Consensus On Management of Gallstone Disease

Ministry Of Health, Malaysia
Academy of Medicine of Malaysia
Malaysian Society of
Gastroenterology & Hepatology
1997


Expert Committee
Consensus on Management of Gallstone Disease

Chairman :   Dato J C Mehta 
Secretary :   Dr S Ganesananthan 
                    Dr Foo Kin Keong
Members :  Independent Evaluators:
                   Dato Dr (Mrs) Kew Siang Tong 
                   Dato Dr P Kandasami 
                   Prof Dato Dr Samad Sakijan 
                   A Prof Dr Mahendra Raj 
                   Dato Dr Syed Noori 
                   Dr Robert Jalleh 
                   Dr Andrew Chua Boon Seng 
                   Dr Yin Thing Phee 
                   Dr Ong Kee Thiam 
                   Dr M Mahadaven 
                   Dr Jason Chin Kuet Tze 
                   Dr Anand Bhupalan 
                   Dr R Krishnan 
Dato Dr Ismail Merican 
A. Prof Dr Goh Khean Lee 
Prof Dr Harun Ahmad 
Dr Ng Chuan Wai 
Dr M M S Krishnan 
Dr Chang Keng Wee 
Dr Ashim Kumar Nandy 
.. 
. 
. 
. 
. 
.


Contents

Introduction
Management of Asymptomatic Gallstones
Management of Symptomatic Gallstones
        1. Operative treatment
                   1.1    Open Cholecystectomy
                   1.2    Mini Cholecystectomy
                   1.3    Laparoscopic Choleystectomy  
                            i.      Oral Bile Acid Treatment       
                            ii.     Contatct Dissolution Therapy
                            iii.    Extracorporeal Shock Wave Lithotripsv ( ESWL )
Management of complications of Gallstone disease
        1.  Acute Cholecystitis
        2.  Acute Cholangitis
        3.  Empyema
        4.  Mucocoele
        5. Gallstone Ileus
        6. Gallstone Pancreatitis
Microlithiasis
Management of Bile Ductstones
        1. Before Cholecystetomy
        2. During Cholecystectomy
        3. After Cholecystectomy
Recurrent Pyogenic Cholangitis
        1. Background
        2. Initial Management
        3. Management of Severe Cholangitis Unresponsive to Conservative Measures
        4. Definitive Management
Appendix I
        1. Liver Function Tests
        2. Full Blood Count
        3. Prothrombin Time
        4. Serum Amylase
Appendix II
Imaging in Gallstone Disease
        1. Plain abdominal film
        2. Ultrasound
        3. Computed Axial Tomography ( CT Scan )
        4. Endoscopic Ultrasonography
        5. magnetic resonance cholangiopancreatic ( MRCP ) imaging
        6. Biliary Scintigraphy
        7. Oral Cholecystography
        8. Intravenous Cholangioraphy
        9. Percutaneous transhepatic Cholangioraphy ( PTC )
       10.Endoscopic Retrograde Cholangiopancreaticcogram ( ERCP )
Appendix III
Bile Salt Therapy/Oral Dissolution therapy
        1. Dissolution therapy - the ideal patient
                        I. Oral Chenodeoxycholic ( Chenodial ) ( CDA )
                        II. Oral Ursodeoxycholic ( Ursodiol ) ( UDCA )
Treatment Protocol
        III.Combination therapy UDCA AND CDCA.
References


INTRODUCTION

Gallstones and their complications are a common medical problem, and they form a substantial part of the workload of general surgeons, gastroenterologist and physicians. The management of these clinical situations is fairly well established.

However, two important issues need to be addressed. First, the introduction of new technologies and therapeutic agents has made a definite impact on the more traditional forms of treatment. These changes need to be evaluated and incorporated into our own practice. Second, any information regarding basic management principles must be disseminated to reach all practitioners, regardless of the level of expertise and geographical location of work.
 
This consensus paper on The Management of Gallstone Disease represents an important contribution of the Malaysian Society of Gastroenterology and Hepatology to the advancement of continuing medical education in this country. It was developed under the auspices of the Academy of Medicine and the Ministry of Health, by a committee of experts who together share a vast and varied experience on the subject. In formulating this Consensus, the committee has spent long hours reviewing local experience and international data on the various aspects of gallstone disease, and then deliberating on each and every one of these issues. Views expressed by profession at large have also been taken into account. Until more local data is available , we have to accept there are limitations in trying to adopt internationally accepted norms to Malaysian medical practice.

 This consensus should be looked upon as a guideline for good medicine. It is not meant to be binding and clearly, it cannot provide for all clinical situations. After all, good medicine must undoubtedly be individualised and the clinician has always to make decisions based on the situation and resources at hand. Nonetheless, it is hoped that the management principles outlined here will allow all of us to make such decisions with clarity of mind and assured confidence.
 
MANAGEMENT OF ASYMPTOMATIC GALLSTONES

It is generally accepted that no active management is indicated in asymptomatic gallstone
disease .

In diabetic patients even when morbidity and mortality rates are higher with emergency operations, prophylactic cholecystectomy is difficult to justify. They should, however, be treated promptly once symptoms appear. The value of prophylactic treatment of asymptomatic gallstones in patients with sickle cell disease and in children is still unclear. Similarly data on prophylactic treatment of pretransplantation and/or immunosuppressed patients who may have marked increased morbidity and mortality from complications are still insufficient.

The indication for cholecystectomy in the asymptomatic patients should be seriously considered in the following situations in view of the risk of malignancy :

Since most asymptomatic gallstones are detected incidentally, subsequent investigations will depend on its initial detection.

         2. If initial investigation was an ERCP - may need to be confirmed by ultrasound.
         3. No further confirmation required if detected by ultrasound or CT scan.


MANAGEMENT OF SYMPTOMATIC GALLSTONES

Symptomatic gallstones require treatment. Once symptoms appear, they tend to recur and are more likely to develop complications. Nearly 90% of patient with typical biliary pain are rendered symptom free after successful treatment of their gallstones.

The clinician may find it difficult to determine which symptoms are due to gallstones. The typical biliary pain is that which is relatively severe, episodic, epigastric or right upper quadrant in location, lasting I to 5 hours and often waking the patient up at night.
Abdominal ultrasound is the investigation of choice in a patient presenting with typical biliary pain. If the ultrasound reveals dilated biliary ducts then ERCP is indicated.

Postprandial pain, painless dyspepsia and other atypical pain patterns are often not caused by gallstone disease, The presence of such symptoms should prompt a work-up for other conditions e.g. Non-Ulcer Dyspepsia, Irritable Bowel Syndrome, Peptic Ulcer Disease and Gastroesophageal Reflux Disease.

For persons with typical biliary pain but without gallstones, the efficacy of operative treatment
has not been established,

1. OPERATIVE TREATMENT

The 'gold standard' treatment for gallstones is cholecystectomy.
Options available include conventional open cholecystectomy , mini cholecystectomy and laparoscopic cholecystectomy. In difficult cases partial cholecystectomy is a surgical option . Operative cholangiography is undertaken in selected cases.

1.1 OPEN CHOLECYSTECTOMY

This operation has been in use for more than I 00 Years and is the standard to which other treatments must be compared. The operation allows direct visualisation and safe dissection . Major complications are rare (0. 1 %) and include common bile duct injury, bleeding, biloma and infections.

1.2 MINI CHOLECYSTECTOMY

This is a modified approach in which a surgical incision of about 5 cm is made, In certain
centers, the overall result of this operation equals that of laparoscopic cholecystectomy.

1.3 LAPAROSCOPIC CHOLECYSTECTOMY

This is the preferred technique because of early recovery and quick convalescence. Most
patients with symptomatic gallstones are candidates for laparoscopic cholecystectomy.

Contraindications to Laparoscopic Cholecystectomy
Absolute
Unable to tolerate general anaesthesia
Uncorrectable coagulopathy
Known cancer of the gallbladder

Relative
Generalized peritonitis
Septic shock from cholangitis
Severe acute pancreatitis
End stage cirrhosis with portal hypertension
Cholecystoenteric fistulas
Patients in the third trimester of pregnancy
Previous upper abdominal surgery
Mirizzi's syndrome

The complication rate of this procedure appears higher at 3 - 6 %. The complications include bleeding , bile leaks and bile duct injury. The incidence of ductal injury is reported at 0. 1-0. 8% compared to 0. 1 % for conventional cholecystectomy.

It is also vital for the Operator to recognise when to convert from a laparoscopic procedure to the open method. This should not be viewed as a failure and patient safety must always come first.
Reasons for conversion during laparoscopic cholecystectomy include

1) known or suspected injury to major blood vessels, viscus or bile duct
2) unclear anatomy
3) unsuspected pathology not amenable to laparoscopic management and
4) common bile duct stones which cannot be removed either laparoscopically or via subsequent ERCP.

Since the outcome of laparoscopic cholecystectomy is greatly influenced by the training, experience, skill and judgement of the surgeon, strict guidelines for training and determination of competence should be developed and implemented.

Other modalities for the treatment of gallstones disease include :

i. Oral Bile Acid Treatment

Currently, indications for bile acid therapy are limited to those unsafe to operate upon and those who choose to avoid an operation. It is a viable option only in patients with a patent cystic duct and small
(< I 5mm) floating, cholesterol stones and a functioning gallbladder. Monotherapy (with ursodeoxycholic acid) or combination therapy (ursodeoxycholic and chenodeoxycholic acid )are both effective and requires 6 to 12 months of therapy.                                                              See Appendix I I I

ii. Contact Dissolution Therapy

Chemical litholysis of cholesterol gallstones using MTBE (methyl tri-butyl ether) though possible is not widely practiced now. This procedure is unlikely to play a major role in gallstones management in Malaysia.

iii. Extracorporeal Shock Wave Lithotripsv ( ESWL )

EWSL is useful in symptomatic gallbladder stones when subjects are precluded from operation by underlying medical conditions. EWSL is only of use when the gallbladder is functioning and technically difficult when it is subcostal. Some centers in the world pioneering the technique have achieved reasonable results in stone clearance especially patients with noncalcified and small ( <30mrn ) stones. Stone clearance is better when pulverisation , rather than mere fragmentation is the end point . Complications include haernaturia, pain and the need for ERCP clearance of bile duct stones. Although the two year recurrence rate is in the order of 5.3% , the long term recurrence rates have been reported to be between 28% to 61%. Comparison of published results is made difficult because of the use of different machines, end points and the use of adjuvant drugs with the treatment. In Malaysia ESWL is hardly used .

 MANAGEMENT OF COMPLICATIONS OF GALLSTONE DISEASE

1) Acute Cholecystitis
Initial treatment is the use of antibiotics and intravenous fluid therapy . Subsequent management is either emergency or elective cholecystectomy.

2) Acute Cholangitis
Clinical features of acute cholangitis are fever with chills, abdominal pain and jaundice. It can range from a mild form to a severe illness with septicaemic shock .The initial management is intravenous antibiotics and fluid replacement, allowing for stone removal later. However, in severe suppurative cholangitis, biliary drainage is life saving.

1) Endoscopic biliary decompression with a nasobiliary drain or stent placement is generally considered the method of choice. Sphincterotomy and ductal clearance  is possible when stones are small and few in numbers.

2) Percutaneous transhepatic biliary drainage is also a viable option .
3) Ernergency surgical decomoression is indicated in severe suppurative cholangitis where facilities and
    expertise for ERCP and percutaneous drainage are not available.

Once the acute episode has resolved a number of options are available for the definitive treatment of residual choledocholithiasis. This will involve cholecystetomy and clearance (endoscopic or operative) of ductal stones.

Endoscopic treatment is the logical choice in patients who already had cholecystectomy. In patients with very large stone/stones, surgery may be the only option. Long term endoprosthesis in high surgical risk patients in whom stone extraction has failed should only be used in selected patients .

3) Empyema

Emergency cholecystectomy / cholecystectomy under antibiotic cover .

4) Mucocole

Cholecystectomy.

 5) Gallstone Ileus

Gallstone ileus is associated with a high mortality and death has been reported in up to 35% of patients.

The demonstration of air in the biliary tree and features of intestinal obstruction on abdominal radiography is sufficient to warrant a laparotomy. Operation should be undertaken under suitable prophylactic antibiotic cover after correction of fluid and electrolyte losses. The operation consists of an enterostomy to remove the affecting calculus/calculi. A cholecystectomy or exploration of the fistula should be generally be avoided under these circumstances.

6 ) Gallstone Pancreatitis

It has been estimated that between 4-8% of patients with cholelithiasis develop acute pancreatitis. Once it occurs there is a 50% chance of another episode of pancreatitis, usually within six months of the first attack.

Diagnosis of gallstones in patients with acute pancreatitis is established by
1) ultrasound examination
2) endoscopic retrograde cholangiopancreaticogram (ERCP)
3) magnetic resonance cholangio-pancreaticogram (MRCP)

The management strategy for gallstone pancreatitis involves
1) establish the diagnosis
2) determine the severity of pancreatitis
3) resuscitation and supportive care
4) treatment of associated biliarv tract disease
5) treatment of complications

In patients with severe pancreatitis and gallstones (proven or suspected), early ERCP should be considered. If ERCP suggests the presence of CBD stones, ES and removal of stones is indicated. However, it must be remembered that this technique is demanding and should be performed only by an endoscopist with considerable skill and experience.

Traditionally, it was recommended that patients undergo surgery 6-8 weeks after the acute attack to allow the inflammatory process to settle. This approach however requires a second admission and it allows the possibility of a repeat attack. Presently, cholecystectomy and if indicated a choledochotomy with stone clearance during the same admission is preferred .
 
MICROLITHIASIS

Microlithiasis is defined as the presence of calcium bilirubinate and cholesterol crystals or both, in the bile when it is examined under light and polarising microscopy following centrifugation of the bile at 2000rpm for 10 minutes. Microlithiasis has been implicated in biliary type pain, abnormal LFT and acute pancreatitis.
Diagnosis is based on a high index of clinical suspicion.

Endoscopic sphinecterotomy plus balloon trawl of the bile duct has been performed in selected
Patients with encouraging results in terms of symptom relief

MANAGEMENT OF BILE DUCT STONES

Detection of common bile duct stones (CBD) can be made prior to, during or after
cholecystectomy.

A. Before Cholecystectomy
Pre-operative diagnosis of choledocholithiasis is desirable so as to allow prior stone clearance and to preclude CBD exploration especially if laparoscopic cholecystectomy is planned. ERCP is recommended for confirmation and initial treatment of CBD stones. An absence of previous pancreatitis, cholangitis or jaundice combined with a normal caliber CBD on ultrasound and a normal alkaline phosphatase are very strong predictors of a CBD without stones.

The options for treatment of choledocholithiasis diagnosed with the gallbladder in situ include
1) open cholecystectomy with CBD exploration
2) pre operative endoscopic stone clearance followed by laparoscopic/open cholecystectomy
3) laparoscopic cholecystectomy with laparoscopic bile duct exploration

The success rate of endoscopic common duct stone extraction approaches 90-95% in expert hands.

Indications for surgical removal of CBD stones are failed ERCP, large stones (>2cm), coexistent stricture requiring surgical repair and previous Roux limb surgery.

As there is good evidence that significant biliary problems will develop despite duct clearance, cholecystectomy is recommended for the surgically fit. For the high risk and elderly patients, a conservative policy is recommended,

B.During Cholecystectomy
Management of CBD stones discovered during:

i. Open cholecystectomy
1) CBD exploration
2) In high risk patients, a T-tube decompression/biliary bypass is sufficient.

ii.Loparoscopic  choleystectomy
In the event an operative cholangiogram is done and a stone is detected, the subsequent options
include:

1) conversion to open cholecystectomy and exploration of CBD
2) laparoscopic removal of CBD stone
3) post cholecystectomy endoscopic stone extraction
4) expectant management for very small stones ( < 4mm )

C. After Cholecystectomy
Patients with retained stones following cholecystectomy may have:

1) removal of stone via T-tube tract
2) endoscopic stone fragmentation / extraction
3) fragmentation by ESWL
4) CBD exploration and internal drainage procedure when indicated

RECURRENT PYOGENIC CHOLANGITIS

Background

This condition, also known as oriental cholangitis, oriental cholangiohepatitis or hepatolithiasis is relatively common in South-East Asia and the Far East. It affects mainly patients from lower socioeconomic groups and is characterized by multiple brown pigment stones in the intra and/or extrahepatic bile ducts. The stones are thought to form de novo within the ducts as opposed to secondary ductal stones which have migrated from the gall bladder. The clinical presentation may be recurrent cholangitis, pain, jaundice or less commonly acute pancreatitis. There is often a history of previous biliary surgery. Repeated episodes of cholangitis may result in multiple biliary strictures. The natural history is progression to atrophy of liver segments, secondary biliary cirrhosis and portal hypertension, Cholangiocarcinoma is a known complication.

Initial Management

The treatment of an acute attack of cholangitis consists initially of resuscitative measures including intravenous fluids and antibiotics. The choice of antibiotics should cover the common organisms involved which include E. Coli, Klebsiella species, and Enterococci. In severe cases, in the presence of recent biliary instrumentation or previous biliary surgery initial coverage should include antibiotics against Pseudomonas species and the anaerobes. Regimens in common use include a combination of an aminoglycoside, ampicillin and metronidazole; a ureidopenicillin with or without metronidazole; and second or third generation cephalosporins in combination with metronidazole. Favourable reports on the use of quinolones as single agents have appeared in the recent literature, In view of the potential renal toxicity of aminoglycosides, careful monitoring of renal function and blood levels of the drug is recommended. Ultrasonography of the hepatobiliary system should be undertaken as soon as possible.

Management of Severe Cholangitis Unresponsive to Conservative Measures

Most cases of acute cholangitis in relation to this entity respond to conservative measures. Data on the optimum emergency management of the minority who do not respond to conservative measures are scarce. The two most widely practiced treatment modalities include endoscopic drainage and stone extraction, and surgery. If initial ultrasonography shows predominantly extrahepatic stones endoscopic (ERCP) intervention is a viable option and can be undertaken along the lines discussed under the section on cholangitis.

The choice between therapeutic endoscopy and surgery as initial treatment is difficult if ultrasonography confirms extensive intrahepatic calculi. In many centres an attempt at endoscopic biliary drainage is made with recourse to early surgery if this fails. The choice of surgery depends on the facilities and expertise available. Clearance of the major ducts should be attempted followed by the placement of a large bore T-tube (1 8-22 Fr ) to facilitate choledochoscopic extraction at a later stage. If full biliary imaging and the technical expertise are available, a more definitive procedure may be undertaken at the initial operation depending on the patient's condition.

Definitive Management

The definitive treatment of this condition requires accurate delineation of the biliary anatomy,the siteof thecalculi and strictures;as well as the degree ofl iver atrophy. Both surgery and endoscopic extraction are viable therapeutic options if the stones are predominantly extrahepatic. However if as is often the case there are extensive intrahepatic calculi, surgery is the only viable option. Definitive surgery should be undertaken in centres with comprehensive imaging facilities and the surgical experience in treating this condition. Some of the surgical approaches include choledochoscopic stone extraction, electrohydraulic lithotripsy, dilatation of strictures and partial hepatic resections. The construction of a hepaticojejunostomy with an access loop has been shown to be useful in permitting easier access of repeated attempts at percutaneous choledochoscopic extraction of persistent stones and at the same time improving biliary drainage.

   APPENDIX I

Liver Function Tests

2. Full Blood Count
An increased leucocyte count is found in acute cholecystitis, acute cholangitis, pancreatitis and sometimes with an underlying malignant disease.

 Prothrombin Time
1) It is prolonged in patients with jaundice
2) Prior to an ERCP

Serum Amylase
   Is at least 4 times the upper limit of normal in acute pancreatitis

APPENDIX II

IMAGING IN GALLSTONE DISEASE

  1) Plain abdominal film

  2) Ultrasound

  3) Computed Axial Tomography ( CT Scan )

  4) Endoscopic ultrasonography

  5) Magnetic resonance cholangiopancreatic ( MRCP ) imaging

  6) Biliary scintigraphy

7) Oral cholecystography

8) Intravenous cholangiography

9) Percutaneous transhepatic cholangiography ( PTC )

10) Endoscopic Retrograde Cholangiopancreaticcogram ( ERCP )

 
APPENDIX III

BILE SALT THERAPY/ORAL DISSOLUTION THERAPY

Bile acids reduce cholesterol saturation in bile and dissolve gallstones.

Dissolution therapy - the ideal patient
1. patients with non calcified ( ie radiolucent ) cholesterol stones < 1 5 mm diameter
2. patients with a functioning gall bladder (opacification on oral cholecystogram or by satisfactory
    contraction of the gall bladder after a fatty meal on ultrasonography or biliary scintigraphy ( HIDA scan
3. compliant patients
4. non obese

Fewer than 20% of patients with uncomplicated gallstones fulfill the requirements for
dissolution therapy,
Contra-indications

Oral chenodeoxycholic acid (Chenodiol ) ( CDCA )

   Even when treatment was reserved for ideal candidates. the dissolution rate after 2 Years was 13%. 'Re side effects are dose related including diarrhoea , elevation of aminotransferases and elevation of scrum low density lipoprotein cholesterol levels, The dose is 15mg/kg/day. Currently, monotherapy with chenodeoxycholic acid has been virtually abandoned

II  Oral ursodeoxycholic acid (Ursodiol) ( UDCA )
     UDCA is used in dissolution of cholesterol gallstones and following fragmentation with
extracorporeal shock wave lithotripsy (ESWL) . It has minimal side effect. Diarrhoea s rare, transient and generally resolves despite continuation of thierapy. No effect on LDL-Cholesterol is noted. However it is expensive.

  Treatment Protocol

      The treatment dose is I 0 to 12 mg/kg/day as a single dose with fluid at bedtime taken regularly for 6 to 24 months. It requires monitoring AST, ALT and GT levels every 4 weeks for the first three months and then at quarterly intervals. Ultrasound examination is required at 6 monthly intervals . If the number and size of the stones have not been clearly reduced after I year, treatment should be discontinued, Avoid simultaneous treatment with colestyramine, colestipol, clofibrate or antacids containing aluminium hydroxide as the absorption of UDCA
may be reduced.
 
                    Average dissolution rate for stones
                    - < 5mm in diameter @ 70% (range to 100%)
                    - 5 to 10 mm in diameter @ 50% (range 0 to 78%)
                    - > 10mm in diameter @ 35% (range 0 to 78%)

III Combination Therapy UDCA AND CDCA
     Combination of ursodeoxycholic and chenodeoxycholic acid is the most cost-effective
method of reducing side effects.

  REFERENCES

1.  AR Dennison, D Azoulav. N0aklev, H Baer. JAParaskevopozilos, GJMaddern. What should I do
     about my patient's gallstones? : Postgrad Med J 11 995; 71:725-729.
2.  NIH Consensus Conferance: Gallstones and Laparoscopic Cholecystectomy: JAMA SEA July
     1993:40-45.
3.  N Soehendra et al. Pulverisation of calcified and non-calcified gall bladder stones: extracorporeal
     shock wave lithotripsy used alone. Gut 1994, 35; 417-422,
4.  Sackmann M et al. The Munich gall bladder lithotripsy study: results of the first 5 vears with 711
     patients, Ann Intem Mcd 1991, 114; 290-6.
5.  Sackmann M, et al. Early gallstone recurrence rate after successful shock wavc therapy.
     Gastroenterologs; 1990.98;392-6
6.  P Bekal et al. Microcalculous pancreatitis: response to ES. AJG 1996; 91. 1934.
7.  V K Parasher et al. Is microlithiasis common in post cholecystectomy patients presenting
     with biliary type pain. AJG 1996, 9 1 ; 1939.
8.  Opic EI. The etiology of acute haemorrhagic pancreatitis. Bull J Hopkins 1901. 12. 82-188.
9.  Neoptolemos et al. ERCP findings and the role of ES in acute gallstone pancreatitis. Br J Surg 1988;
     Vol 75, October. 9534-956.
10. Fan et al. Earlv treatment of acute pancreatitis by endoscopic papillotomv, N Engl J Med1993, 328;
      228-232,
11. KeIly and Wagner. Gallstone pancreatitis: the timing of surgery. Surgery 1988, 345-349.
12. Ranson,JHC The timing of biliary surgery in acute pancreatitis. Ann Surg 1979. 189:654-662.
13. Christian de, Pirgilio et al. Gallstones pancreatitis. Arch Surg Vol 129, Sept 1994.
14. Eddie Tang et al. Timing of laparascopic surgery in gallstone pancreatitis. Arch Surg Vol 130.may
      1995. 
15. John A Windsor. Gallstone pancreatitis. A proposed management strategy. Aust NZ J Surg 1990;
      60;589-594.
16. Pel1igrini CA. Surgery for gallstone pancreatitis, AM J of Surgery Vol 165. April 1993 ; 515-518
17. David L Carr-locke, Role of endoscopy in gallstone pancreatitis. Am J of Surgery Vol 165, April
     1993;9-521.
18. Patti NG, Pelligrini CA. Gallstone pancreatitis. Surg Clinic North Am 1999; 70; 1277-95.
19. Hill.J, Martin DF & Tweedle DEF. Risks of leaving the gallbladder in-situ after endoscopic 
      sphineterotomy for bile duct stones,Br J Surg 1991 Vol 78 May 554-557.
20. Ingoldby CJH et al. Late results of endoscopic sphincterotomy for bile duct stones in elderly
     patients with gallbladders in-situ.Gut 1989; 30; 1129-1131.
21. Dixon et al. Factors affecting morbidity and mortality after surgery for obstructive jaundice: a review
     of 373 patients.Gut 1983: 24; 845-852.
22. Martin DF. Tweedle DEF. Endoscopic management of common duct stones without 
     choecystectomy.Br J Surg 1987; 74; 209-21 1.
23. Davidson BR. Neoptolemos JP. Carr-Locke DL. Endoscopic Sphincterotomy for CBD stones in
      patients with gallbladders in-situ considered unfit for surgery.Gut 1988 ; 29; 114-120.
24. Escourrou Jet al. Earlv and late complications after endoscopic sphincterotomy for biliarv lithiasis
      with and without the gallbladder in-situ.Gut 1984. 25 ; 598-602.
25. Neoptolemos.IP. Carr-Locke DL, Fossard DP. Prospective randomized study of preoperative
     endoscopic sphincterotomy versus surgery alone for common bile duct stones.BMJ Vol 294; 1987;
     470-474.
26. Perissat J et al. Management of bile duct stones in the era of laparoscopic cholecystectomy. Br J
     Surg 1994, 8 1 ; 799-810.
27. Hammarstrom LE et al. Long tenn follow-up of a prospective randomized study of endoscopic versus
     surgical treatment of bile duct calculi in patients with gallbladder in-situ.Br J Surg 1995;82; 6-1521.
28. S. T Fan, TK Choi. J Wong. Recurrent pyogenic cholangitis: Current management . World J Surg,
     1991; 15: 248-253.
29. Ong G. B. A study of recurrent pyogenic cholangitis. Arch. Surg. 1962; 84: 199-225.
30. K. Chijiiwa, Yamashita, J Yoshida, el al. Current management and long term prognosis of
      hetolithiasis, Arch. Surg. 1995 ; 130:194-197.
31. F. Nakayama, R.D Soloway T. Nakama. el al. Hepatolithiasis in East Asia : Retrospective studv,
      Dig,Dis. Sci.1986; 31: 21-26
32. Chou .S. T, Chan C. W Recurrent pyogenic cholangitis: A recropsy study. Pathology 1980; 12:
      415-428.
33. Fan S T. Choi T Lo C et al. Treatment of hepatolithiasis: Improvement of results by a systematic
      approach. Surgery 1991. 109: 474-480.
34. Bala.yegaran M. Hepatic calculi. Ann. Surg. 1972. 175: 149-154.
35. Lai E. C.S. Mok F.P.T. Fan E. S. Y. et al. Endoscopic biliary drainage for severe acute cholangitis.
      NEJM 1992 326: 1582-1586.
36. Leung J W C, Chung S. C.S, Sung JJ Y.. et al. Urgent endoscopic drainage for acute suppurative
      cholangitis. Lancet 1989 ; 1: 1307-1309.
37.  Choi TK Wong J E.R.C.P and endoscopic papillotomy in recurrent pyogenic cholangitis.
       clin.Cjasteroenterol 1986; 15: 393.
38.  Chan F.L, Man S W, Leong L.L. Y., Fan S.T. Evaluation of RPC with CT: Analysis of 50 patients.
       Radiology 1989. 170: 165.
39.  Tanaka. et al. Divergent effects of endoscopic sphincterotomy on the long term effects of
       hepatolithiasis. Gasterointest. Endoscopy 1986; 43: 33-36.
40.  Chen MF., Jan Y. Y. Wang C.S. et al. Interahepatic stones associated with cholangiocarcinoma :
       Clinical analysis of 20 cases with particular reference to the possibility of early diagnosis.Am J
       Gastroenterology 1989;84:391-395
41.  Fan S. T, Choi T K. Chan F.L., et al. Role of CT in the management of RPC, Australian & New
       Zealand J.of Surg, 1990; 60: 599-605.
42.  Fan S. T, Lai Wong J Hepatic resection for hepatolithiasis. Arch. Surg. 1993; 128: 1070-1074.
43.  Fan S T, Mok E Zhang S.S et al. Appraisal of hepaticocutaneous jejunostomy in the management
       of hepatolithiasis.Am J. Surg. 1 993 ; 165: 332-335,
44.  YoshimotoH.,Ikeda S. Tanaka M et al. Choledochoscopic-electrohvraulic lithotripsy and lithotomv
       for stones for CBD, intrahepatic ducts & GB. Ann. Surg. 1989, 210: 576-582.
45.  Chijiiwa K lchimiya H, Kuroki 5, et al. Late development of cholangiocarsinoma after the treatment
       of hepatolithiasis. Surg. Gynecol Obstet 1993; 177: 279-282.
46.  lkeda S. Tanaka M, Yoshimoto H. et aL Improved visualisation of intrahepatic bile ducts by
       endoscopic retrogade balloon catheter cholangiography. Ann. Surg. 1981.1 194: 171-175.
47.  Choi T K., Way J. Partial Hepatectomy for intrahepatic stones. World J. Surg. 1986. 10: 281.
48.  Lai W. Y, Fan S. T, Yip WC., et al. Surgical management of structures of the major bile ducts in
       RPC. Br. J. Surg. 1987; 74: 1 100.
49.  Shulman A. Non-westem pattems of biliary stones and the role of Ascariasis. Radiology 1987; 162:
       425-430.
50.  T F Toufeeq Khan, S. Mahendra Raj, R. Visvanathan. Spectrum of cholangitis in a rural setting in
       North-eastem Peninsular Malaysia. Tropical Doctor 1993; 23: 117-118.51.
51.  Fan S. T. Lai F.C.S., Wong J. Hepatic resection for hepatolithiasis. Arch. Surg. 1993; 128:
      1070-1074.
52.  Khuroo MS., Dar M Y. Yattoo G.N.,el al. Serial cholangiographic appearances in recurrent pyogenic
      cholangitis. Gastrointest. Endosc, 1993; 39: 674-679.
53.  Kar C.G., Hwang C.H.. Chen J.S et al. Eswl for treatment of intrahepatic stones. In vitro and in-vivo
      studies. Hepatogastroenterology 1993; 40: 159-162.
54.  Kar C.G., Kuo K.K., Tsai C.C.. et al. Evaluation of choledochojejunostomy for treatment of
      intrahepatic stones. Int, Surg. 1994, 79: 110-113.
55.  Lin X Z, Chan K. K, Shin JS., et al. Emergency nasobiliary drainage for acute calculous
      supperative cholangitis and its potential use in chemical disolution. J. Gastroenterol Hepatol 1993;8:
      35-38.
56. Nenhaus H. Management of intrahepatic stones. Gastrointest. Endosc. 1995; 42: 94-96.
57. Yeh YH, Huang MH., Dang J C.. et al. Percutaneous trans-hepatic cholangioscopy and lithotripsy
      in the treatment of intrahepatic stones: A study with 5 year follow-up. Gastrointest. Endosc. 1995;
      42: 13-18.
58.  Jan Y.Y., Chan M.F. Percutaneous trans hepatic cholangioscopic lithotornv for hepatolithiasis:
       Long tertn results.
59.  Stain 5 C., Incarbon R., Gutrie C. R.. et al. Surgical treatment of RPC. Arch. Surg. 1995; 130:
      527-532.
60.  Hung Lin P. W. Role of right hepatic lobectomy in the treatment of isolated right-sided
       hepatolithiasis. Surg. 1997; 21: 130-134.
61.  Sato M. Watarabe Y, et al. Long term results of hepatic resection for hepatolithiasis HPB. Surg.
      1995; 9: 37-41.
62.  Jan Y Y , Chan M F., Wang C.S., et al. Surgical treatment of hepatolithiasis-long term results.
       Surgery 1996 ' 120: 509-514.
63.  Ti T.K., Wong C. W., Yuen R., Karunanithy R. Ann Acad. Med. Singapore 1996; 25: 55-258.
64.  Gracie, WA, Ransohoff,DF,: The natural history ofgallstones. Ale innocent gallstone is not a myth,
       New Engl. J Med. 307 (1982) 798-800.
65.  Ransohof,f DF, Gracie WA, Wolfenson, LB, Neuhauser, D: Prophylactic cholecystectomy or
       expectant management for silent gallstones. Ann. Intem. Med. 99 (1983) 199-204.
66.  Johnson AG, Hosking SW,: Appraisal of the management ofbile duct stones. Br. J. Surg. 74(1987)
       555-560.
67.  Paumgartner, G. Carr-Locke. DL, Dubois, F. Roda. E. Thistle. JL.: Strategies in the treatment of
       gallstone disease. Gastroenterology International 6 (1993) 65-75.
68.  Silk. YN, Douglas, HO. Nova. HR. et al.: Carcinoma of the gallbladder.The Roswell Park
       Experience. Ann. Surg. 210 (1989) 751-757.
69.  Sauerbruch, T Paumgartner. G: Gallbladder stones- management. Lancet 33 8(1991)112 1 124.
70.  Misra. SP. Dwivedi M. Pancreaticobilian dLIctal union Gut 1990. 31 1144.
71.  Diehl AK, Gallstone size and the risk of gallbladder cancer. JAMA 1983, 250:2323.
72.  Nicola Villanova et al. Gallstone Recurrence after successful oral bile acid treatment.
      Gastroenterology, 1989; 97:726-31
73.  Pereira SP,Hussaini SH, Kennedy C. Dowling RH: Gallbladder stone recurrence after medical
       treatment. Do gallstones recur true to type? Dig-Dis-Sci. 1995 Dec; 40(12):2568-75    Supported by an educational grantfrom


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