|Year : 2019 | Volume
| Issue : 2 | Page : 63-68
Outcome of combined complete excision of the caudate lobe with partial hepatectomy for treatment of resectable Klatskin tumors
Bilal O Al-Jiffry1, Mohamed Al Saeed1, Majed Al-Mourgi1, Alaa E Younes1, Samir Badr2, Tamer Abdel-Rahman3, Ayman Attalla4, Abdullah Al-Sawat1, Mohamed Hatem5, Mahmoud El-Meteini6, Ali B Al-Jiffry7
1 Department of Surgery, Taif University, Taif, Saudi Arabia
2 Department of Surgery, Taif University, Taif, Saudi Arabia; Department of Surgery, General Organization of Teaching Hospitals and Institutes, Damanhur, Egypt
3 Department of Surgery, Taif University, Taif, Saudi Arabia; Department of Surgery, General Organization of Teaching Hospitals and Institutes, Benha, Egypt
4 Department of Family Medicine, Taif University, Taif, Saudi Arabia
5 Department of Surgery, Taif University, Taif, Saudi Arabia; Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
6 Department of Hepatobiliary Surgery, Ain Shams Center for Organ Transplant, Faculty of Medicine, Ain Shams University, Cairo, Egypt
7 Resident in Anesthesia Department, Ta'if, Saudi Arabia
|Date of Web Publication||6-Sep-2019|
Alaa E Younes
Department of Surgery, Taif University, Taif
Source of Support: None, Conflict of Interest: None
Background and Aim of the Work: Combination of partial hepatectomy with complete excision of the caudate lobe was found to improve the outcome of resectable Klatskin tumors. In this prospective multicenter study, the outcome of these combined resections would be evaluated.
Patients and Methods: This prospective study enrolled 72 patients with resectable Klatskin tumors. The study was conducted in Taif tertiary hospital and Ain Shams University Hospitals from January 2008 to December 2014. All patients underwent partial hepatectomy with complete excision of the caudate lobe after preoperative biliary drainage. The primary outcome was the resection margin (positive or negative), postoperative complications, and patient survival. Other outcomes included; the mean operative time, mean amount of blood loss, and prognostic factors correlated with survival.
Results: The number of patients underwent combined resection were 72 patients, 49 males and 23 females with mean age of 58.3 ± 14.2 years. Mean operative time was 243 ± 57 min and the mean blood loss was 896 ± 211 ml. The recorded postoperative complications included; bile leak in 16.7%, wound infection in 15.3%, pleural effusion in 12.5%, liver failure in 4.2%, and liver abscess in 4.2%. Recorded hospital mortality was 5.6%. The resection margin was negative (R0) in 51/72 patients (70.8%). The overall mean survival during the follow-up was 48 ± 10.2 months. The estimated overall 5-year survival rate was 37.5% increased to 50.1% in R0 patients, and it was 4.8% when the margin was positive. There was a significant positive correlation between the patient survival and the negativity of the resection margin, and a negative significant correlation with the pretreatment level of carcinoembryonic antigen. Age, gender, Bismuth classification, and pretreatment level of carbohydrate antigen 19.9 had insignificant correlation with the survival.
Conclusion: The excision of the caudate lobe with extended hepatic resection by the experienced hepatobiliary surgeon in properly selected patients survival has been proved to be safe and effective.
Keywords: Caudate lobe, Klatskin tumors, partial hepatic resection, resectable
|How to cite this article:|
Al-Jiffry BO, Al Saeed M, Al-Mourgi M, Younes AE, Badr S, Abdel-Rahman T, Attalla A, Al-Sawat A, Hatem M, El-Meteini M, Al-Jiffry AB. Outcome of combined complete excision of the caudate lobe with partial hepatectomy for treatment of resectable Klatskin tumors. Saudi Surg J 2019;7:63-8
|How to cite this URL:|
Al-Jiffry BO, Al Saeed M, Al-Mourgi M, Younes AE, Badr S, Abdel-Rahman T, Attalla A, Al-Sawat A, Hatem M, El-Meteini M, Al-Jiffry AB. Outcome of combined complete excision of the caudate lobe with partial hepatectomy for treatment of resectable Klatskin tumors. Saudi Surg J [serial online] 2019 [cited 2019 Nov 13];7:63-8. Available from: http://www.saudisurgj.org/text.asp?2019/7/2/63/266215
| Introduction|| |
Cholangiocarcinomas are the second most frequent primary hepatic malignancy, and hilar cholangiocarcinoma (Klatskin tumor) is the most common type accounting for more than 60% of cases. The tumors are found in the hepatic duct confluence which is communicated with bile ducts of the caudate lobe, so, most of Klatskin tumors have microscopic invasion to this lobe.,,, Due to the anatomical complexity of the hepatic hilum, this tumor is associated with early lymphatic metastasis and vascular invasion with frequent anterior and posterior ductal infiltration. Numerous studies found that to achieve margin negative resection and better survival in patients with Klatskin tumors, caudate lobectomy with partial resection of the liver has been advocated.,,,,,, Investigators found that this procedure improved the outcome and did not increase postoperative mortality or morbidity.,,,,,,,, In this prospective multicenter study, the outcome of these combined resections would be evaluated.
| Patients and Methods|| |
This prospective multicenter study enrolled 72 patients with resectable Klatskin tumors. The study was conducted in Taif tertiary hospital and Ain Shams University Hospitals from January 2008 to December 2014 after approval of the concerned ethical boards and taking informed written consent from the participants. All the enrolled patients presented with jaundice and they were initially assessed biochemically and by abdominal ultrasound. Biochemical assessment included liver functions and other organ profiles in addition to the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. When the tumor was suspected, computed tomography (CT) was added; however, magnetic resonance imaging (MRI) and magnetic resonance cholangiography were the cornerstones in this study to evaluate tumor status, plan treatment, to assess the potential remaining liver volume before extended resection, and to determine the Bismuth–Corlette tumor stage. Endoscopic retrograde cholangiopancreatography (ERCP) was done for all patients, and the diagnosis was confirmed by combined brush cytology and clamp biopsy. Laparoscopy was used for the assessment of liver and peritoneum in all candidates. To relieve jaundice, preoperative biliary drainage was performed either by ERCP or/and percutaneous transhepatic cholangiography (PTC) for all patients with bilirubin level more than 5 mg/dl. All patients received neo-adjuvant radiotherapy to minimize the risk of tumor implantation. The caudate lobe was completely excised in all patients in addition to partial hepatectomy. The extent of partial resection was determined according to the Bismuth–Corlette type; for Type I, II, and IIIA, the operation was right trisectionectomy with complete excision of the caudate lobe, and for patients with Type IIIB left trisectionectomy with complete excision of the caudate lobe was done. Nontouch en bloc resection was done for all patients. Exclusion criteria included preoperative or operative presence of the following: Bismuth Type IV patients, locally advanced tumor with bilateral extension to secondary biliary radicles, involvement of the contralateral portal vein branch, proximal main portal vein bifurcation encasement, occlusion of the main portal vein, contralateral sectional bile duct extension with atrophy of one hepatic lobe, and patients who have distant metastases, including metastases to lymph node groups beyond the hepatoduodenal ligament. The postoperative discovery of any of these findings in the operative specimen did not exclude the candidate from the study and considered as margin positive case.
All patients received postoperative adjuvant radiotherapy; however, in the past 3 years, chemotherapy was added to radiotherapy (platinum with gemcitabine).
The primary outcome was the resection margin (negative; R0 or positive; R1, microscopical invasion, and R2, macroscopical invasion), postoperative complications, and patient survival. Other outcomes included; the mean operative time, mean amount of blood loss, and prognostic factors correlated with survival. The follow-up continued to December 2017 (Range 35–120 months), and the mean postoperative follow-up was 75.8 ± 16.4 months.
SPSS program, version 22.0 (SPSS Inc., Chicago, IL, USA) was used. The data were expressed in number and percentage (qualitative) whereas, the quantitative data were expressed as means ± standard deviation. The significance between 2 means was tested by Student's t-test. The Chi-square test and Fisher's exact (FE) tests were used to differentiate between two groups. P < 0.05 was considered as statistically significant. The log-rank test was used to determine the actuarial 5-year survival rate of R0 and R1–2 and was presented graphically with the Kaplan–Meier curves. Cox regression survival analysis was used to detect the factors correlated with survival.
| Results|| |
[Table 1] shows demographic data, patient presentations, patient distribution of according to Bismuth–Corlette classification, and preoperative mean tumor marker level.
The recorded complications included; bile leak in 12/72 cases (16.7%), wound infection in 11/72 (15.3%), pleural effusion in 9/72 patients (12.5%), liver failure in 3/72 cases (4.2%), and liver abscess in 3/72 (4.2%). Recorded hospital mortality was 4/72 patients (5.6%). The resection margin was negative (R0) in 51/72 patients (70.8%). The mean survival of patients with negative resection margin was 53 ± 12.2 months and 23 ± 5.1 months for positive resection margin patients. The estimated 5-year survival rate was 50.1% when the resection margin was negative, and it was 4.8% when the margin was positive [Figure 1].
|Figure 1: Cumulative survival curves according to histologic margin clearance|
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[Table 2] shows the results of Cox regression univariate and multivariate analysis where there was a significant positive correlation between the patient survival and the negativity of the resection margin, and a negative significant correlation with the pretreatment level of CEA. Age, gender, Bismuth classification, and pretreatment level of CA19.9 had insignificant correlation with the survival. [Figure 1] shows cumulative survival curves according to histologic margin clearance, [Figure 2] shows the right trisectionectomy. [Figure 3] shows the operative specimen of en bloc right trisectionectomy.
|Table 2: Cox regression univariate and multivariate analysis of prognostic factors correlated with survival|
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|Figure 2: Right trisectionectomy, (a) transaction of the distal part of the bile duct, (b) Biopsy of the distal part of the divided bile duct, (c) division and closure of the right hepatic vein with vascular stapler, (d) hepaticojejunostomy with Roux loop|
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|Figure 3: Right trisectionectomy, yellow arrow points to the right hepatic lobe, green arrow points to the groove of inferior vena cava, and blue arrow points to caudate lobe|
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| Discussion|| |
Cholangiocarcinoma is classified according to the International Classification of Diseases for Oncology to intrahepatic and extrahepatic to hilar, proximal, or central extrahepatic cholangiocarcinoma, the later was first described by Gerald Klatskin in 1965., Klatskin tumors are rare in Western countries, but it is more commonly seen in Asia, and most hilar cholangiocarcinomas are diagnosed at an advanced stage.,,
Klatskin tumors are more common in females than males with a peak incidence around 60 years.,, In the current study, male incidence was higher; however, the mean age was coincident with the findings of the previous studies.
The most common presentation of hilar cholangiocarcinoma is painless jaundice, and other presentations include, abdominal pain, weight loss, fatigue, itching, and nausea.,,,, Various studies found that biliary stones and inflammatory bowel disease are common comorbidities with the disease. Qu et al. and Matsumoto et al. verified in their study that hepatitis B and C virus infection is a risk factor for the development of cholangiocarcinoma., Our findings were similar and supported that of the previous studies.
The difficulty in preoperative staging of Klatskin tumor is related to the complexity of hilar anatomy and the proximity of the small-sized tumor to major vessels; however, acceptable results can be obtained if multidisciplinary diagnostic modalities are considered., Initial abdominal US is usually done which is sensitive for detecting biliary duct dilatation, but less sensitive in localizing the exact site of obstruction, unable to determine the extent of tumor involvement, and has relatively poor sensitivity in identifying lymph node, liver, and peritoneal metastases. CT scan can predict respectability of Klatskin tumor in more than 80% of cases especially in assessing ductal, portal vein, and hepatic artery involvement but not accurately assesses lymph node involvement and peritoneal nodules., MRI and magnetic resonance cholangiopancreatography are considered by most of the authors to be the gold standard for the assessment of extrahepatic cholangiocarcinoma and to evaluate tumor status., MRI scan can judge location and extent of the tumors on the basis of the Bismuth–Corlette classification with a sensitivity of 94% and a specificity of 100%. Researchers documented that the combination of magnetic resonance and CT will raise the diagnostic accuracy.,,, Unfortunately, both procedures do not allow biopsy, biliary drainage, and stent insertion therefore direct cholangiography is still necessary. ERCP is preferred by most of the surgeons than PTC., Preoperative assessment of our patients was in agreement with the findings of the previous studies.
Serum tumor markers, specifically, CA19-9 and CEA have been reported to be valuable for the diagnosis and monitoring of hilar cholangiocarcinoma with sensitivity and specificity reaching up to 89% and 86% respectively when combined with other diagnostic modalities.,, In the majority of publications, the preoperative marker levels correlate with the tumor stage, and it has been proved that, a preoperative serum levels of CA19-9 more than 1000 U/ml and CEA more than 14.4 ng/ml showed a significantly poor resectability rate and survival than patients with lower levels., Loosen et al. reported in their study that CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma. In the present study the preoperative the levels of both tumor markers correlated with the patient survival in univariate analysis; however, only CEA have been proved to be a significant survival predictor in multivariate analysis, a finding that supports that of the previous study.
Various staging systems for hilar cholangiocarcinoma are currently used, and the Bismuth–Corlette system provides a preoperative assessment of local tumor spread and is used to determine the extent of resection. In our study, the extent of resection depended on Bismuth classification, even though, we found no statistically significant correlation between the patient stage and the survival. In agreement with the findings of the current study; Jarnagin and Winston affirmed in their review article that Bismuth–Corlette classification stratifies patients based on the extent of biliary involvement by tumor only concluding that most of the investigators found no correlation with survival and the current staging systems., Blechacz emphasized in their study that the majority of the staging systems have proven to be insufficient for stratifying patients in alignment with therapeutic options and they also lack prognostic accuracy and/or external validation. However, the Memorial Sloan Kettering Cancer Center (MSKCC) classification details local tumor extent while also assessing portal vein involvement and hepatic lobar atrophy.,,, In the current study, we considered the criteria proposed by Jarnagin and Blumgart in MSKCC to exclude irresectable cases.
The majority of patients with peri-hilar cholangiocarcinomas present with obstructive jaundice carrying the risk of cholangitis and liver failure which is considered to be the most common cause of death. Tang et al. reported in their meta-analysis that preoperative biliary drainage reduces jaundice and bacterial translocation, improves liver function and nutritional status, and enhances the ability of the liver to regenerate postoperatively. In addition, some authors recommended neoadjuvant protocols to allow tumor downstaging, improve tumor resectability, and the risk of local recurrence and seeding of the tumor cells. In the current study, we adhered to the previous recommendations in patient management.
Dinant et al. reported that the results of different studies found that the incidence of caudate bile duct invasion by hilar cholangiocarcinoma was recorded in more than 60% of cases (range from 31% to 98%) and the concluded that concomitant complete excision of the caudate lobe for patients with hilar cholangiocarcinoma did not lead to increased morbidity or mortality. in agreement with the previous study Japanese surgeons demonstrated a survival benefit of a more aggressive approach including extended liver resection and concomitant complete excision of the caudate lobe with the removal of any involved regional lymph nodes proximal the hepatoduodenal.,,
Similar results were obtained by Soares et al. who reported R0 in 60%–80% of cases treated by aggressive hilar and hepatic resection with complete caudate lobe resection. Five-year survival obtained from studies included patients whose surgery did not conform to today's radical principles ranged from 12.5% to 32.8%;,, however, the results from patients who were exclusively radically operated reported in the newer studies yielded 5-year survival rates of 35%–72%.,,,,, Ogura et al. in their studies found that the increased rate of margin-negative resections was the most significant independent prognostic factor. Similar Findings has repeatedly been reported in the literature.,,,, The results of the present study support the finding in the previous studies where over 50% 5-year survival rate was recorded in the R0 patients of the current study and a positive significant correlation between the margin negativity and survival was verified. Therefore, the cumulative results of the current and previous studies confirmed the superiority of this radical procedure to achieve a higher rate of R0 resections and improved survival.
Although the oncological targets are best achieved in liver transplantation by means of removing the entire bile duct system, the no-touch technique and wide safety margins, a 5-year survival (17%–36%) is not better than resection and even inferior than that of aggressive modern resections.,
Dinant et al. recorded in their study an overall postoperative morbidity rate of 59% and they emphasized that their results were comparable to that found in recent series which adopted the modern aggressive surgical approach in the treatment of Klatskin tumors. The results of the current study were concordant with the previous study and similar researches. When the previous results are compared to that recorded in studies included patients whose surgeries were less radical, a slight increase in postoperative morbidity has occurred.,,
| Conclusion|| |
The excision of the caudate lobe with extended hepatic resection by experienced hepatobiliary surgeon in properly selected patients survival has been proved to be safe and effective.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]