five percent of the patients with acute calculous cholecystitis had a serum bilirubin level between 34 and 86 mumol/L (2.0 and 5.0 mg/dL) with no common bile duct abnormality and 4% had hyperamylasemia without pancreatitis. Over one third of the patients with acute acalculous cholecystitis had an elevated bilirubin level with a normal common bile duct or an elevated amylase level without pancreatitis.
CONCLUSION: Jaundice and hyperamylasemia can be produced by gallbladder disease alone.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS ACALCULOUS CHOLECYSTITIS
Chronic acalculous cholecystitis: reproduction of pain with cholecystokinin and relief of symptoms with cholecystectomy.Reitter D, Aaning HL.
S D J Med 1999 Jun;52(6):197-200 Abstract quote Over 500,000 patients undergo cholecystectomy annually in the United States for symptoms of upper abdominal discomfort and pain ascribed to gallbladder disease. However, approximately 5%, or 25,000 of these cases do not have gallstones on ultrasound examination but typically present with chronic symptoms of biliary colic. These patients often present as challenging diagnostic dilemmas and are often treated as if their symptoms are secondary to peptic ulcer disease or other gastrointestinal-related disorders.
In 1992, we began to use the cholecystokinin (CCK) challenge test on patients with normal ultrasound examinations of the gallbladder but who had chronic symptoms resembling biliary colic. The CCK test was considered positive if the identical symptoms of discomfort or pain, usually in the right upper quadrant of the abdomen, were reproduced.
This study describes the first 24 patients who had a positive CCK challenge test and chose to undergo cholecystectomy for relief of their symptoms. No patient was lost to follow-up evaluation at 1 to 24 months after operation.
FISTULA
Cholecystoduodenal fistula in a porcelain gallbladder.Delpierre I, Tack D, Moisse R, Boudaka W, Delcour C.
Department of Radiology, CHU-Hopital Civil de Charleroi, 92 Boulevard Janson, 6000 Charleroi, Belgium.
Eur Radiol 2002 Sep;12(9):2284-6 Abstract quote Calcification of the gallbladder wall (porcelain gallbladder) is rare. Its appearance is quite characteristic on plain films, ultrasonography and computed tomography.
Sporadic cases of cholecystitis have been described in porcelain gallbladders. Enterobiliary fistula may complicate acute or chronic cholecystitis in non-calcified gallbladder.
We report a unusual case of acute cholecystitis with cholecystoduodenal fistula in a porcelain gallbladder.
MIRIZZI SYNDROME .
High coincidence of Mirizzi syndrome and gallbladder carcinoma.
Redaelli CA, Buchler MW, Schilling MK, Krahenbuhl L, Ruchti C, Blumgart LH, Baer HU.
Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.
Surgery 1997 Jan;121(1):58-63 Abstract quote BACKGROUND: Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied.
METHODS: Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study.
RESULTS: Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation.
CONCLUSIONS: There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.
PEDIATRIC
Laparoscopic inguinal herniorrhaphy in children: a three-center experience with 933 repairs.Schier F, Montupet P, Esposito C.
University Medical Center, Jena, Germany.
J Pediatr Surg 2002 Mar;37(3):395-7 Abstract quote BACKGROUND/PURPOSE: Laparoscopic inguinal herniorrhaphy has been introduced recently as an alternative to conventional open repair in children. This study was undertaken to evaluate the safety, efficacy, and reproducibility of this minimally invasive approach.
METHODS: A total of 933 laparoscopic inguinal herniorrhaphies were performed on 666 children (597 boys and 69 girls), ranging in age from 3 weeks to 14 years (median, 3.2 years). A 5-mm laparoscope was placed through an umbilical incision, and two 2-mm or 3-mm needle drivers were inserted through the lateral abdominal wall. The neck of the sac was closed with a 4-0 monofilament suture. The needle was inserted directly through the abdominal wall, and removed together with the trocar. Only the umbilical fascia was closed with an absorbable suture. No skin sutures were applied.
RESULTS: A total of 911 indirect inguinal hernia sacs were closed (337 right, 172 left, 402 bilateral) and 22 direct inguinal hernias were repaired (14 boys, 3 girls; 11 right, 3 left, 4 bilateral). The median operating time was 22 minutes (range, unilateral, 7 to 45 min; bilateral, 9 to 51 min). With experience, this time gradually decreased. There were no intraoperative complications. The contralateral asymptomatic processus was unexpectedly open on the left side in 137 of the boys (23%) and 10 of the girls (15%), and on the right side in 131 of the boys (22%) and 21 of the girls (32%). In 16% of the children, the final procedure was modified on the basis of the anatomic findings. No hernia was found in 13 children (1.9%). The recurrence rate was 3.4% (follow-up time ranged from 2 months to 7 years). Hydroceles were observed in 4 children, and a subtle change in testicular position and size was noted in one boy.
CONCLUSIONS: Laparoscopic inguinal repair in children proved safe and reproducible, although the recurrence rate was slightly higher than with the open approach. However, laparoscopy allows easy and precise identification of the type of defect and its correction. In this series, the incidence of direct inguinal hernias was higher, and the incidence of a patent contralateral processus vaginalis was lower than previously reported.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Histologic analysis of chronic inflammatory patterns in the gallbladder: Diagnostic criteria for reporting cholecystitis.Barcia JJ.
Ann Diagn Pathol. 2003 Jun;7(3):147-53. Abstract quote Cholecystectomy is one of the most common surgical procedures. Inflammatory disease is by far the most common pathology of the gallbladder. Terms for describing cholecystitis are numerous, thus there is no uniform terminology.
One hundred cholecystectomies and 10 gallbladders from autopsies were reviewed and inflammatory changes were analyzed. Chronic cholecystitis was seen in 75% of cases with epithelial metaplasia and 73% with regenerative epithelium, the latter being associated with erosion but not with the presence of lithiasis. Muscular thickening and addipose deposits were mostly mild. Inflammation was mild in 28%, moderatein 57%, and severe in 15%. Activity was found in 29% of cases.
Fibrosis was present in all cases: 26% mild, 62% moderate, and 12% severe. Autopsy cases did not show significant changes. A simple and reproducible scoring system of inflammation and fibrosis of the gallbladder is proposed. Three numbers refer to mild, moderate, or severe degrees of chronic inflammation and activity, with a final score that results from adding both values. The fibrosis is classified in three different stages. The final report uses both values to classify the chronic cholecystitis.
A scoring system for chronic cholecystopathy to replace descriptive terms would give an exact traduction of the observed changes in an objective fashion that could not be misinterpreted by physicians or other pathologists.
Histological findings of gallbladder mucosa in 95 control subjects and 80 patients with asymptomatic gallstones.Csendes A, Smok G, Burdiles P, Diaz JC, Maluenda F, Korn O.
Department of Surgery and Pathology, University Hospital, Santiago, Chile.
Dig Dis Sci 1998 May;43(5):931-4 Abstract quote The histological appearance of gallbladder mucosa in 95 control subjects and in 80 patients with asymptomatic gallstones separated according to age and sex was determined in a prospective study.
The number and size of stones in the latter group were also analyzed. Among controls, 33% showed abnormal histological findings, mainly chronic cholecystitis, which increased with age and was frequently seen among women.
All patients with asymptomatic gallstones showed chronic cholecystitis and/or cholesterolosis, and 5% showed acute inflammatory changes. In 55% of them a single stone was found.
These findings suggest that chronic inflammatory changes can occur in the gallbladder mucosa prior to the appearance of macroscopic stones at the gallbladder.
VARIANTS DIFFUSE LYMPHOPLASMACYTIC CHRONIC CHOLECYSTIS
Diffuse lymphoplasmacytic chronic cholecystitis is highly specific for extrahepatic biliary tract disease but does not distinguish between primary and secondary sclerosing cholangiopathy.
Abraham SC, Cruz-Correa M, Argani P, Furth EE, Hruban RH, Boitnott JK.
Am J Surg Pathol. 2003 Oct;27(10):1313-20. Abstract quote
SUMMARY: Previous studies of gallbladder pathology in primary sclerosing cholangitis (PSC) have suggested that a distinctive histologic triad ("diffuse lymphoplasmacytic acalculous cholecystitis," composed of diffuse, mucosal-based, dense lymphoplasmacytic infiltrates) is commonly present in gallbladders of patients with PSC and is relatively specific for that disease. However, prior control populations have included only patients with cholecystitis/cholelithiasis and hepatitis, and have not evaluated patients with non-PSC-associated extrahepatic biliary tract disease.
We recently observed cases of diffuse lymphoplasmacytic chronic cholecystitis in a subset of patients with biliary tract disease associated with lymphoplasmacytic sclerosing pancreatitis and among patients undergoing Whipple resection for pancreatic head malignancy, suggesting that diffuse lymphoplasmacytic chronic cholecystitis is not specific for PSC. We studied 20 gallbladders from patients with obstructive jaundice due to malignancies of the pancreatic head, duodenum, or ampulla and 5 gallbladders from patients with choledocholithiasis, and compared them with 20 gallbladders from patients with PSC and 20 gallbladders with cholelithiasis.
The following histologic features were evaluated: degree of mucosal and deep inflammation, lymphoid nodules, epithelial metaplasia, muscular hypertrophy, Rokitansky-Aschoff sinuses, fibrosis, and cholesterolosis. Gallbladders in malignancy-associated obstructive jaundice were nearly identical to gallbladders in PSC with respect to scores for mucosal inflammation, lymphoid nodules, and frequency of diffuse lymphoplasmacytic chronic cholecystitis (60% vs. 50%, respectively). PSC gallbladders, however, were significantly more likely to contain focal or extensive epithelial metaplasia (P = 0.01). The cholelithiasis control group was characterized by lack of significant mucosal inflammation in the majority of cases (95%) and frequent Rokitansky-Aschoff sinuses, fibrosis, and muscular hypertrophy. Gallbladders in the choledocholithiasis group showed overlapping histologic features with PSC/malignancy-associated obstructive jaundice and cholelithiasis.
These results suggest that a pattern of diffuse lymphoplasmacytic chronic cholecystitis is highly specific for extrahepatic biliary tract disease but does not distinguish between primary and secondary cholangiopathies.GRANULOMA
Gallstone granuloma: a rare complication of laparoscopic cholecystectomy.Tham CH, Ng BK.
Department of Plastic Surgery, Singapore General Hospital, Singapore.
Singapore Med J 2001 Apr;42(4):174-5 Abstract quote Gallstone spillage during laparoscopic cholecystectomy is a relatively common occurrence. These intraperitoneal stones rarely give rise to complications.
We present the case of a 68 female who presented with a 5 cm diameter epigastric mass two years after a laparoscopic cholecystectomy for acute-on-chronic cholecystitis with gallbladder stones. CT abdomen demonstrated an inflammatory mass with central calcification.
Laparotomy and excision of the mass revealed the diagnosis as a gallstone granuloma.
LIVER
Histopathological assessment of the liver in cholelithiasis with cholecystitis.George RK, Agrawal V, Minocha VR, Aggarwal S.
Department of Surgery, University College of Medical Sciences, University of Delhi and Guru Tegh Bahadur Hospital, New Delhi, India.
Int Surg 2002 Apr-Jun;87(2):99-103 Abstract quote Liver function and histology were studied in 62 patients undergoing elective cholecystectomy. Data from 50 of the cases was subsequently analyzed.
Liver function was assessed by biochemical parameters and histological examination of intraoperatively obtained core and wedge liver biopsy. There were no complications associated with the procedure of liver biopsy. Seventy-eight percent of liver biopsies showed some form of abnormality, the commonest being mild portal tract infiltration. Eighteen percent of patients had severe histological abnormalities. Fourteen percent of bile samples were infected. No correlation was found among age, symptom duration, liver function tests, and histological appearance. Biliary infection was associated with a significant incidence of fatty change and inflammatory cell infiltration of parenchyma.
We observed a high rate of abnormal liver histology of unknown clinical significance in patients of calculous cholecystitis. These changes are not reflected in commonly performed tests of liver function. Intraoperative liver biopsy is a safe and sensitive method to detect liver abnormalities.
XANTHOGRANULOMATOUS CHOLECYSTITIS
Mirizzi syndrome caused by xanthogranulomatous cholecystitis: report of a case.Lee KC, Yamazaki O, Horii K, Hamba H, Higaki I, Hirata S, Inoue T.
Department of Surgery, Osaka City General Hospital, Japan.
Surg Today 1997;27(8):757-61 Abstract quote Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder. In severe cases, inflammation extends to adjacent structures, and XGC is sometimes confused with a malignant neoplasm.
We recently diagnosed XGC as the preoperative cause of Mirizzi syndrome in a patient based on the clinical course. The patient was admitted because of obstructive jaundice, with gallbladder carcinoma as the suspected cause. The gallbladder was swollen with gallstones and the serum level of carbohydrate antigen 19-9 (CA19-9) was 3070 U/ml at admission. A percutaneous transhepatic cholangiodrainage (PTCD) was done, and the common hepatic duct as well as the right and left hepatic ducts were found to be obstructed. Later, the CA19-9 level and swelling of the gallbladder decreased and the obstruction of the bile ducts disappeared. A cholecystectomy was performed and the intraoperative pathohistological diagnosis of chronic cholecystitis was made from frozen sections. The pathohistological diagnosis of XGC was made from paraffin-embedded sections. Mirizzi syndrome such as that seen in our patient is a rare complication of XGC. XGC occasionally causes extensive inflammation; thus, performing a conventional cholecystectomy can be unsafe.
However, in our opinion, a total, not subtotal, cholecystectomy should be done whenever possible because the incidence of gallbladder carcinoma accompanied with XGC is higher than that with ordinary cholecystitis or gallstones.
PROGNOSIS CHARACTERIZATION GENERAL
Risk factors for conversion of laparoscopic to open cholecystectomy.Kanaan SA, Murayama KM, Merriam LT, Dawes LG, Prystowsky JB, Rege RV, Joehl RJ.
Northwestern University Medical School, Chicago, IL 60611, USA.
J Surg Res 2002 Jul;106(1):20-4 Abstract quote BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for symptomatic gallstones; however conversion to open cholecystectomy (OC) remains a possibility. Unfortunately, preoperative factors indicating risk of conversion are unclear. Therefore, we aimed to identify risk factors associated with conversion of LC to OC.
PATIENTS AND MATERIALS: Records of 564 patients undergoing LC in 1995 and 1996 were reviewed. Patients were assigned to one of two groups: (1) acute cholecystitis defined by the presence of gallstones, fever, leukocyte count >10(4), and inflammation on ultrasound or histology; (2) chronic cholecystitis that included all other symptomatic patients. Demographics, history, and physical, laboratory, and radiology data, operative note, and the pathology report were reviewed.
RESULTS: 161 of 564 patients, had acute and 403 patients had chronic cholecystitis; 16 acute cholecystitis patients (10%) were converted from LC to OC and 17 chronic cholecystitis patients (4%) had LC converted to OC. Patients having open conversion were significantly older, had greater prevalence of cardiovascular disease, and were more likely to be males. LC conversion to OC in acute cholecystitis patients was associated with a greater leukocyte count; in gangrenous cholecystitis patients, 29% had open conversion.
CONCLUSIONS: Importantly, these risk factors-older men, presence of cardiovascular disease, male gender, acute cholecystitis, and severe inflammation-are determined preoperatively, permitting the surgeon to better inform patients about the conversion risk from LC to OC. While acute cholecystitis was associated with more than a twofold increased conversion rate, only 10% of these patients could not be completed laparoscopically. Therefore, acute cholecystitis alone should not preclude an attempt at laparoscopic cholecystectomy.
Incidence, risk factors, and prevention of biliary tract injuries during laparoscopic cholecystectomy in Switzerland.Krahenbuhl L, Sclabas G, Wente MN, Schafer M, Schlumpf R, Buchler MW.
Department of Visceral Transplantation Surgery, University of Bern, Inselspital, Switzerland.
World J Surg 2001 Oct;25(10):1325-30 Abstract quote Bile duct injury (BDI) during laparoscopic cholecystectomy (LC) which may result in patient disability or death are reported to occur more frequently when compared to open surgery.
The aim of this nationwide prospective study beyond the laparoscopic learning curve was to analyze the incidence, risk factors, and management of major BDI. During a 3-year period (1995-1997) 130 items of all LC data were collected on a central computer system from 84 surgical institutions in Switzerland by the Swiss Association of Laparoscopic and Thoracoscopic Surgery and evaluated for major BDIs. Simple biliary leakage was excluded from analysis. There were 12,111 patients with a mean age of 55 years (3-98 years) enrolled in the study.
The overall BDI incidence was 0.3%, 0.18% for symptomatic gallstones, and 0.36% for acute cholecystitis. In cases of severe chronic cholecystitis with shrunken gallbladder, the incidence was as high as 3%. Morbidity and mortality rates were significantly increased in BDIs. BDI was recognized intraoperatively in 80.6%, in 64% of cases by help of intraoperative cholangiography. Immediate surgical repair was performed laparoscopically (suture or T-drainage) in 21%; in 79%, open repair (34% simple suture, 66% Roux-en-Y reconstruction) was needed. The BDI incidence did not decrease during the last 7 years. In 47%, BDIs were caused by experienced laparoscopic surgeons, perhaps because they tend to operate on more difficult patients.
In conclusion, the incidence of major BDIs remains constant in Switzerland at a level of 0.3%, which is still higher when compared to open surgery. However, most cases are now detected intraoperatively and immediately repaired which ensures a good long-term outcome. For preventing such injuries, exact anatomical knowledge with its variants and a meticulous surgical dissecting technique especially in case of acute inflammation or shrunken gallbladder are mandatory.
Factors affecting mortality in patients over 70 years of age submitted to surgery for gallbladder or common bile duct stones.Burdiles P, Csendes A, Diaz JC, Maluenda F, Avila S, Jorquera P, Aldunate M.
Department of Surgery, Clinical Hospital Jose Joaquin Aguirre, University of Chile.
Hepatogastroenterology 1989 Jun;36(3):136-9 Abstract quote Chile is the country with the highest incidence of gallstone disease in the world. Nearly 44% of the women and 25% of the men over 20 years of age have gallstones. Biliary tract surgery accounts for about 35% of all the operations performed in Chilean general hospitals.
The present paper aims at assessing the risk factors associated with a higher mortality in patients over 70 years of age subjected to elective or emergency surgery for gallstones or common bile duct stones.
No specific factors of mortality were found in the group of elderly patients subjected to elective cholecystectomy. There was also no correlation between types of cholecystitis and postoperative mortality. However, acute suppurative cholangitis made the postoperative mortality rate increase almost 20-fold in patients with common bile duct stones. The mortality also shows a steep increase (up to 12%) if cholecystectomy is performed in acute cholecystitis. Cholecystostomy seems to be associated with a low mortality risk and hence should be appropriate in exceptionally high-risk patients, but is not considered useful by the authors in necrotic or gangrenous cholecystitis, or in cases with common bile duct stones and cholangitis. Postoperative mortality in patients submitted to cholecystectomy alone seems to depend exclusively on the concomitant presence of medical complications, mainly of a respiratory and cardiovascular nature.
Septic complications are important causes of postoperative mortality in emergency cholecystectomy. Patients at high surgical risk are those suspected of cholangitis, those over 80 years of age, and those suffering from Charcot's triad, anemia, uremia, leukocytosis, hyperbilirubinemia or hypoprothrombinemia; in these, an endoscopic procedure could be chosen.
Trends in incidence, clinical findings and outcome of acute and elective cholecystectomy, 1970-1986.Kullman E, Dahlin LG, Hallhagen S, Segersvardh R, Borch K.
Department of Surgery, University Hospital of Linkoping, Sweden.
Eur J Surg 1994 Nov;160(11):605-11 Abstract quote OBJECTIVE: To assess time trends in the incidence, clinical findings, and outcome of conventional acute and elective cholecystectomy.
DESIGN: Single-institution time series analysis.
SETTING: University hospital, Sweden.
SUBJECTS: A consecutive series of 2926 patients operated on for acute or chronic gallbladder disease in a defined Swedish population.
MAIN OUTCOME MEASURES: Changes in the incidence and outcome of acute and elective cholecystectomy.
RESULTS: From period I (1970-1978) to period II (1979-1986), the mean rate of acute operations increased from 10 to 30/100,000 inhabitants/year and that of elective operations decreased from 190 to 120/100,000 inhabitants/year. There was therefore a negative correlation between the rate of elective and acute operations (r = -0.58, p < 0.02). This was strongest when the rate of elective operations in any one year was correlated with the rate of acute operations two years later (r = -0.71, p < 0.01). In both groups the proportion of patients over 70 years old increased significantly. The female:male ratio decreased significantly for acute but not elective operations (mean 2.6 in period I and 1.0 in period II). The length of history and the number of previous admissions to hospital with gallstone disease decreased significantly for both groups, as did prevalence of common bile duct stones detected at cholecystectomy. Morbidity did not seem to change, though a general improvement may have been concealed, because patients were older in period II and postoperative mortality was lower than in period I. Complications were least common among patients with a short or no previous history of symptoms attributable to gallstones.
CONCLUSIONS: The rate of elective cholecystectomy seems to have some influence on the future rate of acute cholecystectomy. When symptoms of gallstone disease develop, treatment should not be delayed unnecessarily.
ACALCULOUS CHOLECYSTITIS
A long-term cohort study of outcome after cholecystectomy for chronic acalculous cholecystitis.Jagannath SB, Singh VK, Cruz-Correa M, Canto MI, Kalloo AN.
Division of Gastroenterology, The Johns Hopkins Hospital, Room 419, 1830 E. Monument St., Baltimore, MD 21205, USA.
Am J Surg 2003 Feb;185(2):91-5 Abstract quote BACKGROUND: Cholecystectomy is effective therapy for chronic calculous cholecystitis (CCC). The long-term outcome of patients treated with cholecystectomy for chronic acalculous cholecystitis (CAC) is unknown.
METHODS: A controlled, retrospective cohort study assessing biliary pain (preoperative and at follow-up) in postcholecystectomy patients with CAC or CCC was performed.
RESULTS: In 19 CAC and with matched CCC control patients, the mean duration of symptoms before surgery was 38.3 months (95% CI, 16.4 to 60.2) and 8.1 months (95% CI, 5.4 to 10.8), respectively. The mean follow-up for both groups was 8.37 +/- 1.13 years. Both groups benefited from cholecystectomy (P <0.001), and both were equally likely to be pain-free upon long-term follow-up (95% CAC versus 84% CCC, P >0.05).
CONCLUSIONS: There was no difference in outcome between the groups after an average follow-up of 8.37 years. Postcholecystectomy patients with chronic cholecystitis and no gallstones have long-term, complete pain resolution, similar to patients with gallstones.
MALIGNANCY
Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones.Tazuma S, Kajiyama G.
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Langenbecks Arch Surg 2001 Apr;386(3):224-9 Abstract quote Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established risk factor for gallbladder carcinoma, and the risk seems to correlate with stone size.
Metaplastic changes of the gallbladder epithelium present in chronic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladder carcinoma when their characteristics are echopenic, sessile, and high cell density. Endoscopic ultrasound is the most useful technique to detect the early changes of malignancy in polyps. Anomalous junction of pancreaticobiliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder is an additional risk factor for gallbladder malignancy. At the molecular level, it has been proposed that chronic inflammation of the gallbladder may lead to the loss of p53 gene heterozygosity and excessive expression of p53 protein.
Furthermore, a proposed mechanism underlying the high risk of gallbladder carcinoma in patients with AJPBD is that chronic reflux of pancreatic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras.
In contrast, the causal relationship between porcelain gallbladder and malignancy is yet to be established. In this article, recognition of risk factors for gallbladder carcinoma was summarized with special attention to gallstones and chronic inflammation.
Primary gallbladder cancer: recognition of risk factors and the role of prophylactic cholecystectomy.Sheth S, Bedford A, Chopra S.
Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Am J Gastroenterol 2000 Jun;95(6):1402-10 Abstract quote The objective of this article is to review the available literature on the epidemiology, predisposing factors, and conditions associated with primary gallbladder cancer, and to discuss the role of prophylactic cholecystectomy in high-risk patient populations. Gallbladder cancer is a highly malignant tumor with a poor 5-yr-survival rate. It is a tumor of the elderly and has striking genetic, racial, and geographic characteristics, with an extremely high prevalence in Native Americans and Chileans.
Cholelithiasis is a well-established risk factor for gallbladder cancer and the risk seems to correlate with stone size. Polyps that are >1 cm, single, sessile, and echopenic are associated with a higher risk of malignancy. Anomalous junction of pancreaticobiliary ducts (AJPBD), especially without choledochal cyst, and porcelain gallbladder are additional factors that predispose to gallbladder cancer. Lesser associations include chronic bacterial infections of the gallbladder, typhoid carrier state, certain occupational and environmental carcinogens, hormonal changes in women, and certain social, dietary, and familial factors. It is important to identify high-risk groups for gallbladder cancer because of the dismal nature of this tumor. In patients with porcelain gallbladder and anomalous junction of the pancreatic and biliary ducts, cholecystectomy is recommended provided that the patient is a good operative candidate. Patients with large solitary polyps or gallstones require close ultrasonic follow-up. With the advent of endoscopic ultrasound it is expected that early changes of malignancy in polyps will be reliably detected, and more patients will potentially be cured with a simple cholecystectomy.
Through a MEDLINE/PAPERCHASE search we identified and reviewed articles regarding gallbladder cancer published in English-language journals between 1966 and 1999, using the key words biliary tract and gallbladder diseases, cancer, neoplasms, surgery, cholelithiasis, gallstones, cholecystitis, gallbladder polyps, risk factors, chemical industry, occupational diseases, typhoid, porcelain gallbladder, bacteremia, and precancerous conditions. We also used the bibliography of relevant articles to increase our search. A total of 122 publications were selected using the mentioned data source.
PEDIATRIC
Laparoscopic cholecystectomy in children and adolescents.Zilberstein B, Eshkenazy R, Ribeiro Junior MA, Sallet JA, Ramos AC.
Servico de Cirurgia do Aparelho Digestivo do Hospital Nove de Julho, Sao Paulo, Brazil.
Rev Paul Med 1996 Nov-Dec;114(6):1293-7 Abstract quote During the period between August 1991 and November 1995, seven patients under age 17 were submitted to videolaparoscopic cholecystectomy (LC). Two were males and five females with ages ranging from 12 to 16 years (mean 13.8 years). The diagnosis of chronic cholecystitis with gallstones was made by the clinical history and physical and ultrasonographic examinations.
There was no evidence of an association with hemolytic diseases, familial hyperlipidemia or Glucose-6-phosphate dehydrogenase (G6PD) deficiency. The surgery was performed under general anesthesia and the abdomen approached by four ports: a 10 mm umbilical incision, a 5 mm cystic, a 5 mm one at the xiphoid appendix and a 10 mm one at the left lateral margin of the left rectus abdominal muscle between the umbilical scar and the xiphoid appendix. Operative time averaged 120 minutes (105-150 min). One case required conversion to laparotomic approach because of Mirizzi's Syndrome, which was diagnosed by intraoperative cholangiography performed in all cases. There were no deaths or major postoperative complications. Hospital stays ranged from 1-3 days in the six patients submitted to LC.
Thus LC in children can be considered a good method, requiring only more care regarding the use of proper equipment, complete and careful dissection of the biliary hilus, and intraoperative cholangiography. The latter is indispensable, as these children can present a higher rate of anatomic anomalies. The advantages of this techniques include a less painful postoperative period with a faster recovery, and it is especially recommended in children, who are less tolerant to physical restriction and pain than adults.
TREATMENT CHARACTERIZATION GENERAL LITHOTRIPSY
Impaired gallbladder mucosal function in aged gallstone patients suppresses gallstone recurrence after successful extracorporeal shockwave lithotripsy.Tazuma S, Nishioka T, Ochi H, Hyogo H, Sunami Y, Nakai K, Tsuboi K, Asamoto Y, Sakomoto M, Numata Y, Kanno K, Yamaguchi A, Kobuke T, Komichi D, Nonaka Y, Chayama K.
First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan.
J Gastroenterol Hepatol 2003 Feb;18(2):157-61 Abstract quote BACKGROUND: Absorption of water, as well as emptying of bile, are important functions of the gallbladder. We studied the changes of gallbladder function with age in gallstone patients and their influence on the outcome of extracorporeal shockwave lithotripsy (ESWL).
METHODS: (i) A total of 123 consecutive patients with complete stone clearance by ESWL were examined. Gallbladder emptying was assessed before treatment using intravenous cholecystography. After stone clearance, the recurrence of gallstones was monitored by using ultrasonography. Cox regression analysis was used to determine the risk factors associated with stone recurrence. (ii) Gallbladder bile was sampled from 59 gallstone patients during surgery. Biliary cholesterol, phospholipids, and total bile acids were simultaneously quantified by using gas-liquid chromatography.
RESULTS: Impaired gallbladder function, but not gallstone recurrence, was more frequently observed in older patients (>/=65 years old) than in younger patients (<65 years old). Cox regression analysis revealed that poor gallbladder emptying was an independent predictor of stone recurrence after ESWL in the total study population, but not in the older patients (>/=65 years old). Analysis of bile from surgically treated patients with cholesterol stones showed a significantly higher total lipid concentration and a shorter nucleation time in the younger group (<65 years old), but the cholesterol saturation index did not differ between the younger and older groups.
CONCLUSIONS: Our data suggest that the reduced concentrating function of the gallbladder in elderly gallstone patients helps to counteract stone recurrence despite their abnormal gallbladder motility. Therefore, aged gallstone patients may be preferentially treated by a non-surgical strategy.
Does adequate patient selection reduce the risk of gallstone recurrence after successful extracorporeal shockwave lithotripsy?Kratzer W, Mason RA, Janowitz P, Tudyka J, Maier C, Wechsler JG, Adler G.
Abteilung fur Endokrinologie, Ernahrungswissenschaft, Gastroenterologie und Stoffwechselkrankheiten, Universitat Ulm.
Z Gastroenterol 1994 Mar;32(3):170-3 Abstract quote To determine the risk of gallbladder stone recurrence in these patients, 58 of the first consecutive 61 patients with solitary stones achieving complete stone clearance after ESWL and adjuvant bile acid therapy were included in a prospective study.
All patients were observed for at least 12 months following discontinuation of oral bile acids. Twenty-one patients fulfilled our postulated ideal criteria (solitary radiolucent stones between 10-20 mm initial diameter, initial stone density < 50 HU, gallbladder ejection fraction > 70%). The remaining patients (n = 37) fulfilled the criteria of the Munich study group. In patients fulfilling our ideal criteria, stone recurrence was not observed in any patient, while in those fulfilling solely the criteria of the Munich group, five instances of stone recurrence were observed (13.5% [n = 37], p < 0.1). Initial stone count is only one factor influencing the probability of gallstone recurrence following ESWL and discontinuation of oral bile acids.
Our data suggest that factors such as low initial stone density at gallbladder CT and good gallbladder function not only accelerate initial stone clearance but also reduce the risk of stone recurrence after ESWL once oral bile acids have been discontinued.
SURGERY
A population-based cohort study comparing laparoscopic cholecystectomy and open cholecystectomy.
Zacks SL, Sandler RS, Rutledge R, Brown RS Jr.
Department of Medicine, University of North Carolina at Chapel Hill, USA.
Am J Gastroenterol 2002 Feb;97(2):334-40 Abstract quote OBJECTIVES: Laparoscopic cholecystectomy (LC) has become a popular alternative to open cholecystectomy (OC). Previous studies comparing outcomes in LC and OC used small selected cohorts of patients and did not control for comorbid conditions that might affect outcome. The aims of this study were to characterize the morbidity, mortality, and costs of LC and OC in a large unselected cohort of patients.
METHODS: We used the population-based North Carolina Discharge Abstract Database (NCHDAD) for January 1, 1991, to September 30, 1994 (n = 850,000) to identify patients undergoing OC and LC. We identified the indications for surgery, complications, and type of perioperative biliary imaging used. We compared length of stay, hospital charges, complications, morbidity, and mortality between OC and LC patients. To account for variations in outcomes from differences in age and comorbidity between the OC and LC groups, we used the age-adjusted Charlson Comorbidity Index in regression analyses quantifying the association between type of surgery and outcome.
RESULTS: Our cohort consisted of 43,433 patients (19,662 LC and 23,771 OC). The mean age-adjusted Charlson Comorbidity Index score was slightly higher for the OC compared to the LC group (4.3 vs 4.1, p < 0.05). The OC patients had longer hospitalizations, generated more charges ($12,125 vs $9,139, p < 0.05), and required home care more often. The crude risk ratio comparing risk of death in OC to LC was 5.0 (95% CI = 3.9-6.5). After controlling for age, comorbidity, and sex, the odds of dying in the OC group was still 3.3 times (95% CI = 1.4-7.3) greater than in the LC group. In the LC group, the number of patients with acute cholecystitis rose over the study period, whereas the number of patients with chronic cholecystitis declined. In the OC group, the number of patients with acute and chronic cholecystitis declined. The use of intraoperative cholangiography was greater in the OC group but declined in both groups over the study period. The use of ERCP was greater in the LC group and increased in both groups over time.
CONCLUSIONS: The introduction of LC has resulted in a change in the management of cholecystitis. Despite a higher proportion of patients with acute cholecystitis, the risk of dying was significantly less in LC than in OC patients, even after controlling for age and comorbidity. Based on lower costs and better outcomes, LC seems to be the treatment of choice for acute and chronic cholecystitis.
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