Tıp Fakültesi / Faculty of Medicine
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Item Papanicolaou Smear Findings in Solid-Organ Transplant Recipients Compared With Normal Subjects According to the Bethesda 2001 System(2015) Atilgan, Alev Ok; Tepeoglu, Merih; Haberal, A. Nihan; Durukan, Elif; Kuscu, Esra; Haberal, Mehmet; 0000-0002-9894-8005; 0000-0002-3462-7632; 0000-0001-9852-9911; 0000-0001-8595-8880; 0000-0002-0992-6980; 0000-0002-8579-5564; 25894158; AAK-5222-2021; AAJ-8097-2021; AAK-4587-2021; AAK-3333-2021; AAI-8792-2021; AAJ-8621-2021Objectives: Solid-organ transplant recipients are at increased risk of developing cancer including cervical cancer compared with woman in the general population, mostly due to long-term immunosuppressive therapy. The Papanicolaou smear remains the primary method of screening cervical pathology including preinvasive and invasive lesions. The objective of this study was to evaluate Pap smear findings in solid-organ transplant recipients, determine the prevalence of abnormal smears, and compare these patients with the general population. Materials and Methods: We retrospectively examined 111 women patients who received liver or kidney transplant between January 1990 to December 2012 at Baskent University Ankara Hospital. Pap smear findings were compared with normal control patients matched for same age and technical procedure of cervical cytology. To selection of control patients, propensity score matching program was performed. All Pap smears were re-examined according to Bethesda 2001 criteria. Results: In 111 transplant patients, 2 patients (1.8%) had atypical squamous cells of undetermined significance, 8 patients (7.2%) had low-grade squamous intraepithelial lesion, 15 patients (13.5%) had Candida infection, 2 patients (1.8%) had Trichomonas vaginalis, 1 patient (0.9%) had herpes simplex infection, 13 patients (11.7%) had bacterial vaginosis, 15 patients (13.5%) had reactive changes due to inflammation, and 18 patients (16.2%) had atrophy. When we compared our results with the control group, there were statistically significant differences (P <= .05) between the 2 groups in epithelial cell abnormalities (low-grade squamous intraepithelial lesion), Candida infection, bacterial vaginosis, and atrophy. Conclusions: Pap smear screening potentially may help recognize cervical preinvasive and invasive lesions. The risk of developing cervical intraepithelial neoplasia is greater in transplant recipients because of immunosuppressive therapy. The incidence of low-grade squamous intraepithelial lesion was significantly greater in transplant recipients than the general population. Intensive follow-up with Pap smear in transplant recipients is important in the early detection of these lesions.Item Significance of Colonoscopic Findings in Patients After Kidney Graft(2015) Ensaroglu, Fatih; Harmanci, Ozgur; Ocal, Serkan; Korkmaz, Murat; Moray, Gokhan; Ozdemir, Handan; Colak, Turan; Selcuk, Haldun; Haberal, Mehmet; 0000-0002-7528-3557; 0000-0003-3719-9482; 0000-0002-8445-6413; 0000-0002-8372-7840; 0000-0003-2498-7287; 0000-0002-9333-782X; 0000-0002-3462-7632; 0000-0002-0643-4980; 26640913; X-8540-2019; ABH-4817-2020; AAJ-6976-2021; AAJ-8554-2021; AAE-1041-2021; AAM-1330-2020; AAJ-8097-2021Objectives: We aimed to investigate the colonoscopy findings in patients after kidney transplant. Materials and Methods: We retrospectively analyzed kidney transplant patients who had colonoscopy examinations for various indications between 2011 and 2015. Results: Eighty-one patients (25 women and 56 men) with a mean age of 39 years (range, 18-64 y) were identified. Mean follow-up after transplant was 9 years (range, 1-29 y). The most common indications for colonoscopy were diarrhea (41%), anemia (29%), gastrointestinal bleeding (12%), abdominal pain (12%), and unexplained weight loss (6%). Either colitis or ileitis or both were diagnosed in 20 patients (25%), whereas polyps were found in 9 patients (11%). One patient presented with hematochezia, which was diagnosed as cytomegalovirus colitis. The remaining cases of colitis or ileitis were diagnosed as nonspecific inflammation. Indications for colonoscopy were not correlated with age, duration after transplant, or use of immunosuppressive drugs. A subgroup analysis for mycophenolate-induced colitis found that 88% of patients used mycophenolate, but presence of colitis or ileitis had no statistical correlation with its use. In patients with poor gastrointestinal symptoms, the only significant predictor of presence of colitis or ileitis was a high C-reactive protein value (> 5 mg/dL; P=.02). Conclusions: Incidence of colitis and/or ileitis is a relatively common finding in patients after kidney transplant. Opportunistic infections, mycophenolate use, and mild degree of indeterminate colitis or ileitis disease may be the underlying condition. Cytomegalovirus infection should be screened in all recipients because it may cause serious complications or death in chronically immuno-compromised patients.Item COVID-19 Infections in Pediatric Renal Transplant Recipients(2022) Yilmaz, Aysun Caltik; Baskin, Esra; Gulleroglu, Kaan; Karakaya, Deniz; Akdur, Aydincan; Moray, Gokhan; Haberal, Mehmet; https://orcid.org/0000-0003-0774-4419; https://orcid.org/0000-0003-1434-3824; https://orcid.org/0000-0002-3462-7632; 35384829; AAD-1877-2021; AAJ-8833-2021; AAJ-8097-2021Objectives: The new coronavirus SARS-CoV-2 (COVID-19) first appeared in Turkey in March 2020, spread rapidly, and caused many deaths. Although COVID-19 is mostly a respiratory disease, it can cause kidney and multiorgan failure in some cases. We believe that by sharing information about the course and effects of COVID-19 infection in kidney transplant recipients receiving long-term immunosuppressive therapy our understanding will improve. Materials and Methods: Between March 2020 and October 2021, COVID-19 was researched in kidney transplant recipients under the age of 20 years who were followed at the Baskent University Transplantation Center. We documented the clinical characteristics and prognosis of pediatric kidney transplant recipients with COVID-19 disease. Results: Our study group included 23 patients with COVID-19 infection from 215 pediatric kidney transplant recipients. The mean age of the patients was 14.6 +/- 4.7 years; there were 9 female patients. The mean follow-up time posttransplant was 62.3 +/- 43.2 months. In 13 patients (56.5%), fever was the most frequent symptom. Most patients (n = 18, 78%) had minor symptoms and recovered completely after receiving supportive treatment. Four patients (17%) required hospitalization. One was diagnosed with COVID-19 infection 1 week after being treated with rituximab for acute antibody-mediated rejection. That patient died because of significant lung disease and multiorgan failure. Conclusions: Despite the fact that most of our pediatric transplant recipients had mild symptoms of COVID-19, we believe that particular caution should be observed in patients who have recently received intensive immunosuppressive medications. As a result of potential new vaccines, national immunization programs, and the emergence of novel virus strains, the clinical picture may change in the future. We believe that, as information sharing increases, we will learn more about COVID-19 in renal transplant recipients.Item Use of Eculizumab in Pediatric Patients with Late Antibody-Mediated Rejection After Kidney Transplantation(2022) Siddiqui, Meraj Alam; Baskin, Esra; Karakayali, Feza Yarbug; Gemici, Atilla; Gulleroglu, Kaan; Yilmaz, Aysun Caltik; Moray, Gokhan; Haberal, Mehmet; 0000-0002-3462-7632; 0000-0003-0774-4419; 0000-0003-1434-3824; 0000-0002-5739-6590; 35570600; AAJ-8097-2021; AAD-1877-2021; AAJ-8833-2021; ABF-7609-2022Late antibody-mediated rejection triggered by donor-specific antibodies is a leading cause of kidney allograft failure. Effective treatment options for late antibody-mediated rejection are limited in renal transplant recipients. Here, we report 2 pediatric cases of severe late antibody-mediated rejection resistant to conventional immunosuppressive therapy who were successfully treated with eculizumab. Two patients who fulfilled the late antibody-mediated rejection diagnostic criteria (positive donor-specific antibodies, elevated mean fluorescence index, acute and/or chronic morphological lesions in the microvasculature, and abnormal kidney function test) were included in this study. Both patients were previously unsensitized with negative panel-reactive antibody. Case 1 was a 12-year-old male patient with kidney failure secondary to vesicoureteral reflux who underwent related-living donor kidney transplantation 2 years ago. Eleven months later, he was diagnosed with late antibody-mediated rejection. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted. After the patient was treated with 2 doses of eculizumab, his mean fluorescence index dropped and serum creatinine decreased from 3.8 to 1.5 mg/dL. Case 2 was an unsensitized 16-year-old male patient with kidney failure secondary posterior urethral valve who underwent related-living donor kidney transplantation 4 years ago. Two years later, he was diagnosed with late antibody-mediated rejection. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted. After treatment with 2 doses of eculizumab, his mean fluorescence index dropped and serum creatinine decreased from 2.1 to 1.01 mg/dL. In both patients, eculizumab therapy effectively reduced the markers of late antibody-mediated rejection and improved the kidney function.Item Cervical Carcinoma in a Renal Transplant Recipient: A Case Report(2016) Tuncer, Hasan Aykut; Kirnap, Mahir; Dursun, Polat; Ayhan, Ali; Moray, Gokhan; Haberal, Mehmet; https://orcid.org/0000-0002-5434-1025; https://orcid.org/0000-0003-2498-7287; https://orcid.org/0000-0002-3462-7632; 25807337; K-1760-2018; AAH-9198-2019; AAJ-5802-2021; AAE-1041-2021; AAJ-8097-2021A range of cancer types, at increased rates, is described in renal transplant recipients receiving immunosuppression. Aside from immunodeficiency, heightened medical surveillance for cancer, lifestyle, and other risk factors all play a role. Although the relation between cancer risk and degree of immunodeficiency might not be linear, and might be different for a wide range of cancer subtypes, human papillomavirus-related cancers in long-term transplant recipients may suggest the role of even modest immunosuppression, when present long enough. High-risk human papillomavirus types are recognized as the cause of cancer of the cervix. We report a 49-year-old female renal transplant recipient diagnosed with cervical squamous cell carcinoma, 5 years after the transplant. Based on this patient, we highlight difficulties in surgical approach and the importance of close clinical follow-up including regular gynecologic screening for cervical premalignant and malignant lesions.Item Colon Biopsy Findings of Renal Transplant Patients(2016) Tastepe, Firdevs Zeynep; Ozgun, Gonca; Ozdemir, Binnaz Handan; Tepeoglu, Merih; Haberal, Mehmet; 0000-0002-3462-7632; 0000-0002-9894-8005; 0000-0002-3462-7632; 27805519; AAJ-8097-2021; AAK-5222-2021; AAJ-8097-2021Objectives: The purpose of this study was to evaluate colonic pathologies in renal transplant recipients. Materials and Methods: Patients with colon biopsies were selected from 1816 renal transplant recipients from January 1990 to December 2012 at Baskent University Hospital (Ankara, Turkey). Demographic and clinical findings with colon biopsies were examined. Results: There were 84 patients who had colon biopsies after renal transplant. There were 57 male and 27 female patients (median age at renal transplant was 33 y). Chronic diarrhea was the most common clinical finding at the time of colon biopsy. The median interval from renal transplant to first colon biopsy was 48.1 +/- 47.5 months. On microscopic evaluation, there were no pathologic changes in 17 patients. The remaining 67 patients had colitis (38 patients), polyps (17 patients), cytomegalovirus colitis (8 patients), and amyloidosis (4 patients). The mean interval between transplant and the diagnosis of colitis was 49.08 +/- 42.6 months, amyloidosis was 47.5 +/- 79.28 months, cytomegalovirus colitis was 5 +/- 3.5 months, and polyps was 77.65 +/- 58.8 months. There was a statistically significant difference between biopsy diagnosis and the time interval between transplant and colon biopsy (P <.01). Among 84 renal transplant recipients with colonic biopsies, 40 patients never had acute rejection episodes and 44 patients had at least 1 acute rejection episode. Seven of 8 patients with cytomegalovirus colitis, 19 of 38 with colitis, 3 of 4 with amyloidosis, and 5 of 17 with polyps had acute rejection episodes. Conclusions: In our report on colonic manifestations in renal transplant recipients, the most common colonic lesion was noninfectious colitis. Cytomegalovirus colitis is an important infection that affects immuno-suppressed individuals, such as transplant recipients. Cytomegalovirus must be kept in mind, and thorough sectioning and immunohistochemical staining should be used if necessary in the presence of any clinical or histologic suspicion for infective colitis.Item Clinical Characteristics of Acinetobacter baumannii Infection in Solid-Organ Transplant Recipients(2018) Serifoglu, Irem; Dedekarginoglu, Balam Er; Bozbas, Serife Savas; Akcay, Sule; Haberal, Mehmet; 0000-0002-7230-202X; 0000-0002-8360-6459; 0000-0002-7230-202X; 0000-0002-3462-7632; 29528021; AAS-6628-2021; AAI-8064-2021; AAB-5175-2021; AAJ-8097-2021Objectives: Acinetobacter baumannii, depending on the immune status of the host, may result in one of the most serious hospital infections. Infections involving A. baumannii infection have been recently rising. However, little is known about the clinical features of A. baumannii infection in solid-organ transplant recipients. We aimed to share our clinical experiences with A. baumannii infection in our transplant recipients. Materials and Methods: Between 2011 and 2017, 41 solid-organ transplant patients developed A. baumannii infection at Baskent University Hospital. Medical records were reviewed, and patient demographics, microbiology results, and overall outcome data were noted. Results: Of 41 solid-organ transplant patients with A. baumannii infection, 29 were male and 12 were female patients with mean age of 47.15 +/- 13.24 years. Our infection rate with A. baumannii infection was 6.1%. The most common sites of infection were deep tracheal aspirate (48.8%)and bloodstream (36.6%). Onset of infection 1 year post-transplant was identified in 58.5% of recipients. Risk factors included presence of invasive procedures (56.1%) and administration of high-dose corticosteroids for rejection 1 year before infection (68.3%). Thirty-day mortality rate was 41.5% (17/41 patients)and was not associated with the infection site, microbiological cure, clinical cure, and drug resistance in our study group. Conclusions: Acinetobacter baumannii is an important cause of hospital-acquired infection and mortality worldwide. A major problem with A. baumannii infection is delayed initiation of appropriate antibiotic treatment and the rising numbers of extensively drugresistant organisms. Predicting the potential risk factors, especially in the already at-risk solid-organ transplant population, has an important role in patient outcomes.Item Nonmelanoma Skin Cancers in Solid-Organ Transplant Recipients: A Single Center Experience(2018) Albayati, Abbas; Ozkan, Burak; Eyuboglu, Atilla Adnan; Uysal, Ahmet Cagri; Ertas, Nilgun Markal; Haberal, Mehmet; 0000-0003-2806-3006; 0000-0003-3093-8369; 0000-0002-9805-9830; 0000-0001-6236-0050; 0000-0002-3462-7632; 29528001; AAC-3344-2021; AAI-5063-2020; AIC-3493-2022; AAJ-2949-2021; AAJ-8097-2021Objectives: Skin cancers are one of the most common malignancies in solid-organ transplant recipients. Increased age and immunosuppressive drug use are risk factors for posttransplant skin malignancies. We evaluated nonmelanocytic skin cancer incidence and development time in transplant patients. Materials and Methods: We reviewed 1833 patients who received kidney, liver, and heart grafts between 1996 and 2016 at Baskent University. We excluded melanocytic skin cancers, premalignant lesions, and benign skin tumors. Results: Of 1833 patients, 1253 were male (68.4%) and 580 were female (31.6%), composed of 1133 kidney (61.8%), 512 liver (27.9%), and 120 heart recipients (6.5%). Of these, 22 patients (18 kidney/3 liver/1 heart) developed 23 different types of skin cancer. Prevalence of skin cancer was 1.20%. Mean age at presentation was 55.8 years (range, 37-71 y). Average time from transplant to skin malignancy was 6.1 years (range, 1-13 y), with the most common being basal cell carcinoma (43%, 10 cases), followed by squamous cell carcinoma (39%, 9 cases) and Kaposi sarcoma (13%, 3 cases). Tumor sites included head and neck (15 case), trunk (2 cases), lower extremity (2 cases), and upper extremity (2 cases). Neither local recurrence nor distant metastasis was shown. Conclusions: Skin cancer risk is increased in solid-organ transplant recipients versus the general population. Although squamous cell carcinoma is the most common tumor in this patient population, followed by basal cell carcinoma, we found this reversed in our patients. The low prevalence of skin malignancy (1.20%) may be associated with close clinical follow- up to detect premalignant skin lesions and the low-dose immunosuppressive drug regimen. We believe that local recurrence and distant metastasis were absent because we use a wide surgical margin of excision and provide strict follow-up. Routine dermatologic follow-up visits of transplant recipients are recommended to detect and treat early skin cancer and premalignant lesions and thus lower morbidity and mortality.Item Effect of Adipose-Derived Stem Cells on Colonic Anastomosis in Rats Immunosuppressed With Everolimus: An Experimental Study(2021) Karakaya, Emre; Akdur, Aydincan; Atilgan, Alev Ok; Uysal, Ahmet Cagri; Ozer, Huriye Eda Ozturan; Yildirim, Sedat; Haberal, Mehmet; 0000-0002-3462-7632; 0000-0002-8726-3369; 34269651; AAJ-8097-2021; AAA-3068-2021Objectives: Immunosuppressed patients sometimes require colorectal surgery. We investigated whether adipose tissue-derived stem cells contributed to anastomosis healing in rats immunosuppressed with the mTOR inhibitor everolimus. Materials and Methods: Sixty male Sprague-Dawley rats were randomly divided into 4 groups of 14 each, with all groups undergoing descending colon anastomosis; the 4 remaining rats were used for stem cell retrieval. Group 1 (control) underwent surgery only, group 2 received stem cell injection, group 3 received everolimus only, and group 4 received everolimus plus stem cell injection. After treatment, each group was randomly divided into 2 equal subgroups according to the day of euthanasia (posttreatment day 4 or day 7). We measured anastomosis bursting pressure and tissue hydroxyproline level and performed histopathological evaluation. Results: At both posttreatment days 4 and 7, median weight loss in group 3 was higher than in group 1, group 3 had higher severity of intraabdominal adhesion than group 4, and group 2 had mean hydroxyproline level higher than the other groups. At posttreatment day 4, mean bursting pressure was significantly different in group 1 versus groups 2 and 4 (P = .002) and group 2 versus groups 3 and 4 (P < .001). No significant differences were shown in pathological analysis except for vascular proliferation on day 7 (P = .003). Conclusions: Injection of adipose tissue-derived stem cells in the anastomosis site prevented anastomosis leakage by contributing to healing. Injection of adipose tissue-derived stem cells in the anastomosis region, especially in the early period after solid-organ transplant in recipients and after gastrointestinal surgery in immunosuppressed patients, may help reduce mortality and morbidity.Item De Novo Malignant Neoplasms in Renal Transplant Patients(2016) Akcay, Eda Yilmaz; Tepeoglu, Merih; Ozdemir, Binnaz Handan; Deniz, Ebru; Borcek, Pelin; Haberal, Mehmet; 0000-0002-3462-7632; 0000-0002-9894-8005; 0000-0002-7528-3557; 0000-0001-6831-9585; 27805524; AAJ-8097-2021; AAK-5222-2021; X-8540-2019; AAK-1960-2021Objectives: The aim of this study was to evaluate the incidence of posttransplant malignancy in kidney transplant patients and investigate the clinical and histopathologic features of these patients. Materials and Methods: We retrospectively reviewed information on donor and recipient characteristics, patient and graft survival, and cancer incidence after transplant for 867 kidney transplant patients. Patients with neoplasms prior to transplant were excluded. A follow-up study estimated cancer incidence after transplant. Results: Neoplasms were diagnosed in 59 patients (6.8%), 41 men and 18 women; 22 (37.3%) had skin tumors, 19 (32.2%) had solid tumors, 10 (16.9%) had posttransplant lymphoproliferative disorders, and 8 (13.6%) had Kaposi sarcoma. The mean age at the time of malignant tumor diagnosis was 42.7 +/- 13.6 years, and statistically significant differences were found between tumor groups (P < .01). The average latency period between transplant and diagnosis of malignant tumors was 99.8 +/- 56.9 months for solid tumors, 78.4 +/- 52 months for skin tumors, 64.5 +/- 48.8 months for posttransplant lymphoproliferative disorders, and 13.5 +/- 8.8 months for Kaposi sarcoma, with significant difference found between tumor groups (P < .01). Ten patients (16.9%) had more than 1 malignant tumor. Eighteen patients died, with a mean time to death of 31.5 +/- 22.8 months after tumor diagnosis. A significant positive association was found between survival and the number of tumors (P = .001); 5-year survival after tumor diagnosis was 81% and 40% for patients with 1 malignant tumor and patients with more than 1 malignant tumor, respectively. Conclusions: Malignancy is a common cause of death after renal transplant. Early detection and treatment of posttransplant malignancies is an important challenge. Screening these patients for malignancies posttransplant is crucial, and efforts should be directed to define effective immunosuppressive protocols that are associated with a lower incidence of malignancy.