Comparison of severity and complication rates of acute cholecystitis during pandemic and pre-pandemic periods?

BACKGROUND: Cancellations of surgeries for elective cases and late admissions of symptomatic cases during the pandemic period might have increased the number of cases of acute cholecystitis and its complications. PURPOSE: To compare the severity of acute cholecystitis and complication rates during the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We evaluated the computed tomography (CT) findings observed for the diagnosis of complications for both acute simple and acute complicated cholecystitis during both the pandemic and pre-pandemic periods. Patients admitted to the hospital between March 2020 and December 2020 made up the study group and the corresponding appropriate patients from one year earlier were studied as the control group. In addition to the CT findings, clinical and laboratory findings, co-morbidities such as diabetes, as well as the admission time to hospital from the onset of the initial symptoms to hospital admission were also evaluated. RESULTS: A total of 88 patients were evaluated (54 in the study group, 34 in the control group; mean age = 64.3 ± 16.3 years). The male-to-female ratio was 51/37. The number of patients diagnosed with complicated cholecystitis were significantly higher in the study group (P = 0.03). Murphy finding and diabetes status were similar between the two groups (P = 0.086 and P = 0.308, respectively). Admission time to the hospital was significantly different for study and control groups in simple cholecystitis patients (P = 0.045); with no significant difference in cases of complicated cholecystitis (P = 0.499). CONCLUSION: Our study reveals the course of acute cholecystitis during the pandemic period was much more serious with higher complications.

Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients.

INTRODUCTION: The CHEK2 gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline CHEK2 mutations are linked to an increased risk of breast cancer. Therefore, the aim of this study was to identify the prevalence of CHEK2 variants in BRCA1/2 and PALB2 negative early-onset patients with breast cancer and/or ovarian cancer in a Turkish population for the first time. METHODS: The study included 95 patients with BRCA1/2 and PALB2 negative early-onset breast cancer and/or ovarian cancer and also 60 unaffected women. All the intron/exon boundaries and coding exons of CHEK2 were subjected to mutational analysis by heteroduplex analysis and DNA sequencing. RESULTS: A total of 16 CHEK2 variants were found in breast cancer patients within the Turkish population. CHEK2 c.1100delC mutation studied in the CHEK2 gene most frequently was not detected in our study. The prevalence of variants of uncertain significance in CHEK2 was found to be 7.3% (n= 7) in BRCA1/2 and PALB2 mutation negative Turkish patients with early-onset breast and/or ovarian cancer. DISCUSSION/CONCLUSION: The present study may shed light on alternative variations that could be significant for understanding the prevalence and clinical suitability of the CHEK2 gene.

Outcome of split liver transplantation vs living donor liver transplantation: A systematic review and meta-analysis.

BACKGROUND: The outcomes of liver transplantation (LT) from different grafts have been studied individually and in combination, but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT (DD-SLT) and living donor LT (LDLT). AIM: To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis. METHODS: This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The following databases were searched for articles comparing outcomes of DD-SLT and LDLT: PubMed; Google Scholar; Embase; Cochrane Central Register of Controlled Trials; the Cochrane Database of Systematic Reviews; and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The search terms used were: "liver transplantation;" "liver transplant;" "split liver transplant;" "living donor liver transplant;" "partial liver transplant;" "partial liver graft;" "ex vivo splitting;" and "in vivo splitting." RESULTS: Ten studies were included for the data synthesis and meta-analysis. There were a total of 4836 patients. The overall survival rate at 1 year, 3 years and 5 years was superior in patients that received LDLT compared to DD-SLT. At 1 year, the hazard ratios was 1.44 (95% confidence interval: 1.16-1.78; P = 0.001). The graft survival rate at 3 years and 5 years was superior in the LDLT group (3 year hazard ratio: 1.28; 95% confidence interval: 1.01-1.63; P = 0.04). CONCLUSION: This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.

Evaluation of the Trend of Biochemical Functions in the Early Period After Cadaveric Liver Transplantation.

BACKGROUND: Monitoring biochemical parameters to detect early complications after liver transplantation (LT) is important. Thus, we aimed to investigate parameter trends indicating liver function in patients who did not develop complications after cadaveric LT. METHODS: A total of 266 cadaveric LT operations performed by a single center between 2007-2022 were included in the study. Patients with any early complications were excluded from the study. During the first 15 days, the parameters reflecting the patients' liver integrity and synthesis functions were evaluated. All parameters studied were evaluated at the same time of day and by a single laboratory. RESULTS: Regarding synthesis functions, the coagulation parameters (prothrombin time and international normalized ratio) peaked on the first day and then decreased. Regarding tissue hypoxia, there was no significant change in lactate values. Total and direct bilirubin values also decreased after peaking on the first day. No significant change was observed in albumin, another liver synthesis value. CONCLUSIONS: Although an increase in aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, prothrombin time, and international normalized ratio, which was especially seen on the first day, is considered normal, values that do not decrease after the second day or lactate values that increase gradually should be a warning in terms of possible early complications.

Investigation of the Effectiveness of Oleuropein in a Three-Dimensional In Vitro Hepatocellular Tumor Sphere Model.

OBJECTIVES: This study was conducted to examine the dose-related effects over time of oleuropein on the proliferation and area of tumor spheroids in hepatocellular carcinoma cells. MATERIALS AND METHODS: We examined the possible effects of 100 to 500 µM dose concentrations of oleuropein on HepG2 cell proliferation using a real-time cell analyzer. A 3-dimensional hepatocellular carcinoma tumor spheroid model was established by seeding HepG2 cells at a density of 160 cells/well in custom 96-well microplates with low attachment surfaces and culturing for 3 days. Tumor spheres were treated with increasing oleuropein doses for 72 hours, and images were captured every 24 hours. The dose-dependent effects of oleuropein on tumor sphere size were analyzed by measuring the area of tumor spheres with ImageJ software. We conducted oleuropein viability and cytotoxicity analyses using calcein acetoxymethyl ester-based and propidium iodide-based staining in the tumor model. RESULTS: Oleuropein inhibited cell proliferation; as the dose concentration of oleuropein increased, so did its capacity to inhibit cell proliferation (P < .001). The size of untreated tumor spheres increased at 72 hours (P < .001). However, treatment with 100 to 500 µM oleuropein reduced tumor size by 63.56% to 88.06% compared with untreated cells at the end of 72 hours (P < .001). With increasing concentrations, oleuropein inhibited the viability of tumor spheres, eliminating necrotic death caused by tumor hypoxia. CONCLUSIONS: Overall, oleuropein reduced the size of tumors by inhibiting tumor proliferation and viability. In this context, oleuropein could be a candidate molecule for further extensive studies to reduce hepatocellular carcinoma tumors to meet Milan criteria for liver transplant.

Effect of Locoregional Treatments in Hepatocellular Carcinoma: What Are the Pathologic/Radiologic Milan Criteria?

OBJECTIVES: Milan criteria is the most commonly used criteria for patients with hepatocellular carcinoma awaiting liver transplant. The effects of locoregional therapy on downstaging or bridging before liver transplant on survival remain controversial. Considering that the tumor size may change with locoregional therapy and formalin fixation after explantation, we aimed to evaluate the effects of locoregional therapy on radiological and pathological Milan criteria and survival. MATERIALS AND METHODS: Demographic data, etiology, preoperative alpha-fetoprotein value, Child-Pugh and Model for End-Stage Liver Disease-Na scores, status of being inside or outside of radiological Milan criteria, status of being inside or outside of Milan criteria in explant (pathological Milan criteria), and the locoregional therapy types and combinations were evaluated for their effects on inclusion in Milan criteria and survival. RESULTS: During the study period, 396 patients underwent liver transplant at our center, with 97 because of cirrhosis and hepatocellular carcinoma. When we viewed patients according to preoperative radiologic evaluations, 67.9% were within Milan criteria and 32.1% were outside. When we viewed according to explant (pathological) evaluations, 80.7% of patients were within Milan criteria. Among 97 patients, 71 (73.2%) had locoregional therapy (22 [30.9%] for downstaging, 49 [69.0%] for bridging to transplant), and 12 patients (12.3%) were within Milan criteria on explant examination while outside of Milan criteria before LT. One-year, 3-year, and 5-year survival rates were 80.7%, 76.1%, and 71.6%, respectively. CONCLUSIONS: As a result of radiological evaluations, in patients who were outside of Milan criteria and underwent locoregional therapy, explant pathology within Milan criteria had a positive effect on survival; however, after locoregional therapy, there was no significant effect on survival in patients who were still outside of Milan criteria.

Duration of operation and diagnosis of hepatitis B (HBV) is an independent risk factor for surgical site infections after liver transplantation.

Objectives: Surgical site infections (SSI) are the most common complications after liver transplantation (LT). Although there are some risk factors known in the literature after LT, the available data is insufficient for routine use. In the present study, it was aimed to define the parameters that may be used to clearly determine the risk of SSI after LT in our clinic. Material and Methods: In the present study, we evaluated 329 patients who underwent liver transplantation with regard to risk factors for surgical site infections. The relation between demographic data and SSI was evaluated using SPSS, Graphpad, and Medcalc statistical programs. Results: In a total of 329 patients, SSIs were determined in 37 (11.24%). Among the 37 patients, 24 were classified as organ space (64.9%) and 13 as deep SSI (35.1%). None of these patients developed superficial incisional infection. SSI showed statistically significant relation with operation time (p= 0.008), diabetes (p= 0.004), and cirrhosis due to hepatitis B (p <0.001). Conclusion: As a result, deep and organ space infections are much more observed in patients undergoing liver transplantation with hepatitis B, diabetes mellitus and prolonged surgery. This is thought to have developed because of chronic irritation and increased inflammation. Since data on hepatitis B and duration of surgery are limited in the literature, this study is considered to be a contribution to the literature.

Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List.

BACKGROUND: As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. METHODS: Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. RESULTS: In our study, 46.7% (n = 28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P = 0.001). CONCLUSIONS: Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.

Does Liver Transplant Improve Neurological Symptoms in Wilson Disease? Report of 24 Cases.

OBJECTIVES: Wilson disease is an inherited disorder that results in copper accumulation in the tissues with liver injury and failure. Orthotopic liver transplant is one of the treatments of choice for this disease. The aim of this study was to compare the neurological symptoms, before and after orthotopic livertransplant, of patients with liver cirrhosis due to Wilson disease, who represent a special group of patients with liver failure. MATERIALS AND METHODS: Between 2007 and 2020, there were 24 patients with Wilson disease resistant to medical treatment who underwent deceased donor orthotopic livertransplant and were followed up for 1 year, 5 years, and 10 years for evaluation with neurological scoring systems. Patients were also evaluated for postoperative complications and survival. RESULTS: Of the 24 patients evaluated, there were 13 (54.2%) female patients and 11 (45.8%) male patients, and the mean age was 34 years (range, 14-57 years). One of the patients died from early postoperative sepsis. After orthotopic livertransplant, disease scores returned to normal in 16 patients and improved in the remaining patients. Before transplant, all patients required help in their daily activities. After transplant, there were significant improvements in some symptoms, and the patients became more independent in their daily lives. CONCLUSIONS: Our study shows that orthotopic liver transplant provides significant improvement in neurological symptoms and quality of life in patients with Wilson disease.

Liver Transplantation in Alstrom Syndrome: A Case Report.

Alstrom syndrome is a genetic disorder with autosomal recessive inheritance and multiple organ failure. Hearing loss, childhood obesity, diabetes mellitus, and nonalcoholic fatty liver disease are common disorders in this disease. Degree of nonalcoholic fatty liver disease ranges from benign steatosis to cirrhosis. Since it first description in 1959, 89 cases have been reported, and none in the literature underwent liver transplant. In this report, we describe a 19-year-old male patient with a diagnosis of hearing loss, obesity, and diabetes mellitus started since childhood. He was evaluated for bloody vomiting, and grade 3 esophageal varices were detected, with liver cirrhosis findings made with abdominal tomography. The patient had a Model for End-Stage Liver Disease score of 23, and deceased donor liver transplant was planned. After an appropriate donor was identified, the patient underwent liver transplant with an operation lasting approximately 6 hours. Cold ischemia time was about 5 hours, and anastomosis time was about 30 minutes. The patient was extubated on posttransplant day 1. On posttransplant day 10, his vital parameters remained normal, but he had blurred consciousness and loss of orientation. Neurological examination and imaging revealed minimal subdural effusion and mild cerebral cortical dysfunction in electroencephalogram. The patient's symptoms improved after medical treatment, and the patient was discharged on day 13 posttransplant. At the month 24 outpatient follow-up, the patient had no problems. Alstrom syndrome is an autosomal recessive genetic disorder with multiple organ failure. Although various degrees of liver disease have been described in the literature that may progress to cirrhosis of the liver, our present case is considered original because of the absence of liver transplant descriptions in the literature.

Myelitis After Liver Transplant: A Case Report.

We report a case of neurotoxicity as a side effect of a calcineurin inhibitor (tacrolimus), which is used as an immunosuppressive drug after liver transplant. Our patient had chronic hepatic failure due to Budd-Chiari syndrome and underwent a liver transplant after an appropriate deceased donor organ was obtained. After organ transplant surgery, he was kept under the effect of an immunosuppressive drug (tacrolimus) with daily control of the level of drug in his blood to avoid drug toxicity. Despite the level of drug in his blood being within the ideal range, the patient developed neurotoxicity that presented as weakness of his extremities. Appropriate diagnostic tests were done, and all proved that these signs and symptoms were related to the use of tacrolimus. Therefore, the drug was changed to cyclosporine. After a few months, the patient regained normal neurological functions of his extremities. We should take precautions to monitor neurological symptoms and signs while we administer calcineurin inhibitors.

Persistency of high proinflammatory cytokine levels from colostrum to mature milk in preeclampsia.

OBJECTIVES: Recent evidence suggests a role of an excessive maternal inflammatory response in the pathogenesis of preeclampsia. Whether this imbalance can be transferred from mother to breast milk remains to be established. DESIGN AND METHODS: 15 preeclamptic and 15 healthy pregnant women were recruited in this study. Colostrum and milk samples were collected postpartum in the first 48 h and at 30 days, respectively. Samples were analyzed for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and soluble IL-2R (sIL-2R) levels with chemiluminescence enzyme immunometric assays. RESULTS: Colostrum cytokine levels corrected for gestational age and type of delivery were not significantly different in the two groups. Cytokine levels significantly decreased in mature milk versus colostrum in the control group (P < 0.05), but did not significantly decrease in the preeclampsia group (P > 0.05), except for TNF-alpha (P < 0.05). Mature milk IL-8 and TNF-alpha levels were higher in the preeclampsia group versus controls (P < 0.05). CONCLUSION: Results of this study show that proinflammatory cytokines in breast milk exhibit biological variation at different periods of human lactation. In preeclampsia, high cytokine levels persist at least for 30 days. These results suggest that preeclampsia may affect milk cytokine balance and offer an immunological signal for the host defense in high-risk neonates.

Effects of three different sterilization methods on utero-ovarian Doppler blood flow and serum levels of ovarian hormones.

OBJECTIVE: The aim of the study was to assess pre-operative and post-operative serum levels of ovarian hormones and changes in utero-ovarian arterial blood flow by Doppler ultrasonography in women in whom one of three different sterilization methods was applied. STUDY DESIGN: The Pomeroy method of tubal ligation, fimbriectomy, or laparoscopic bipolar coagulation were applied in 42 patients. Serum levels of sex hormones were checked, and utero-ovarian arterial Doppler measurements were performed pre-operatively and post-operatively. The presence or absence of dysmenorrhea was noted before and after the operations. RESULTS: We detected a significant increase in the average uterine arterial resistivity index (RI) and both ovarian arterial pulsatility index (PI) values in the Pomeroy method group (p<0.05). There was a significant increase in dysmenorrhea complaints in the total number of patients (p<0.05), particularly in the fimbriectomy group. CONCLUSION: The significant increase in uterine arterial Doppler measurements with the Pomeroy method may be due to the removal of a larger tubal segment. Even though the increase is not statistically significant, fimbriectomy should not be applied in young women, because it may increase dysmenorrhea and the procedure is not reversible.

Increased plasma levels of Urotensin-II in preeclampsia-eclampsia: a new mediator in pathogenesis?

OBJECTIVE: To assess the possible role of human Urotensin-II (hU-II), a vasoactive peptide, in the pathophysiology of preeclampsia-eclampsia prospectively. STUDY DESIGN: Sixty subjects, 30 with a diagnosis of preeclampsia-eclampsia (group I) and 30 control subjects (group II), who had been admitted between January, 2002 and December, 2002, were taken into the study. Patients in group I had an increase in blood pressure after 28th week of gestation, without any history of hypertensive disease and/or preeclampsia or eclampsia. hU-II levels were assessed using a radioimmunoassay method. RESULTS: No statistically significant difference in terms of age, gestational age, gravidity, abortion and parity was detected among groups (P > 0.05). Plasma hU-II levels in the preeclampsia-eclampsia and control groups were 10.11 +/- 5.94 pg/mL and 3.93 +/- 1.73 pg/mL, respectively. Difference between plasma hU-II levels of the two groups was found to be statistically significant (P < 0.00001). Also there was correlation between hU-II levels and mean arterial pressures in both groups (r = 0.73, P < 0.0001 and r = 0.72, P < 0.0001 for groups I and II, respectively). CONCLUSION: Results of our study strongly suggest an important role for hU-II in the pathophysiology of preeclampsia-eclampsia. Further studies concerning placenta and cord blood samples will more clearly elucidate the role of Urotensin-II in the pathogenesis of preeclampsia-eclampsia, and its feto-maternal effects.

Decreased adrenomedullin and total nitrite levels in breast milk of preeclamptic women.

OBJECTIVE: To observe the adrenomedullin (AM) and total nitrite levels in the milk of preeclamptic and normal pregnant women. DESIGN AND METHODS: Fifteen women with preeclampsia and 15 normal pregnant women were included in the study. Total nitrite was quantitated by Griess reaction, while AM was measured by HPLC. RESULTS: The levels of AM and total nitrite in colostrum and 30th-day breast milk were decreased in preeclamptics. Total nitrite levels (micromol/l) were 56.09 +/- 11.18 vs. 82.20 +/- 12.01, P < 0.05, in colostrum of preeclamptics and controls, respectively. The level of total nitrite was 37.75 +/- 12.10 vs. 53.28 +/- 10.25, P < 0.05, in 30th-day milk of same patients. AM levels (pg/ml) were 11.18 +/- 1.11 vs. 16.59 +/- 1.24, P < 0.0001, in colostrum of preeclamptics and controls, respectively. In 30th-day milk of same patients, AM levels were 8.41 +/- 1.39 vs. 12.18 +/- 1.48, P < 0.005, respectively. CONCLUSION: This report shows for the first time that human milk has decreased levels of AM and total nitrite in preeclampsia.

Primary pure ovarian choriocarcinoma mimicking ectopic pregnancy: a report of fulminant progression.

Nongestational choriocarcinoma of the ovary is a germ cell tumor with a worse prognosis than gestational choriocarcinoma. In this report we present a nongestational choriocarcinoma that was referred to our hospital as an ectopic pregnancy. The clinical features, management, and outcome are discussed.

Adenosine deaminase activity in serum and placenta of patients with anembryonic pregnancies and missed abortions.

AIM: The aim of this study is to assess adenosine deaminase (ADA) activity in the serum and placenta of patients with missed abortions, anembryonic pregnancies, and voluntary abortions. METHODS: Nine cases of anembryonic pregnancies and 21 cases of missed abortions (group I, n=30), and voluntary dilatation and curettage cases (group II, n=30) were included in this prospective study. Adenosine deaminase activity in serum and placental tissue was measured according to the Giusti method. The t-test was applied for statistical evaluation with the help of SPSS 9.0. RESULTS: The mean serum ADA level in the abortion cases (group I) was 9.13+/-1.59 U/l, while it was 17.06+/-6.5 U/l in the control group (group II; p<0.05). Also, the mean placental ADA levels in abortion cases and in the control group were 11.8+/-4.7 nmol/mg protein/min and 25.8+/-6.6 nmol/mg protein/min respectively (p<0.05). CONCLUSIONS: These results suggest that ADA may have a modulatory role in the implantation and duration of pregnancy. Low levels of ADA in early pregnancy may lead to an accumulation of products toxic to DNA and to the subsequent loss of the pregnancy.