Laparoscopic Cholecystectomy in Cirrhotics: A Prospective Randomized Study Comparing the Conventional Diathermy and the Harmonic Scalpel for Gallbladder Dissection

Introduction

Cholelithiasis in patients with cirrhosis occurs twice as often as in the general population with reported rates of 9.5%–13.7% versus 5.2% in patients without cirrhosis. ¹ A review of ∼4895 autopsy records in the literature showed that the frequency of cholelithiasis was 29.4% in patients with cirrhosis, whereas it was 12.8% in patients without cirrhosis. ² The morbidity and mortality rates for open cholecystectomy in patients with cirrhosis were reported to be as high as 17%–27%. ³ Such poor results were mainly due to either excessive blood loss with subsequent postoperative liver failure and/or sepsis. ³ Laparoscopic cholecystectomy (LC), on the other hand, has been shown to offer the advantages of less blood loss, shorter operative time, and shorter length of hospitalization in patients with cirrhosis.^4–8

Standard LC is commonly performed by means of specialized instruments. For gallbladder dissection, the electrosurgical hook, spatula and/or scissors using high frequency monopolar technology have been used in most centers. Occlusion by simple metal clips was the most frequently used technique to achieve both cystic duct and artery closure. Several studies have described the use of ultrasonic technology in LC, where the harmonic shears were used as the sole instrument (apart from the camera and retraction forceps) to achieve both dissection of the gallbladder and closure/division of the cystic duct and artery.^9–13 These studies demonstrated that the harmonic shears provided a superior alternative to the currently used high-frequency monopolar technology in terms of shorter operative time and lower incidence of gallbladder perforation.^9,12–14 Further, the harmonic shears were as safe and effective as the commonly used metallic clips in achieving safe closure and division of the cystic duct in LC.^9–14 The above-mentioned advantages may prove beneficial in patients with cirrhosis undergoing LC. The aim of the present prospective randomized study was to compare the surgical outcome of LC performed by the harmonic shears to that performed by the conventional diathermy in patients with cirrhosis.

Patients and Methods

The study was approved by the Ethics Committee of the Faculty of Medicine of the University of Alexandria. An informed consent was obtained from all patients included in the study. Inclusion criteria included patients with Child-Pugh's classes A and B and with symptomatic uncomplicated gallstones disease. Patients with Child-Pugh's class C were excluded. Other exclusion criteria included acute cholecystitis, patients with common bile duct stones, suspicion of gallbladder malignancy based on ultrasonography, and subsequent computed tomography findings. No intraoperative cholangiograms were performed. Patients presenting with associated abnormal alkaline phosphatase and gamma-glutamiltransferase levels and/or abnormal ultrasonographic findings (e.g., dilated common bile duct >8 mm) underwent an endoscopic retrograde cholangiopancreatography (ERCP). Associated common bile duct stones were treated by sphincterotomy and stone extraction. Failure to extract common bile duct stones preoperatively was considered an exclusion criterion. The diagnosis of cirrhosis was determined according to clinical history, laboratory data, findings on ultrasonography, and the presence of varices on upper gastrointestinal endoscopy and was confirmed by liver biopsy.

The following preoperative data were collected: age, sex, Child-Pugh classification, associated co-morbidities, and history of previous lower abdominal surgery. After preoperative evaluation and preparation for surgery, patients were randomly assigned using the sealed envelope technique to either the Harmonic scalpel LC group (HSLC group) in which the Harmonic ACE™ (Ethicon Endo-Surgery, Cincinnati, OH) was the only instrument used for both dissection and closure/division of cystic duct and artery or the conventional diathermy LC group (CDLC group)

Operative procedures were performed with the patient under general anesthesia and placed in the standard supine, crucifix, and reverse-Trendelenburg position with the right shoulder up. A uniform technique of LC was applied, including the use of the standard four trocar technique; a pneumoperitoneum was created using carbon dioxide with a maximized pressure of 15 mmHg and a 0° optical scope. In patients in whom laparoscopic subtotal cholecystectomy (LSC) was performed, the Palanivelu et al. classification was used to define the variant of LSC performed (LSC I; LSC was performed by leaving the posterior wall intact with the liver and the remnant mucosa was electrofulgrated. LSC II; the infundibulum was divided circumferentially as close to the junction of the gallbladder and cystic duct as safely possible, the mucosa in the proximal remnant was electrofulgrated and the flap was sutured with continuous suture of polygalactin 3–0. LSC III; this is a combination of LSC I and LSC II). ¹⁵

Open laparoscopy at the umbilical port site was performed in all patients. In patients with evident collateral circulation around the umbilicus (Caput medusae), the periumbilical area was avoided to prevent injury of the umbilical vein. Other ports were placed by prior transillumination of the abdominal wall through the scope of the umbilical port. The sub-xiphoid port was placed more to the right of the midline to avoid the Falciform ligament and its accompanying umbilical vein. Dissection of the gallbladder was initiated at the triangle of Calot with identification and skeletonization of both cystic duct and artery. In the HSLC group, the Harmonic ACE was used for dissection in the triangle of Calot and closure/division of both cystic duct and artery with the power level set at “2,” which translated into less cutting and more coagulation. In the presence of dense adhesions with sizable collateral veins around and/or within the calot triangle where dissection may induce bleeding that will obscure the operative field, an LSC II was performed as follows. The caudal cystic duct-gallbladder junction was identified, and multiple sequential applications of the Harmonic ACE at the level of the gallbladder infundibulum as close as possible to the cystic duct-gallbladder junction were applied to achieve complete division/closure of the gallbladder from both the cystic duct and artery. In the CDLC group, dissection of the triangle of Calot was performed with an atraumatic dissecting forceps. Closure of the cystic duct and artery was achieved by applying simple titanium clips, whereas division of both structures was achieved by scissors in the usual manner. Dissection of the gallbladder from the liver bed started posteriorly at the triangle of Calot and proceeded anteriorly. In the HSLC group, the peritoneum covering the gall bladder was incised using the active blade of the Harmonic ACE starting posteriorly and proceeding anteriorly on both sides of the gall bladder. Next, the jaws of the Harmonic ACE were closed over a bite of the tissues in the plane of dissection. Finally, the harmonic shears were activated to achieve both cutting and coagulation of the tissues grasped between the jaws of the Harmonic ACE. This process was repeated until the gall bladder was completely dissected from the liver bed. In the case of the liver bed ooze, hemostasis was easily achieved by applying the active blade of the Harmonic ACE tangentially to tissue and no electrocautery was used. In the CDLC group, dissection of the gallbladder from the liver bed was performed using the electrosurgical hook or spatula in the usual manner. In the presence of difficult dissection between the gallbladder and its liver bed, an LSC I was performed as follows. The posterior wall of the gallbladder was not dissected from the liver bed but rather separated from the rest of the gallbladder and its mucosa was destroyed by electrocautery. Every effort was made to retrieve spilled stones. Finally, the gallbladder was removed through the sub-xiphoid port, and a sub-hepatic tube drain was routinely placed through the most lateral port as is our standard practice. All access ports were checked internally just before completion of the procedure to detect possible bleeding.

The operative time was recorded by an independent observer. Intraoperative events, for example, bleeding, gallbladder perforation, and conversion to open cholecystectomy were recorded. The postoperative complications and the hospital stay were also recorded. The sub-hepatic drain was removed on the morning of postoperative day 1, and its wound was stitched under local anesthesia.

At the end of the first postoperative week, patients underwent clinical examination and an abdominal ultrasonography with special attention to the presence or absence of any sub-hepatic (or otherwise) fluid collections. At the end of the first postoperative month, clinical examination and abdominal ultrasonography were repeated. In addition, blood was sampled for bilirubin, aminotransferase, alkaline phosphatase, and gamma-glutamiltransferase levels.

All data analysis was performed with the Statistical Package for the Social Sciences version 15 software (SPSS, Chicago, IL). The Mann–Whitney U test was used for continuous variables. The Chi-squared and the Fisher's exact test were used for categorical variables. All P values were two-sided. A P < .05 was considered statistically significant.

Results

The present study included 40 patients. There were 23 men (57.5%) and 17 women (42.5%). Their age ranged from 38 to 58 years with a median of 48 years. Preoperative ERCP was performed in three patients (7.5%) in the present study. In two patients (5%), associated common bile duct stones were successfully treated for sphincterotomy and stone extraction. In the third patient (2.5%), ERCP revealed no stones in the common bile duct. After preoperative evaluation and preparation for surgery, patients were randomly assigned to either the Harmonic scalpel LC group (HSLC group) or the CDLC group. There was no statistically significant difference between both studied groups as regards age and sex distribution, etiology of cirrhosis, Child-Pugh classes, associated co-morbidities, and previous lower abdominal surgery, as shown in Table 1.

Intraoperative events encountered in both studied groups are illustrated in Table 2. The median estimated intraoperative blood loss was statistically significantly less in the HSLC group compared with the CDLC group (50 vs. 120 mL respectively, P = .000). In the CDLC group, failure to control liver bed bleeding in two patients (10%) and cholecystohepatic triangle bleeding in another patient (5%) necessitated conversion to open cholecystectomy in these three patients (15%). On the other hand, all procedures were laparoscopically completed in the HSLC group. The difference in the conversion rate between both studied groups was statistically insignificant (P = .231).

In the HSLC group, LSC II was performed in eight patients (40%), whereas LSC I was not performed in any patient. On the other hand, in the CDLC group, LSC I was performed in six patients (30%), whereas LSC II was not performed in any patient. The incidence of intraoperative gallbladder perforation was statistically significantly lower in the HSLC group than in the CDLC group (10% vs. 70%, respectively, P = .000). Intraoperative gallbladder perforation in the CDLC group included both gallbladders inadvertently perforated during dissection (8 patients; 40%) and those deliberately perforated to perform an LSC I (6 patients; 30%). The difference was still statistically significant when the patients in whom the gallbladder was deliberately perforated to perform a LSC were excluded (P = .028). The median operative time was statistically significantly shorter in the HSLC group than in the CDLC group (55 vs. 82.5 minutes respectively, P = .000)

There were no mortalities in the present study. The postoperative complications encountered in the present study are illustrated in Table 3. Postoperative complications were encountered in five patients (25%) in the HSLC group compared with seven patients (35%) in the CDLC group with the difference being statistically insignificant. Postoperative deterioration of liver function was the most common complication encountered in both studied groups. All three patients (15%) of the CDLC group in whom the procedure was converted to an open one suffered from postoperative deterioration of liver function. The postoperative complications encountered in both studied groups were successfully managed conservatively by routine measures throughout the first postoperative month. Neither minor nor major bile leaks were encountered in either group. Similarly, no bile duct injuries were encountered in the present study.

The hospital stay was 2 days in the HSLC group. In the CDLC group, it ranged from 2 to 5 days with a median of 2 days. The difference in the median hospital stay between both studied groups was statistically insignificant (P = .075).

Discussion

The main finding of the present study is that the use of the Harmonic ACE in LC in patients with cirrhosis is associated with a statistically significant shorter median operative time, less median intraoperative blood loss, and lower incidence of intraoperative gallbladder perforation, compared with the use of the conventional diathermy.

El-Nakeeb et al., in the only prospective randomized study comparing clipless LC using the harmonic shears to the traditional LC using the clip and cautery technique in patients with cirrhosis, confirmed the safety and efficacy of the harmonic shears in achieving complete hemobiliary stasis. ¹⁴ The findings of the present study are in total agreement with this conclusion. In the present study, the absence of either minor or major bile leaks add further confirmation to the safety and efficacy of the harmonic shears in achieving complete hemobiliary stasis in patients with cirrhosis undergoing LC. Further, in El-Nakeeb et al. study as well as the present study, the use of the harmonic shears has been shown to be associated with a statistically significant shorter mean/median operative time, less mean/median intraoperative blood loss, and lower incidence of gallbladder perforation. ¹⁴

Earlier studies have demonstrated that the use of the harmonic shears in LC in patients without cirrhosis was associated with a statistically significant shorter mean/median operative time compared with the conventional clip and cautery technique.^9,12–14 This has been attributed to several factors. First, the Harmonic ACE is a multifunctional instrument that replaces four instruments routinely used in LC, namely the dissector, clip applier, scissors, and electrosurgical hook or spatula. Its use, therefore, prevents the frequent blind extraction and reinsertion of these different instruments with subsequent avoidance of time loss. Second, the activation of the Harmonic ACE does not form smoke although mist may be generated by vibration, therefore allowing the surgeon to work in a clear operative field throughout the operation. On the other hand, the use of electocautery causes smoke formation in the abdominal cavity and decreases visibility. Moreover, smoke must be evacuated by opening the valves of the trocars, thus causing repeated loss of pneumoperitoneum and subsequent loss of time. Finally, the use of the Harmonic ACE in LC has been shown to be associated with a statistically significant lower incidence of gallbladder perforation, which resulted in subsequent avoidance of time loss in abdominal lavage and spilled stones retrieval.^9,12,13 The statistically significant shorter median/mean operative time encountered in the present study and that of El-Nakeeb et al. demonstrates that the above-mentioned advantages of the harmonic shears are reproducible when attempting LC in patients with cirrhosis. ¹⁴

LC is the standard treatment for symptomatic cholelithiasis in patients with cirrhosis who are fit for surgery. The operation entails complete removal of the gallbladder, which, whenever possible, should remain to be the target of LC even in patients with cirrhosis. However, LSC may be an acceptable alternative in patients with cirrhosis to avoid intraoperative bleeding from the liver bed or during dissection of the cholecystohepatic triangle with subsequent open conversion and its associated high morbidity and possible mortality. LSC for patients with cirrhosis has been described as early as 1993. ¹⁶ The safety and efficacy of LSC in patients with cirrhosis has been demonstrated by others.^5,15–17 In the present study, although LSC was resorted to in eight patients (40%) in the HSLC group compared with six patients (30%) in the CDLC group, however, the types and techniques differed.

Palanivelu et al. standardized the technique of LSC by classifying it into three categories: LSC I, LSC II, and LSCIII. ¹⁵ LSC I was recommended in patients with portal hypertension in whom large collateral vessels may be present in the liver bed to prevent avulsion of the gallbladder and subsequent bleeding. ¹⁵ In this variant of LSC, the posterior wall of the gallbladder was left intact with the liver and the remnant mucosa was electrofulgrated. ¹⁵ Deliberate iatrogenic gallbladder perforation with stone spillage is an inevitable step in LSC I with subsequent loss of time in abdominal lavage and stone retrieval. In the present study, LSC I was resorted to in six patients (30%) of the CDLC group compared with no patient in the HSLC. In the HSLC group, the gallbladder was separated from its liver bed using multiple bites of the Harmonic ACE on the tissues in the plane of dissection without deliberately perforating the gallbladder. The absence of liver bed bleeding necessitating open conversion in the HSLC group provided evidence to the safety and efficacy of such practice. Using this technique seemed to obviate the need for LSC I in this group of patients.

LSC II was recommended in the setting of a “high risk hilum”. ¹⁵ In patients with cirrhosis, the presence of neovascularity in the hilar region or cavernomatous transformation of the portal vein renders hilar dissection dangerous. This may be aggravated by other risk factors such as the deeply seated hilum, pericholecystic fibrosis, or aberrant anatomy. In this operation, the infundibulum was divided circumferentially as close to the junction of the gallbladder and cystic duct as safely possible; the mucosa in the proximal remnant was either removed by mucosectomy or electrofulgrated; and the flap was sutured with continuous suture of polygalactin 3–0. ¹⁵ Deliberate iatrogenic gallbladder perforation with stone spillage is an inevitable step in LSC II when performed using the conventional electrocautery. On the other hand, the performance of LSC II using the Harmonic ACE offers several advantages over the traditional method. First, the Harmonic ACE is placed on the infundibulum as close as possible to the cystic duct-gallbladder junction, thus rendering the remnant of the gallbladder negligible in size. Palanivelu et al. reported that relaparotomy for a stone in the gallbladder remnant was required in three patients (1.1%). ¹⁵ The use of the Harmonic ACE results in a nearly total cholecystectomy rather than a subtotal cholecystectomy and such a problem has not been encountered in the present study. Second, the Harmonic ACE achieves complete and safe closure of both cut ends. The absence of either minor or major bile leaks in patients who underwent LSC II in the present study denotes that the Harmonic ACE achieved safe and complete closure of the gallbladder stump. Palanivelu et al. reported bile leakage from the closed stump in 94.1% of their patients who underwent LSC II using the traditional method. ¹⁵ Further, since the gallbladder was not perforated, neither bile nor stones were spilled into the peritoneal cavity and no time was lost in abdominal lavage or spilled stones retrieval. Finally, the use of the Harmonic ACE rendered separation of the gallbladder from hilar structures almost bloodless. The absence of common bile duct injuries in those patients adds further evidence to the safety of LSC II when performed using the Harmonic ACE.

The findings of the present study demonstrated two additional benefits to the use of the harmonic shears when attempting LC in patients with cirrhosis. First, the use of the Harmonic ACE has seemed to facilitate the performance of LSC II. The avoidance of bleeding during dissection of a high-risk hilum, gallbladder perforation, and leaving a sizable remnant of the gallbladder in which stones may form are the main advantages of using the Harmonic ACE in LSC II. Second, the use of the Harmonic ACE seemed to obviate the need for LSC I, which is associated with deliberate iatrogenic gallbladder perforation. This was achieved without liver bed bleeding necessitating open conversion. Further, since the LSC I was avoided, consequently LSC III was avoided as well. Although larger numbers are still required to draw more definite conclusions on the safety and efficacy of the Harmonic ACE in the performance of LSC II, however, the absence of bile leaks, common bile duct injury, and open conversion in the HSLC group seem to provide encouraging evidence.

Conclusions

In patients with cirrhosis, the use of the harmonic shears in LC provided a superior alternative to the conventional diathermy in terms of shorter operative time, less intraoperative blood loss, and lower incidence of gallbladder perforation, partly through facilitating the performance of LSC.