EDUCATION

Asymptomatic gallstones in the laparoscopic era

A.W. MESHIKHES

Department of Surgery, Dammam Central Hospital, Dammam, Eastern Province, Saudi Arabia

Introduction Case for expectant management The case against expectant management Asymptomatic gallstones in patients with diabetes Asymptomatic gallstones in transplant patients

Asymptomatic gallstones in sickle cell disease Asymptomatic gallstones in cirrhotic patients Incidental cholecystectomy Asymptomatic gallstones and cancer Conclusion References

Keywords: Asymptomatic, gallstones, cholecystitis, gallbladder cancer, laparoscopy, sickle cell disease, diabetes, cirrhosis, transplantation, porcelain gallbladder

Recent introduction of new treatment options has significantly altered the approach towards gallstone management. There is now general agreement that cholecystectomy is the treatment of choice for symptomatic gallstones. Controversy, however, exists as to the management of asymptomatic gallstones. The ready availability of abdominal ultrasonography for the investigation of a wide range of abdominal symptoms has resulted in the increased diagnosis of asymptomatic gallstones. Management of such accidentally discovered gallstones poses a dilemma as conclusive evidence of the benefits of cholecystectomy is lacking. This is further complicated by the fact that the majority of asymptomatic gallstones remain so and patients rarely experience symptoms or complications. Furthermore, cholecystectomy is associated with a low but recognised morbidity. Recent introduction of laparoscopic cholecystectomy as the treatment of choice of symptomatic gallstones has further complicated the issue of asymptomatic gallstone management. This article reviews the current management of asymptomatic gallstones in the era of laparoscopic cholecystectomy

J. R. Coll. Surg. Edinb., December 2002, 742-748

INTRODUCTION

Since the introduction of laparoscopic cholecystectomy (LC) in 1989, there has been a significant increase in the number of cholecystectomies performed worldwide.^1-4 This may reflect a change in surgeons’ attitudes towards some of the indications for cholecystectomy, for example for asymptomatic gallstones (GSs).^1,2 This lowered threshold for surgery and liberal attitude towards operative indications has been brought about by the change in risk-benefit ratio caused by the introduction of LC.^1-3 This procedure is now offered to almost all patients with symptomatic GSs including young children, females of childbearing age, diabetics, patients with sickle cell disease, individuals with very large stones, transplant and other immunosupressed patients and some cases with chronic acalcular biliary disease. This liberal surgical attitude has been further promoted by a lower referral threshold by physicians and the demand of minimally invasive surgery by patients.² This article reviews the evidence for and against cholecystectomy in asymptomatic GSs with special reference to the modern laparoscopic era.

THE CASE FOR EXPECTANT MANAGEMENT

The natural history of asymptomatic GSs suggests that a large number of affected individuals will remain asymptomatic throughout life; only 1-4% per year will develop symptoms or complications of GS disease.^5,7 Only 10% will develop symptoms in the first five years after diagnosis and approximately 20% by 20 years; fewer complications developing in later years than in the early years after GS documentation.^6,7 Studies also suggest that almost all patients will experience symptoms for a period of time before they develop any complication.6 None of the local factors such as the number, size, nature, alteration in wall thickness or gallbladder (GB) contractility were found to be a predictive factor of symptoms or severe complications such as acute cholecystitis, jaundice, pancreatitis or GB cancer in patients with asymptomatic GSs.⁸ General factors such as age, sex, associated medical diseases such as diabetes or recent organ transplant were also non-predictive. Only a few patients with a porcelain GB or GB polyps larger than 10mm in diameter were at high risk of cancer and, hence, prophylactic cholecystectomy was advocated in such patients.^8-11 Therefore, with few exceptions prophylactic treatment of asymptomatic patients cannot be justified.⁶ Cost-effective analyses have not demonstrated a substantial difference between patients with silent GSs who undergo immediate open cholecystectomy (OC), compared with watchful waiting.⁷ In a study of 139 patients with silent GSs discovered coincidentally during ultrasonography for evaluation of other medical conditions (e.g. abdominal aortic aneurysm, malignancy, lower abdominal pain etc.) only 15 patients (11%) developed symptoms suggestive of biliary colic over the next five years; nine underwent cholecystectomy, in three of whom it was incidental to other abdominal procedures. It was concluded that ultrasound-detected coincidental GSs are infrequently clinicaly significant.¹² This lends support to the expectant management of most patients with coincidental GSs. This approach was also advocated in patients with GSs who had occasional mild symptoms and no history of complications.^13-16 Therefore, the natural history of asymptomatic GSs is so benign that surgery is generally not recommended and watchful waiting is the best course of management (Table 1).

US: ultrasonography, GSs: gallstones, LC: laparoscopic cholecystectomy, SCD: sickle cell disease

Table 1: Summary of the case for and against expectant management of asymptomatic gallstones

THE CASE AGAINST EXPECTANT MANAGEMENT

Although the majority of patients with silent GSs remain asympatomatic, some may develop symptoms and GS-related complications. Emergency surgery in such patients presenting with complications is associated with a significant morbidity and recognised mortality. On the other hand, elective LC is safe with a low morbidity and virtually no mortality. For these reasons, Patino and Quintero (1998) proposed a high-risk criteria for elective cholecystectomy in patients with asymptomatic GSs (Table 2).¹⁷

In the laparoscopic era, the mean operative time for LC in acute cholecystitis is significantly longer than that for elective LC and with a longer average hospital stay.¹⁸ There was no difference, however, regarding conversion rates (7.3% vs. 7.6%) and morbidity rates (8.7% vs. 9.6%).18 Binder and Katz (1978) argued that the risk of an individual with silent GSs developing complications is high enough to justify prophylactic cholecystectomy, which is safe if performed in young and fit patients.¹⁹ This argument is even stronger following the introduction of LC with all its associated advantages. Some authors reserve cholecystectomy for patients at risk e.g. diabetics, patients with porcelain GBs and for stones detected at laparotomy for other abdominal conditions.⁵ Wacha and Ungehever (1986) found that up to 50 % of individuals with silent GSs will be operated on or develop symptoms within 10-20 years after the initial diagnosis.²⁰ Diehl (1983) found that those with large GSs to be at greater risk of GB cancer.²¹ This finding may have implications for the management of silent GSs in areas where there is a high incidence of GB cancer.²¹ In summary, early surgery for silent GSs is recommended in high-risk patients while they are medically fit and in areas where the incidence of GB cancer is high. Nevertheless, the indication for surgery remains an individual decision (Table 1).²⁰

ASYMPTOMATIC GALLSTONES IN PATIENTS WITH DIABETES

It has been suggested that diabetic patients are at an increased risk of developing GSs and stone-related complications.²² Landau et al (1992) found patients with diabetes to have a higher rate of infected bile, gangrenous changes and perforation of the GB, in comparison with non-diabetic patients. Also, the mortality rate of surgery for acute cholecystitis was significantly higher (21% vs. 9%) in diabetic patients.²³ It is believed that the autonomic neuropathy in diabetics may mask the pain and signs associated with acute cholecystitis.²⁴ Earlier reports found the risk of acute cholecystitis and perioperative morbidity and mortality for treatment of diabetics with acute cholecystitis to be significant enough to warrant the performance of an early cholecystectomy.^1,17,25,26 Therefore, surgeons were urged to consider diabetics as a high-risk group and prophylactic cholecystectomy was recommended till the natural history of GSs in diabetics had been better defined.^25,26 Recent evidence, however, has shown that the rates of operative morbidity and mortality for biliary surgery in diabetics are comparable with rates in non-diabetics.^22,27 Diabetics have an increased morbidity primarily as a result of older age and concomitant medical diseases such as cardiovascular and renal diseases.²⁸

The natural history of GSs in diabetics is now known to be generally benign, and there is a low risk of a major complication.²⁹ Moreover, the cumulative percentage of initially asymptomatic non-insulin dependant diabetic patients who presented with symptoms and complications was small (14.9% and 4.2%, respectively).³⁰ Also, diabetes as an independent risk factor for GS formation has been recently questioned and the prevalence of GSs was found to be similar among diabetic patients (14.4%) and control subjects (12.5%) in a case-control analysis.³¹ Furthermore, prophylactic cholecystectomy for silent stones in diabetics does not appear to increase either the duration or quality of life, but may in fact reduce it.³² The frequency of silent GSs is less common in diabetic than in non-diabetic women.³³ In view of this recent evidence adult diabetics with silent or incidental GSs should be managed expectantly and preemptive surgery should not be routinely recommended.^22,27-30 However, early elective LC is advocated once symptoms develop.³¹

ASYMPTOMATIC GALLSTONES IN TRANSPLANT PATIENTS

Multivariate analysis has shown GSs to be significantly more prevalent in patients who have had a heart transplant but only a minority with silent stones will become symptomatic after transplantation.³⁴ When patients do become symptomatic, cholecystectomy can be performed safely. Therefore, prophylactic cholecystectomy and screening ultrasonography are not indicated in asymptomatic transplant patients and cholecystectomy is to be reserved only for symptomatic recipients.^34,35 Some authors have recommended screening for GSs and subsequent prophylactic cholecystectomy for patients awaiting a renal transplant,^36-38 with a view to removal of a possible septic focus that carries a potential for severe complications in immunosuppressed patients. Recently, however, this view has been challenged by Greenstein et al (1997) who followed-up 21 renal transplant patients with silent GSs for four years.³⁹ Thirteen patients (87%) remained asymptomatic, and two patients (one had diabetes) developed acute cholecystitis and underwent LC with no complications.³⁹ It was concluded that prophylactic cholecystectomy in asymptomatic patients awaiting a transplant is not justified as the incidence and morbidity of GSs after renal transplantation is low. Moreover, they are not at an increased risk for developing GSs compared with non-transplant patients and GSs do not have a negative impact on graft survival.⁴⁰

Even if surgical treatment for GSs is needed, it has a low risk and does not represent an increased rate of complications in renal transplant patients with one-, two- and five-year graft survival of 98%, 96% and 80% respectively.⁴⁰

The safety of LC in the transplant community has recently been reported in 26 transplant patients (renal, heart, double lung and heart-lung recipients); 73% had asymptomatic GSs and, in patients who had previously undergone combined renal and pancreas transplantation, had minimal morbidity and no mortality.^41,42 In summary, expectant policy should be exercised in transplant patients with silent GSs. Once the GSs become symptomatic, LC can be safely performed with no adverse impact on graft survival.

ASYMPTOMATIC GALLSTONES IN SICKLE CELL DISEASE

Patients with sickle cell disease (SCD) are at an increased risk of developing pigmented GSs as a result of repeated haemolytic crises. The presence of GSs causes diagnostic confusion in patients presenting with abdominal sickling crises. Therefore, some authors advocate prophylactic cholecystectomy in SCD patients with asymptomatic GSs to avoid future stone-related complications and diagnostic confusion. This view, till recently, was not generally accepted, as surgery in SCD was associated with a high morbidity and mortality due to vasoocclusive crises (VOCs).^43,44 Cholecystectomy was not recommended for asymptomatic GSs in the pre-laparoscopic era.⁴⁴ However, with the introduction of LC and the establishment of its safety in SCD patients with GSs,45-47 more SCD patients (adults and children) with asymptomatic GSs are increasingly being referred for LC.^45-47 Moreover, paediatricians have started screening their patients for GSs and refer them for LC before symptoms develop.⁴⁸ The reported recent safety record of LC in SCD patients cannot be attributed solely to minimally invasive procedures. Better anaesthetetic techniques, greater awareness of risk factors predisposing to VOCs and better pre-, peri- and postoperative care are important contributing factors. Reduction of Hb-S to a level lower than 50% by preoperative partial exchange transfusion is believed to be associated with a lower risk of VOCs.^43,49,50 Avoidance of OC during acute sickling crises or acute cholecystitis has been advocated.⁵¹ In the laparoscopic era, while surgery should be avoided during VOCs, LC for acute cholecystitis is not a contraindication provided that all the precautions to guard against a VOC are taken.⁵²

ASYMPTOMATIC GALLSTONES IN CIRRHOTIC PATIENTS

In a review of 64 cirrhotic patients with GSs (representing 17 % of all those with cirrhosis), 14 patients (22%) developed biliary complications necessitating cholecystectomy.⁵³ There was one complication secondary to postoperative variceal bleeding and one death due to acute respiratory failure. The remaining 50 patients (78%) were asymptomatic; 33 of whom had their stones discovered at porta-systemic shunt procedures (eight were treated by cholecystectomy and 25 by cholecystolithotomy). There was no difference in postoperative morbidity and mortality rates in these 33 patients, compared with the rates in 170 patients without stones who underwent portal surgery alone during the same period. It was concluded that although there is a high incidence of GSs in cirrhotic patients, GS complications are not frequent but emergency surgery carries a high risk in these patients.⁵³ Elective surgical treatment of asymptomatic GSs at the time of portal diversion does not have an increased risk. In such situations, cholecystolithotomy is easier and probably safer than cholecystectomy.⁵³ Early in the laparoscopic era liver cirrhosis was considered a contraindication to LC. In a recent retrospective review of 25 cirrhotic patients (Child’s A and B only) who underwent LC over a five year period, morbidity (32%) consisted of wound haematoma, pneumonia and ascites. There were no deaths and the mean hospital stay was 1.7 days.⁵⁴ Lacy et al (1995) reported no morbidity, 9% conversion rate and an average hospital stay of less than two days.⁵⁵ Laparoscopic cholecystectomy, therefore, was safe and was proposed as first-line surgical treatment in symptomatic patients with cirrhosis and well-compensated liver function. Nevertheless, asymptomatic patients with cirrhosis should be managed expectantly and offered LC once symptoms develop.

INCIDENTAL CHOLECYSTECTOMY

Management of Gs discovered incidentally during abdominal surgery is controversial. In a study of 109 patients who underwent colorectal, gastric and gynaecological procedures over a four year period, 78 patients (72%) had a cholecystectomy performed and 31 (28%) had the GB left in situ. In the former group, only two patients developed complications attributable to the cholecystectomy. In the latter group, 12 remained asymptomatic and 13 developed symptoms, seven of whom needed OC (four were acute) 2-11 weeks after the initial laparotomy.⁵⁶ Due to the relatively high number of OCs after major laparotomy, cholecystectomy en passant is recommended unless there are specific contraindications.⁵⁶ In another study, incidental GSs were encountered in 56 patients at the time of laparotomy; 33 underwent concomitant cholecystectomy and 23 had the GB left in-situ.⁵⁷ There was only one complication (3%) attributable to the cholecystectomy in the former group. In the latter, 16 developed GS complications (11 acute cholecystitis, three biliary colic and two jaundice) within six months of laparotomy. Fifteen patients (65%) needed OC and six of them required common bile duct exploration.⁵⁷ It was concluded that concomitant cholecystectomy added minimal morbidity to the operation and should be performed unless specific contraindications exist. Left untreated, the long-term risk that previously silent GSs would become symptomatic and cause complications, requiring operative intervention with greater morbidity, was substantial. Therefore, many authors now accept that incidental cholecystectomy is safe during gastrointestinal surgery and preoperative detection of GSs by ultrasonography is recommended in planning the incision and obtaining the patient’s consent for cholecystectomy.^2,58,59 The decision is more difficult in case of pelvic (gynaecologicaloperations as this may require an additional incision. However, this poses no problem if the pelvic procedure is conducted laparoscopically.

ASYPMTOMATIC GALLSTONES AND CANCER

Gallbladder cancer, although rare in most Caucasian populations, is amongst the most frequently observed cancers in native populations of North and South America, and in the Maori population of New Zealand. In all populations, there is a strong correlation between GSs and GB cancer. The risk of GB cancer is approximately four-five times higher in cases with than in those without GSs. It is estimated that one third of all GB cancers occur in association with calculi, especially in patients with large stones (equal or more than 3 cm), and patients with GB polyps larger than 10 mm in diameter.^5,10,60 However, prophylactic cholecystectomy is not generally indicated to prevent future GB cancer.⁵ Nevertheless, this association may have some implications for management of silent GSs.^51,60 As the overall prognosis of GB cancer is very poor, it is suggested that prophylactic cholecystectomy is carried out for silent GSs in areas where GB cancer is prevalent.⁶¹ However, this cannot be justified for the control of GB cancer, but the increasing frequency of this procedure in many countries, secondary to the widespread use of LC and lower threshold for referral, will clearly lower the incidence and mortality rates for this lethal disease.⁶²

PORCELAIN GALLBLADDER AND CANCER

Porcelain or calcified GB is a pathological entity, which is characterised by the presence of a brittle GB with a bluish discolouration due to extensive calcification of the wall.⁶³ The prevalence of calcified GB in cholecystectomy specimens ranges from 0.06 to 0.8%, with a female predominance.⁶⁴ The incidence of carcinoma in porcelain GB specimens ranges from 12.5-25%.65,66 This reasonably high incidence has led many surgeons to believe that cholecystectomy is highly recommended in cases of an asymptomatic porcelain GB. In a recent retrospective study of 15 patients with histologically-proven porcelain GB, 33% were asymptomatic and none showed evidence of GB cancer.⁶⁷ Furthermore, none of the 88 patients with GB cancer in the same study had GB wall calcification on histological examination. This contradicts the theory proposed by some authors that the mucosal epithelium is sloughed off completely in a porcelain GB and is completely replaced by connective tissue and calcium carbonate.⁶⁶ If this is the case, then the risk of carcinoma no longer exists. But even patients with partial calcification in this recent study had no evidence of cancer.⁶⁷ This view has been challenged most recently by Stephen and Berger (2001), who found that a calcified GB is definitely associated with an increased risk of GB cancer, but at a lower rate than previously estimated.⁶⁸ The incidence, however, depends on the pattern of calcification. Selective mucosal calcification poses a significant risk of cancer whereas diffuse intramural calcification does not.⁶⁸

In the light of this recent evidence, it seems that porcelain GB is associated with cancer, especially in presence of selective mucosal calcification. Therefore, LC should be offered to asymptomatic patients till further evidence confirms that there is no increased risk of GB cancer.

Table 2: High-risk criteria for cholecystectomy in asymptomatic gallstones¹⁷
Reproduced by permission of Springer-Verlag GmbH & Co, Patino JF, Quintero GA. Asymptomatic cholelithiasis revisited, World J Surg 1998; 22: 1119-24

CHOLECYSTECTOMY AND COLONIC CANCER

The study by Ekbom et al (1993) clearly demonstrated that there is no increased overall risk of colorectal cancer following cholecystectomy.⁶⁹ However, it is noted that women have a slight increase in the risk of proximal colon cancer following cholecystectomy. The reasons for this finding remain unclear. Since this finding has been consistently documented in several studies, it is probably not an artifact, but a true association that may warrant further investigation.⁷⁰ It is possible that the association noted between cholecystectomy and colorectal cancer is due not to the cholecystectomy per se, but to the reason behind the presence of GSs and for which cholecystectomy was performed. Another explanation is that excess secondary bile acids may be carcinogenic or the factors which cause the formation of GSs may also increase the risk for developing colorectal cancer.⁷⁰ In a nationwide cohort of gallstone patients, the hypothesis that GSs are associated with an increased risk of colon cancer was evaluated. In the Danish Hospital Discharge Register 42,098 patients with GSs diagnosed in 1977-1989 were identified and their risks of colorectal and other cancers during follow-up to the end of 1992 was assessed.⁷¹ There was a weak association for colonic cancer. A non-significantly increased risk of breast cancer was also seen in women five years after initial discharge for GSs.⁷¹ In another investigation for a possible association, cases with multiple carcinomas had a significantly higher incidence of GSs than cases with a solitary carcinoma (24.2% and 5.5%, respectively).⁷² These results suggest that the higher levels of the same causative factors, such as dietary fat, are associated with GS formation and colorectal cancer development as demonstrated by multiple colorectal carcinoma cases. One may argue that with the increasing number of LCs performed in the laparoscopic era, one should witness an increase in the incidence of colorectal cancer, especially as it is almost 15 years since the introduction of LC. However, this is not the case. For the time being and until further conclusive evidence emerges, there is no need to be concerned about any future increased risk of colorectal cancer on deciding to perform LC, especially in symptomatic individuals.⁷⁰

CONCLUSION

The management of most patients with asymptomatic GSs should be expectant, albeit it is still a controversial issue. In the era of LC, although most of the guidelines for surgery are the same as they were in the prelaparoscopic era, a consensus appears to be emerging regarding LC in selected groups of patients with asymptomatic GSs:

•     Patients with diabetes, transplant recipients and patients with cirrhosis and asymptomatic GSs  should be managed expectantly and early surgery             offered when relevant symptoms develop.

•      The management of SCD patients with asymptomatic GSs is changing in the laparoscopic era and LC is now offered to all SCD patients with              asymptomatic GSs.

•      Incidental cholecystectomy is safe and is recommended during abdominal surgery, unless specific contraindications exist.

•      Laparoscopic cholecystectomy is recommended for silent GSs in areas where GB cancer is prevalent and in patients with porcelain GBs due to its           association with cancer.

•     In general, there seems to be a lower threshold for referral of patients with asymptomatic GSs for surgery since the introduction of LC.

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Copyright: 4 November 2002

Correspondence: Dr A.W. Meshikhes, P.O. Box 18418, Qatif 31911, Saudi Arabia

Addendum

Due to a lack of space in the August edition of the Journal, two abstracts from the Audit Symposium held on 8 March 2002 were omitted. We are happy to include them in this edition.

Outcome following open lung biopsy

O.A. KHAN, S. MAJUMDAR, C. RICHARDS, W.E. MORGAN, F.D. BEGGS & J.P. DUFFY Department of Thoracic Surgery, Nottingham City Hospital, Hucknall Road, Nottingham

Background: Lung biopsy is a procedure which has in the past been associated with considerable morbidity, particularly in the immunosuppressed.The aim of our study was to analyse our experience with patients undergoing open lung biopsy. Method: The case notes of 56 patients (29 males, 27 females; age range 21-73) who underwent an open lung biopsy between 1988 and 1997 were reviewed retrospectively. Note was made of the patients pre-operative diagnosis, any previous invasive diagnostic procedures, as well as the final diagnosis on lung biopsy. The morbidity and mortality of the patients was also recorded. Results: Of the 56 lung biopsies performed, 55 were performed electively and one as an emergency. 47 patents were immunocompetent and nine (16%) were immunosuppresssed. 13 patients (23%) had previous invasive diagnostic investigations (six had a CT-guided biopsy, five had a trans-bronchial biopsy and two had a bronchoalveolar lavage) which were inconclusive. In 55 cases (98%), open lung biopsy provided a definitive diagnosis. In 41 cases (73%), open lung biopsy altered the patient’s clinical diagnosis, and in 20 cases (36%) this resulted in a change in therapy. Post operatively, only two adverse outcomes were noted, both in immunocompetent patients. In one case, a patient who underwent an emergency open lung biopsy died 5 days post-procedure with ARDS. In the remaining case, a tetracyline pleurodesis had to be performed post-procedure for pleural effusion. Conclusion: Elective open lung biopsy is a safe procedure with minimal mortality and morbidity. It provides a very high diagnostic yield and frequently alters patients’ management.

Diagnostic delay in colorectal carcinoma

E. ONG, H.L. CHEONG and C. MAKIN

Wirral Hospital NHS Trust, Upton, Wirral

Introduction: An audit by our pathology department showed a significant number of gastric and duodenal biopsies were performed in colorectal carcinoma patients. Most were performed prior to the diagnosis of colorectal carcinoma. Some patients were initially referred to non-coloproctologists. These may be the possible causes of delay in diagnosis. The audit was to examine these causes and implement any changes to achieve a better quality of care in colorectal cancer. Methods: Review of our database between January and August 2000 identified 24 cases of colorectal carcinoma in which they were seen initially by non-coloproctologists. A proforma was used to record the presenting complaints, date of General Practitioner (GP) referral and hospital appointment, investigations performed, date of diagnosis and referral to coloproctologists. Results: 13 cases were referred acutely by GP and 11 cases were seen at outpatients department. The presenting complaints were various gastrointestinal symptoms or anaemia. 82% of non-acute cases were seen within 4 weeks of referral. The average time between the date seen by non-coloproctologists and diagnosis of colorectal carcinoma was 50 days for acute cases and 77 days for non-acute cases. 42% of all cases underwent upper gastrointestinal investigation prior to the diagnosis of colorectal carcinoma. Conclusion: There was a reasonable delay in the diagnosis of colorectal carcinoma in cases that were seen initially by non-coloproctologists. Significant number of cases underwent upper gastrointestinal investigation prior to the diagnosis, which may have contributed to the delay. Some literatures suggested that delay in diagnosis has not been correlated with survival. This is highly debatable and does not make the delay an acceptable practice. The audit has highlighted the importance of GP referral to the appropriate specialty and raised a greater awareness of the possibility of colorectal carcinoma in patients with various gastrointestinal symptoms and anaemia.