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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 7  |  Page : 1002-1007

Is there any relationship between clinical parameters and histopathologic features of gallbladder specimens obtained from living liver donors?


1 Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
2 Department of Surgery, Umraniye Education and Research Hospital, Istanbul, Turkey
3 Department of Pathology, Inonu University Faculty of Medicine, Malatya, Turkey
4 Department of Nursing Care, Inonu University Faculty of Medicine, Malatya, Turkey
5 Department of Biostatistics, Inonu University Faculty of Medicine, Malatya, Turkey

Date of Acceptance08-Mar-2019
Date of Web Publication11-Jul-2019

Correspondence Address:
Assoc Prof. S Akbulut
Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, Malatya - 44280
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_353_18

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   Abstract 


Objective: To investigate whether there is any relationship between the clinical parameters and the histopathological features of the gallbladder (GB) specimens obtained from living liver donors (LLDs). Methods: The demographic (age, sex, height, weight, and BMI), clinical (liver graft type, liver graft weight, and GB volume), microbiological (bile culture), and histopathological (width, length, wall thickness, and microscopic properties of the GB specimen) data of 169 LLDs, who underwent living donor hepatectomy between October 2015 and October 2017, were prospectively recorded and retrospectively analyzed. The LLDs were compared with respect to sex (male vs. female) and the histopathological features of the GB (normal structure vs. chronic cholecystitis vs. cholesterolosis/polyps/cholelithiasis). Results: There were no significant differences between both sexes with respect to age, graft type, and some features of GB (volume, wall thickness, width, length, and bile culture). On one hand, there were significant differences between both sexes with regard to height (P < 0.001), weight (P < 0.001), BMI (P < 0.001), histopathological findings (P = 0.003), and graft size (P = 0.003). Comparison with regard to GB's histopathological features revealed no significant differences between the three groups with respect to age, weight, and some features of GB (volume, length, width, and bile culture). On the other hand, the three groups were significantly different in terms of sex (P = 0.003), height (P = 0.008), BMI (P = 0.002), and wall thickness (P = 0.044). Bile culture proliferation occurred in none of the patients except for one patient. Conclusion: This study is the first to assess GB's volume, dimensions, and bile culture in healthy individuals such as LLDs.

Keywords: Bile culture, gallbladder dimensions, gallbladder volume, histopathological features, living liver donors


How to cite this article:
Akbulut S, Uylas U, Tolan K, Samdanci E, Araci A, Isik B, Yologlu S, Yilmaz S. Is there any relationship between clinical parameters and histopathologic features of gallbladder specimens obtained from living liver donors?. Niger J Clin Pract 2019;22:1002-7

How to cite this URL:
Akbulut S, Uylas U, Tolan K, Samdanci E, Araci A, Isik B, Yologlu S, Yilmaz S. Is there any relationship between clinical parameters and histopathologic features of gallbladder specimens obtained from living liver donors?. Niger J Clin Pract [serial online] 2019 [cited 2019 Jul 22];22:1002-7. Available from: http://www.njcponline.com/text.asp?2019/22/7/1002/262520




   Introduction Top


Since the first performance of successful liver transplantation (LT) by Starzl and colleagues in 1967, LT has become the standard therapy for many liver disorders, mainly chronic liver disease. While liver grafts are supplied by the deceased donor pool for most transplant procedures in the developed western countries, living donors constitute a significant proportion of donor pool in many Asian countries including Turkey.[1],[2] To protect the all-healthy living liver donor (LLD) candidates from potential complications, all of them are subjected to preoperative screening tests consisting of demographic, clinical, biochemical, and radiological studies. Since Raia and colleagues.[3] performed the first living donor liver transplantation in 1989, many advances have been made in living donor hepatectomy (LDH) techniques, and standards for surgical techniques, about which consensus has mostly been reached, have been established. To both visualize, the structure of the biliary tree and to determine the demarcation line on the basis of bile duct bifurcation, cholecystectomy, followed by cholangiography, is performed. As in many organ surgeries, gallbladder (GB) specimens obtained after cholecystectomy are routinely sent to the pathology laboratory. To date, no study has been performed to answer the uncertainties about the histopathological properties of GB obtained from LLDs, i.e., healthy individuals; GB volume in healthy persons; and whether any bacteria could be reproduced in the culture of bile inside the GB. To our best knowledge, a total of two studies on the structure of GBs obtained from LLDs have been published to date, one of which was a retrospective study and the other one was a congress presentation, both of which were published from our clinic.[4],[5] We intended to design a more systematic study by standardizing the experiences we gained in that study because data that will be obtained from this study will reflect healthy individuals' GB structure.


   Materials and Methods Top


Definition of study and patient selection

LDH was performed to a total of 1,659 healthy donor candidates at Inonu University Faculty of Medicine, Liver Transplant Center between September 2005 and October 2017. All donors undergoing LDH were subjected to preoperative clinical, biochemical, and radiological assessment. After obtaining approval from the ethics committee formed by the governorship for donor candidates having no kinship with the recipient, preparations for surgery were done. All donors were asked to sign a volunteer consent form at the preoperative period. The LLD candidates were operated after at least 8 h fasting and all received antibiotics prophylaxis with a first-generation cephalosporin or ampicillin + sulbactam 1 h before anesthesia induction. Considering the parameters of recipient's weight, graft-to-recipient weight ratio, donor age, and remnant liver's ratio (%), one of the procedures of right lobe LDH, left lobe LDH, and left lateral segment LDH was applied. The details of the surgical techniques were provided elsewhere.[6],[7] To summarize, in all cases, laparotomy was done with a J incision, and the liver's macroscopic structure was examined. After the confirmation of the absence of signs of liver steatosis or fibrosis, cholecystectomy was done in compliance with the current standards, followed by a cholangiogram to define biliary tree's anatomy. GB specimens obtained after cholecystectomy were routinely sent to the pathology laboratory to be examined. The pathology department prepared a report mentioning the GB diameter, length, wall thickness, and microscopic properties and recorded the report in the patient information system. In October 2015, we sought to find an answer to the question whether there was a relationship between donor GB size and demographic variables. To fulfill that objective, the clinical and demographic data of 169 liver donors who were operated with LDH on elective basis between October 2015 and October 2017 were prospectively recorded. After obtaining approval from the Inonu University Rectorate Ethics Committee (Approval No: 2017/19-2), patients' medical records were retrospectively reviewed. Subjects who were operated at working hours on weekdays, who had their GB volume measured, and who had their GB aspiration fluid culture studied were included. However, those who had their GB perforated during dissection, and those who had problems with laboratory access of their specimens were excluded from the study. After the completion of cholecystectomy, all bile in the gall bladder was aspirated with an injector under sterile conditions to both quantify GB volume and study GB bile culture. The 169 subjects enrolled by this study were put under analysis for age, sex, height (m), weight (kg), BMI (kg/m 2), GB size (length, width, and wall thickness-mm-), GB volume (ml), graft weight (g), graft type (right, left, and left lateral), histopathological findings (normal structure, chronic cholecystitis with/without cholelithiasis, and cholesterolosis/cholesterol polyps/cholelithiasis), and bile culture results.

Objectives

First, to determine a potential relationship between sex and the GB's morphological and histopathological properties, two groups were formed on the basis of patient sex: male (n = 102) and female (n = 67). Second, to determine a potential relationship between GB specimen's histopathological properties and clinical parameters, three groups were formed on the basis of the pathology reports: normal structure (n = 105), chronic cholecystitis with/without cholelithiasis (n = 20), and cholesterolosis/cholesterol polyps/cholelithiasis (n = 31).

Statistical analysis

The statistical analyses were performed using IBM SPSS Statistics v 22.0 (Statistical Package for the Social Sciences, Inc., Chicago, IL, USA). The quantitative variables were expressed as Mean ± SD, Median, Min-Max, and interquartile range; the qualitative variables were reported as number and percent. Normality tests were used to assess normality of quantitative variables' distribution. The unpaired t test and Mann Whitney-U test were used to compare quantitative variables, and Pearson Chi-square test and Chi-square test with Monte Carlo simulation to compare qualitative variables, between the two groups formed on the basis of sex. The comparisons of the quantitative variables between the three groups formed on the basis of histopathological properties were done with Kruskal-Wallis and one-sided variance analysis; the qualitative variables were compared using the Pearson Chi-square test. LSD and Conover's tests were utilized to determine which groups showed statistical significance. A P value of less than 0.05 was considered statistically significant.


   Results Top


Comparison of variables in terms of donor sex characteristics

This study included a total of 169 patients aged 18 to 47 years, of whom 102 were male and 67 female. There was no significant difference found between both sexes with regard to age (P = 0.06). The male patients had a significantly greater mean height (P < 0.001) and body weight (P < 0.001) than female patients. However, the female patients had a greater mean BMI than male patients (P < 0.001). Both sexes had statistically similar GB volume (P = 0.99), GB wall thickness (P = 0.18), GB width (P = 0.98), and GB length (P = 0.75). Although the male patients had a significantly greater liver graft weight than female patients (P = 0.003), no similar statistically difference was found for graft type (P = 0.73).

One of the most notable differences between both sexes was observed in GB specimen's histopathological features. Among GB specimens obtained from male patients, 71.3% showed normal structure, 17% chronic cholecystitis, and 11.7% cholesterolosis/cholesterol polyp/cholelithiasis. Among GB specimens obtained from female patients, 61.3% showed normal structure, 6.5% chronic cholecystitis, and 32.3% cholesterolosis/cholesterol polyp/cholelithiasis. As is seen, the rates of chronic cholecystitis and normal structure were greater among male patients, whereas polyps and GB stones were more prevalent among female patients (P = 0.003). Further, we will present these results one more time, referring to their different aspects. Among 166 patients with available GB culture results, only one had  Staphylococcus epidermidis Scientific Name Search oduced and that result was statistically non-significant (P = 0.61). The details of sex-based comparisons were presented on [Table 1].
Table 1: Comparison of patients' characteristics according to sex (male versus female)

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Comparison of variables in terms of histopathological findings

Among 156 patients with available histopathological findings, 105 (67.3%) had normal structure, 31 (19.9%) had cholesterolosis/cholesterol polyp/cholelithiasis, and 20 (12.8%) had chronic cholecystitis. While a significant majority of patients with normal structure (63.8% vs. 36.2%) and chronic cholecystitis (80% vs. 20%) were male patients, a significantly greater proportion of patients with polyp/stone were female patients (64.5% vs. 35.5%) (P = 0.003).

The groups formed on the basis of histopathological findings showed no significant differences with respect to age (P = 0.058), body weight (P = 0.744), GB volume (P = 0.332), GB length (P = 0.964), and GB width (P = 0.296). However, the three groups had statistically significant differences in terms of sex (P = 0.003), height (P = 0.008), BMI (P = 0.002), and GB thickness (P = 0.044). To determine which group created these differences, post hoc tests were performed. The subjects in the cholesterolosis/cholesterol polyp/cholelithiasis group had significantly greater BMI than those in the normal structure and chronic cholecystitis groups (P = 0.001). Moreover, the subjects in the cholesterolosis/cholesterol polyp/cholelithiasis group had significantly lower body height than the normal structure (P = 0.006) and chronic cholecystitis groups (P = 0.001). As for GB wall thickness, the subjects in the chronic cholecystitis group had significantly greater GB wall thickness than the subjects in the other two groups. However, the statistical significance for GB thickness only existed between the difference between the cholesterolosis/cholesterol polyp/cholelithiasis group and the normal structure group (P = 0.04). Other details of the comparisons between histopathological findings were presented on [Table 2].
Table 2: Comparison of patients' characteristics according to histopathological findings

Click here to view



   Discussion Top


Although there are plenty of controlled studies in the literature that radiologically examine how GB's structure is altered by GB stone diseases, almost no study, except for ours, has ever directly measured GB's properties of healthy persons without using radiological tools. Anyway, apart from healthy subjects undergoing cholecystectomy for donor hepatectomy, it is hardly possible to carry out cholecystectomy for academic studies because of ethical concerns. Hence, we had no choice other than comparing our findings with studies according to radiological measurements.

In a study by Ewunonu on healthy individuals from Nigeria revealed that men had a greater height, weight, and BMI than women.[8] The same study also indicated that GB mural thickness and GB length were greater in men than women.[8] Adeyekun et al., however, denied any significant differences between both sexes in respect to GB diameter, GB mural thickness, and GB length.[9] Our study demonstrated a greater BMI in women than men. Furthermore, we not found any significant difference between both sexes with regard to GB thickness, GB length, and GB width.

The relationship between GB volume and sex has been scrutinized by several studies. While there exist some studies indicating that there was no relationship between GB volume and sex, some others have pointed a (even statistically significantly) greater GB volume in men.[8],[10] Although Adeyekun et al.[9] showed that GB volume was greater in men, the difference did not reach statistical significance. Although in contrast to the available literature data, GB volume in the present study was greater among women than men, the difference did not reach statistical significance. One of the most notable findings of our study is the relationship between GB histopathology and sex. While the prevalence of chronic cholecystitis was greater among men, GB stone/polyps/cholesterolosis were more prevalent among women. Another finding of the present study is the relationship between the histopathological data and the demographic and clinical patient data. GB mural thickness was found to be significantly greater among those with chronic cholecystitis than the other groups. This finding is also consistent with the finding of a greater mural thickness among men than women. Patients with GB stone/polyps/cholesterolosis had a greater BMI than the other groups. This finding is also in agreement with the finding that women had a greater BMI than men. To our opinion, one limitation of the current study's design is the absence of the assessment of donors with preoperative ultrasonography. If we had ultrasonographic measurements of GB, we could have performed a correlation analysis between radiological and macroscopic measurements and provide a clearer interpretation about such a relationship.

Hence, we would like to state that we have designed a novel study to address this point. In conclusion, we may summarize the highlights of the present study as follows:

  • Although the male donors were taller and heavier than female donors, the female donors had a greater BMI than male donors.
  • Liver graft weight obtained from the male donors was greater than that obtained from female donors.
  • While the prevalence of chronic cholecystitis was greater in men, the prevalence of cholesterolosis/cholesterol polyp/cholelithiasis was greater among female donors.
  • The height of donors with cholesterolosis/cholesterol polyp/cholelithiasis was shorter than the other donors.
  • The wall thickness of GB specimens of those with chronic cholecystitis was greater than those with cholesterolosis/cholesterol polyp/cholelithiasis and normal structure groups.
  • This study is the first in the literature to study the relationship between GB, bile culture, and donor demographic data among healthy persons. Hence, to convey a more robust message, its findings should be supported by future studies.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Akbulut S, Yilmaz S. Liver transplantation in Turkey: Historical review and future perspectives. Transplant Rev (Orlando) 2015;29:161-7.  Back to cited text no. 1
    
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 syndrome for living-donor liver transplantation? Case report. Transplant Proc 2012;44:1640-3.  Back to cited text no. 2
    
3.
Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet 1989;2:497.  Back to cited text no. 3
    
4.
Akbulut S, Karagul S, Ertugrul I, Aydin C, Yilmaz M, Yilmaz S. Histopathologic findings of cholecystectomy specimens in patients who underwent donor hepatectomy for living donor liver transplantation. Transplant Proc 2015;47:1466-8.  Back to cited text no. 4
    
5.
Tolan K, Akbulut S, Yilmaz S. Evaluation of morphological and microbiological characteristics of gall bladder in living liver donors: A prospective descriptive study. The 2017 Joint International Congress of ILTS, Elite&Licage, 2017 May24-27, Prague, Czech Republic (P-98).  Back to cited text no. 5
    
6.
Usta S, Ates M, Dirican A, Isik B, Yilmaz S. Outcomes of left-lobe donor hepatectomy for living-donor liver transplantation: A single-center experience. Transplant Proc 2013;45:961-5.  Back to cited text no. 6
    
7.
Dirican A, Ozsoy M, Ates M, Ersan V, Gonultas F, Isik B, et al. Consequences of the use of extended criteria donors in living donor liver transplantation. Ann Transplant 2015;20:211-7.  Back to cited text no. 7
    
8.
Ewunonu EO. Sonographic evaluation of gallbladder dimension in healthy adults of a South-Eastern Nigerian population. JSIR 2016;5:96-9.  Back to cited text no. 8
    
9.
Adeyekun AA, Ukadike IO. Sonographic evaluation of gallbladder dimensions in healthy adults in Benin City, Nigeria. West Afr J Radiol 2013;20:4-8.  Back to cited text no. 9
  [Full text]  
10.
Akintomide AO, Eduwem DU. Ultrasonographic assessment of the fasting gallbladder volume in healthy adults in calabar; correlation with body weight. JDental Med Sci 2013;4:64-8.  Back to cited text no. 10
    



 
 
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