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Updates Surg (2011) 63:243247 DOI 10.

1007/s13304-011-0110-7

ORIGINAL ARTICLE

Laparoscopic fenestration of non-parasitic liver cysts and health-related quality of life assessment
C. Kamphues M. Rather S. Engel S. C. Schmidt P. Neuhaus D. Seehofer

Received: 23 July 2011 / Accepted: 5 September 2011 / Published online: 17 September 2011 Springer-Verlag 2011

Abstract Although laparoscopic fenestration has become an established treatment in symptomatic liver cyst patients in the recent years, the success of surgical treatment cannot only be evaluated by post-operative morbidity and mortality. Therefore, the aim of this study was to analyze the safety of laparoscopic fenestration of non-parasitic liver cysts and to assess the impact of this therapy on patients quality of life. A total of 43 patients who underwent laparoscopic fenestration of non-parasitic liver cysts at our center were included in this study. Post-operative course was assessed and patients quality of life was evaluated before surgery and at present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30). The results were that, post-operative morbidity and mortality rates were 0%. After a median follow-up of 49 months (1997 months) the recurrence rate was 11.1% for simple liver cysts (SLC) and 42.9% for polycystic liver disease (PCLD). Thirty-one out of 43 patients (72.1%) completed the EORTC C-30 questionnaire. There was highly signicant post-operative improvement in global health status (p \ 0.001) as well as in physical (p = 0.002), role (p = 0.004), emotional (p = 0.003) and social (p = 0.001) functioning. Furthermore, a signicant reduction of symptoms could be shown for pain (p \ 0.001), nausea and

vomiting (p = 0.001), appetite loss (p = 0.006), insomnia (p = 0.04) and fatigue (p = 0.025). To conclude, laparoscopic fenestration of symptomatic non-parasitic liver cysts is a safe procedure with good long-term results and the patients benet of this intervention is excellent as shown by highly signicant improvement in patients quality of life. Keywords Liver cysts Quality of life Laparoscopy

Introduction For long time, non-parasitic liver cysts had been considered rare, but due to the development of new imaging techniques and their increasing use in the recent years, liver cysts now represent a relatively common pathology, with a prevalence of 35% [1]. Cysts are uid-lled cavities lined by cubical or columnar epithelium, not communicating with the intrahepatic biliary tree and are believed to be congenital malformations arising from the abnormal development of intrahepatic bile ducts (Meyenburg complexes) [2, 3]. Depending upon whether this pathology is inherited or not, this group is differentiated into simple liver cysts (SLC) (solitary or multiple) and polycystic liver disease (PCLD) [3, 4]. The non-parasitic liver cysts need to be differentiated from neoplastic cysts (biliary cystadenomas and cystadenocarcinomas) which may mimic these lesions on imaging studies and in presentation but need different surgical approach based on oncologic principles [5]. The majority of patients with non-parasitic liver cysts are asymptomatic. However, about 1016% becomes symptomatic, usually presenting later in life and more often in women [2, 68]. The presentation is non-specic

The authors C. Kamphues and M. Rather contributed equally to this manuscript. C. Kamphues (&) M. Rather S. Engel S. C. Schmidt P. Neuhaus D. Seehofer Department of General, Visceral and Transplantation Surgery, Universitatsklinikum Charite, University Medicine, Campus Virchow Clinic, Humboldt-Universitat, Augustenburger Platz 1, 13353 Berlin, Germany e-mail: carsten.kamphues@charite.de

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mainly due to increasing cyst size, with abdominal pain, early satiety, nausea, vomiting, and dyspnea [8, 9]. Complications such as intracystic hemorrhage, infection, or rupture are rare forms of presentation [8, 10]. Surgical treatment is indicated if the cyst is complicated or of progressive size and if all other possible causes for the symptoms have been excluded. The surgical treatment options available include percutaneous aspiration with sclerosing agent injection, laparoscopic fenestration, open fenestration, cystojejunostomy, hepatic resection and liver transplantation [11]. There is still some controversy about the most preferable procedure, but most studies seem to agree on laparoscopic fenestration as the initial approach for the majority of simple liver cysts [1113]. However, almost all of these studies have used post-operative morbidity, mortality and recurrence rates to measure the clinical outcome. Based on the modern concept of health-related quality of life (HR-QoL), the principle criterion guiding the patients acceptance of treatment is often the patients subjective feeling [14]. This reects a number of biologic, social and clinical parameters that are meaningful for the patient, especially in a disease like nonparasitic liver cysts, where recurrence rates are high. Since it is not possible to cure the disease in many patients, the aim of most surgeons is to get symptomatic relief which cannot be evaluated by the standard parameters morbidity and mortality. Hence, in such a disease the patients outcome based on the quality of life becomes the most important factor which to our knowledge has rarely been evaluated so far [15, 16]. The aim of our study was to assess the safety and efcacy of laparoscopic fenestration of non-parasitic liver cysts, using an evaluative QoL instrument, in addition to the standard parameters.

Materials and methods The study was conducted at the Department of General, Visceral and Transplantation Surgery of the Charite University Hospital, Campus Virchow Clinic in Berlin, Germany. All patients who underwent laparoscopic fenestration for symptomatic non-parasitic liver cysts at our center from April 2002 to May 2008 were included in this study. All the patients eligible for the study were identied from a prospective database and following data were collected in each case; demographics, diagnosis, indication, pre-operative laboratory and radiologic results, details of surgical procedure, complications, length of post-operative stay, nal pathology, and follow-up. After this, all the patients were contacted by telephone to enquire about recurrent symptoms and a questionnaire was sent to the

patients to assess the QoL before surgery and at present time. In all the patients, surgery was indicated only when they presented with clinical symptoms related to radiologically conrmed large liver cysts, after all other possible medical causes for their symptoms were excluded. Parasitic cysts were ruled out by imaging studies in combination with serological tests. Accordingly, neoplastic lesions were excluded by computed tomography or MRI scan and in case of doubt additional determination of tumor markers. Surgery was performed in all the patients according to the standard operation procedures. The patients were positioned in reverse Trendelenburg position and pneumoperitoneum was established by supra-umbilical introduction of a Verres needle. Three to four ports were placed according to the position of the cysts. After thorough inspection of abdominal cavity, the cysts were punctured and aspirated, followed by wide fenestration by de-roong using ultrasonic coagulation shears (Harmonic scalpel, Ethicon). The dissected wall and cavity oor of the cysts were thoroughly inspected for bile leakage and bleeding. Omentoplasty was performed for the dominant cysts if possible. HR-QoL was retrospectively assessed by a QoL questionnaire before surgery and after surgery at present time. Since there is no specic questionnaire for non-parasitic liver cyst disease, we used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30, Version 3.0). This questionnaire is a cancer specic QoL instrument originally used in cancer clinical trials [17, 18]. However, this tool was chosen because it addressed all the symptoms that are seen in non-parasitic liver cyst patients and represents a validated tool. The questionnaire consists of 30 items incorporating ve functional scales (physical, role, social, emotional, and cognitive), nine symptom scales (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and nancial difculties) and a global health and QoL scale. Twenty-eight of these 30 items have a 4-point scale, whereas global health and overall QoL have a 7-point scale [17]. The answers were scored using the EORTC QLQ-30 scoring manual [19]. Additionally to the questionnaire, all patients were asked if they would again undergo laparoscopic fenestration due to non-parasitic liver cysts from their present point of view. For this study ethical, approval was obtained from the Institutional Ethics Committee and all patients gave informed consent prior to the enrolment to the study. Statistical analysis was performed using SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) and the R statistical software (Version 2.8.1, GNU/Linux). All quantitative data were expressed as median and range, unless otherwise

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indicated. Differences between quality of life parameters were tested using the Wilcoxon-test for paired samples. A p-value of less than 0.05 was regarded statistically signicant.

intra-operative mortality and no patient required postoperative management in the intensive care unit. No patient required transfusion of blood products. Post-operative complications and follow-up

Results Patient demographics The study population consisted of 43 patients who underwent laparoscopic fenestration of symptomatic non-parasitic liver cysts at our center. There was an expected majority of female patients in the study population and preoperative blood samples did not reveal limited liver function in any of our patients. All relevant demographics and pre-operative parameters of the entire cohort and the quality of life sub-group are depicted in Table 1. Diagnosis and indications Thirty-six patients (83.7%) had simple liver cysts, whereas seven patients (17.3%) had polycystic liver disease. Four patients (9.3%) had recurrent disease after previous laparoscopic fenestration. Indication for surgery was highly symptomatic non-parasitic liver cysts in all the patients. The post-operative pathological examination conrmed the pre-operative diagnosis of benign non-parasitic liver cysts in all patients. Operative procedure Laparoscopic wide fenestration with omentoplasty was possible in all cases with a 0% conversion rate. The median operative time of 94 min (30195 min) and the median numbers of cysts fenestrated was 1 (17). Additional operative procedures were done in six patients (14.0%), ve cholecystectomies and one ovariectomy. There was no
Table 1 Demographics and pre-operative liver values of all patients and the quality of life subpopulation All patients (n = 43) Age (years) Gender ratio (male:female) Biggest cyst size (mm) Pre-operative bilirubine level (mg/dl) Pre-operative AST (U/l) Pre-operative ALT (U/l) Pre-operative quick value (%) Values are median (range) 58 (2690) 1:20.5 80 (20270) 0.50 (0.201.40) 24 (1061) 23 (8106) 98 (63127) QoL group (n = 31) 58 (2677) 1:30 80 (25180) 0.50 (0.201.20) 24 (1061) 20 (8103) 98 (74124)

The post-operative morbidity and mortality was 0%. The median hospital stay was 5 days (28 days). After median follow-up of 49 months (1997 months), seven patients had a recurrence of milder symptoms, resulting in a recurrence rate of 16.3% in the whole cohort. The recurrence rates for the sub-groups SLC and PCLD were 11.1 and 42.9%. Only two patients (4.7%) required further surgical therapy, whereas most of the recurrences could be managed conservatively. All recurrences could be regarded as symptom recurrence due to residual or partial residual cysts. Quality of life assessment A total of 31 (72%) patients who completed the questionnaire were included in the QoL assessment. In this subgroup the median number of fenestrated cysts was 1 (17) and the median hospital stay was 4 days (28 days). Demographic as well as diagnostic and operative details of the QoL sub-population revealed no signicant differences compared to the entire cohort (Table 1). Therefore, the QoL assessment may be regarded as the representative for the entire cohort. Statistical analysis revealed a signicantly improved global health status after laparoscopic fenestration of the liver cysts in this cohort (44 vs. 69, p \ 0.001). The Wilcoxon-test for paired samples also showed highly signicant improvement in four out of ve functional scales; physical (p = 0.002), role (p = 0.004), emotional (p = 0.003), and social (p = 0.001) functioning. Furthermore, there was a signicant improvement in ve relevant symptoms after fenestration of the liver cysts: pain (p \ 0.001), nausea and vomiting (p = 0.001), appetite loss (p = 0.006), insomnia (p = 0.04) and fatigue (p = 0.025). A detailed analysis of the EORTC QLQ C-30 questionnaire is summarized in Table 2. Lastly, all patients (100%) who responded to the questionnaire showed willingness to undergo similar procedure again if required from their present point of view.

Discussion The management of non-parasitic liver cysts has been debated since long time. However, there is still no consensus on the optimal management in these patients. As the symptoms are non-specic, their causal relationship to the

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246 Table 2 Results of EORTC QLQ C-30 questionnaire before surgery and at present time Before surgery Mean Global health status Functional scales Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Symptom scales Fatigue Nausea and vomiting Pain Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difculties 46 18 63 40 51 17 24 12 11 30 26 34 35 34 29 35 20 23 36 06 33 31 42 09 17 10 11 27 13 31 32 31 21 31 18 23 0.025 0.001 <0.001 0.145 0.04 0.006 0.20 0.44 1.00 72 53 54 79 68 22 35 27 23 31 85 73 68 81 84 16 13 24 19 22 0.002 0.004 0.003 0.16 0.001 44 SD 28 At present time Mean 69 SD 20 <0.001 p

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p \ 0.05 is considered signicant and in bold

presence of large liver cysts needs to be established beyond doubt in each case by excluding all other causes. Ignoring this fact leads to poor long-term results, as reported by Gigot et al. [6] in a multicenter trial. In the present study, each case was thoroughly evaluated and all other possible causes were ruled out. It remains a fact that there still is a danger of misdiagnosing a neoplastic cysts as non-parasitic liver cyst as reported by many studies [5, 21]. But due to the recent advancements in radiologic imaging techniques and maintaining high index of suspicion for neoplastic cysts during pre-operative evaluation we did not have any case of mistaken diagnosis on post-operative histopathology reports. Since its rst application in 1991 [22, 23] laparoscopic fenestration appears to be favored by most studies as a rstline treatment [8, 21, 24]. Most of these studies based their conclusions on the fact that the technique is safe with low post-operative morbidity and mortality, which is also supported by a mortality and morbidity of 0% in this cohort. Meticulous technique and routine use of omentoplasty may have reduced the post-operative morbidity in this study. The median operative time was 94 min (30195 min) which is similar to what is reported for open fenestration [15], but there was a reduced hospital stay in this study compared to reports of open procedures. No conversion to an open surgical approach was necessary, which is in line with the very low conversion rate (\5%) in

most of the recent studies [13, 24, 25]. Some studies reported high conversion rates (623%) in beginning era [20, 21, 26], mainly due to the initial learning curve of this procedure or a different selection of patients. However, the Achilles heel for this procedure is its recurrence rate which has been reported to be 44% for SLC [20] and 89% for PCLD [27] in long-term follow-up studies. In the present study after a median follow-up of 49 months (1997 months), the recurrence rates were 11.1% for SLC and 42.9% for PCLD, maybe because several techniques have been used to prevent recurrence including wide cyst de-roong, ablation of cyst lining and omentoplasty. It is known that in benign diseases, survival is not an issue and therefore the decision to accept an intervention cannot be based only on the usual post-operative outcomes like mortality, morbidity and recurrence. It is equally important to consider the patients subjective perceptions as a meaningful post-operative outcome, in order to assess the effect of the intervention on patients actual QoL. This modern concept of HR-QoL has become an important decision making tool for hepatobiliary surgeons in the last decade [18, 28, 29]. Nowadays the patient is considered as an active participant rather than a passive entity in the treatment and intervention process. To follow this modern concept different HR-QoL tools like the EORTC QLQ-C30 or the short-form 36 (SF 36) have been developed during the last 15 years in order to measure the effect of different therapeutic strategies on patients life, mainly in oncologic patients [17, 30]. No disease specic validated QoL tool for non-parasitic liver cysts exists, but we used QLQ-C30 as it encompasses all relevant symptoms of non-parasitic liver cysts and additionally represents a validated tool. There are few studies evaluating QoL in patients with non-parasitic liver cysts so far. Orozco et al. [16] reported good QoL after surgical treatment of non-parasitic liver cysts, whereas majority of these patients underwent laparoscopic fenestration. Gall et al. [15] found no signicant differences in QoL between any of the surgical procedures for non-parasitic liver cysts, and did not evaluate preoperative base line QoL and therefore, could not present individual treatment options. There have been many studies evaluating laparoscopic fenestration which showed significant reduction in severity of symptoms but most of them focused only on few symptoms [12, 31]. The present study is, to our knowledge, the rst to focus on a variety of different symptoms leading to a wide impression of patients subjective feelings after laparoscopic treatment of liver cysts. In a cohort of 31 patients, a highly signicant improvement in global health status could be demonstrated. Furthermore, this study showed a signicant improvement in ve out of six symptoms, including pain, nausea and

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247 11. Mazza OM, Fernandez DL, Pekolj J et al (2009) Management of nonparasitic hepatic cysts. J Am Coll Surg 209(6):733739 12. Loehe F, Globke B, Marnoto R et al (2010) Long-term results after surgical treatment of nonparasitic hepatic cysts. Am J Surg 200:2331 13. Fiamingo P, Tedeschi U, Veroux M et al (2003) Laparoscopic treatment of simple hepatic cysts and polycystic liver disease. Surg Endosc 17:623626 14. Troidl H, Kusche J, Vestweber KH, Eypasch E, Koeppen L, Bouillon B (1987) Quality of life: an important endpoint both in surgical practice and research. J Chronic Dis 40:523528 15. Gall TMH, Oniscu GC, Madhavan K, Parks RW, Garden OJ (2009) Surgical management and longterm follow-up of nonparasitic hepatic cysts. HPB 11:235241 16. Orozco H, Mercado MA, Hinojosa CA (2001) Evaluation of 20 years of experience and quality of life in patients surgically treated for liver cystic disease. Rev Gastroenterol Mex 66:179186 17. Aaronson NK, Ahmedzai S, Bergman B et al (1993) The European Organization for Research and Treatment of Cancer QLQC30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365376 18. Sajid MS, Iftikhar M, Rimple J, Baig MK (2008) Use of healthrelated quality of life tools in hepatobiliary surgery. Hepatobiliary Pancreat Dis Int 7:135137 19. Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, EORTC Quality of Life Group (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European Organisation for Research and Treatment of Cancer, Brussels 20. Gigot JF, Legrand M, Hubens G, de Canniere L, Wibin E, Deweer F et al (1996) Laparoscopic treatment of nonparasitic liver cysts: adequate selection of patients and surgical technique. World J Surg 20:556561 21. Gigot JF, Metairie S, Etienne J, Horsmans Y, Van Beers BE, Sempoux C et al (2001) The surgical management of congenital liver cysts: the need for a tailored approach with appropriate patient selection and proper surgical technique. Surg Endosc 15:357363 22. Zgraggen K, Metzger A, Klaiber C et al (1991) Cysts of the liver: treatment by laparoscopic surgery. Surg Endosc 5:224225 23. Paterson-Brown S, Garden OJ (1991) Laser-assisted laparoscopic excision of liver cyst. Br J Surg 78:1047 24. Regev A, Reddy KR, Berho M, Sleeman D, Levi JU, Livingstone AS et al (2001) Large cystic lesions of the liver in adults: a 15 year experience in a tertiary center. Am Coll Surg 193:3645 25. Zalaba Z, Tihanyi TF, Winternitz T, Nehez L, Flautner L (1999) The laparoscopic treatment of non-parasitic liver cysts. Five years experience. Acta Chir Hung 38:221223 26. Katkhouda N, Hurwitz M, Gugenheim J et al (1999) Laparoscopic management of benign solid and cystic lesions of the liver. Ann Surg 229:460466 27. Kabbej M, Sauvanet A, Chauveau D et al (1996) Laparoscopic fenestration in polycystic liver disease. Br J Surg 83:16971701 28. Poon RT, Fan ST, Yu WC, Lam BK, Chan FY, Wong J (2001) A prospective longitudinal study of quality of life after resection of hepatocellular carcinoma. Arch Surg 136:693699 29. Martin RC, Eid S, Scoggins CR, McMasters KM (2007) Healthrelated quality of life: return to baseline after major and minor liver resection. Surgery 142:676684 30. Sloan JA, Loprinzi CL, Kuross SA et al (1998) Randomized comparison of four tools measuring overall quality of life in patients with advanced cancer. J Clin Oncol 16:36623673 31. Van Keimpema L, Ruurda JP, Ernst MF et al (2008) Laparoscopic fenestration of liver cysts in polycystic liver disease results in a median volume reduction of 12.5%. J Gastrointest Surg 12:477482

vomiting, appetite loss, insomnia, and fatigue. The fact that 100% of the patients would undergo the same procedure again from their present point of view proves the positive effect of this procedure on patients satisfaction. The present study may be limited by the lack of disease specic QoL tools, but can reliably elucidate the impact of laparoscopic fenestration of liver cysts on a number of different functions and symptoms in these patients. Furthermore, it has to be admitted that the results of the QoL assessment may be biased by the retrospective character of this study and so, further prospective studies are urgently needed in order to conrm the present results. Large studies should also focus on the question if the recurrence rate has an impact on the QoL of patients with SLC compared to patients with PCLD since this cannot be answered by the present study due to the small study size. To sum up, the present study demonstrates that laparoscopic fenestration of non-parasitic liver cysts can be performed safely with good long-term results. Although disease recurrence remains a problem, the patients benet of this intervention is excellent in symptomatic patients. This is underlined by a highly signicant improvement in the overall QoL as well as in a reduction of major symptoms.
Conict of interest The authors certify that no actual or potential conict of interest exists in relation to this article.

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