STUDY OF BILE LEAK AFTER HEPATIC HYDATID CYST SURGERY IN BASRAH

Conservative surgery (partial peri-cystectomy and cyst contents evacuation with cavity management by external drainage, omentoplasty or capitonnaige) for uncomplicated hydatid cysts of the liver is known to be safe but is often associated with bile leak in rate of 18.81% and its sequela. The cause of bile leak is almost always due to cysto-biliary communication, this is usually occult and difficult to be diagnosed pre-operatively, if remain undiagnosed intra-operatively it will be presented as post-operative bile leak. In this study, several laboratory and radiological predictors used to evaluate those patients having high risk of bile leak after conservative hepatic hydatid cyst surgery. Also it aimed to study the fate of bile leak, it’s complications, how to avoid it and the way of management. This study is a combined prospective (from 2004-2010) & retrospective cases study performed in basrah hospitals, Iraq; (Al-Mawani Hospital, Basrah General Hospital, Al-Sader Teaching Hospital, and some of Private Hospitals); we analyzed records of 183 cases of hepatic hydatid cyst undergoing conservative surgery, of them 15 patient had bile leak intra-operatively and 20 patients had bile leak post-operatively. Patients with intra-biliary rupture of hydatid cyst or obstructive jaundice are excluded from this study. Bile leak occur in 35 patients (18.81%) from total 183 patients of which intra-operative bile leak seen in 15 patients (43%) and 20 patients (57%) as post-operative bile leak represented as external biliary fistula. L aboratory predictors of biliary leakage were alkaline phosphatase >250 U/L, total serum bilirubin >17 umol/l, cyst diameter >8 cm, multilocular or degenerative cyst also increase risk of bile leak. Post-operative complications are more in patients with bile leak (57%) than those without bile leak (12%). Hospital stay is longer in patients with bile leak 4.9 weeks while it is 1.06 week in those without bile leak. In conclusion, bile leak is not uncommon after hepatic hydatid cyst surgery, it can be predicted by certain laboratory and radiological factors thus indicate the need for additional procedures during operation to detect the cysto-biliary communication and manage the biliary leakage and its complications. Introduction iver hydatid disease is a common health problem in the middle east including Iraq, it is caused by larval stage of a tape worm, Echinococcus granulosus, and in 70-80% of cases occur in the liver 1-6 . Surgery is the mainstay of treatment and it is the only curative approach, medical treatment (albendazol, mebendazol) is of limited use 1-3,6,7 . The objectives of surgical approach are: inactivate scolices, prevent spillage of cyst contents, eliminate viable daughter cysts and manage the residual cavity by external drainage, omentoplasty or capitonnage 1,6 . The safest surgical approach is open partial peri-cystectomy (de-roofing) with endo-cystectomy (complete cyst evacuation) and external drainage, L Study of bile leak after hepatic hydatid cyst surgery in Basrah Nazar J. Sawady & Zaki Al-Faddagh Bas J Surg, March, 18, 2012 41 although this surgery is safe, simple, faster, easier, less blood loss, used in very large cyst and used in management of deep cysts of liver hydatidosis, but it has variaties of complications 1,2,8,9 . The most common complication is being bile leak from a cysto-biliary communication and its sequels like prolong biliary-cutaneous fistula through the drain placed during surgery 2,7,8 . Pathophysiology of bile leak: intra-cystic pressure is 30-80mm H2O, while normal biliary pressure is 15-20 mmH2O so the flow is toward biliary system into duodenum through ampulla of Vater; the pericyst acts as a mechanical barrier, after surgery this pressure gradient will be reversed &bile leak occur if there is cysto-biliary communication 1,4 . Almost always, cases of the bile leak is due to cysto-biliary communication, the clinical findings and radiological features (U/S,CT-scan, MRI) are non specific and non valuable in detecting occult cystobiliary communication pre-operatively 2,6 . The occult cysto-biliary communication may be diagnosed at surgery and managed intra-operatively, but if remain undetected &unrepaired, postoperative bile leak will ensue this will result in prolong biliary drainage and it will increase morbidity & hospital stay 8,9 . Thus it is important to predict cystobiliary communication pre-operatively and concentrate on intra-operative diagnosis to prevent post-operative bile leak 8-10 . Intra-operative bile leak may be seen when bile stained aspirate is found or swapping of the cavity or direct bile leak seen in the cavity from a small or a large bile ducts after endocystectomy 7,8,11 . Small intra-operative bile leak is managed by suturing of cysto-biliary communication with external drainage or omentoplasty or capitonnaige. Large intra-operative bile leak managed by internal drainage (cysto-enterostomy) 12,13 . These management are successful in prevention of post-operative bile leak in most cases of intra-operative bile leak 7,8,11-13 . Post-operative bile leak appears as controlled external fistula in most cases, it may be presented as bilioma (intraabdominal bile collection) or biliary peritonitis especially when drain is removed.other clinical findings also common like right upper quadrant pain, fever and leucocytosis 7,9 . There are several laboratory predictors pre-operatively that can predict biliary leakage due to occult cysto-biliary communication these are: alkaline phosphatase >250 u/l; total serum bilirubin >17 umol/l; alanine aminotransferase (ALT) >33.5 u/l; aspartate aminotransferase (AST) >29.5 u/l elevation above these. Limits are found to be associated with increase post-operative bile leak 6,7,13 ; Certain Radiological features of the hydatid cyst of liver e.g Cyst diameter >8cm; multilocular cyst and degenerative cysts are also associated with high risk of bile leak 7,6,14 . No relation between bile leak and age, sex, region and symptoms; also no difference was found in terms of nature of cyst whether primary or recurrent; single or multiple; and their location (right, left or both) these did not affect the risk of biliary leakage in most of series 6,15,16 . The major morbidity of conservative surgery is post-operative bile leak its incidence is ~25%; other complications may occur e.g; wound infection; subhepatic abscess; cavity infection and others (pulmonary complications e.g atelectasis or pneumonia) 1,6,7,13,15 . Fate of post-operative bile leak: most series suggest spontaneous closure of bilio-cutaneous fistula in median time 40120 days 6,9,13,15,16 . If fistula did not close or it is of high output (>300ml/day), this suggest a large cysto-biliary communication and it need ERCP for confirmation of diagnosis & treatment by endoscopic sphincterotomy and the success rate 90-100% 7-9 . Study of bile leak after hepatic hydatid cyst surgery in Basrah Nazar J. Sawady & Zaki Al-Faddagh Bas J Surg, March, 18, 2012 42 Patients with prolonged bile leak may need re-operation for suturing of cystobiliary fistula if visible; or biliary decompression procedures e.g (t.tube drainage; trans-duodenal sphincterotomy; choledocho-duodenostomy); or may need internal drainage (cysto-enterostomy) 1,3,7,9 .


Introduction
iver hydatid disease is a common health problem in the middle east including Iraq, it is caused by larval stage of a tape worm, Echinococcus granulosus, and in 70-80% of cases occur in the liver [1][2][3][4][5][6] .Surgery is the mainstay of treatment and it is the only curative approach, medical treatment (albendazol, mebendazol) is of limited use [1][2][3]6,7 .
The objectives of surgical approach are: inactivate scolices, prevent spillage of cyst contents, eliminate viable daughter cysts and manage the residual cavity by external drainage, omentoplasty or capitonnage 1,6 .The safest surgical approach is open partial peri-cystectomy (de-roofing) with endo-cystectomy (complete cyst evacuation) and external drainage, L although this surgery is safe, simple, faster, easier, less blood loss, used in very large cyst and used in management of deep cysts of liver hydatidosis, but it has variaties of complications 1,2,8,9 .The most common complication is being bile leak from a cysto-biliary communication and its sequels like prolong biliary-cutaneous fistula through the drain placed during surgery 2,7,8 .Pathophysiology of bile leak: intra-cystic pressure is 30-80mm H2O, while normal biliary pressure is 15-20 mmH2O so the flow is toward biliary system into duodenum through ampulla of Vater; the pericyst acts as a mechanical barrier, after surgery this pressure gradient will be reversed &bile leak occur if there is cysto-biliary communication 1,4 .
Almost always, cases of the bile leak is due to cysto-biliary communication, the clinical findings and radiological features (U/S,CT-scan, MRI) are non specific and non valuable in detecting occult cystobiliary communication pre-operatively 2,6 .The occult cysto-biliary communication may be diagnosed at surgery and managed intra-operatively, but if remain undetected &unrepaired, postoperative bile leak will ensue this will result in prolong biliary drainage and it will increase morbidity & hospital stay 8,9 .Thus it is important to predict cystobiliary communication pre-operatively and concentrate on intra-operative diagnosis to prevent post-operative bile leak [8][9][10] .Intra-operative bile leak may be seen when bile stained aspirate is found or swapping of the cavity or direct bile leak seen in the cavity from a small or a large bile ducts after endocystectomy 7,8,11 .Small intra-operative bile leak is managed by suturing of cysto-biliary communication with external drainage or omentoplasty or capitonnaige.Large intra-operative bile leak managed by internal drainage (cysto-enterostomy) 12,13 .These management are successful in prevention of post-operative bile leak in most cases of intra-operative bile leak 7,8,[11][12][13] .Post-operative bile leak appears as controlled external fistula in most cases, it may be presented as bilioma (intraabdominal bile collection) or biliary peritonitis especially when drain is removed.otherclinical findings also common like right upper quadrant pain, fever and leucocytosis 7,9 .There are several laboratory predictors pre-operatively that can predict biliary leakage due to occult cysto-biliary communication these are: alkaline phosphatase >250 u/l; total serum bilirubin >17 umol/l; alanine aminotransferase (ALT) >33.5 u/l; aspartate aminotransferase (AST) >29.5 u/l elevation above these.Limits are found to be associated with increase post-operative bile leak 6,7,13 ; Certain Radiological features of the hydatid cyst of liver e.g Cyst diameter >8cm; multilocular cyst and degenerative cysts are also associated with high risk of bile leak 7,6,14 .No relation between bile leak and age, sex, region and symptoms; also no difference was found in terms of nature of cyst whether primary or recurrent; single or multiple; and their location (right, left or both) these did not affect the risk of biliary leakage in most of series 6,15,16 .The major morbidity of conservative surgery is post-operative bile leak its incidence is ~25%; other complications may occur e.g; wound infection; subhepatic abscess; cavity infection and others (pulmonary complications e.g atelectasis or pneumonia) 1,6,7,13,15 .Fate of post-operative bile leak: most series suggest spontaneous closure of bilio-cutaneous fistula in median time 40-120 days 6,9,13,15,16 .If fistula did not close or it is of high output (>300ml/day), this suggest a large cysto-biliary communication and it need ERCP for confirmation of diagnosis & treatment by endoscopic sphincterotomy and the success rate 90-100% [7][8][9] .

Results
Total number of patients included in this study is 183 having hepatic hydatid disease underwent surgical removal of hydatid cyst, from them 35 patients (18.81%) have bile leak: 15 patients (43%) intra operative and 20 patients (57%) post-operative; the rest 148 patients have no bile leak; In patients with bile leak mean age was 43.80 year, while in patients without bile leak mean age was 40.20 year ( Figure 1).Of the 35 patients with bile leak 24 patients (70%) came from rural areas and 11 patients (30%) were came from urban region; while patients without bile leak that came from rural areas were 83 patients (56%) and those came from urban region were 65 patients (44%) (fig.4).There is no difference in risk of bile leak between patients came from rural or urban areas p value > 0.05.The most significant laboratory factor, in terms of increasing the risk of biliary leakage due to an occult cysto-biliary communication, was an ALP level greater than 250 u/l(p<0.001),itssensitivity about 90%, and specificity about 85% other results of sensitivity and specificity of laboratory factors derived using statistical parameters to predict biliary leakage seen in table IV.The mean post-operative hospital stay in patients with bile leak was 4.9 weeks; while it was 1.06 week in patients without bile leak as in figure 5 the mean time is much greater in patients with bile leak (p<0.001).

Discussion
Partial pericystectomy with cyst evacuation followed by cavity management (external drainage, capitonnage or omentoplasty) consider simple and safe conservative technique in management of hepatic hydatid cyst, however their main disadvantage is high frequency of biliary leakage from a cystobiliary communication which is about 18.81% in this study; which is found to be 20-25% in other series 1,6,7,9,11,15 .In this study Females are more affected than male by hydatid liver disease this probably due to females deal with infected vegetables this explain why bile leak is more in females than in males.We found no significant difference in incidence of bile leak regarding sex factor between patients with and without bile leak p value >0.05.Hepatic hydatid cyst is more common in patients from rural areas this because people in rural areas their job involves dealing with animals and they don't care to disinfection of their food, this explain why bile leak was more in patients came from rural regions p value >0.05.In this study no significant differences were found between patients with and without bile leakage in terms of sex, age, and place of residence (rural or urban) this finding is similar to other studies, Demircan et al 6,7,17,18 .The nature of cyst whether it is primary or recurrent; single or multiple; and the location of cyst (right, left or both) did not affect the risk of biliary leakage in patients with hepatic hydatid cyst surgery p value >0.05, these findings are consistent with those of other studies 6,12,15,[18][19][20] .We study certain laboratory predictors that can predict biliary leakage due to occult cysto-biliary communication these are ALP>250u/l; ALT>33.5u/l;AST>29.5u/l;TSB>17umol/l ;and we found that these factors when present they associated with occult cysto-biliary communication presented as biliary leakage, these findings are similar to other studies, Demircan et al 6,7,17,18 . in this study ALP level is the most important factor associated with biliary leakage (sensitivity 90%).The explanation is high intra-cystic pressure causing intermittent passage of cyst fluid, scolices and minor fragments into biliary system can cause elevated ALP, ALT, AST and TSB, these findings are similar to several studies reported by Kayaalp&colleages 17 ; and, Atli&colleagues 18 .We found that certain radiological features of liver hydatid cyst have releation with occult cysto-biliary communication like mean cyst diameter 11cm (sensitivity 76%) and this was significant predictor of biliary leakage, this is because sudden drope of intracystic pressure after evacuation of the cyst; Atli and colleages 18 found that cysts above 13cm was an significant laboratory predictors of biliary leak due to occult cysto-biliary communication.Kaayalp and colleages 17 found that that 65% of cysts <10cm causing biliary leakage.We found that biliary leak is more common with multilocular cysts and degenerative cysts (sensitivity is 73%) and p <0.01 whitch are similar to findings of Bedrili and colleages 21 , Our aim is to diagnose occult cysto-biliary communication during operation that can not be demonstrated pre-operativly by imaging studies to decrease pos-operative bile leak; and clear cystic fluid aspirate does not exclude cysto-biliary communication consequently we should inspect cyst contents and the openings of communication with biliary tree are sought 19,13,24 , the usual method used in our hospitals is filling the evacuated cyst cavity by saline with pericystic packing and waiting for bile stains if present.Intra-operative methods used to detect bile leak in the residual cyst cavity are packing the cyst with gauze soaked in hypertonic saline and wait for bile stains to appear or filling the cavity with normal saline and /or injection of air from cystic duct or injection of methylen blue from gall bladder; these reveal bubbles or bile stained saline or methylen blue from an occult openings,Jabbour&colleages 8 .Ozmen & Coskun 20 , describe easy and reliable technique by using telescope for visualization of the cavity after conservative surgery of hepatic hydatid cysts especially when openings are difficult to be seen.In our study 4/15 patients (26.6%) have the opening of occult cysto-biliary communication is found during operation it was sutured with absorbable sutures and externally drains the cyst cavity; 2/15 patients(13.4%)no biliary opening is seen while bile is still leaking in the cyst cavity in small amount these treated by external drainage only, 4 patients(26.6%)treated by capitonnage and 4 patients (26.6%) treated by omentoplasty; one patient (6.8%) treated by cysto-enterostomy because of large bile leak which can not be sutured., these similar to other series, 20 Few series suggest routin common bile duct exploration plus t-tube in large bile leak and unavailability of ERCP 7 .We did not do this because it increase morbidity and usually it needs cholecystectomy, 20/35patients (57%) of patients have post-operative bile leakage after hepatic hydatid cyst surgery presented as external biliary fistula through the drain in this study, 16/20 patients(80%) with low output fistula were dealt with conservatively for spontaneous closure in median time about 40-90 days, this is corresponding to other series 6,7,13 , 4 patients (20%) with persistent or high output post-operatve bile leak need intervention for biliary decompression procedures to facilitate fistula closure as follow:one patient (5%) referred for ERCP sphincterotomy; one patient (5%) treated by common bile duct exploration with t-tube drainage; one patient (5%) treated by trans-duodenal sphincterotomy and one patient (5%) treated by internal drainage (cysto-enterostomy) these done because of high output fistula.These findings are similar to other series 6,9,[21][22][23] except in rate of endoscopic sphincterotomy which is higher than our rate; unfortunately, this because unavailability of ERCP in our city, also these series used ERCP for diagnosis and treatment of biliary fistula (papillotomy or stenting) after hydatid surgery in most of patients with bile leak 22 , 20/35 patients (57%) of patients with bile leak have post-operative complications this is significant p<0.05.In patients without bile leak the rate of complications were 12/148 patients (8%); the most prevalent post-operative complication in patients with bile leak were wound infection which is seen in 14 patients (40%) while in patients without bile leak it is only seen in 4 patients (2.7%) this is similar to other series 24,25 .The mean post-operative hospital stay is about 4.9 weeks in patients with bile leak this longer than that for patients without bile leak this is due to higher rate of postoperative complication in patient with bile leak this is similar to other series 7,13 .There was no mortality in our study.

Conclusion
Cysto-biliary communication is almost always presented in patients with biliary leakage after hepatic hydatid cyst surgery; it may be occult but can be predicted by several laboratory and radiological predictors of hepatic hydatid cyst e.g ALP, ALT, AST, TSB, cyst diameter, multilocular or degenerative cysts.Post-operative bile leak associated with high rate of post-operative complications, prolong hospital stay and increase morbidity.Additional procedures performed in the intra-operative period help to prevent biliary leakage and its morbid complications.When post-operative biliary fistula developed, it should be treated first by conservative methods regarding that the amount of bile leak is decreasing and the patient general conditions are well as we do in our hospitals, if the conservative treatment is failed or the patient general conditions are unwell or the fistula of high output then intervention done.

Recommendations
Patients with certain laboratory and radiological features of hepatic hydatid cyst pre-operatively should alert to an occult cysto-biliary communication intraoperatively.Intra-operative bile leak should be carefully sought with meticulous inspection of residual cyst cavity after evacuation of cyst contents by placing a white laparotomy pade in the cavity for few minutes or using a telescope.Avoid usage of coloured scolicidal agents, because it may interfere with visualization of cysto-biliary communication that presented with bile leak.(maskingeffect).Low output biliary fistulae usually treated by conservative treatment.High output fistulae better to be treated by endoscopic sphincterotomy which is the most important diagnostic and therapeutic tool, endoscopic stenting or papillotomy reduces the high intra-biliary pressure and promote early closure of fistulae even in absence of distal common bile duct obstruction.In order to reduce bile leak and it's morbid complications:recent reports suggest routin decompression with t-tube in patients with cysto-biliary communication especially when ERCP not available.

Figure 1 :
Figure 1: Mean age of patients with and without bile leak

Figure 2 :
Figure 2: Gender distribution in patients with bile leak.

Figure 3 :
Figure 3: Gender distribution in patients without bile leak.

Figure 4 :
Figure 4: Distribution of patients according to region.

Figure 5 :
Figure 5: Meantime of post-operative hospital stay in patients with & without bile leak

Table II : Characteristics of hydatid cyst in patients with &without bile leak. Cyst features Patients with bile leak no.(%)20 patient post-operative and 15 intra-operative.
The demographic characteristics of patients with and without bile leak were compared, we found no differences in age, sex and place of residence between the two groups (p>0.05).Primary hydatid cyst found in 30 patients (85.72%) of patients with bile leak while 5 patients (14.28%) had recurrent cyst; tableII.In patient without bile leak primary hydatid cysts were 138 patients (93.24%) and 10 patients 6.76% were recurrent cysts.tableII.The frequency of biliary leakage was not affected by cysts being single or multiple (p=0.80),primary or recurrent (p=0.06) or in which hepatic lobe they occurred (p=0.40);tableII.The mean cyst diameter was 11cm in patients with bile leak and 8cm in patients without bile leak; cyst diameter was significantly higher in patients with biliary leakage (p<0.001).The sensitivity of cyst diameter>8 cm in prediction of post-operative bile leak is 76% and its specificity is 73%.TableII&IV.Unilocular cysts occurred in 7 patients (20%) in patients with bile leak group, 15 patients (42.86%) are multilocular and 13 patients (37.14%) are degenerative; while in patients without bile leak the unilocular cysts occurred in 74 patients (50%);