Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series.

BACKGROUND: With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias. OBJECTIVE: This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia. STUDY DESIGN: Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate. RESULTS: The median age was 20 years (interquartile range, 15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41-120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5-4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18-57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20-74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for immunochemical leukemia markers. CONCLUSION: Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by nongonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy before allogeneic hematopoietic stem cell transplantation.

Role of PD-1/PD-L1-mediated tumour immune escape mechanism and microsatellite instability in the BCG failure of high-grade urothelial carcinomas.

BACKGROUND: Intravesical BCG treatment fails inexplicably in 30%-45% of patients for high-grade nonmuscle-invasive bladder cancer (NMIBC). We aimed to investigate the role of PD-1/PD-L1 interaction on BCG failure of high-grade NMIBC and to identify biomarkers for predicting BCG responsive cases. METHODS: Thirty BCG responsive and 29 nonresponsive NMIBCs were included in the study. Expressions of PDL1(SP-263), MSH2, MSH6, PMS2, and MLH1 were evaluated on pre- and post-BCG transurethral resection (TUR-B) specimens by immunohistochemistry. PD-L1(SP-263) expression was categorised as negative/low, high. DNA mismatch repair protein (MMR) expressions were classified as "reduced" if ≤30% of nuclei stained, "preserved" if >30% of nuclei stained. Microsatellite instability (MSI) testing was performed by PCR using five mononucleotide markers. RESULTS: Reduced DNA MMR protein expression was found to be significantly higher in the pretreatment biopsies of BCG-responsive group than the BCG nonresponsive tumour group (p = 0.022). PD-L1 expression did not show any significant difference between the pre- and posttreatment TUR-B specimens of the BCG nonresponsive tumour group or between the pretreatment TUR-B specimens of BCG nonresponsive and the BCG responsive groups (p = 0.508, p = 0.708, respectively). DISCUSSION: Immune escape of tumour cells by PD-1/PD-L1 interaction does not seem to have any role in BCG failure of NMIBCs. Reduced MMR expression may help to determine cases that will respond well to BCG therapy. A better antitumour activity of BCG in NMIBCs with reduced MMR expression may be related to the ongoing accumulation of cancer neoantigens in correlation with increased tumour mutation load as a result of DNA repair defects.

The role of unfolded protein response in the pathogenesis of endometriosis: contribution of peritoneal fluid.

RESEARCH QUESTION: Endoplasmic reticulum stress (ERS) is caused by the accumulation of the misfolded or unfolded proteins in the endoplasmic reticulum and induces the unfolded protein response (UPR). Peritoneal fluid is important in the pathogenesis of endometriosis. In this study, the role of UPR associated with ERS in endometriosis, and peritoneal fluid, were investigated. DESIGN: Normal, eutopic and ectopic endometrium tissues were divided into menstrual cycle phases, and endometrial stromal cells (ESC) were treated with 10-20% concentration of control peritoneal fluid and peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min, and 24 and 48 h. The UPR signalling proteins were analysed immunohistochemically and immunocytochemically. Data were compared statistically. RESULTS: p-IRE1 was increased in ectopic glandular and stromal cells in the early proliferative phase compared with normal and eutopic endometrium. p-PERK increased in ectopic glandular and stromal cells in the late proliferative phase compared with normal endometrium. ATF6 was increased in ectopic glandular epithelium compared with normal endometrium in the proliferative phases, versus eutopic endometrium in the late secretory phase. p-IRE1 and p-PERK were increased in high concentrations of ESC treated with peritoneal fluid obtained from women with endometriosis for 10, 30 and 60 min compared with controls. In ESC treated with peritoneal fluid from women with endometriosis, p-IRE1 decreased at 24-48 h compared with 30 min. CONCLUSIONS: In endometriosis, UPR pathways are activated as highly dependent on cell type and phase. Also, p-PERK and p-IRE1 increased because of exposure to high-dose peritoneal fluid from women with endometriosis in stromal cells. Our findings provide a basis for further studies searching for a potential biomarker for the diagnosis of endometriosis.

First pregnancy and live birth in Turkey following frozen-thawed ovarian tissue transplantation in a patient with acute lymphoblastic leukemia who underwent cord blood transplantation.

PURPOSE: To report the first live birth after frozen-thawed ovarian transplantation in Turkey and the second case for an acute lymphoblastic leukemia (ALL) survivor in the world. METHODS: A 19-year-old patient underwent ovarian tissue cryopreservation (OTC) before cord blood transplantation in 2010. She was diagnosed as ALL with a bone marrow biopsy revealing 90% blast ALL-L2 type, and karyotype analyses indicated reciprocal translocation at t(9;22)(q34;q11). The patient received the Berlin-Frankfurt-Munster (BFM) protocol, and complete remission was achieved before fertility preservation. Serum AMH level was measured as 1.5 ng/ml, and 12 antral follicles were counted on ultrasound. She was informed about fertility preservation options and decided to proceed with OTC, with her signed consent before cord blood transplantation in April 2011. Ovarian tissue transplantation (OTT) was performed in 2017 when the patient was menopausal with serum FSH levels > 100 IU/ml and estradiol < 20 pg/ml and hematologically in molecular remission. Detailed molecular analysis, standard histology, and immunohistochemistry demonstrated that the thawed tissue is free of malignant cells. RESULTS: Six months following OTT, she had spontaneous menstruation with serum FSH 11 IU/ml and estradiol 53 pg/ml. Two consecutive IVF cycles yielded three top-quality embryos. Following three embryo transfer cycles, one fresh and two frozen, a healthy term live birth was achieved. Frozen-thawed-transplanted tissues were extracted during caesarean delivery upon the patient's request after a total period of 25 months in vivo, and histopathological evaluation revealed that the tissue was free of leukemic infiltration. CONCLUSION: The authors report the first pregnancy and live birth in Turkey and the second live birth in the world following transplantation of frozen-thawed ovarian tissue in a leukemia survivor. As the transplanted tissues were removed during caesarean delivery, histological findings prove the functionality and the malignant-free status of the transplanted tissue during the grafted period.

Risk factors for failure of sentinel lymph node mapping using indocyanine green/near-infrared fluorescent imaging in endometrial cancer.

PURPOSE: Side-specific systematic lymphadenectomy is suggested if sentinel lymph node (SLN) mapping failed in early stages endometrial cancer. This study aimed to evaluate the risk factors associated with failed mapping which may lead to modify SLN mapping technique, increase the success of SLN mapping and reduce the necessity of systematic lymphadenectomy. METHODS: Patients with early stage endometrial cancer were included in this study. All patients underwent SLN mapping with indocyanine green/near-infrared compatible surgical platforms. Indocyanine green was injected intracervical. "Bilateral mapping" and "failed bilateral SLN mapping (unilateral or bilateral failed mapping)" groups were compared for demographic, clinical, surgical, and pathological features. RESULTS: 101 cases were analyzed. The overall, unilateral, and bilateral SLN detection rates were 94.1%, 19.8%, and 74.3%, respectively. The failed (unilateral or no mapping) bilateral detection rate was 25.7%. Failed bilateral mapping rates were higher in patients with longer cervical and uterine longitudinal lengths, deep myometrial invasion and larger tumor size without statistical significance. Body mass index and operation type were not related with failed mapping. Increasing number of operations or injection of larger volume of indocyanine green (4 mL vs. 2 mL) did not improve mapping rate significantly. CONCLUSION: Cervical indocyanine green injection may overcome the negative effect of obesity on bilateral mapping. Although there was a negative correlation trend between the longitudinal cervical and uterine lengths and bilateral mapping, this possible relation needs to be confirmed in further studies.

Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a challenging disease, affecting thousands of people all around the world, especially women. Although there have been numerous theories regarding IC/BPS etiology, the physiopathology of the disease still remains unclear and there is a lack of certain treatment. OBJECTIVES: The aim of the study was to assess the role of nerve fibers and nerve growth factor (NGF) in the etiopathogenesis of IC/BPS symptoms by demonstrating if there is a correlation between urine NGF levels, amount of peripheral nerves in bladder mucosa and symptom severity. MATERIAL AND METHODS: A prospective clinical study was conducted with 15 IC/BPS patients and 18 controls. Urine NGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Bladder punch biopsies were obtained from 15 IC/BPS patients and 9 controls. Immunohistochemistry was performed for S-100 to highlight peripheral nerve twigs in bladder mucosa. The O'Leary-Sant Interstitial Cystitis Symptom and Problem Index (OSICSPI) was used to assess symptom severity and effects of the disease on the patients' life. RESULTS: NGF normalized to urine creatinine (NGF/Cr) levels in IC/BPS patients were significantly higher than in controls, 0.34 ±0.22 and 0.09 ±0.08 pg/mL: mg/dL, respectively (p < 0.001). The mean symptom score in IC patients was 12.27 ±2.4 (median: 12) and the mean problem score was 10.9 ±2.3 (median: 12). The mean mucosal nerve (S-100 stained) area in the IC/BPS group was significantly higher than in the controls, 2.53 ±1.90 vs 1.0 ±0.70, respectively (p = 0.018). In correlation analyses, the NGF/Cr level in IC/BPS patients was found significantly correlated with the O'Leary-Sant IC Symptom and Problem Index scores independently (p = 0.001 and p = 0.028, respectively). CONCLUSIONS: NGF seems to be a promising biomarker in IC/BPS. It may help clinicians in diagnoses and patient follow-up. Thus, unnecessary, expensive and invasive tests, interventions and treatments might be avoided.

Laparoscopic near-infrared fluorescent imaging as an alternative option for sentinel lymph node mapping in endometrial cancer: A prospective study.

BACKGROUND: To evaluate feasibility of sentinel lymph node (SLN) mapping by using near-infrared fluorescent imaging and indocyanine green (NIR/ICG) integrated laparoscopic system in clinically uterine-confined endometrial cancer. MATERIALS AND METHODS: Patients with clinically early-stage endometrial cancer were included in this prospective study. ICG was injected to the uterine cervix and NIR/ICG integrated laparoscopic system (Spies Full HD D-Light P ICG technology, Karl Storz, Tuttlingen, Germany) was used during the operations. SLN and/or suspicious lymph nodes were resected. Side specific lymphadenectomy was performed when mapping was unsuccessful. Systematic lymphadenectomy was completed following SLN algorithm steps. RESULTS: Seventy-one eligible patients were analyzed. The overall, unilateral and bilateral SLN detection rates were 95.7%, 18.3%, 77.4%, respectively. There were 8 (11.2%) patients with lymph node metastasis. One of them was isolated para-aortic node metastasis. Negative predictive value, sensitivity and false negative rate for detecting lymphatic spread were 98.4%, 87.5% and 1.5%, respectively. CONCLUSION: Sentinel lymph node mapping can easily be performed with high accuracy by using NIR/ICG integrated conventional laparoscopic system in endometrial cancer and almost all lymphatic spread can be detected.

Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue.

PURPOSE: CD44 expression in both the early and metastatic phases of many epithelial and non-epithelial cancers is strongly prognostic. The objective of the study is to evaluate whether there is any relationship between the expression of CDD44v6 and endometrial cancer (EC) staging and prognosis. METHODS: This retrospective study included 60 EC patients for whom surgical staging was performed between 2000 and 2006. Twenty-eight randomly selected patients with normal endometria served as the control group. We immunohistochemically evaluated membranous and cytoplasmic CD44v6 staining in tissue paraffin blocks. The results were graded as positive or negative. RESULTS: Membranous staining in both advanced and early stage EC patients was significantly higher than that in the control group (p = 0.002). The extent of either membranous or cytoplasmic staining in both advanced- and early stage patients did not differ significantly by age, tumor grade, stage, extent of myometrial invasion, lymph node involvement, cytology, adnexal involvement, or omental spreading. In advanced-stage patients, neither papillary serous not clear cell cancers exhibited cytoplasmic staining. CONCLUSIONS: CD44v6 membranous staining can be useful for differentiating malignant from benign endometrial tissue. However, staining is not associated with EC staging or prognosis.

[B-cell non-Hodgkin's lymphoma with the involvement of inferior turbinate: a case report]. / Alt konka tutulumu gösteren B-hücreli non-Hodgkin lenfoma: Olgu sunumu.

The non-Hodgkin's lymphoma is a significant malignant disease that can involve in the extranodal region of the head and neck. It does not show any specific symptoms when it resides in this region. Swelling, pain and ulceration are important clinical findings. In this article, we report a 57-year-old male patient diagnosed with B cell non-Hodgkin's lymphoma by histopathologic examination, who had nasal blockage, snoring and headache complaints for one year, whose endoscopic nasal examination revealed a mass arising from the right inferior turbinate and the mass was removed surgically by endoscopic approach.

Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

INTRODUCTION: The aim of this study was to assess whether epidermal growth factor receptor (EGFR) overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC) and whether its prognostic significance was affected by immunohistochemical expression patterns. MATERIALS AND METHODS: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG) as low-NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2), or locally invasive (pT3, 4). Clinical disease was grouped by clinical stage as early stage (stage I, II), or late stage (stage III, IV). Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt), and membranous (EGFR Mem) staining. RESULTS: EGFR Cyt correlated with high NG (P = 0.001), lymphovascular invasion (P = 0.028), regional lymph node involvement (P = 0.027), metastasis (P = 0.001), late stage (P = 0.003), cancer-specific death (P = 0.036), and was a predictor for disease-specific survival (P = 0.012) whereas EGFR Mem correlated with only local invasion (P = 0.021) and perirenal invasion (P = 0.009) and did not show any correlation with cancer-specific death or disease specific survival. CONCLUSION: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.

Single-organ vasculitis of the cervix accompanying human papillomavirus infection.

Single-organ vasculitis (SOV) has rarely been reported to involve the female genital tract but mostly the uterine cervix. A 39-year-old woman was diagnosed to have a high-grade cervical intraepithelial lesion and was treated by large loop excision of the transformation zone. Histopathological evaluation of the excised specimen confirmed the diagnosis of cervical intraepithelial neoplasia grade III accompanied by human papillomavirus infection. The excised second specimen showed the evidence of vasculitis of medium-sized vessels of the cervix, which is a quite rare form of SOV. It seems to be important to be aware of the localized form of polyarteritis nodosa limited to the female genital tract to prevent unnecessary immunosuppressive therapies.

Small Cell Carcinomas of the Bladder Highly Express Somatostatin Receptor Type 2A: Impact on Prognosis and Treatment--A Multicenter Study of Urooncology Society, Turkey.

Small cell carcinoma (SmCC) is a rare and aggressive neuroendocrine carcinoma of the bladder. Neuroendocrine carcinomas expressing somatostatin receptors (SSTR) in other viscera such as lung, pancreas, and gastrointestinal system respond to therapy with somatostatin analogs. In the present study, expressions of SSTRs 1 to 5 including type 2A are investigated by immunohistochemistry (IHC) and their relationship with clinicopathologic factors was evaluated. Hundred primary bladder SmCC cases were collected from 12 centers in Turkey. Forty-three cases were pure SmCC. Other cases had mostly papillary urothelial carcinoma as a second component. The percentage of the SmCC component ranged from 5% to 100%. SSTR-2A expression was membranous, whereas the other receptors showed cytoplasmic staining. The percentages of positive cases for SSTR-1, SSTR-2A, SSTR-3, SSTR-4, and SSTR-5 were 4% (3/75), 61.4% (54/88), 2.4% (2/84), 24.4% (20/82), and 6.25% (5/80), respectively. The percentage of SmCC component was positively correlated with the percentage of SSTR-2A expression (P=0.003) while negatively correlated with patient age (P=0.032). SSTR-2A expression was correlated with survival as a bad prognostic factor (P=0.018). SSTR-1, SSTR-3, SSTR-4, and SSTR-5 expressions did not show any statistical significance with any parameter. In conclusion, although the limited number of cases with adequate term follow-up, SSTR-2A expression could be a prognostic factor and somatostatin analogs therapeutic candidate for SmCCs of the bladder as these tumors show high percentage of SSTR-2A expression.

Esthesioneuroblastoma With Poor Outcome Despite Extensive Treatment.

Esthesioneuroblastoma is a rare malignant tumor of neuroectodermal origin. It usually presents with nonspecific symptoms, such as nasal obstruction, epistaxis, and pain, but has an aggressive course if the treatment is delayed. The authors report a case of esthesioneuroblastoma in a 47-year-old woman, treated with extensive surgical resection, radiotherapy, and chemotherapy. Despite intensive treatment, the patient developed a local recurrence with systemic metastasis and succumbed 4 months later.

An Unusual Manifestation of Renal Angiomyolipoma: Pulmonary Fat Embolism.

Renal angiomyolipoma (AML) is the most common benign renal mesenchymal tumors. AMLs are usually asymptomatic and frequently affect women. Only epithelioid variant has malignant potential. Although life-threatening complications related to retroperitoneal bleeding and massive hematuria are possible, it is often detected incidentally. Pulmonary embolism as the first symptom is extremely rare. Herein, we present a case of renal AML who admitted with pulmonary embolism symptoms.

Gelsolin, NF-κB, and p53 expression in clear cell renal cell carcinoma: Impact on outcome.

OBJECTIVES: To examine the prognostic significance of Gelsolin, NF-κB, and p53 in clear cell renal cell carcinoma (CRCC), which has an unpredictable behavior and tendency for recurrence and metastasis. MATERIALS AND METHODS: Immunohistochemistry was performed on 100 consecutive cases of CRCC using antibodies against Gelsolin, NF-κB, and p53. Tumors were grouped by nuclear grade (NG) as low NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2) or locally invasive (pT3, 4). Clinical stage was grouped as early stage (stage I, II) or late stage (stage III, IV). Evaluation was based on cytoplasmic (NF-κB(Cyt)) and nuclear (NF-κB(Nuc)) expression for NF-κB, nuclear expression for p53, membranous and cytoplasmic expression for Gelsolin. RESULTS: Gelsolin expression correlated with high NG (p = 0.001), metastasis (p = 0.003), late stage (p = 0.008), and cancer death (p = 0.001). NF-κB(Cyt) expression correlated with high NG (p = 0.002), perirenal invasion (p = 0.010), local invasion (p = 0.020), and late stage (p= 0.003). NF-κB(Nuc) expression failed to predict the prognosis of CRCC. p53 expression correlated with high NG (p = 0.045), lymphovascular invasion (p = 0.05), metastasis (p = 0.001), late stage (p = 0.028), and cancer death (p = 0.034). However, only Gelsolin was found to correlate with disease-specific survival, (p = 0.006), and neither NF-κB nor p53 showed such relation. CONCLUSION: Expressions of Gelsolin, NF-κB(Cyt), and p53 associated with aggressive behavior of CRCC, while Gelsolin expression specifically indicated poor disease-specific survival. The results of the present study served to determine biomarkers for predicting high-risk patients with CRCC, expected to show aggressive phenotype.

Myeloid sarcomas: a clinicopathologic study of 20 cases.

OBJECTIVE: Myeloid sarcoma is a tumoral mass of mature or immature myeloid blasts in extramedullary anatomic locations. It can be seen de novo or in association with acute myeloid leukemia, myeloproliferative neoplasias, or myelodysplastic syndrome. Isolated myeloid sarcoma can be seen as a relapse in cases with allogenic bone marrow transplantation. Although it may involve any tissue in the body, the most common locations are skin, soft tissues, lymph nodes, and the gastrointestinal tract. Immunohistochemically, most cases show myelomonocytic or pure monoblastic differentiation. We reviewed the clinicopathological features of 20 cases of myeloid sarcoma diagnosed in our institute in view of the literature. MATERIALS AND METHODS: The cases diagnosed between 2005 and 2012 at the Ankara University Faculty of Medicine, Department of Pathology, were selected. Clinicopathological findings including the age and sex of the patients; symptoms; anatomic location; accompanying hematological disease; and the morphological, immunohistochemical, and cytogenetic features of the cases were noted. RESULTS: Sixteen of the patients were male and 4 were female. The median age at diagnosis was 47 years. The most commonly involved locations were the lymph nodes and skin. Immunohistochemically, eleven cases were of the myelomonocytic and 7 cases were of the myeloid phenotype, whereas 2 cases showed pure monoblastic differentiation. The median follow-up period for the 18 cases with known clinical data was 33 weeks. Five patients died of the disease in an average of 36 weeks. CONCLUSION: Myeloid sarcoma is a rare presentation of leukemias, myeloproliferative neoplasias, or myelodysplastic syndrome, composed of immature myelomonocytic cells in extramedullary tissues. It may present with variable morphological and phenotypic features, always creating a challenge in pathological diagnosis.

Clinical and histopathologic predictors of reoperation due to recurrence of leiomyoma after laparotomic myomectomy.

OBJECTIVE: To assess clinical and histopathologic risk factors for reoperation after laparotomic myomectomy due to leiomyoma recurrence. METHODS: A case-control study was conducted of patients who underwent their first myomectomy for leiomyoma without receiving gonadotropin-releasing hormone analogues at Ankara University School of Medicine, Ankara, Turkey, between January 2000 and December 2004. Medical records and histopathologic samples were reviewed, and participants completed a telephone interview. Patients in the case group had undergone reoperation within 5 years; those in the control group had not required further surgery. RESULTS: There were 51 patients in the case group and 61 controls. The number of women who had given birth after the index surgery was lower among cases than controls (4 [7.8%] vs 13 [21.3%]; P=0.048), as was the median size of the largest leiomyoma removed (4 cm [range 3-10] vs 5 cm [range 3-25]; P=0.009). Reoperation was more likely among patients aged at least 40 years at index surgery (OR 1.10; 95% CI 1.18-7.78; P=0.021) and those with myxoid change (OR 2.04; 95% CI 1.07-55.41; P=0.043). The number of leiomyomas removed was negatively associated with reoperation (OR 0.30; 95% CI 0.58-0.93; P=0.012). CONCLUSION: Young age, removal of many or large leiomyomas, and pregnancy after myomectomy decreased reoperation risk, whereas myxoid change increased risk.

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

AIM OF THE STUDY: Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). MATERIAL AND METHODS: We reviewed reports of primary SCC of the thyroid gland published in the English literature. RESULTS AND CONCLUSIONS: We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Effect of topically applied sildenafil citrate on wound healing: experimental study.

Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention.This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total) were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels.Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day.

Scintigraphic and histopathologic evaluation of combined bone grafts.

OBJECTIVES: We aimed to assess various bone grafts on bone formation using bone scintigraphy and histology, especially the first study that evaluated the demineralized bone matrix (DBM) + tricalcium phosphate (TCP) + hyaluronic acid (HA) combination. MATERIALS AND METHODS: A total of 44 pieces in groups of autogenous bone graft, TCP, DBM, DBM + TCP combination, and DBM + TCP + HA combination were applied to parietal bones of 24 New Zealand rabbits. Bone scintigraphies of the rabbits were performed at 2, 6, and 12 weeks. The uptake ratios were compared for the different types of grafts. In addition, in 2, 6, and 12 weeks, the graft areas were taken from the sacrificed rabbits and examined histologically. RESULTS: In the 2-week evaluation, DBM + TCP combination and DBM + TCP + HA combination had more osteoblastic activity accumulation than the TCP and DBM groups. These findings supported that the DBM + TCP combination group showed new bone formation earlier in the histopathological evaluation. The DBM + TCP + HA combination had more uptake than the TCP and DBM groups on bone scintigraphy at 2 weeks, and this uptake ratio decreased in the following weeks. It was thought that the increased uptake in DBM + TCP + HA combination at 2 weeks was due to severe inflammation seen in the histopathological evaluation. CONCLUSION: The DBM + TCP + HA combination should not be used for graft repair, although it was thought to be a good combination in the early weeks.