Evaluation of the effects of Ankaferd haemostat application on bone regeneration in rats with calvarial defects: histochemical, immunohistochemical and scintigraphic study.

BACKGROUND: Bone wax, a haemostatic agent, is widely used in craniospinal surgical procedures for a long time, in spite of controversial results regarding its negative influence upon bone regeneration. In this experimental study, the effects of Ankaferd Blood Stopper (ABS), as an alternative haemostatic agent, were evaluated through histochemical, immunohistochemical and scintigraphic studies. MATERIALS AND METHODS: The total of 30 adult female Wistar albino rats was randomly divided into three groups: intact control group (n = 10), bone wax group (n = 10), and ABS group (n = 10). Surgically, a 3.0 mm hole in diameter was drilled on the right side of calvarium of the rats using a Class Mini Grinder set in all three groups, as described previously. At the end of 8 weeks, bone healing and connective tissue alterations surrounding drilled calvarial defect areas of the rats were determined via haematoxylin and eosin and the Mallory's trichrome staining and anti-bone sialoprotein immunohistochemistry. Image Pro Express 4.5 programme was used for histomorphometric calculation of new bone and fibrotic tissue areas. All statistical analyses were made with SPSS 25.0 and analysis of variance (one-way ANOVA) followed by Bonferroni post hoc test was performed, p < 0.001 was considered as significance level. RESULTS: Histomorphometrically, it was found that he had the largest hole diameter and the least fibrotic scar area in the bone-wax group. In the bone wax group, it was observed that the material closed the hole and there was only a fibrotic scar tissue in the area between the bone tissue at the edge of the hole and bone wax, and a fibrotic tissue was formed in the bone wax area. During the histological procedure, this bone-wax material was poured and the sections were seen as a gap in this area. In the ABS haemostat group, the smallest hole diameter and the least fibrotic scar tissue were observed. Fibrotic scar tissue close to each other was found in the ABS haemostat and bone wax groups. Histological analysis of samples also showed a statistical significance for fibrotic connective tissue area between groups (p < 0.05). Scintigraphically, osteoblastic activity related to blood flow in the animal taken from the group with application of ABS haemostat was more pronounced compared to the other two groups. CONCLUSIONS: In our study, it has been concluded that the ABS yields affirmative effects on the bone healing, while bone wax leads to negative impact on the bone regeneration. Scintigraphic, histochemical and immunohistochemical data support the affirmative impact of the ABS haemostat application upon the bone regeneration apart from the quick stop of haemorrhage.

The effect of diode laser application on restoration of non carious cervical lesion: Clinical follow up.

AIMS: The aim of this study is to evaluate the effect of the diode laser used for dentin sensitivity on the clinical success of non-carious cervical lesion (NCCL) restorations restored with different adhesive systems. METHODS: 20 NCCLs were restorated with Universal Single Bond (Self Etch) (3M, USA) and Grandio (Voco, Germany), 20 NCCLs were restorated with Universal Single Bond (Total Etch) and Grandio. After diode laser application, 20 NCCLs were restorated with Universal Single Bond and Grandio, 20 NCCLs were restorated with Universal Single Bond (Total Etch) and Grandio. The restorations were clinical evaluated by two examiners at baseline, for 6 and 18 months using modified United States Public Health Service (USPHS) Criteria. Chi-square test was used for statistical analyse. RESULTS: The lowest rates of retention was found in the Group 1. There was no statistically significant difference among the groups in marginal discoloration, marginal integrity, sensitivity (P > 0.05). CONCLUSION: Diode laser application prior to the restoration of teeth with NCCL don't reduce the retention rate of restorations, may reduce hypersensitivity and may affect the success of restoration. However, further laboratory and clinical studies are required.

Long-term Results of Living Donors in Simultaneous Kidney and Liver Transplantations.

INTRODUCTION: Because of the shortage of organs available for transplantation, living related sequential transplantation with the use of liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative. However, there is insufficient literature about the complications that living donors experience after simultaneous kidney and liver transplantations. METHODS: From December 2001 to October 2009, 5 living donors provided simultaneous donation of livers and kidneys and 1 living donor donated first her kidney and then her liver. Demographic data of the donors and information concerning the surgery and postoperative observation were collected prospectively. RESULTS: All of the donors were female. The median age was 27.5 (range, 19-36) years. Indications requiring the simultaneous transplantation of livers and kidneys were primary hyperoxaluria type 1 (PH1) in 5 potential recipients and cirrhosis due to chronic hepatitis B infection and idiopathic chronic renal insufficiency in 1 potential recipient. Four recipients underwent right hepatectomy (segments 5-8) and right nephrectomy; 1 recipient underwent left hepatectomy (segments 2-4) and right nephrectomy; and 1 recipient underwent left lobectomy (segments 2-3) and right nephrectomy. There were no complications except in 1 donor (postoperative ileus). No donor developed hypertension or microalbuminuria. CONCLUSIONS: With the right indications, appropriate preoperative evaluation, meticulous surgical technique, proper postoperative care, and long-term close monitoring to minimize morbidity and mortality risks, liver and kidney donation from the same donor can be considered for simultaneous kidney and liver transplantation.

Hepatic Artery Reconstruction With Autologous Inferior Mesenteric Artery Graft in Living Donor Liver Transplant Recipients.

INTRODUCTION: In living donor liver transplantation (LDLT), hepatic arterial continuity is crucial to avoid biliary leakage, biliary stricture, cholangitis, and graft and patient loss. Sometimes there exist factors making anastomosis difficult or even impossible. In these cases, a vascular graft may be needed to bridge the two arteries for revascularization. METHOD: Medical records of 297 patients who underwent LDLT between June 2000 and July 2016 at the Hepatopancreatobiliary Surgery and Liver Transplantation Unit of Dokuz Eylul University Hospital were reviewed retrospectively. Twenty-eight (9%) patients younger than the age of 18 were excluded from the study. The remaining 269 patients were included in the study. We analyzed data of patients who developed hepatic arterial complications during or after LDLT and underwent revascularization using autologous interposed inferior mesenteric artery (IMA) grafts. RESULTS: In 8 (2.9%) of the 269 patients who underwent LDLT and were included in the study, autologous interposed IMA grafts were used for the hepatic artery revascularization. All of the patients were males. Their mean age was 42 (range, 25-57). The mean duration of follow-up was 83.25 months (range, 3-144 months). One patient developed intraoperative hepatic arterial thrombosis (HAT) after autologus IMA reconstruction and this patient needed retransplantation. No arterial complications developed in the other 7 patients. CONCLUSION: Autologous interposed IMA graft could be used as an alternative vascular graft in hepatic artery revascularization to provide tension-free hepatic arterial continuity.

Laboratory in complicated appendicitis prediction and predictive value of monitoring.

OBJECTIVES: The purpose of the study was that monitoring, which is used in diagnosis of acute appendicitis, and laboratory values, were evaluated for verifying diagnosis of complicated appendicitis and these parameters revealed cut-off values in complicated acute/non-complicated appendicitis. METHODS: 195 patients, who had had an operation for acute appendicitis between January 2012 and March 2015 and who were proved to have acute complicated/non-complicated appendicitis from the results of histopathology consideration, were included in this study. Patients' age, preoperative serum, WBC, CRP, NLR and BT with USG results were evaluated.    RESULTS: Among the groups, there were no meaningful differences in the sense of age. Meaningful difference was obtained in between (p > 0.05), WBC, NLR, CRP and appendix diameter values.Serum in WBC >13800 (AUC = 0.614, p = 0.006, %95 GA: 0.541-0.682), in NLR > 4.87 (AUC = 0.641, p = 0.001, %95 GA: 0.569-0.708), in CRP > 5.98 (AUC = 0.651, p 11 mm (AUC = 0.630, p = 0.002, %95 GA: 0.558-0.698) values were obtained. The values that were obtained, were confirmed to be descriptive in analysis of complicated appendicitis and non-complicated appendicitis.According to the obtained cut-off values, serum WBC, diameter of appendicitis, NLR and CRP values', (OR) ratios were calculated for complicated appendicitis by being classified (odds ratio respectively; 3.103 (1.713-5.621), 2.765 (1.496-5.109), 3.025 (1.665-5.494), 2.313 (1.295-4.130)). CONCLUSION: It is important that treatment options are evaluated to be able to discriminate complicated appendicitis fast and with a high accuracy. In the case that serum WBC is higher than 13800. CRP is higher than 5.98, NLR is higher than 4.87 and appendicitis diameter is longer than 11mm, inflammation of appendicitis is complex with gangrene, perforation and abscess and it emphasizes the suggestion of surgical treatment option to patients (Tab. 4, Fig. 1, Ref. 28).

Risk factors for early bacterial infections in liver transplantation.

OBJECTIVE: Our aim was to determine perioperative risk factors for early bacterial infection after liver transplantation. METHODS: Retrospectively examining medical records using Centers for Disease Control and Prevention (CDC) definitions to identify nosocomial infections, we analyzed data on 367 adult patients. RESULTS: The incidence of infection was 37.3% (n = 137): namely, surgical site (n = 74; 20.2%) [corrected], blood stream (n = 64; 17.4%), pulmonary (n = 49; 13.4%), urinary system (n = 26; 7.1%). Significant risk factors within the first 30 days were as follows: deceased donor, Model for End-Stage Liver Disease (MELD) >20, albumin level <2.8 g/dL, intraoperative erythrocyte transfusion >6 U, intraoperative fresh frozen plasma >12 U, bilioenteric anastomosis, postoperative intensive care unit stay >6 days, and postoperative length of stay >21 days. Significant risk factors detected within the first 90 days were as follows: MELD >20, preoperative length of stay >7 days, reoperation, postoperative length of intensive care unit stay >6 days, and postoperative length of stay >21 days. Variability was observed in risk factors according to localization of infection. As a result, except for MELD, type of donor, and biliary anastomosis, the others are preventable factors for early bacterial infection. In addition, the same risk factors showed variability according to the site of infection.

Cost analysis of liver transplantation in Turkey.

The study sought to determine the costs of liver transplantation in Turkey. All costs except physician charges were retrospectively investigated in the period from hospitalization to discharge. Liver transplantation was performed in 326 patients between 1999 and 2009. After exclusion of patients whose records could not be accessed (n=5), who underwent second transplantations in the same hospitalization (n=3) or who died before discharge (n=39), 279 patients were eligible for the study. The mean cost of liver transplantation was 30.823 dollars. The mean cost in 2008 was significantly higher than for all other years; thereafter it decreased. Costs were shown to be higher among patients with model for end-stage liver disease (MELD) scores>15. Although there was no significant cost difference among United Network for Organ Sharing (UNOS) groups, the mean costs of subjects of the B group were significantly lower than those of the Child C subjects C (P=.01). When we evaluated the relationship between etiological groups and costs the highest expenses were noted among hepatitis B virus (HBV) and hepato cellular carcinoma (HCC) patients with 75% HBV-positivity together. There was no significant difference between age, gender, and body mass index (BMI) of recipients. The costs did not significantly change with the presence of diabetes mellitus (DM) or portal vein thrombosis before transplantation or antibiotic use after transplantation. Although there was no difference between donor age and costs, living donor transplantation showed significantly higher costs than cadaveric donor cases (P=.01). In conclusion, liver transplantation is an effective treatment in end-stage liver diseases with high cost, albeit in Turkey it is relatively lower than other countries.

Anesthesia-related complications in living liver donors: the experience from one center and the reporting of one death.

Living donor liver transplantation has become an alternative therapy for patients with end-stage liver disease. Donors are healthy individuals and donor safety is the primary concern. The objective of this study was to evaluate the anesthetic complications and outcomes for our donor cases; we report one death. The charts of the patients who underwent donor hepatectomy from February 1997 to June 2007 were retrospectively reviewed. Right hepatectomy (resection of segments 5-8) was done in 101 donors, left lobectomy (resection of segments 2-3) in 11 donors, and left hepatectomy (resection of segments 2-4) in one donor. Minor anesthetic complications were shoulder pain, pruritus and urinary retention related to epidural morphine, and major morbidity included central venous catheter-induced thrombosis of the brachial and subclavian vein, neuropraxia, foot drop and prolonged postdural puncture headache. One of 113 donors died from pulmonary embolism on the 11th postoperative day. This procedure has some major risks related to anesthesia and surgery. Although careful attention will lower complication rate, we have to keep in mind that the risks of donor surgery will not be completely eliminated.

Combined liver-kidney transplantation and follow-up in primary hyperoxaluria treatment: report of three cases.

INTRODUCTION: Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disorder caused by impaired activity of the hepatic peroxisomal alanine-glyoxilate aminotransferase, which leads to end-stage renal disease (ESRD) and requires combined liver-kidney transplantation (CLKT). Herein, we have reported 3 children diagnosed with PH1 who received CLKT. CASE 1: A 4.5-year-old boy with an elder brother diagnosed with PH1 was diagnosed during family screening when the sonography showed multiple calculi. Within 5 years he experienced flank pain, hematuria attacks, and anuric phases due to obstruction and received hemodialysis (HD) when ESRD appeared. CLKT was performed from his full-match sister at the age of 9.5. He is doing well at 5.5 years. CASE 2: A 7-year-old boy was admitted with polyuria, polydypsia, and stomach pain with renal stones on sonography. PD was instituted when serum creatinine and BUN levels were measured as high values. At the age of 10, CKLT was performed from his mother. His liver and renal function tests are well at 14 months after CKLT. CASE 3: A 2.5-year-old girl had attacks of dark urine without any pain; renal stones were imaged on sonography. She was diagnosed with PH1 and operated on several times due to obstruction. She received peritoneal dialysis and a cadaveric CLKT was performed when she was 9 years old. At the age of 16, she experienced chronic allograft nephropathy requiring HD and subsequent cadaveric donor renal transplantation at 1.5 years after initiation of HD. CONCLUSION: Herein, we have presented the favorable clinical outcomes of patients with CKLT to indicate the validity of this treatment choice for PH1.

Efficacy of right anterior sector drainage reconstruction in right-lobe live-donor transplantation.

BACKGROUND: Without including the middle hepatic vein (MHV) into right-lobe grafts, venous drainage of the anterior segment (AS) has always been a concern. The efficacy and the necessity of additional venous reconstruction in the AS for graft viability and function are still controversial. METHODS: Since February 2002, 57 right-lobe grafts were implanted into adult recipients. The mean graft to ideal recipient weight ratio (GRWR) was 1.3% (minimum: 0.8%, maximum 2.1%). All minor venous tributaries to the MHV less than 5 mm in diameter were ligated. The management of MHV tributaries was categorized into three groups: (A) no major tributaries (n = 33); (B) major tributaries ligated (n = 11); and (C) major tributaries reconstructed (n = 13). Reconstructions were established using vascular grafts (PTF, n = 8; cadaveric, n = 2) or joining with right hepatic vein orifice (n = 6). The groups were homogenous in age, gender, MELD (17 +/- 6, 16 +/- 4, 18 +/- 7), graft weight (817 +/- 181, 838 +/- 152, and 855 +/- 159 g), and graft/ideal liver weight ratio (0.54 +/- 0.12, 0.57 +/- 0.13, and 0.57 +/- 0.1, respectively). We investigated the volume of ascites, serum bilirubin, albumin, and liver enzyme levels and INR on postoperative day 4 (POD4) and POD21. RESULTS: Two patients died of MRSA sepsis on POD18 and POD23 (MELD: 24 and 28) after initial graft function. Their graft weights were 800 g and 980 g, and their volumes were 47% (group B) and 62% (group A) of the ideal liver mass of the recipients, respectively. One PTF and another cadaveric vascular graft were found occluded 4 and 7 days after implantation without any negative consequence. At 6-month follow-up, the remaining 55 patients were alive with primary liver grafts. Vascular reconstructions were patent except for 2 early occlusions. Among the 3 groups, no significant difference was found on POD4. Three weeks after transplantation, the mean AST level in the major ligation group (46.7 +/- 8.14) was significantly higher than in the minor ligatation group (29.6 +/- 8.6) but not in the major reconstruction group (33.7 +/- 3.7; P = .03 and P = .29). The mean albumin level was highest after minor ligation (3.2 +/- 0.18), which was significantly better than the major reconstruction (2.7 +/- 0.1) but not the major ligation (3.1 +/- 0.14) cohorts (P = .02 and P = .13). CONCLUSIONS: In this study of a limited number of cases, right-lobe liver grafts with GRWR of > or =1.1% displayed optimal graft function without additional venous reconstruction to the AS.

Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation.

The combination of hepatitis B immunoglobulin (HBIG) and antivirals (nucleos[t]ide analogs) has extended the applicability of orthotopic liver transplantation (OLT) for patients with hepatitis B virus (HBV)-related liver disease. However, HBIG administrations have an extremely high cost. Herein, we evaluated our results with low-dose, on-demand, intramuscular HBIG plus lamivudine (LAM) prophylaxis after OLT. The HBV DNA status in 40 patients at the time of OLT determined the treatment: group A (n = 22), HBV DNA (-), no antiviral pretreatment; group B (n = 11), HBV DNA (-), after LAM; group C (n = 3), HBV DNA (+) after LAM (LAM resistance/Adefovir [ADV] unavailable); group D (n = 2), HBV DNA (+), no antiviral pretreatment; and group E (n = 2), HBV DNA (-) after LAM + ADV (LAM resistance/ADV available). Five patients died within 12 months after OLT unrelated to HBV infection. The remaining 35 patients were followed for a median duration of 16 months (range, 6-93 months). Only two recipients from group C, who were transplanted despite LAM resistance + no ADV pretreatment, revealed recurrent HBV infections at 14 and 16 months posttransplantation; they were then treated successfully with ADV as it became available. The third group C recipient had undetectable HBV DNA at 18 months after OLT. The mean cumulative doses of HBIG administered within the first, second, and third years were 34,014, 5258, and 5090 IU, respectively. In conclusion, low-dose, on-demand, intramuscular HBIG plus (LAM +/- ADV) prophylaxis is a safe, efficient, and cost-effective regimen to prevent recurrent HBV infection following OLT. OLT despite untreated LAM resistance may require sustained higher serum HBsAb levels after surgery.

First graduates' perceptions on a problem-based and task-based learning curriculum.

INTRODUCTION: Determination of graduates' perceptions and suggestions is essential in the evaluation of educational programmes. Dokuz Eylul University School of Medicine (DEUSM), the country's first medical school implementing a Problem-Based Learning (PBL) and Task-Based Learning (TBL) programme, graduated the first students of its new educational programme starting from the 2002-2003 academic year. The aim of the present study is to determine first graduates' perceptions on their self-efficacy and school's educational programme's efficacy. METHODS: In June 2003, 51 graduating students were asked to use five-point scales to evaluate: the content of the educational programme, the educational methods, communication with educators, assessment methods and instruments, the efficacy of each year of their undergraduate programme and the overall program, their satisfaction levels about educational programme regarding the acquisition of knowledge and skills, their self-efficacy and contentment level of being a physician. RESULTS: In the content of educational programme, the highest score was attributed to "acquisition of behavioural objectives" and the lowest score to "acquisition of basic science knowledge". Regarding the efficacy of educational programme, the highest score was attributed to "communication with educators". The highest scores regarding the satisfaction levels on the acquisition of knowledge and skills provided by the School were attributed to "implementing basic professional procedures" and "history taking" and the lowest score to "selecting appropriate treatment". CONCLUSION: The graduating students' mainly positive evaluations regarding the efficacy of DEUSM's new educational programme were considered as supportive reflections on the new educational programme. Further studies to monitor our graduates' future professional performances are being envisaged.

Incarcerated inferior lumbar (Petit's) hernia.

Petit's hernia is an uncommon abdominal wall defect in the inferior lumbar triangle. Colonic incarceration through the inferior lumbar triangle, which causes mechanical obstructive symptoms, necessitates particular diagnostic and management strategy. We present a rare case of inferior lumbar hernia, leading to mechanical bowel obstruction, successfully treated with prosthetic mesh reinforcement repair.

Myocardial performance index combining systolic and diastolic myocardial performance in doxorubicin-treated patients and its correlation to conventional echo/Doppler indices.

This study was designed to evaluate the utility of myocardial performance index (MPI) in anthracycline cardiotoxicity. The MPI measures the ratio of total time spent in isovolumic activity (isovolumetric contraction time and isovolumetric relaxation time) to the ejection time, thus giving a global index combining systolic and diastolic myocardial performance. In this study, MPI was measured in 35 doxorubicin-treated children (aged 108.5+/-55.31 months, 23 males and 12 females) in sinus rhythm and 32 age-matched controls, and it was compared with conventional Doppler echocardiographic parameters. The isovolumetric contraction time was prolonged (38.37+/-24.43 vs 26.37+/-15.53, p <0.02) and ejection time was shortened (231.91 +/- 28.87 vs 256.21+/-19.55, p<0.001) in doxorubicin-treated patients compared to that in normal children. The isovolumetric relaxation time did not show significant difference between patients and control group (60.11+/-10.92 vs 61.06+/-12.12, p>0.05). MPI was significantly increased in doxorubicin-treated patients compared with that in control groups (0.42+/-0.07 vs 0.34+/-0.06, p<0.001), and significant correlation was observed between MPI and fractional shortening, ejection fraction, and left ventricular end diastolic and end systolic diameters (respectively, r = -0.508, p <0.002; r = -0.532, p<0.001; r = 0.467 p<0.005; r=0.606, p<0.001). Also, a weak correlation was found between MPI and duration of the disease and patient ages (r = 0.393, p < 0.02; r = 0.379; p < 0.02). However, there was no correlation between MPI and cumulative doxorubicin dose (r = 0.311, p > 0.05) and diastolic Doppler parameters in doxorubicin-treated patients. We think that MPI may be a useful parameter in monitoring left ventricular dysfunction in anthracyline-treated patients.

Protective effects of carnitine in an experimental ischemia-reperfusion injury.

BACKGROUND/AIMS: We aimed to determine the role of exogenous carnitine to prevent ischemia-reperfusion damage in liver tissue in experimental model. METHODS: Rats were divided into four groups as Sham (SG), 30% Hepatectomy (HG), ischemia-reperfusion +30% hepatectomy (IRHG) and ischemia-reperfusion+30% hepatectomy+carnitine (IRHCG). Serum AST, ALT and GGT levels have been determined in systemic blood samples (post-hepatic vena cava) and liver tissue and serum carnitine levels in blood samples from portal vein (pre-hepatic blood samples). RESULTS: Serum carnitine levels were significantly higher in IRHCG compared to SG (P < 0.01). Each of the serum AST, ALT and GGT levels were statistically higher in HG, IRHG and IRHCG than SG (P < 0.001). While these values in IRHG were also higher than those in HG (P < 0.001), in IRHCG enzyme levels were significantly lower than IRHG (P < 0.001). Liver tissue damage was less in IRHCG than IRHG statistically (P < 0.001). CONCLUSIONS: This animal model implies that exogenous carnitine supplementation may be helpful in preventing free oxygen radical damage and inflammatory reactions in liver tissue.

Pseudoachondroplasia in a child with prolapse of the mitral valve.

Pseudoachondroplasia is an autosomal dominant variant of osteochondroplasia that results in mild to severe short-limb dwarfism and early-onset of osteoarthrosis. It has been linked to results from mutations in the gene for cartilage oligomeric matrix protein. We describe a 4-year-old boy with pseudoachondroplasia who also had prolapse of the mitral valve. To the best of our knowledge, this association has not previously been reported.

Cholangiocytic apoptosis in chronic ductopenic rejection.

The significance of cholangiocytic apoptosis as a mechanism of ductopenia in liver rejection remains controversial. In a previous study, the presence but not the extent of ductal apoptosis was assessed by electron microscopy. Other previously published studies using an in situ hybridization method (in situ end labeling) produced conflicting results (no apoptosis v massive apoptosis). We studied 47 liver needle biopsies from 8 patients with chronic ductopenic rejection confirmed by pathologic examination of the failed grafts. These biopsies were performed because of graft dysfunction, during a period of several months before retransplantation, and they showed cholangiocytic injury with progressive ductal paucity. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) was used to detect apoptosis (tissue digestion with proteinase K 20 microg/mL for 20 minutes). The interlobular bile ducts did not show labeling, even in lymphocytic cholangitis with obvious epithelial injury. However, there was minimal staining of ductular nuclei. Lymphocytic nuclei were also labeled. Apoptosis was not detectable in the vanishing interlobular bile ducts, even when more representative samples were studied and a more sensitive method was used. Unless apoptosis of cholangiocytes is an exceptionally rapid process escaping detection by conventional methods, ductopenia results mainly from ordinary, nonprogrammed cholangiocytic death. Apoptosis could still be involved in the pathogenesis of ductopenia by depleting cholangiocytic precursors, generally presumed to reside in ductules. This is a possible mechanism suggested by the following: (1) the established role of apoptosis in the homeostatic control of immature/progenitor cells, (2) the paucity of ductular proliferation in chronic rejection, (3) the previously reported decrease of ductular bcl-2 expression in rejection, and (4) the sporadic ductular TUNEL labeling seen in this study.