Histopathologic Findings of Cholecystectomy Specimens in Patients Who Underwent Donor Hepatectomy for Living Donor Liver Transplantation S. Akbulut*, S. Karagul, _I. Ertugrul, C. Aydin, M. Yilmaz, and S. Yilmaz Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 44280 Malatya, Turkey
ABSTRACT Background. The aim of this study was to discuss the macroscopic and microscopic properties of gallbladder specimens obtained from living liver donors. Methods. The study retrospectively analyzed the clinical and histopathological data of 1088 donors who underwent living donor hepatectomy between March 2005 and September 2014 at Inonu University Faculty of Medicine, Liver Transplantation Center. Age, sex, macroscopic, and microscopic properties of the gallbladder (bladder length, diameter, content, and histopathological properties) were recorded by 2 researchers. Results. A total of 1009 donors aged 17 to 66 years (31.1 9.5) met the inclusion criteria, whereas 79 donors were excluded due to missing data. In total, 587 donors were male (30.5 9.1 years [16e63 years]) and 422 were female (31.8 9.8 years [18e66 years]). Preoperative tests revealed Gilbert syndrome in 3 subjects, whereas other donors’ biochemical tests were within normal ranges. The macroscopic examination of gallbladders revealed mean gallbladder wall thickness, length, and width of 1.82 0.8 mm (1e10 mm), 72 11.4 mm (40e120 mm), and 52.5 14 mm (15e90 mm), respectively. The microscopic gallbladder examination showed that 740 donors had a normal gallbladder, 193 had chronic cholecystitis (1 donor had antral metaplasia and 1 had intestinal metaplasia), 40 had cholesterolosis (1 donor had both tubular adenoma and intestinal metaplasia), 15 had minimal chronic cholecystitis (1 donor had pyloric metaplasia), 14 had cholelithiasis, 2 had adenomyosis, 2 had muscular hypertrophy, 1 had papillary hyperplasia, 1 had microdiverticulitis, and 1 had mucosal lymphatic ectasia. Conclusion. The results of this study reflect the actual gallbladder pathologies that can be detected in healthy people. Clearer conclusions can be reached about the epidemiological data on gallbladder as the number of living liver donors increases in the future.
S
INCE the first successful liver transplantation by Starzl et al in 1967, liver transplantation has become the standard therapy for many liver disorders, mainly chronic liver disease [1e3]. Although organ requirement in the majority of liver transplantations in Western countries is met by cadaveric donors, in many Asian countries, including Turkey, it is mainly dependent on living donors [2,3]. Due to the location of the gallbladder, cholecystectomy is routinely performed during hepatectomy in all living donor liver transplantations (LDLTs). It is the general approach that all gallbladder specimens be histologically examined even when no macroscopic pathology is observed [4]. The aim of this study was to discuss the
macroscopic and microscopic properties of gallbladder specimens obtained from living liver donors. MATERIALS AND METHOD A total of 1088 living donor hepatectomy operations were performed to be used in LDLT between March 2005 and September 2014 at Inonu University Faculty of Medicine, Transplantation *Address correspondence to Sami Akbulut, MD, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey. E-mail: akbulutsami@gmail. com
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.059
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1466
Transplantation Proceedings, 47, 1466e1468 (2015)
HISTOPATHOLOGICAL FINDINGS AFTER HEPATECTOMY Center. The suitability of these donor candidates was assessed by a 5-step algorithm with international validity [5,6]. Blood tests and pathology reports were accessed in 1009 of 1088 patients who underwent living donor hepatectomy, whereas medical data for the remaining 79 patients were lacking. Age, sex of the patients, and length (mm), diameter (mm), wall thickness (mm), and microscopic properties of the gallbladder were retrospectively analyzed. Two independent researchers formed 2 separate excel files containing medical data of the patients, and both files were compared to confirm the validity of the study data. All pathology specimens were examined by pathologists from our hospital’s pathology department who were experienced at hepatobiliary system pathology.
RESULTS
This study included a total of 1009 living liver donors aged 16 to 66 years (31.1 9.5 years). Of the study population, 587 (58.2%) donors were male [30.5 9.1 years (16e63 years)] and 422 (41.8%) were female [31.8 9.8 years (18e66 years)]. Preoperative tests revealed Gilbert syndrome in 3 subjects, whereas other donors’ biochemical tests were within normal ranges. The macroscopic examination of gallbladders revealed mean gallbladder wall thickness, length, and width of 1.82 0.8 mm (1e10 mm), 72 11.4 mm (40e120 mm), and 52.5 14 mm (15e90 mm), respectively. Microscopic examination revealed that 740 (73.3%) donors had a normal gallbladder, 191 (18.9%) had chronic cholecystitis, 39 (3.86%) had cholesterolosis, 14 (1.38%) had minimal chronic cholecystitis, 14 (1.38%) had cholelithiasis, 2 had adenomyosis, 2 had muscular hypertrophy, 1 had papillary hyperplasia, 1 had microdiverticulitis, 1 had mucosal lymphatic ectasia, 1 had minimal chronic cholecystitis plus pyloric metaplasia, 1 had cholesterolosis plus tubular adenoma plus intestinal metaplasia, 1 had chronic cholecystitis plus antral metaplasia, and 1 had chronic cholecystitis plus intestinal metaplasia. The clinic and histopathologic features of 1009 living liver donors were summarized in Table 1. DISCUSSION
Gallbladder diseases are among the most common gastrointestinal disorders in developed societies. The most common gallbladder pathology is gallbladder stone disease, with an incidence of 10% to 25% [7]. Depending on the size and number of bile stones, various inflammatory and histopathological changes may occur in the gallbladder. Ultrasonography is the first and most commonly employed radiological procedure to assess the structure of the gallbladder in both epidemiological surveys and symptomatic individuals [7]. Many pathologies related to gallbladder may be incidentally detected at radiological studies performed for other indications. However, all noninvasive radiological studies, whether performed for epidemiological surveys in healthy persons or for diagnostic purposes in symptomatic subjects, provide information only about major anatomic properties of the gallbladder. In other words, radiological studies fall short in providing precise pathological information about the macroscopic and microscopic structure of gallbladders of healthy persons. The histopathological properties of specimens obtained from the cases undergoing cholecystectomy for gallbladder
1467 Table 1. Clinic and Histopathologic Characteristics of 1009 Patients Who Underwent Living Liver Hepatectomy Patients Characteristics
Results
Patients, N 1009 Age, y 31 9 (16e63) Gender Male 587 (58.2%) Female 422 (41.8%) Macroscopic features of the gallbladder Length (mm) 72 11.4 (40e120) Diameter (mm) 52.5 14 (15e90) Wall thickness (mm) 1.82 0.8 (1e10) Histopathologic characteristics Normal 740 (73.3%) Chronic cholecystitis 191 (18.9%) Cholesterolosis 39 (3.86%) Minimal chronic cholecystitis 14 (1.38%) Cholelithiasis 14 (1.38%) Adenomyomatosis 2 Muscle hypertrophy 2 Papillary hyperplasia 1 Microdiverticulitis 1 Mucosal lymphatic ectasia 1 Minimal chronic cholecystitis þ 1 pyloric metaplasia Cholesterolosis þ tubular adenoma þ 1 intestinal metaplasia Chronic cholecystitis þ antral metaplasia 1 Chronic cholecystitis þ intestinal metaplasia 1
pathologies (stone, tumor, polyp, etc.) are usually different from those of the gallbladder specimens obtained from healthy persons. That is, it is very erroneous to conclude about healthy population’s gallbladders by referencing the articles about gallbladders in the literature. The only exception to that is the gallbladder specimens obtained from subjects undergoing living donor hepatectomy, because living donor candidates undergo some evaluation steps before being operated. Hence, donor candidates possess almost all characteristics of a healthy population. In other words, the histopathological properties of gallbladder specimens obtained at cholecystectomy performed as a routine part of operation in living donors may directly reflect those of a healthy human population. There are no literature studies to date covering the histopathological and macroscopic properties of gallbladders obtained from liver donors. Thus, this study will be the first of its kind. After all, we would like to raise the awareness of this subject. In many countries, mainly Asian ones, living donors constitute a major part of liver donor pool; all these donors routinely undergo cholecystectomy during hepatectomy. The obtained gallbladder specimen should routinely be evaluated histopathologically and its pathology report carefully reviewed. This is of utmost importance for 3 reasons: first, to reveal the gallbladder structure and anatomy in healthy persons to be used in epidemiological studies; second, to demonstrate the importance of geographical variations (diet, environmental factors etc.) altering gallbladder structure in gallbladder pathologies; and third, to detect
1468
precancerous lesions and frank cancers incidentally, although these are rare. In the 4 cases presented in this study we detected intestinal metaplasia (2 cases), pyloric metaplasia (1 case), and antral metaplasia (1 case). Previous studies have shown that such types of metaplasias develop in response to irritation occurring on the basis of bile stone and cholecystitis. Some studies have advocated that antral and intestinal metaplasia, particularly at young ages, are the precursor lesions for gallbladder dysplasia [8,9]. In conclusion, this is the first study in the literature with respect to its study population. All gallbladder specimens, whether obtained from diseased or healthy persons, should be histopathologically examined in detail and clinicians should be informed about the precursor lesions of cancer. REFERENCES [1] Aydin C, Ince V, Otan E, Akbulut S, Koc C, Kayaalp C, et al. Storage of allogeneic vascular grafts: experience from a high-volume liver transplant institute. Int Surg 2013;98:170e4. [2] Yilmaz M, Unal B, Isik B, Ozgor D, Piskin T, Ersan V, et al. Can an extended right lobe be harvested from a donor with Gilbert’s
AKBULUT, KARAGUL, ERTUGRUL ET AL syndrome for living-donor liver transplantation? Case report. Transplant Proc 2012;44:1640e3. [3] Yilmaz S, Kayaalp C, Ara C, Yilmaz M, Isik B, Aydin C, et al. Single-center analysis of the first 304 living-donor liver transplantations in 3 years. Hepatogastroenterology 2013;60: 1105e9. [4] Agarwal AK, Kalayarasan R, Singh S, Javed A, Sakhuja P. All cholecystectomy specimens must be sent for histopathology to detect inapparent gallbladder cancer. HPB (Oxford) 2012;14: 269e73. [5] Valentín-Gamazo C, Malagó M, Karliova M, Lutz JT, Frilling A, Nadalin S, et al. Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center. Liver Transpl 2004;10:1087e96. [6] Araújo CC, Balbi E, Pacheco-Moreira LF, Enne M, Alves J, Fernandes R, et al. Evaluation of living donor liver transplantation: causes for exclusion. Transplant Proc 2010;42: 424e5. [7] Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver 2012;6:172e87. [8] Mukhopadhyay S, Landas SK. Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med 2005;129:386e90. [9] Kaur A, Dubey VK, Mehta KS. Gallbladder mucosal changes associated with chronic cholecystitis and relationship with carcinoma gallbladder. JK Science 2012;14:89e92.
ABSTRACT Background. The aim of this study was to discuss the macroscopic and microscopic properties of gallbladder specimens obtained from living liver donors. Methods. The study retrospectively analyzed the clinical and histopathological data of 1088 donors who underwent living donor hepatectomy between March 2005 and September 2014 at Inonu University Faculty of Medicine, Liver Transplantation Center. Age, sex, macroscopic, and microscopic properties of the gallbladder (bladder length, diameter, content, and histopathological properties) were recorded by 2 researchers. Results. A total of 1009 donors aged 17 to 66 years (31.1 9.5) met the inclusion criteria, whereas 79 donors were excluded due to missing data. In total, 587 donors were male (30.5 9.1 years [16e63 years]) and 422 were female (31.8 9.8 years [18e66 years]). Preoperative tests revealed Gilbert syndrome in 3 subjects, whereas other donors’ biochemical tests were within normal ranges. The macroscopic examination of gallbladders revealed mean gallbladder wall thickness, length, and width of 1.82 0.8 mm (1e10 mm), 72 11.4 mm (40e120 mm), and 52.5 14 mm (15e90 mm), respectively. The microscopic gallbladder examination showed that 740 donors had a normal gallbladder, 193 had chronic cholecystitis (1 donor had antral metaplasia and 1 had intestinal metaplasia), 40 had cholesterolosis (1 donor had both tubular adenoma and intestinal metaplasia), 15 had minimal chronic cholecystitis (1 donor had pyloric metaplasia), 14 had cholelithiasis, 2 had adenomyosis, 2 had muscular hypertrophy, 1 had papillary hyperplasia, 1 had microdiverticulitis, and 1 had mucosal lymphatic ectasia. Conclusion. The results of this study reflect the actual gallbladder pathologies that can be detected in healthy people. Clearer conclusions can be reached about the epidemiological data on gallbladder as the number of living liver donors increases in the future.
S
INCE the first successful liver transplantation by Starzl et al in 1967, liver transplantation has become the standard therapy for many liver disorders, mainly chronic liver disease [1e3]. Although organ requirement in the majority of liver transplantations in Western countries is met by cadaveric donors, in many Asian countries, including Turkey, it is mainly dependent on living donors [2,3]. Due to the location of the gallbladder, cholecystectomy is routinely performed during hepatectomy in all living donor liver transplantations (LDLTs). It is the general approach that all gallbladder specimens be histologically examined even when no macroscopic pathology is observed [4]. The aim of this study was to discuss the
macroscopic and microscopic properties of gallbladder specimens obtained from living liver donors. MATERIALS AND METHOD A total of 1088 living donor hepatectomy operations were performed to be used in LDLT between March 2005 and September 2014 at Inonu University Faculty of Medicine, Transplantation *Address correspondence to Sami Akbulut, MD, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey. E-mail: akbulutsami@gmail. com
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.059
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1466
Transplantation Proceedings, 47, 1466e1468 (2015)
HISTOPATHOLOGICAL FINDINGS AFTER HEPATECTOMY Center. The suitability of these donor candidates was assessed by a 5-step algorithm with international validity [5,6]. Blood tests and pathology reports were accessed in 1009 of 1088 patients who underwent living donor hepatectomy, whereas medical data for the remaining 79 patients were lacking. Age, sex of the patients, and length (mm), diameter (mm), wall thickness (mm), and microscopic properties of the gallbladder were retrospectively analyzed. Two independent researchers formed 2 separate excel files containing medical data of the patients, and both files were compared to confirm the validity of the study data. All pathology specimens were examined by pathologists from our hospital’s pathology department who were experienced at hepatobiliary system pathology.
RESULTS
This study included a total of 1009 living liver donors aged 16 to 66 years (31.1 9.5 years). Of the study population, 587 (58.2%) donors were male [30.5 9.1 years (16e63 years)] and 422 (41.8%) were female [31.8 9.8 years (18e66 years)]. Preoperative tests revealed Gilbert syndrome in 3 subjects, whereas other donors’ biochemical tests were within normal ranges. The macroscopic examination of gallbladders revealed mean gallbladder wall thickness, length, and width of 1.82 0.8 mm (1e10 mm), 72 11.4 mm (40e120 mm), and 52.5 14 mm (15e90 mm), respectively. Microscopic examination revealed that 740 (73.3%) donors had a normal gallbladder, 191 (18.9%) had chronic cholecystitis, 39 (3.86%) had cholesterolosis, 14 (1.38%) had minimal chronic cholecystitis, 14 (1.38%) had cholelithiasis, 2 had adenomyosis, 2 had muscular hypertrophy, 1 had papillary hyperplasia, 1 had microdiverticulitis, 1 had mucosal lymphatic ectasia, 1 had minimal chronic cholecystitis plus pyloric metaplasia, 1 had cholesterolosis plus tubular adenoma plus intestinal metaplasia, 1 had chronic cholecystitis plus antral metaplasia, and 1 had chronic cholecystitis plus intestinal metaplasia. The clinic and histopathologic features of 1009 living liver donors were summarized in Table 1. DISCUSSION
Gallbladder diseases are among the most common gastrointestinal disorders in developed societies. The most common gallbladder pathology is gallbladder stone disease, with an incidence of 10% to 25% [7]. Depending on the size and number of bile stones, various inflammatory and histopathological changes may occur in the gallbladder. Ultrasonography is the first and most commonly employed radiological procedure to assess the structure of the gallbladder in both epidemiological surveys and symptomatic individuals [7]. Many pathologies related to gallbladder may be incidentally detected at radiological studies performed for other indications. However, all noninvasive radiological studies, whether performed for epidemiological surveys in healthy persons or for diagnostic purposes in symptomatic subjects, provide information only about major anatomic properties of the gallbladder. In other words, radiological studies fall short in providing precise pathological information about the macroscopic and microscopic structure of gallbladders of healthy persons. The histopathological properties of specimens obtained from the cases undergoing cholecystectomy for gallbladder
1467 Table 1. Clinic and Histopathologic Characteristics of 1009 Patients Who Underwent Living Liver Hepatectomy Patients Characteristics
Results
Patients, N 1009 Age, y 31 9 (16e63) Gender Male 587 (58.2%) Female 422 (41.8%) Macroscopic features of the gallbladder Length (mm) 72 11.4 (40e120) Diameter (mm) 52.5 14 (15e90) Wall thickness (mm) 1.82 0.8 (1e10) Histopathologic characteristics Normal 740 (73.3%) Chronic cholecystitis 191 (18.9%) Cholesterolosis 39 (3.86%) Minimal chronic cholecystitis 14 (1.38%) Cholelithiasis 14 (1.38%) Adenomyomatosis 2 Muscle hypertrophy 2 Papillary hyperplasia 1 Microdiverticulitis 1 Mucosal lymphatic ectasia 1 Minimal chronic cholecystitis þ 1 pyloric metaplasia Cholesterolosis þ tubular adenoma þ 1 intestinal metaplasia Chronic cholecystitis þ antral metaplasia 1 Chronic cholecystitis þ intestinal metaplasia 1
pathologies (stone, tumor, polyp, etc.) are usually different from those of the gallbladder specimens obtained from healthy persons. That is, it is very erroneous to conclude about healthy population’s gallbladders by referencing the articles about gallbladders in the literature. The only exception to that is the gallbladder specimens obtained from subjects undergoing living donor hepatectomy, because living donor candidates undergo some evaluation steps before being operated. Hence, donor candidates possess almost all characteristics of a healthy population. In other words, the histopathological properties of gallbladder specimens obtained at cholecystectomy performed as a routine part of operation in living donors may directly reflect those of a healthy human population. There are no literature studies to date covering the histopathological and macroscopic properties of gallbladders obtained from liver donors. Thus, this study will be the first of its kind. After all, we would like to raise the awareness of this subject. In many countries, mainly Asian ones, living donors constitute a major part of liver donor pool; all these donors routinely undergo cholecystectomy during hepatectomy. The obtained gallbladder specimen should routinely be evaluated histopathologically and its pathology report carefully reviewed. This is of utmost importance for 3 reasons: first, to reveal the gallbladder structure and anatomy in healthy persons to be used in epidemiological studies; second, to demonstrate the importance of geographical variations (diet, environmental factors etc.) altering gallbladder structure in gallbladder pathologies; and third, to detect
1468
precancerous lesions and frank cancers incidentally, although these are rare. In the 4 cases presented in this study we detected intestinal metaplasia (2 cases), pyloric metaplasia (1 case), and antral metaplasia (1 case). Previous studies have shown that such types of metaplasias develop in response to irritation occurring on the basis of bile stone and cholecystitis. Some studies have advocated that antral and intestinal metaplasia, particularly at young ages, are the precursor lesions for gallbladder dysplasia [8,9]. In conclusion, this is the first study in the literature with respect to its study population. All gallbladder specimens, whether obtained from diseased or healthy persons, should be histopathologically examined in detail and clinicians should be informed about the precursor lesions of cancer. REFERENCES [1] Aydin C, Ince V, Otan E, Akbulut S, Koc C, Kayaalp C, et al. Storage of allogeneic vascular grafts: experience from a high-volume liver transplant institute. Int Surg 2013;98:170e4. [2] Yilmaz M, Unal B, Isik B, Ozgor D, Piskin T, Ersan V, et al. Can an extended right lobe be harvested from a donor with Gilbert’s
AKBULUT, KARAGUL, ERTUGRUL ET AL syndrome for living-donor liver transplantation? Case report. Transplant Proc 2012;44:1640e3. [3] Yilmaz S, Kayaalp C, Ara C, Yilmaz M, Isik B, Aydin C, et al. Single-center analysis of the first 304 living-donor liver transplantations in 3 years. Hepatogastroenterology 2013;60: 1105e9. [4] Agarwal AK, Kalayarasan R, Singh S, Javed A, Sakhuja P. All cholecystectomy specimens must be sent for histopathology to detect inapparent gallbladder cancer. HPB (Oxford) 2012;14: 269e73. [5] Valentín-Gamazo C, Malagó M, Karliova M, Lutz JT, Frilling A, Nadalin S, et al. Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center. Liver Transpl 2004;10:1087e96. [6] Araújo CC, Balbi E, Pacheco-Moreira LF, Enne M, Alves J, Fernandes R, et al. Evaluation of living donor liver transplantation: causes for exclusion. Transplant Proc 2010;42: 424e5. [7] Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver 2012;6:172e87. [8] Mukhopadhyay S, Landas SK. Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med 2005;129:386e90. [9] Kaur A, Dubey VK, Mehta KS. Gallbladder mucosal changes associated with chronic cholecystitis and relationship with carcinoma gallbladder. JK Science 2012;14:89e92.
