Evaluation of Bone Mineral Metabolism After Liver Transplantation by Bone Mineral Densitometry and Biochemical Markers.

AIM: This study aimed to evaluate the course of bone and mineral metabolism after liver transplantation (LT) in patients with chronic liver disease. METHODS: One hundred four patients who had undergone LT and had a minimum of 6 months of follow-up after LT were included in this prospective cohort study. The following parameters were evaluated for each patient: preoperative and postoperative (postoperative day [POD]30, POD90, POD180) osteocalcin, bone-specific alkaline phosphatase (BALP), type 1 collagen, beta-C-terminal end telopeptide (ß-CTx), vitamin D, parathyroid hormone (PTH), ALP, calcium, phosphate, sedimentation, and bone mineral densitometer scores (L2, L4, L total, and F total). The parameters were compared in terms of sex, presence of liver tumor (hepatocellular carcinoma [HCC; n = 19] vs non-HCC [n = 85]), and presence of autoimmune liver disease (autoimmune liver disease [ALD; n = 8] vs non-ALD [n = 96]). RESULTS: The median age of the patients (n = 81 men and n = 23 women) was 52 years (95% CI, 50-56). There was a significant change in the defined time intervals in parameters such as osteocalcin (P < .001), BALP (P < .001), ß-CTx (P < .001), vitamin D (P < .001), PTH (P < .001), ALP (P = .001), calcium (P < .001), phosphate (P = .001), L2 (P = .038), L total (P = .026), and F total (P < .001) scores. There was a significant difference in POD90 ALP (P = .033), POD180 calcium (P = .011), POD180 phosphate (P = .011), preoperative sedimentation (P = .032), and POD180 F total (P = .013) scores between both sexes. There was a significant difference in POD180 osteocalcin (P = .023), POD180 ß-CTx (P = .017), and preOP calcium (P = .003) among the HCC and non-HCC groups. Furthermore, we found significant differences in preoperative ALP (P = .008), preoperative sedimentation (P = .019), POD90 (P = .037) and POD180 L2 (P = .005) scores, preoperative (P = .049) and POD180 L4 (P = .017), and POD180 L total (P = .010) and F total (P = .022) scores between the patients with and without ALD. CONCLUSION: This study shows that the bone and mineral metabolism of the LT recipients was negatively affected after LT. In addition, we showed that bone and mineral metabolism was more prominent in patients with HCC, and bone mineral density scores were higher in patients with ALD.

Prediction of Perforated and Nonperforated Acute Appendicitis Using Machine Learning-Based Explainable Artificial Intelligence.

BACKGROUND: The primary aim of this study was to create a machine learning (ML) model that can predict perforated and nonperforated acute appendicitis (AAp) with high accuracy and to demonstrate the clinical interpretability of the model with explainable artificial intelligence (XAI). METHOD: A total of 1797 patients who underwent appendectomy with a preliminary diagnosis of AAp between May 2009 and March 2022 were included in the study. Considering the histopathological examination, the patients were divided into two groups as AAp (n = 1465) and non-AAp (NA; n = 332); the non-AAp group is also referred to as negative appendectomy. Subsequently, patients confirmed to have AAp were divided into two subgroups: nonperforated (n = 1161) and perforated AAp (n = 304). The missing values in the data set were assigned using the Random Forest method. The Boruta variable selection method was used to identify the most important variables associated with AAp and perforated AAp. The class imbalance problem in the data set was resolved by the SMOTE method. The CatBoost model was used to classify AAp and non-AAp patients and perforated and nonperforated AAp patients. The performance of the model in the holdout test set was evaluated with accuracy, F1- score, sensitivity, specificity, and area under the receiver operator curve (AUC). The SHAP method, which is one of the XAI methods, was used to interpret the model results. RESULTS: The CatBoost model could distinguish AAp patients from non-AAp individuals with an accuracy of 88.2% (85.6-90.8%), while distinguishing perforated AAp patients from nonperforated AAp individuals with an accuracy of 92% (89.6-94.5%). According to the results of the SHAP method applied to the CatBoost model, it was observed that high total bilirubin, WBC, Netrophil, WLR, NLR, CRP, and WNR values, and low PNR, PDW, and MCV values increased the prediction of AAp biochemically. On the other hand, high CRP, Age, Total Bilirubin, PLT, RDW, WBC, MCV, WLR, NLR, and Neutrophil values, and low Lymphocyte, PDW, MPV, and PNR values were observed to increase the prediction of perforated AAp. CONCLUSION: For the first time in the literature, a new approach combining ML and XAI methods was tried to predict AAp and perforated AAp, and both clinical conditions were predicted with high accuracy. This new approach proved successful in showing how well which demographic and biochemical parameters could explain the current clinical situation in predicting AAp and perforated AAp.

Measurement of Heavy Metal and Antioxidant-Oxidant Levels in Tissues Obtained From Three Different Localizations of Explant Hepatectomy of Patients With Hepatocellular Carcinoma.

BACKGROUND: To reveal any difference in terms of heavy metal and antioxidant/oxidant levels of liver tissues obtained from 3 different locations of hepatectomy specimens of patients with hepatocellular carcinoma (HCC). METHODS: Total hepatectomy materials of patients who underwent liver transplantation for HCC were objects of this study. Three liver tissue samples were obtained from each material, one from HCC tissue, one adjacent from the border of HCC, and one at least 3 cm distant from HCC, each 10 × 10 mm in diameter. Samples are preserved at -70°C. Levels of heavy metals (As, Cd, Cu, Mn, Pb, Se, and Zn) and oxidant-antioxidant parameters (catalase, glutathione peroxidase [GSHPx], superoxide dismutase [SOD], nitric oxide, prolidase, glutathione, malondialdehyde, total oxidant status, antioxidant status, oxidative stress index, total-thiol, native thiol, and disulphid) are measured. RESULTS: This study included 22 patients (18 men, 4 women with an age range of 3 to 66 years. There were significant differences in terms of Cd, Pb, Zn, GSHPx, SOD, nitric oxide, and native thiol levels between liver tissues derived from 3 different locations. Cd, Pb, and Zn levels were significantly different in tumor tissues, whereas GSHPx and SOD levels were significantly different in tumor and neighboring tissues. Nitric oxide levels were relatively different in tumor tissues compared with tumor-neighboring tissues. Native thiol levels differed significantly in tumor tissues compared with tissues distant from tumor. CONCLUSIONS: The aim of this study is unique in medical literature, which reveals that the amount of heavy metals and antioxidant/oxidant accumulation are variable in the same liver tissue in different locations because of multiple and yet unknown factors.

Effect of the COVID-19 pandemic on patients with presumed diagnosis of acute appendicitis.

BACKGROUND: Acute appendicitis (AAp) is the most frequent cause of acute abdominal pain, and appendectomy is the most frequent emergency procedure that is performed worldwide. The coronavirus disease 2019 (COVID-19) pandemic has caused delays in managing diseases requiring emergency approaches such as AAp and trauma. AIM: To compare the demographic, clinical, and histopathological outcomes of patients with AAp who underwent appendectomy during pre-COVID-19 and COVID-19 periods. METHODS: The demographic, clinical, biochemical, and histopathological parameters were evaluated and compared in patients who underwent appendectomy with the presumed diagnosis of AAp in the pre-COVID-19 (October 2018-March 2020) and COVID-19 (March 2020-July 2021) periods. RESULTS: Admissions to our tertiary care hospital for AAp increased 44.8% in the COVID-19 period. Pre-COVID-19 (n = 154) and COVID-19 (n = 223) periods were compared for various parameters, and we found that there were statistically significant differences in terms of variables such as procedures performed on the weekdays or weekends [odds ratio (OR): 1.76; P = 0.018], presence of AAp findings on ultrasonography (OR: 15.4; P < 0.001), confirmation of AAp in the histopathologic analysis (OR: 2.6; P = 0.003), determination of perforation in the appendectomy specimen (OR: 2.2; P = 0.004), the diameter of the appendix (P < 0.001), and hospital stay (P = 0.003). There was no statistically significant difference in terms of interval between the initiation of symptoms and admission to the hospital between the pre-COVID-19 (median: 24 h; interquartile range: 34) and COVID-19 (median: 36 h; interquartile range: 60) periods (P = 0.348). The interval between the initiation of symptoms until the hospital admission was significantly longer in patients with perforated AAp regardless of the COVID-19 or pre-COVID-19 status (P < 0.001). CONCLUSION: The present study showed that in the COVID-19 period, the ultrasonographic determination rate of AAp, perforation rate of AAp, and duration of hospital stay increased. On the other hand, negative appendectomy rate decreased. There was no statistically significant delay in hospital admissions that would delay the diagnosis of AAp in the COVID-19 period.

Tissue Heavy Metals in Liver Diseases.

BACKGROUND: Our objective was to determine the levels of heavy metals, oxidants, and antioxidants in liver tissue of patients with chronic liver disease (CLD) compared with healthy living liver donors (LLDs). METHODS: We obtained liver specimens from patients undergoing liver transplant for CLD. Samples were also obtained from LLDs. Biochemical analyses were performed on all samples, and the levels of liver tissue, heavy metal, and oxidant-antioxidants biomarker levels in patients with CLD were compared with those measured in LLDs. RESULTS: One hundred and eighteen individuals were included for analyses. Fifty-nine were patients with CLD, and 59 were LLDs. The median levels of liver tissue of superoxide dismutase (P = .009), glutathione peroxidase (P = .042), total oxidant status (P = .006), oxidative stress index (P < .001), and copper (P = .035) were prominently more elevated in CLD than LLDs. On the other hand, the median levels of liver tissue of cadmium (P < .001), selenium (P = .042), and zinc (P < .001) levels were more elevated in the LLDs than patients with CLD. The 2 groups were similar in terms of total antioxidant status, manganese, arsenic, and lead levels. CONCLUSIONS: Superoxide accumulation in the liver was higher in patients with CLD. Concerning heavy metals, only the median tissue copper was elevated in patients with CLD with higher Cu/Zn ratio. Cadmium, selenium, and zinc were significantly higher in the healthy LLDs.

High-Level Procalcitonin in Patient with Mixed Fibrolamellar Hepatocellular Carcinoma: A Case Report and Literature Review.

Course of blood procalcitonin levels by days.

Acute Pancreatitis: A Rare but Serious Complication for Living Liver Donors; Risk Factors and Outcomes.

OBJECTIVES: The purposes of this study were to determine the incidence of acute pancreatitis after living donor hepatectomy and to investigate potential risk factors and outcomes. MATERIALS AND METHODS: Clinical data of all donors who underwent donor hepatectomy between January 2015 and December 2016 in our liver transplant institute were reviewed. Donor data were obtained from a prospectively maintained database. The donors were divided into 2 groups according to whether they developed postoperative pancreatitis. The following data were compared between the 2 groups: demo-graphic information (age, sex), body mass index, type of hepatectomy (right, left, or left lateral), intraoperative cholangiographic findings, operative time, blood loss, graft data (graft weight, remnant liver ratio), duration of postoperative hospital stay, and postoperative morbidity and mortality (if any). Pancreatitis severity and treatment outcomes were also examined in patients with postoperative pancreatitis. RESULTS: Our study included 348 donors who underwent donor hepatectomy for living-donor liver transplant. Postoperative pancreatitis developed in 6 donors (1.7%). We found no statistical differences between patients with and without postoperative pancreatitis in terms of demographic and intra-operative findings. Neither loco-regional nor systemic complications of pancreatitis developed in any of the patients. Therefore, all were classified as having mild pancreatitis according to revised Atlanta classification. The mean APACHE II score was 5.2 ± 1.2 points (range, 4-7 points). All patients with postoperative pancreatitis received conservative-supportive treatment. CONCLUSIONS: Although postoperative pancreatitis is a rarely reported complication in living liver donors, it should always be considered, especially in patients who unpredictably deteriorate in the postoperative period. Proper recognition and timely treatment can help avoid s erious consequences.

Portal vein reconstruction with cryopreserved vascular grafts: A two-edged sword.

BACKGROUND: Portal vein anastomotic complications related to size discrepancy are important causes of morbidity and mortality in pediatric liver transplantation. Interposed vascular grafts in portal vein anastomosis can solve this problem. The aim of this study is to evaluate the results of pediatric liver transplantations performed using cryopreserved interposed vascular grafts between graft portal vein and superior mesenteric vein (SMV)-splenic vein (SpV) confluence. METHODS: Twenty-nine pediatric patients received liver transplantation using cryopreserved venous grafts in our Liver Transplant Institute between 2013 and 2020 were included in this study. Demographic, clinical, and operative characteristics and postoperative follow-up were analyzed. RESULTS: Sixteen patients (55.2%) had portal hypoplasia and five patients (17.2%) had portal vein thrombosis. In total, six patients (20.6%) suffered portal vein thrombosis in the early postoperative period. Three patients (10.3%) experienced portal vein thrombosis in the late postoperative period. Late portal vein thrombosis rate was significantly higher in patients with early portal vein thrombosis (3/6 patients [50%] versus 0/23 patients [0%]; p = .034). Lack of portal flow was significantly higher in patients with both early (50% versus 0%; p = .002) and late portal vein thrombosis (66.7% versus 6.7%; p = .03). CONCLUSION: Preoperative portal vein thrombosis and insufficient flow are important factors affecting success of liver transplant in children. The use of interposed vein grafts in problematic portal anastomoses can overcome portal flow problems.

An investigation into the factors predicting acute appendicitis and perforated appendicitis.

BACKGROUND: To investigate the factors predicting acute appendicitis (AAp) and perforated AAp in patients who underwent surgery with a preliminary diagnosis of AAp. METHODS: Between May 2009 and December 2018, 1316 patients underwent appendectomy with a presumed diagnosis of AAp. To investigate the factors predicting AAp, patients were divided into two groups considering the histopathological presence of inflammatory changes in the appendix: AAp positive (AAp group; n=1043) and AAp negative (Non-AAp group; n=273). Also, to investigate the factors predicting appendiceal perforation, patients with AAp were divided into two groups considering the presence of perforation: non-perforated AAp (n=850) and perforated AAp (n=193). ROC curve analysis was used to identify optimum cut-off values of quantitative variables. The groups were compared using univariate analysis methods and parameters with a p≤ 0.20 were taken into a multivariate logistic regression model. RESULTS: Multivariate analysis method related to factors predicting AAp showed that gender (male; p=0.034; OR=1.4), WBC (≥10.900; p=0.022; OR=1.5), MPV (≥29.1; p=0.006; OR=1.6), TBil (≥0.61; p=0.034; OR=1.4), CRP (≥0.725; p=0.002; OR=1.7), NLR (≥5.13; p=0.034; OR=1.5), PNR (<24.04; p=0.001; OR=1.9) and US findings (AAp+; p<0.001; OR=2.9) were independent factors for predicting AAp. Multivariate analysis method related to factors predicting appendiceal perforation showed that age (≥32 years; p<0.001; OR=2.5), TBil (≥0.67; p=0.046; OR=1.5), CRP (≥3.75; p<0.001; OR=3.0) and NLR (≥5.69; p=0.006; OR=1.8) were independent factors for predicting perforated AAp. CONCLUSION: We believe that predicting both AAp and perforation will help the clinician evaluate patients who applied to the emergency unit with presumed diagnosis AAp. This approach will also contribute to reducing the negative appendectomy and perforation rates.

Short-term experiences of a liver transplant centre before and after the COVID-19 pandemic.

BACKGROUND/AIM: With the COVID-19 pandemic, managing the process of solid organ transplantation has become a significant matter for transplant centres. In this study, we report our experiences on evaluating the effects of COVID-19 in patients with recent liver transplants. MATERIALS AND METHODS: We evaluated patients who received liver transplants during three close consecutive periods of time. For transplants conducted between October 1 and December 31, 2019, January 1 and March 10, 2020 and March 11 and June 22, 2020, the lung tomographies of patients were inspected for radiological signs of viral pneumonia. For patients after March 11, 2020, the hospital's electronic database system was scanned for preoperative and postoperative SARS-CoV-2 testing from Real-time Polymerase Chain Reaction (RT-PCR) of the respiratory tract samples. RESULTS: A total of 149 patients over the age of 18 who received liver transplants at our centre between October 1, 2019 and June 22, 2020 were evaluated. During this time span, our centre conducted liver transplants on patients from 34 different provinces and also abroad. Within this time period, a total of nine patients had respiratory samples with a positive SARS-CoV-2 RT-PCR test. PCR of respiratory tract samples was performed in 21 (14%) patients to identify the other potential infective agents in the respiratory tracts; Rhinovirus and Influenza A were detected in two and respiratory syncytial virus (RSV) was detected in one patient. During the transplant periods, 99 (67.1%) patients were evaluated with computed tomography (CT). The CT findings of 18 (12%) patients were consistent with viral pneumonia. There was a statistically significant difference between the groups only in terms of air bronchogram findings (P = .012). CONCLUSION: The clinical status of our short-term liver transplant patients was far better than we originally anticipated, but it remains obvious that the necessary precautions should continue to be taken.

Analysis of risk factors affecting the development of peptic ulcer perforation: case-control study.

AIM: The aim of the to determine the risk factors associated with increased risk of peptic ulcer perforation (PUP). MATERIAL AND METHODS: The demographic, clinic, and biochemical parameters of 65 patients (PUP group) who underwent PUP surgery at our clinic between June 2009 and September 2016 were compared with the data of 134 patients (control group) who underwent endoscopy at a gastroenterology clinic for dyspeptic complaints. The control group were matched at random in a 1 : 2 ratio with the PUP group. Univariate analyses were used to compare different variables and variables with clinical significance, and p ≤ 0.05 was used in the backward stepwise logistic regression model. RESULTS: This study included 65 patients with peptic ulcer perforation aged 17 to 92 years (PUP group) and 134 patients with dyspeptic complaints aged 18 to 87 years (control group). Univariate analysis showed that statistically significant differences were found between groups in terms of non-steroidal anti-inflammatory drugs usage (p = 0.042; OR = 1.868), smoking (p < 0.001; OR = 5.124), old age (p = 0.003), low body mass index (BMI) (p < 0.001), and low hemoglobin (Hb) (p = 0.002). However multivariate analysis showed that increasing age (p = 0.004; OR = 1.035), smoking (p = 0.007; OR = 3.591), decreasing Hb (p = 0.042; OR = 1.277), and decreasing BMI (p < 0.001; OR = 1.669) were independent clinically significant risk factors for development of PUP. CONCLUSIONS: This study showed that decreased BMI, decreased Hb, increased age, and smoking were independent risk factors for development of PUP. Thus, this group of patients needs particular attention paid to suggestive symptoms with early diagnosis and optimal management of peptic ulcer disease.

Differential diagnosis of the granulomatous appendicitis: Retrospective analysis of 16 cases.

BACKGROUND: This study aims to present the usability of real-time polymerase chain reaction (PCR) and interferon-gamma release assay (IGRA) in the differential diagnosis of granulomatous appendicitis (GAp), especially in areas where tuberculosis (TB) is endemic. METHODS: Sixteen patients underwent appendectomy with presumed diagnosis of acute appendicitis were retrospectively analyzed for histopathological diagnosis of GAp. Real-time PCR method was used to show the whether presence of DNA of the tubercle bacilli in paraffin-embedded tissue blocks. IGRA test was used to investigate whether tubercle bacilli- specific interferon gamma was present in peripheral blood. RESULTS: Sixteen patients (male: 10 female: 6) aged between 21 and 82 years were included in this study. All patients had acute appendicitis and three of them also had appendiceal perforation. Histopathologically, necrotizing granulomatous inflammation was detected in all appendectomy specimens. Acid-fast bacilli were not detected in any of the pathology slides stained with Ehrlich-Ziehl-Neelsen. Real-time PCR was studied in paraffin-embedded tissue blocks of all patients with GAp, but the TB bacilli DNA was amplified in only three patients. IGRA test was studied in peripheral blood samples of 12 patients with GAp and results were as follows: negative (n=9), positive (n=2) and indeterminate (n=1). CONCLUSION: We believe that the use of anamnesis, histopathological findings, tissue PCR, blood IGRA and clinical findings together are important for differential diagnosis of GAp, especially where TB is endemic. We also suggest that all appendectomy specimens should be sent to the laboratory for histopathological evaluation even if specimens appear macroscopically normal.

Xanthogranulomatous appendicitis: A comprehensive literature review.

BACKGROUND: Xanthogranulomatous inflammation is characterized histologically by a collection of lipid-laden macrophages admixed with lymphocytes, plasma cells, neutrophils, and often multinucleated giant cells with or without cholesterol clefts. AIM: To review the medical literature on xanthogranulomatous appendicitis (XGA). METHODS: We present a patient with XGA and review published articles on XGA accessed via the PubMed, MEDLINE, Google Scholar, and Google databases. Keywords used were "appendix vermiformis," "appendectomy," "acute appendicitis," and "XGA." The search included articles published before May 2020, and the publication language was not restricted. The search included letters to the editor, case reports, review articles, original articles, and meeting presentations. Articles or abstracts containing adequate information about age, sex, clinical presentation, white blood cells, initial diagnosis, surgical approach, histopathological and immunohistochemical features of appendectomy specimens were included in the study. RESULTS: A total of 29 articles involving 38 patients with XGA, were retrospectively analyzed. Twenty (52.6%) of the 38 patients, aged 3 to 78 years (median: 34; IQR: 31) were female, and the remaining 18 (47.4%) were male. Twenty-five patients were diagnosed with acute appendicitis, ruptured appendicitis, or subacute appendicitis, and the remaining 13 patients underwent surgery for tumoral lesions of the ileocecal region. Twenty-two of the patients underwent urgent or semi-urgent surgery, and the remaining 16 patients underwent interval appendectomy. CONCLUSION: Xanthogranulomatous inflammation rarely affects the appendix vermiformis. It is associated with significant diagnostic and therapeutic dilemmas due to its variable presentation. It is often associated with interval appendectomies, and a significant number of patients require bowel resection due to the common presentation of a tumoral lesion. XGA is usually identified retrospectively on surgical pathology and has no unique features in preoperative diagnostic studies.

Evaluation of liver transplant recipients underwent incidental appendectomies.

OBJECTIVE: To assess the clinicopathological features of liver transplant recipients underwent incidental appendectomies. METHODS: Between September 2002 and July 2019, 2500 patients underwent liver transplantation at our Liver Transplant Institute, including 38 (24 males, 14 females) who also underwent incidental appendectomies. Incidental appendectomies were performed on 24 patients during recipient hepatectomies and on 14 during relaparotomies due to various surgical conditions. The following patient parameters were retrospectively evaluated: age, sex, underlying liver disease, liver transplant type, appendectomy indication, appendix length (mm) and diameter (mm), presence of appendicitis, and histopathological findings. RESULTS: The 38 patients who underwent incidental appendectomies had a mean age of 18.3±21.7 (range: 1-66) years and median appendix lengths and diameters of 55 (range: 19-90) mm and 6 (range: 4-20) mm, respectively. Histopathologically, the appendectomy specimens were classified as follows: vermiform appendix (n=16), lymphoid hyperplasia (n=13), acute appendicitis (n=3), fibrous obliteration (n=3), perforated appendicitis (n=1), mucinous cystadenoma (n=1), and appendiceal serosa invasion by sigmoid adenocarcinoma (n=1). There were no postoperative complications, including wound infections, abscesses, or leakage from the appendiceal stumps, related to the incidental appendectomies. CONCLUSION: This study demonstrated that incidental appendectomies can be successfully performed in immunosuppressed patients. However, additional studies are required to confirm these results.