|Home | About | Journals | Submit | Contact Us | Français|
Polycystic liver disease (PLD) has a low frequency overall in the worldwide population. As the patient's symptoms are produced by the expansion of hepatic volume, the different therapeutic alternatives are focused on reducing it. Surgery is still considered the most effective treatment for symptomatic PLD. The aim of this study was to evaluate the long-term outcomes of laparoscopic surgery for PLD.
This study included 14 patients who were diagnosed with symptomatic PLD and underwent surgery by a laparoscopic approach between 2004 and 2012. It involved collecting data on the characteristics of those patients and their liver disease, surgical procedures, intra- and postoperative complications, and the long-term follow-up.
Twelve laparoscopic multiple-cyst fenestrations and two segmentary liver resections associated with remaining-cyst fenestration were performed. One procedure required conversion to laparotomy and the other was complicated by anhepatic severe bleeding. The rest of the procedures were uneventful. One patient developed persistent self-limited ascites in the immediate postoperative period. Symptoms disappeared after surgical intervention in all patients. During a median follow-up of 62 months (range 14-113 months), there were two clinical recurrences and one asymptomatic radiological recurrence. One patient required further surgery.
Laparoscopic cystic fenestration and laparoscopic liver resection are safe and long-term, effective procedures for the treatment of symptomatic PLD. Severity and morphological characteristics of the hepatic disease will determine the surgical indication and the optimal approach for each patient.
Polycystic liver disease (PLD) represents a group of genetic disorders presenting with multiple hepatic cysts. To be diagnosed as PLD, a sporadic case must present at least 20 hepatic cysts, whereas, if there were familiar precedents, four cysts are enough to make the diagnosis.[1,2,3] PLD may occur in isolated form as autosomal dominant polycystic liver disease (ADPLD) or in association with autosomal dominant polycystic kidney disease (ADPKD). Estimated incidences are 0.01% and 0.2%, respectively,[1,4,5] and both entities present a dominant autosomic hereditary pattern. Symptoms will appear in 20% of patients with PLD, generally due to the expansion of hepatic volume.
The therapeutic alternatives available for the management of patients are: Surgical, pharmacological, and interventional radiological treatments. Surgical treatment is the only one that was proved to be effective in symptomatic patients. Despite laparoscopic surgery being considered a useful tool for simple hepatic-cyst treatment, a few series of studies have been published more recently describing long-term outcomes after laparoscopic procedures for PLD.
A retrospective study was performed based on patients with symptomatic PLD who were treated with laparoscopic surgery between 2004 and 2012 at our center. Data concerning patients' epidemiological and clinical features, surgical procedures, the immediate postoperative period, and long-term outcomes were collected. All patients had been earlier diagnosed with PLD, defined as the presence of at least 20 hepatic cysts larger than 1 cm without infectious, parasitic, or traumatic processes. Patients who met these criteria but not those of ADPKD were diagnosed with ADPLD. The characteristics of hepatic involvement were reevaluated for this study based on computed tomography (CT) or magnetic resonance imaging (MRI) images.
Our laparoscopic surgical technique used for cystic fenestration begins with cystic puncture, after which the cyst's content is drawn out and its surface wall is resected. Then, wide electrocoagulation of the hepatic surface is performed. Transfixion sutures are usually made for hemostasis and biliostasis. The intervention is completed with the placement of an aspirative drain. For laparoscopic resections the principles of anatomical liver resections were followed.
Perioperative complications and mortality data included those that occurred during the patient's hospitalization and in 30 days following the operation. In accordance with our protocol, the patients received clinical and ultrasound (US) evaluation 3 months and 1 year after surgery, respectively. Subsequently, asymptomatic patients continued to receive annual evaluation. Radiological recurrence was defined as the presence of a cyst detected by US or CT in the same location as the original. Clinical recurrence was defined as the reappearance of symptoms associated with radiological recurrence.
In the period under study, 14 patients underwent a laparoscopic procedure. It was performed in 12 women and 2 men, whose average age was 65.7 (47-78) years. Six of the patients (43%) had PLD within the diagnosis of ADPKD and eight (57%) were diagnosed as ADPLD. Abdominal pain conditioned the indication for surgery in 11 patients. In the other three, intervention was indicated for portal vein compression, painless jaundice, and cyst abscessification.
Surface cysts predominated in 64% of the patients, while in 36% of them the cyst's spreading was diffuse. Two patients had received prior treatment: For one, a laparoscopic cyst fenestration performed in another hospital and for the other, successive percutaneous esclerotic treatments. The average readings in the preoperative blood analyses were as follows: aspartate aminotransferase (AST) 38.71 U/L (range: 12-169), alanine aminotransferase 35.79 U/L (range: 9-135), alkaline phosphatase (AP) 164.64 U/L (range: 46-589), gamma-glutamyl transpeptidase (GGT) 102.93 U/L (range: 6-457) and total bilirubin 0.93 micromol/L (range: 0.30-3.08).
Twelve multiple laparoscopic fenestrations were performed; additionally performed were one left lateral sectionectomy and one right posterior sectionectomy, both by a laparoscopic approach; and associated fenestration of the remaining cysts. Six patients also underwent laparoscopic cholecystectomy (43%). The median operating time was 122 min (range 60-210 min) and the average hospital stay was 3.7 days (range 1-7 days). A conversion to open laparotomy was required in one patient due to previous surgical adherences. One patient presented profuse intraoperative bleeding, which was remedied with a hemostatic laparoscopic suture. Blood transfusion was not required in all patients. One patient developed persistent ascites, self-limited, in the immediate postoperative period. There was no perioperative mortality. During a median follow-up of 62 months (range 14-113), there were two (14%) cases of clinical and radiological recurrence at 12 months and 32 months and one case (7%) of radiological asymptomatic recurrence at 42 months.
One patient with the left lobe predominantly affected who had initially undergone laparoscopic multiple-cyst fenestration, had a symptomatic recurrence at 32 months, and 10 months later she underwent an open left lobectomy. The other symptomatic recurrence was in an elderly woman presenting mild symptoms, who refused any further surgical or radiological procedure.
The association between ADPKD and PLD was described by Bristowe in 1856. Liver involvement is the most frequent nonrenal manifestation of ADPKD, being present in 67-83% of patients. Until 20 years ago, ADPKD and PLD were considered to be the same disease, and cases of patients without renal involvement and multiple liver cysts were attributed to differences in expression of the underlying genetic mutations.
Recent studies have shown that ADPLD has a different genetic basis from that of ADPKD,[7,8] such that they have to be considered different diseases. The mutations associated with ADPKD are the basis of practically all cases: They occur in the genes PKD1 (85%) and PKD2 (15%), which encode the proteins polycystin-1 and polycystin-2. The situation is different with ADPLD, with only 21% of the cases presenting a characteristic mutation, predominantly those of the genes PRKCSH and SEC63.
The natural history of PLD is characterized by a continuous increase in the size and the number of cysts.[1,2,3,4] PLD presentation and the development of massive cyst involvement are more frequent in women. Exposure to estrogen promotes the progression of the disease. Other favorable factors are advanced age and severity of renal involvement in ADPKD patients.[2,3,4]
The clinical course of PLD is asymptomatic in 80% of patients. Symptoms are produced by the increase of hepatic volume, which leads to compression of the surrounding structures. The most related symptoms are: Abdominal pain and bloating, postprandial fullness, gastroesophageal reflux, and symptoms resulting from biliary or venous obstruction (compression of the portal vein, Budd-Chiari syndrome, and inferior vena cava syndrome).[4,6] The potential complications of cysts include their rupture, torsion, infection, and bleeding.
In our study, 57% of the patients had ADPLD, which contrasts with the few cases of this entity described in the literature compared to ADPKD patients. Recent publications have described similar findings. It is known that ADPLD has less penetration into the liver than ADPKD into the kidney, and thus the development of symptomatic hepatic cysts in these patients may not occur or may not appear until advanced age. Although both entities are often asymptomatic, in ADPKD patients these cases can be casually detected more frequently, during the surveillance of kidney disease.
In asymptomatic PLD patients the biochemical markers tend to be normal. The symptomatic patients, as is the case in our study, may have alterations in AP, GGT, AST, and total bilirubin. Liver function is typically normal. The most-used diagnostic radiological tests are US and CT scanning. The MRI is more sensitive and specific to hepatic cysts and it presents a useful alternative for patients with renal disease and allergies to contrast mediums.
Intracranial aneurysms (16%), mitral valve prolapse and colonic diverticulosis (both 25%) are entities associated with ADPKD, while being not so prevalent in ADPLD. After the diagnosis of PLD (both ADPKD and ADPLD), it is recommended to perform an angio-MRI of the brain in patients older than 30 years or with a familiar history of intracranial aneurysms or hemorrhagic stroke.[1,5,10]
Asymptomatic PLD patients do not require any treatment. For symptomatic patients, the cessation of a previous regime of estrogenic therapy is the first step in management. Pharmacological therapy has been considered an alternative in symptomatic patients with massive hepatic involvement. The most commonly used drugs are somatostatin analogs, but they have failed to produce improvement in gastrointestinal symptoms.
Interventional radiology treatments include arterial embolization and percutaneous sclerotherapy. Both can potentially produce an improvement in the symptoms by reducing the volume of hepatic cysts.[2,12] Despite the lack of clear evidence about their effectiveness in PLD patients, these approaches might be useful in patients unfit for surgical treatment.
Surgical options include the following: Cyst fenestration, liver resection, and liver transplantation. Fenestration of hepatic cysts was first described by Lin in 1968. Laparoscopic fenestration is the standard treatment for benign hepatic cysts. Fenestration can be performed by either a laparoscopic or an open surgical approach, and many cysts can be treated during a single procedure. Patients with a few large cysts on the anterior surface of the liver are the best candidates for fenestration.[5,15] Patients with extensive invasion by small cysts have worse postoperative outcomes.
Despite the difficulty laparoscopically approaching segments VI-VIII usually entails,[14,17] we have been able to perform laparoscopic fenestration on them satisfactorily. We systematically fenestrated every accessible cyst, but did not perform routine epiploplasty[18,19,20] on the residual cavity. The only case of a previously laparoscopically operated liver was handled successfully.
Cyst fenestration decreases liver volume in PLD patients and produces symptomatic improvement. In available data, based on patients who predominantly underwent an open surgery, relief of the immediate symptom after the procedure is 92%, with cyst and symptom recurrence at 24% and 22%, respectively. This recurrence was higher than observed in our study. Morbidity related to the procedure appeared in 23% of the patients, with a mortality rate of 2%, also higher than we report. As we observed of other studies concerning laparoscopic surgery for PLD, with fewer patients than the present and reporting only cyst fenestration, the results seemed comparable with previously published with the open approach.[15,17,18,19,21]
Hepatic resection has been used traditionally in patients with disabling symptoms due to massive expansion of the liver, but few studies about its use in PLD have been published recently. In the largest study of open resection in PLD patients, a postoperative morbidity rate of 63% was observed, being higher than for resections for other causes, and the mortality rate was 3%. The higher complication rate can be attributed to the alteration of normal vascular and biliary architecture produced by the cysts. Laparoscopic liver resection reduces hospital stay and blood loss compared to the traditional open approach, and obtains similar results. As we observed, it will be a useful tool for PLD surgical management. The addition of laparoscopic fenestration of the remaining cysts allows for an optimal procedure from the therapeutic point of view, while preserving liver function, with minimal morbidity and quick postoperative recovery.
The most frequent postoperative complications for both cyst fenestration and hepatic resection for PLD are ascites, pleural effusion, bile leaks, abscesses, and hemorrhagic complications. Adhesions caused by the procedures may complicate a potential subsequent transplant. The distortion in vascular and biliary architecture caused by cysts makes essential the optimization of preoperative and intraoperative explorations. Laparoscopic cholecystectomy had already been added to laparoscopic cyst fenestration in other published cases. We added cholecystectomy in six patients. In our studied group it was performed on all patients with cholelithiasis in the preoperative study, and also on those patients for whom the freeing of the vesicular bed brought an improvement in surgical approach to the cyst. In those cases, laparoscopic cholecystectomy is a safe procedure that avoids the risk of clinical recurrence due to previously masked biliary symptomatology. It also prevents the need for a second procedure on a liver that has already been operated on, with the increased risk of vascular and biliary injury, if symptoms of cholelithiasis arise in the future.
Both cyst fenestration and liver resection procedures, while not being able to completely eliminate the disease, are only considered symptomatic treatments. Potential candidates for treatment are those with symptomatic PLD for whom surgical intervention could significantly reduce hepatic cystic volume without compromising liver function. In livers that are extensively affected by small cysts, fenestration and resection cannot work on the deepest cysts and therefore cannot achieve optimal reduction of the hepatic volume to improve the symptoms.
Liver transplantation is the only curative treatment for PLD. It should be considered for patients with disabling symptoms not treatable with other surgical techniques. As patients with PLD usually have normal liver function, indication for a transplant requires use of the Model for End-stage Liver Disease (MELD) exception criteria. Before the decision for liver transplantation is taken, it is necessary to weigh up the severity of the patient's symptoms and the possibility of a definitive treatment against the risks of the transplantation procedure and a lifetime of immunosuppression.
There are several classifications for PLD. Gigot's classification is the most commonly used at present, but it does not distinguish between asymptomatic and symptomatic patients. Moreover, as the current standard for diagnosing PLD is a minimum of 20 cysts, Gigot's type 1 is only considered PLD if it presents in patients with four to 10 hepatic cysts and a family history of PLD. Like Gigot's, Morino's classification also does not distinguish between asymptomatic and symptomatic patients. Schnelldorffer's classification is based on a study of more than 100 open surgeries. In this classification, the asymptomatic patients (type A) are distinguished from those with symptoms (types B, C, and D), making the distinction between the latter on the basis of degree of hepatic cyst involvement, which will then determine the best therapeutic alternative to be used [Table 1].
The current literature limits to 20 the minimum number of cysts for the inclusion of the patient as PLD and also highlights the advantages and new possibilities offered by laparoscopic surgery over the traditional open approach to PLD treatment. As previously published classifications do not take account of these aspects, our team classifies patients diagnosed with PLD depending on the clinical and therapeutic characteristics of the patient's illness, thus simplifying both the allocation of patients to different groups and the therapeutic decision.
The first group would consist of asymptomatic patients without compressive complications, independently of the number and size of the cysts. These patients should not receive the treatment. The second group would consist of patients with symptoms or complications caused by cyst compression, but not presenting multiple deep liver involvement by small cysts. Cystic fenestration and liver resection associated with fenestration of the remaining cysts, preferably by the laparoscopic approach, is the treatment of choice in these patients if they meet the operability criteria. The third group would consist of symptomatic patients who present multiple and deep small-cyst involvement, and these would be potential candidates for a liver transplant.
In conclusion, laparoscopic cystic fenestration and laparoscopic liver resection are safe and long-term, effective procedures for the treatment of symptomatic PLD. Meanwhile, as new studies appear, interventional radiology procedures or medical treatment should be reserved for patients who are unfit for surgical treatment.
Source of Support: Nil
Conflict of Interest: None declared.