Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study.

PURPOSE: To compare the incidence and severity of acute and chronic hematologic toxicity (HT) in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for curative treatment of cervical cancer and to ascertain the dosimetric parameters of two techniques associated with acute and chronic HT. MATERIALS AND METHODS: A total of 127 patients with cervical cancer receiving concomitant pelvic radiotherapy (RT) and cisplatin were evaluated. Pelvic bone marrow (BM) was contoured for each patient and divided into five sub-regions: lumbosacrum (LS), ilium (IL), lower pelvis (LP), pelvis (P), and whole pelvis (WP). The volume of each BM region receiving 10, 20, 30, and 40 Gy was calculated (V10, -V20, -V30, and -V40). The lowest level of hemoglobin, leukocyte, neutrophil, and platelet counts were obtained during chemoradiotherapy and six months after RT. The nadir values were graded according to Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Grade 2 or greater acute anemia, leukopenia, neutropenia, thrombocytopenia was observed in 2%, 41.5%, 12% ,and 0% in 3DCRT group and in 27%, 53%, 24.5%, and 4.5% in IMRT group, respectively. Grade 2 or greater chronic anemia, leukopenia, neutropenia, and thrombocytopenia was observed in 11%, 10%, 6%, and 0% in 3DCRT group and in 11%, 9%, 4.5%, and 0% in IMRT group, respectively. LS-V30, 40; IL-V10, 20, 30, 40; LP-V10, 20 ,40; P-V10, 20, 30, 40, and TP-V10, 20, 30, 40 were significantly reduced with IMRT planning compared to 3DCRT planning. Logistic regression analysis of potential predictors showed that none of the dosimetric parameters were significant for predicting acute and chronic HT. CONCLUSION: The present findings showed that IMRT planning reduced irradiated BM volumes compared to 3DCRT planning. However, no difference between the two techniques was observed in terms of acute and chronic HT. Further studies are needed to confirm these results.

Effect of GnRH antagonist therapy on the expression of MUC-1 and heparin binding growth factor expression in the endometrium of hyperstimulated rats.

PURPOSE: To determine the effect of GnRH-antagonist therapy on the expression of heparin binding-epidermal growth factor (HB-EGF) and MUC-1 glycoprotein in hyperstimulated rat ovaries. METHODS: 30 female Wistar rats were divided into three groups (control, FSH and FSH+cetrorelix). Control rats were given 0.2 ml oil/saline mixture for four days beginning from the day of estrus. In the second group, 30 IU/ml purified hFSH was injected SC for four days beginning from the day of estrus. The rats of the third group were injected 30 IU FSH for four days and 10 IU cetrorelix SC for three or four days. The rats were sacrificed and the staining intensity of HB-EGF and MUC-1 of the epithelial cells and stromal cells of the endometrium of the rats was calculated by H-score. RESULTS: Slight MUC-1 immunoreactivity was seen in the epithelial and decidual cells of the control and FSH groups. In the FSH+cetrorelix group, moderate MUC-1 immunostaining appeared in the epithelial and desidual cells. In rats in the control and FSH+cetrorelix groups, HB-EGF immunoreactivity in the epithelial cells and decidual cells was moderate. Strong immunoreactivity was seen in the FSH group. When the MUC-1 H-score values were compared statistically with the control and other groups, FSH+cetrorelix immunoreactivity in epithelial and decidual cells were significantly different from control and FSH groups. HB-EGF immunoreactivity of the epithelium and decidua was similar in the control and FSH+cetrorelix groups, but epithelial and decidual immunoreactivity of the FSH group was different from the other two groups. CONCLUSION: Our findings suggest that GnRH antagonists exert direct effects on the expression of HB-EGF and MUC-1 expression in the rat endometrium.

Vitamin D intoxication due to misuse: 5-year experience.

INTRODUCTION: Vitamin D intoxication (VDI) is a well-known cause of hypercalcemia in children and leads to serious kidney, heart, and neurological problems. In the treatment of VDI, the goal is to correct hypercalcemia. Our aim was to evaluate the clinical features of patients with VDI, identify the causes of VDI in our region, and help guide precautions and treatment of VDI. MATERIALS AND METHODS: The medical records of patients with VDI presenting between January 2015 and December 2019 were retrospectively analyzed. RESULTS: In total, 38 patients aged 0.3-4 years including 20 males (52.6%) were included in the study. Vomiting (65.8%), loss of appetite (47.4%), and constipation (31.6%) were the most common symptoms. The cause of intoxication was prescribed D3 vials in 23 patients, non-prescribed D3 vials in nine patients, and incorrectly produced fish oil supplement in six patients. Admission serum calcium and 25 (OH) D levels were 3.75±0.5mmol/L and 396±110ng/mL, respectively. A statistically significant correlation was found between the serum calcium levels at the time of diagnosis and the dose of vitamin D received, serum 25 (OH) D, phosphorus, and parathyroid (PTH) levels. Nephrocalcinosis was present in 15 (39.5%) patients. The mean time to achieve normocalcemia was 6.18±2 days. The mean time to achieve normocalcemia in patients treated with pamidronate was 5.94±0.7 days. CONCLUSION: Stoss therapy should not be administered for children of families with problems of adherence to treatment. It should be noted that VDI may develop as a result of improperly produced nutritional supplements. General practitioners and pediatricians must be aware of VDI risks and explain them to parents. Pamidronate is effective for treating VDI in children.

Gamma knife radiosurgery in non small cell lung cancer patients with brain metastases: treatment results and prognostic factors.

PURPOSE: To evaluate the efficacy of gamma knife radiosurgery (GKRS) for the treatment of brain metastases from non small cell lung cancer (NSCLC) and find out the prognostic factors for overall survival. METHODS: Between February 1997 and August 2003 100 patients underwent treatment for 184 brain metastases from NSCLC, either for recurrence (n=49) or with a new diagnosis (n=51). Median age was 55 years and 77 patients were male. Seventy-eight of the patients received whole brain radiotherapy (WBRT) prior to or after GKRS and 26 patients had surgical removal of the metastasis. Imaging and clinical status were monitored every 3 months following treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis were used. RESULTS: The median follow up after the procedure was 8 months and after the diagnosis 11 months. The median overall survival for all patients was 9 months from the date of GKRS and 14 months from the diagnosis of brain metastasis. Local tumor control was achieved in 95% of the lesions. In multivariate analysis, adenocarcinoma histology, Karnofsky performance status (KPS) score > 80, 1-3 metastases and tumor diameter <2 cm were related to longer survival. Addition of WBRT did not have any effect on overall survival. CONCLUSION: Gamma knife surgery appears to be effective in treating patients with brain metastases from NSCLC, either alone or with WBRT in selected groups of patients.

Effects of Oenothera biennis L. and Hypericum perforatum L. extracts on some central nervous system myelin proteins, brain histopathology and oxidative stress in mice with experimental autoimmune encephalomyelitis.

We investigated the effects of Oenothera biennis L. and Hypericum perforatum L. extracts on brain tissue histopathology, myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in mice with experimental autoimmune encephalomyelitis (EAE). Forty-seven C57BL/6J mice were divided into the following groups: multiple sclerosis (MS), control (healthy mice), MS + H. perforatum treated (MS + HP), MS + O. biennis treated (MS + OB). All groups except the control group were immunized by EAE methods. Two weeks after the immunization, the mice in the MS + HP group were fed normal food containing 18 - 21 g/kg H. perforatum extract, the mice in MS + OB group were fed normal food containing 18 - 21 g/kg O. biennis extract, and the mice in control and MS groups were fed normal food for six weeks. Brain tissue samples were collected from all mice for histopathological and biochemical analysis. Clinical signs of the disease were scored using functional systems scores (FSS) daily. The H. perforatum and O. biennis extracts ameliorated the increased brain tissue MOG and MBP values for animals with MS. H. perforatum and O. biennis extract decreased the TOS and OSI values for brain tissue and increased TAS levels in brain tissue of animals with MS. In addition, H. perforatum and O. biennis extracts decreased the clinical signs at the end of the experiment compared to the beginning of extract administration. We found that myelin was lost in MS group vs. control group. H. perforatum and O. biennis extract treatments decreased the amount of myelin loss in the MS + HP and MS + OB groups. We also observed amyloid deposition on vascular walls, in the cytoplasm of the neurons and in the intercellular space in the MS group. O. biennis and H. perforatum treated groups exhibited neither abnormal amyloid deposition nor obvious cell infiltration. The beneficial effects of O. biennis and H. perforatum for attenuating myelin loss and amyloid deposition suggest their therapeutic utility for treatment of MS.

Mode of delivery and pelvic floor muscle strength and sexual function after childbirth.

OBJECTIVE: To investigate the respective roles of the mode of delivery and strength of pelvic floor muscles in the sexual function of women. METHOD: Thirty-two women who were delivered vaginally and 21 women who underwent cesarean delivery at the Celal Bayar University School of Medicine Obstetrics Department were enrolled in the study, and 15 nulliparas were recruited as controls. Sexual function was assessed in all women by a validated questionnaire (the Female Sexual Function Index). Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured separately, and pelvic floor muscle strength was assessed by a perineometer. Sexual function was compared among the 3 groups. The correlation between pelvic floor muscle strength and sexual function was also investigated. RESULTS: Pelvic floor muscle strength was significantly lower in the group vaginally delivered compared with the group delivered by cesarean section and the nulliparous group (P<0.05). There was no difference between the groups regarding sexual function (P>0.05), and there was also no correlation between sexual function and pelvic muscle strength. CONCLUSION: Pelvic floor muscle strength and mode of delivery did not affect sexual function in our study participants. The muscular component of female sexual function should be further investigated.

Colposcopically directed cone biopsies in the management of cervical intraepithelial neoplasia.

Thirty-three patients with severe dysplasia and carcinoma in situ had a colposcopically directed cone biopsy in the operating room immediately prior to vaginal hysterectomy. In 3 cases (9%), the hysterectomy specimen showed the same type of residual disease as in the cone biopsy; in the remainder no residual disease was evident in the hysterectomy specimen. If colposcopically directed biopsies were performed, the long-term debate over the use of cone biopsy or hysterectomy for intraepithelial neoplasms would be resolved. Selected patients could be treated adequately by cone biopsy with a small number of patients requiring hysterectomy as indicated by direct examination with the colposcope.

Suburethral paraganglioma.

Masses presenting beneath the urethra are not uncommon. Besides ureteral diverticula, which account for the vast majority of these masses, a multiplicity of heterogeneous benign and malignant tumors have been encountered in this region. To the best of our knowledge, we report the first case of a neuroendocrine tumor, a paraganglioma, discovered in the anatomical compartment between the urethra and vagina. When evaluating a patient with a suburethral mass, it is important to consider paraganglioma as part of the differential diagnosis because unwitting surgical removal of a functional catecholamine-secreting tumor may precipitate a severe hypotensive episode and/or death.

Partial and total skinning vulvectomy in treatment of carcinoma in situ of the vulva.

From July 1974 to December 1984, 24 skinning vulvectomies (17 partial and seven total) were performed in 24 patients with carcinoma in situ of the vulva. The objective for partial skinning vulvectomy was preservation of the cosmetic and functional integrity of the vulva in younger and sexually active patients in whom a steady increase in the incidence of vulvar intraepithelial neoplasia has been observed in the last decade. Two groups selected for partial skinning vulvectomy with skin graft were patients with multicentric vulvar intraepithelial neoplasia with colposcopic evidence of normal skin, and patients with localized but a wide surface area of vulvar intraepithelial neoplasia such that poor cosmetic results would be unavoidable should excision be approximated with primary skin closure. Only patients with involvement of the entire vulva were subjected to total skinning vulvectomy with total skin graft replacement. Recurrence and/or persistence were observed in two patients, both treated with total skinning vulvectomy. At present, all 24 patients remain free of detectable neoplasia on follow-up of six months to 11 years and all have very good cosmetic and functional results.

Paraaortic lymphadenectomy in gynecologic malignancies confined to the pelvis.

Eighty-six patients with pelvic malignancies had paraaortic node dissection; 30% had positive paraaortic lymph nodes. At the time of laparotomy, 77 patients had malignancies apparently confined to the pelvis after extensive work-up and histologic examination of tissue biopsies outside the pelvis; 20 (26%) had metastatic cancer in the paraaortic lymph nodes. Thirteen of 49 patients with cancer of the cervix, 5 of 18 with uterine cancer, and 2 of 10 with ovarian cancer had positive paraaortic lymph nodes. The value of paraaortic dissection in patients with pelvic malignancies apparently confined to the pelvis is discussed.

Vulvar intraepithelial neoplasia.

The authors reviewed the records of 50 patients with carcinoma in situ of the vulva seen at the State University of New York at Buffalo affiliated hospitals. Five patients (10%) were found to be immunosuppressed and 12 (24%) had other preinvasive and invasive genital or extragenital neoplasia. Of 43 patients whose symptomatology was available, almost half (46.5%) were asymptomatic. The most common symptom was vulvar itching in 18 (42%), and 32 (65%) patients had white vulvar lesions. Thirteen patients underwent vulvectomy, 23 underwent wide local excision, 8 underwent skinning and skin graft, 3 underwent topical 5-fluorouracil treatment, and 2 underwent CO2 laser treatment. On follow-up there were 6 patients with recurrent and/or persistent disease. Two recurrences followed wide local excision. Topical 5-fluorouracil failed in all 3 patients and CO2 laser failed in 1 of the 2 underwent laser treatment. There were 5 patients with invasive disease. In 3, diagnostic biopsy failed to reveal invasive neoplasia before surgical excision, and invasion was noted after 5-fluorouracil application in one and after CO2 laser treatment in another. All recurrences responded to therapy. In 41 patients followed up for 3 months to 11 years, there were no cancer-related deaths.

Topical 5-fluorouracil treatment of vaginal intraepithelial neoplasia.

In a prospective study, 27 patients with intraepithelial vaginal neoplasia diagnosed by colposcopically directed biopsies were treated with topical 5-fluorouracil. The cream was applied daily to the entire vagina until mucosal irritation occurred (5 to 10 days). Courses were repeated every 2 weeks for a total of 2 to 3 courses, which were considered 1 treatment, before response was evaluated. Those found to have persistent neoplasia as designated by positive vaginal cytology and/or colposcopically directed biopsies received a second 3-course treatment and were evaluated again. Except for 2 patients (1 who died from intercurrent disease during the treatment and another, evaluated prematurely after the first course of therapy, who was found to have persistent disease and was treated by other means), all patients responded with complete regression of vaginal intraepithelial neoplasia. Three patients developed reactivation of disease within 1 year, were retreated, and are currently completely free of disease. The authors believe the results of this study are very encouraging.

Extracellular matrix-coated culture dishes: an in vitro model for primary human gynecologic tumors.

Culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells were utilized to investigate human gynecologic carcinomas of epithelial origin. A high culture success rate was achieved for both solid tumor (83%) and ascitic fluid (75%) derived from specimens from 59 patients. Because of the high percentage of tumor cells attaching to the ECM and actively proliferating, a variety of in vitro studies (karyotypic analysis, morphologic appearance on ECM, and ability to digest the ECM) could be done. A preliminary in vitro profile of the various tumor cell types could be made on the basis of these studies. In addition, five long-term cultures were established utilizing the ECM model system.

Borderline malignant serous tumors of the ovary maintained on extracellular matrix: evidence for clonal evolution and invasive potential.

Four cases of advanced stage (II or III) and one case of early stage (IC) borderline malignant serous cystadenocarcinomas of the ovary were maintained on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Cells harvested for chromosomal analysis after 2-3 days showed diploid or near-diploid modalities in all cases. Banded chromosome studies in two cases revealed nonrandom clonal abnormalities with trisomy 2, 7, and 12 in seven of 13 metaphases. No structural abnormalities were noted. These cytogenetic findings differ from those found in malignant serous tumors of the ovary. In addition, borderline tumor cells digested the ECM in all cases and formed a cribiform pattern within a few days of primary culture. This study suggests clonal progression from early to advanced stages of borderline malignant serous tumors; readily distinguishable from overtly malignant serous tumors of the ovary. Ability of tumor cells derived from both primary tumors and metastatic implants to digest the ECM implies the possibility that borderline serous tumors have invasive potential.

Prospective trial of cisplatin, adriamycin, and dacarbazine in metastatic mixed mesodermal sarcomas of the uterus and ovary.

Twenty-four patients with advanced or recurrent uterine (13) and ovarian (11) mixed mesodermal sarcomas received a combination of cisplatin. Adriamycin and dacarbazine (PAD) as initial therapy after surgical debulking. Of the 13 patients with metastatic uterine sarcoma, six (46.1%) remained without evidence of disease (NED) from 8 to 36 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 68%, 68%, and 51%, respectively. Of the 11 ovarian sarcoma patients, five (45.4%) were NED at 5, 7, 32, 56, and 59 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 70%, 35%, and 35%, respectively. The PAD regimen is an active regimen in patients with metastatic uterine and ovarian mixed mesodermal sarcomas and progression-free survival may be improved by maximum debulking surgery prior to the initiation of PAD chemotherapy.

Outcome of rectal and sigmoid carcinoma patients receiving adjuvant chemoradiotherapy in Marmara University Hospital.

Adjuvant chemoradiotherapy is the standard treatment in resected stage II/III rectosigmoid carcinoma. We report a retrospective analysis of 33 patients who received adjuvant chemoradiotherapy. Patients received 5-fluorouracil (375mg/m2/day x 5days) and calcium leucovorin (20mg/m2/day x 5days), q4weeks, two courses before and two courses after radiotherapy. The 5-fluorouracil dose was reduced to 225mg/m2/day given continuously as protracted short-term infusion on the first and last 3 days during radiotherapy. Radiotherapy was started at 7th week and 45-50.4 Gy was given to pelvic region. Median age was 63 years. Median follow-up was 38 months starting from the operation date. Four-year local and distant control rates were 78% and 69%, respectively. Four-year disease-free survival and overall survival were 60% and 62%, respectively. Protracted short-term infusion of 5-fluorouracil during pelvic irradiation is a safe treatment modality. Further studies are needed to improve the local control of high-risk rectal and sigmoid carcinomas.

Assessment of the effectiveness of postmenopausal tibolone therapy on neural functions by measuring visual evoked potentials: a placebo-controlled study.

OBJECTIVE: To assess the effect of hormone replacement therapy on neural transmission in postmenopausal women using tibolone by a non-invasive, objective way. STUDY DESIGN: In a randomised, 3 cycle, placebo-controlled study, neurovisual transmission in optic pathways were evaluated by measuring visual evoked potentials (VEP). After neuroophtalmologic examination, eligible subjects were randomised into two groups. Treatment group (n=38) were given tibolone 2.5mg daily continuously for 3 months and control group (n=20) were treated with placebo. A baseline VEP measurement before the treatment and then at the end of first, second and third month were obtained by the EMG-evoked system in the Department of Neurology, University of Celal Bayar, Manisa, Turkey. RESULTS: Data from 31 women from treatment group and 16 from control group were available for evaluation. The mean P(100) latency values, which indicate the transition time period between the optic stimuli and electrical change recorded on the occipital area by the skin electrodes, have showed a significant decrease for the study group (from 100.39+/-0.58 to 97.90+/-0.65 ms, P<0.01) at the end of the first month of treatment according to the baseline values. This difference between two groups has remained constant during the study period. CONCLUSION: The change in latency measurements of VEP, reflecting the functional status in optic pathways from retina to occipital cortex were significantly different in the treatment group than in that of control. We concluded that a facilitating effect of tibolone was observed on neurovisual transmission.

VQ-adaptive block transform coding of images.

Two new design techniques for adaptive orthogonal block transforms based on vector quantization (VQ) codebooks are presented. Both techniques start from reference vectors that are adapted to the characteristics of the signal to be coded, while using different methods to create orthogonal bases. The resulting transforms represent a signal coding tool that stands between a pure VQ scheme on one extreme and signal-independent, fixed block transformation-like discrete cosine transform (DCT) on the other. The proposed technique has superior compaction performance as compared to DCT both in the rendition of details of the image and in the peak signal-to-noise ratio (PSNR) figures.

Promoter hypermethylation-mediated down-regulation of RUNX3 gene in human brain tumors.

BACKGROUND: The Runx family proteins, including RUNX3, are tissue-restricted transcription factors and play role in neuronal development and tumorigenesis. RUNX3 has an important role in glioblastoma (GBM) tumorigenesis because of its promoter hypermethylation. AIM: We aimed to evaluate the methylation-mediated expression regulation of RUNX3 gene in brain tumors. PATIENTS AND METHODS: Cases of meningiomas WHO grade III (3), anaplastic astrocytomas (3), diffuse astrocytoma (3), and GBM (12) were recruited into this study. Real-time quantitative PCR was performed for analyses of DNA promoter methylation and analyses of methylation-mediated expression status of RUNX3 gene was performed by real-time quantitative RT-PCR. RESULTS: There was no significant difference between methylated and unmethylated quantitative ratio of RUNX3 gene promoter region and also no significant difference in relative ratio of RUNX3 gene expression in brain tumor groups. Methylated and unmethylated ratio in anaplastic astrocytoma, diffuse astrocytoma, GBM, meningioma (WHO grade III) and in all groups were; 1.44, 1.09, 1.51, 1.52 and 1.43, respectively. One allele was found methylated necessarily. No methylation was detected in one case of GBM group and one case of anaplastic astrocytoma group. There was no unmethylated promoter in one of the GBM cases. There were significant differences between relative ratio of RUNX3 gene expression and methylated/unmethylated ratio rates for all cases (p = 0.001) and GBM groups (p = 0.041). CONCLUSION: This study overemphasized the RUNX3 gene importance in brain tumors, due to the existence of at least one methylated allele.

Dosimetric comparison of robotic and conventional linac-based stereotactic lung irradiation in early-stage lung cancer.

We aimed to compare dosimetric characteristics of conventional linear accerator-based treatment plans to those created using the robotic CyberKnife® (CK) treatment planning system for patients with early-stage lung cancer. Eight early-stage lung cancer patients treated with stereotactic body radiotherapy (SBRT) using a conventional linac-based (LIN) system were included in this study. New treatment plans were created for the patients with the CK treatment planning system in order to compare the two platforms' dosimetric characteristics. Planning computed tomographies (CT) were obtained in three phases: free-breathing, full exhalation and inhalation. The three GTVs were then added together for internal target volume (ITV) with LIN, whereas no ITV was used for CK. Planning target volumes (PTV) were constituted by adding 5-mm margin to GTV and ITV. Treatment plan was 54 Gy in three fractions. Five-field, seven-field, and dynamic-conformal arc planning techniques were used in LIN plans. Plans were compared according to dose heterogenity (D(max)-maximum dose), volume of 54 Gy (V54) and 27 Gy isodose (V27), conformity index (CI(54) and CI(27)) and lung volumes. PTVs were significantly smaller in CK plans (p=0.012). D(max) was significantly lower in ARC plans (p=0.01). Among all plans, CK had significantly tightest isodose shell received 54 Gy and 27 Gy (p=0.0001). Among LIN plans, V54 was significantly (p=0.03) smaller in ARC plans; but no difference was observed for V27 values. LIN plans have better plan quality (CI(27) and CI(54)) than CK. No statistically significant difference was observed for lung volumes. CK plans had superior V54 and V27 values compared to LIN plans due to smaller PTV. LIN plans had better CI(27) and CI(54) values. Advantages of LIN treatment were no neccessity for fiducial marker use, which may cause pneumothorax, and significantly shorter beam-on treatment times. Both CK and LIN methods are suitable for lung SBRT.