BACKGROUND: "Intestinal-type" mucinous carcinoma of the vulva is extremely rare with very few cases reported in the literature. CASE REPORT: The authors report two patients who had diagnosis of intestinal-type mucinous adenocarcinoma of the vulva after excisional biopsy. In both cases, restaging was perfomed with total body computed tomography (CT) scan, gastroscopy, and colonoscopy that showed no other site of disease. A radical vulvectomy with bilateral systematic inguinal lymphadenectomy was performed, and in both cases no residual disease was found. A patient developed metastatic (liver, bone marrow) colonic cancer 36 months after primary surgery, received multiple lines of chemotherapy, and died of disseminated disease 18 months after diagnosis. The other patient was found to have dysplastic polyp in the sigmoid colon, and is alive without disease at 39 months after primary diagnosis. CONCLUSION: Intestinal-type mucinous carcinoma of the vulva has a poor prognosis. Strict endoscopic follow-up of the colon is mandatory in such cases, considering the high propensity of associated gastrointestinal (GI) tumors.

Objectives The aim of this study was to assess the accuracy of transvaginal sonography (TVS) in the preoperative staging of endometrial carcinoma, because accurate preoperative staging of the disease would assist in planning the optimal course of treatment. We investigated the ability to distinguish between cases with < 50% and > 50% myometrial invasion (FIGO Stage Ia -Ib vs. Stage Ic), and tumor extension to the cervical stroma (Stage IIb) according to the old FIGO classification. Methods 140 women with pathologically-proven of endometrial cancer, referred to our institution between 2007 and 2010, were included in this study. All underwent TVS examination about seven days before the surgical staging. Histological findings of myometrial and cervical stroma invasion were used as the reference standard. Results The histological subtypes comprised 75% endometrioid adenocarcinoma, 9% serous papillary, 6% endometrioid villoglandular, 4% villoglandular, 3% adenosquamous and 3% clear cells; there were 60% well differentiate, 15% moderately differentiate and 25% poorly differentiate cancers. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for TSV in the evaluation of < 50% myometrial infiltration were 82%, 77%, 79%, 80% and 48%; of > 50% myometrial infiltration were 86%, 90%, 86%, 90%, and 57%; for cervical invasion were 80%, 100%, 100%, 89% and 63% respectively. Conclusions The transvaginal sonography shows good accuracy in the staging of endometrial carcinoma. Our results support a potential role of TVS for the prediction of strome cervix infiltration of endometrial cancer.

This study evaluates the efficacy and toxicity of dose-dense weekly paclitaxel and carboplatin as neoadjuvant chemotherapy in locally advanced cervical cancer (LACC). We collected 23 cases of LACC treated with weekly paclitaxel and carboplatin for nine cycles: 20 patients had complete or partial response to chemotherapy and were submitted to surgery, 3 with poor response received chemoradiation therapy. Pathologic examination showed complete response in four patients, myometrial invasion <50% in nine and >50% in seven patients, parametrial involvement in two, vaginal metastasis in one and lymphovascular space invasion, with positive margins, in another case. Despite seven patients had radiological evidence of lymph nodes involvement at diagnosis, only one had nodal metastases. Five patients showed grade 3-4 of hematologic toxicity.

The creation of new blood vessels from existing ones, which is a mechanism called "angiogenesis", is essential in cancer to supply cancerous growth. Moreover, the development and the progression of the tumor and its metastases are the result of an efficient vascular response. Cancer cells release and activate different angiogenic growth factors and their receptors in the tumor microenvironment to promote the angiogenic process. The most important pro-angiogenic factor is the "Vascular Endothelial Growth Factor" (VEGF) because of its mitogen activity on vascular endothelium. Bevacizumab is a monoclonal antibody that obstructs the binding of circulating vascular endothelial growth factor to its receptors and has been approved for the treatment of primary and recurrent ovarian cancer but also for many other solid tumors.

Objective: To objectively assess anorectal dysfunction following nerve-sparing radical hysterectomy in stage I-II cervical carcinoma patients. Material and Methods: Between 2008 and 2012, 21 patients with primary cervical cancer stage FIGO I-II were enrolled in this prospective study. All women underwent nerve-sparing radical hysterectomy. Anorectal manometry was performed preoperatively and 6 months after surgery. A paired Student t test was used to assess the statistical difference between the manometric evaluations. A p value <0.05 was considered statistically significant. Results: Twenty-one patients were available for follow-up. Maximal and mean anal resting and squeezing pressures were unaffected by the surgical procedure, rectoanal inhibitory reflex and length of the high anal pressure zone did not change after the operation. The minimal volume to elicit rectal sensation, urge to defecate and maximal tolerable volume did not change significantly in the postoperative period, although they decreased in 2 and increased in 3 patients. In addition, rectal compliance did not change after surgery. Furthermore, no significant differences were found between patients who were or were not treated with adjuvant radiotherapy. Conclusions: Our findings suggest that nerve-sparing radical hysterectomy for cervical cancer does not seem to be associated with long-term anorectal dysfunction

Vulvar cancer rapresents 5% of gynaecological malignancies. Aimof this study is to identify factors that influence the survival of these patients. 122 patients were analyzed with a follow-up of 60.74 months. The characteristics analyzed were: age at diagnosis, type of surgical treatment, FIGO stage, histological type, grade, surgical margins, adjuvant therapy, interval diagnosis-relapse, site of recurrence. The statistical analysis showed that the prognostic factors are: FIGO stage, relapse free interval, the site of recurrence, positive lymph nodes and surgical margins in the histological examination. While age at diagnosis, grading and type of surgery seem not to influence the survival of patiens with vulvar cancer.

Objectives: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. Patients and Methods: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values &lt;0.05 considered significant. Results: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cyto-reductive surgery with residual tumors &lt;2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. Conclusions: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population. Copyright (C) 2011 S. Karger AG, Basel

Carcinosarcoma is a well-recognized tumor even if it is an uncommon entity. Neoplasms usually occur in the oral cavity, pharynx, esophagus, larynx and skin, and have been rarely documented in the female genital tract. This case reports a patient with a diagnosis of vulvar carcinosarcoma that has been treated with radical vulvectomy and a left inguinal lymphadenectomy but she died two months later of progressive disease. Because of the extreme rarity and severe prognosis of the tumor, we believe that this is a useful addition to the literature and might serves as a reminder to physicians that a multidisciplinary approach for management should be undertaken for treatment.

Objectives: To analyze the clinicopathological characteristics and prognostic factors associated with survival in patients with central nervous system (CNS) metastases from epithelial ovarian cancer. Methods: Twenty patients with CNS involvement from ovarian carcinoma were evaluated in this retrospective study; their features and survivals were analyzed using Kaplan-Meier and log-rank test methods. Results: The incidence of CNS metastases was 5%, among 400 patients with ovarian cancer treated in our single institution. The median age at diagnosis of the ovarian cancer was 55 years. The median interval to the brain involvement and the median survival were 33 and 18 months, respectively. Prognostic factors associated with survival were the International Federation of Gynecology and Obstetrics stage, the surgical resection, the multimodal treatment, and the response after the therapy of the brain metastases. Conclusions: Brain involvement from ovarian cancer is uncommon but is increasing in incidence. Although the prognosis is usually poor, a multimodal approach can result in a long-term remission of the metastases and in an improvement of the overall survival.

Objective: To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer. Methods: The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 19821994 were compared with those of 20 patients treated during 1995-2010 at the same center. Results: No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010. Conclusion: An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Paclitaxel is a member of the taxane agents that has demonstrated efficacy in ovarian cancer, both in first- and in second-line therapy. Counted among the side-effects of this drug are neurological disorders. In the present study, a rare case of a non-neuropathic ocular disorder, known as cystoid macular edema (CME), due to paclitaxel in patients treated for ovarian cancer is described. Macular edema, or CME, is a common cause of visual impairment that has been classically demonstrated by fluorescein angiograms, showing capillary leakage. CME without fluorescein leakage is rare, and its most common causes are juvenile X-linked retinoschisis, Goldmann-Favre syndrome, and niacin toxicity. At the present time, the mechanism associated with the form of CME that does not exhibit any signs of fluorescein leakage has not been elucidated due to an absence of histopathological studies. Several mechanisms have been proposed, although it is considered to occur due to disruption of the normal blood-retinal barrier by molecules with a molecular weight lower than that of fluorescein, which leads to fluid accumulation in the intracellular space. It is well known that taxane agents cause fluid retention, represented by edema, weight gain, and third-space fluid collection (pericardial, pleural, ascites), and this appears to be associated with their cumulative dose. The present case study confirms that macular edema associated with paclitaxel use exhibits spontaneous resolution following discontinuation of the causative agent. Taxane-associated maculopathy has been scarcely reported in the literature, but the gynecological oncologist should be alert to its possible development, and an ophthalmologic evaluation should be offered to all patients using paclitaxel

The aim of the study was to investigate the management and outcome of inguinal recurrence in vulvar carcinoma patients. A retrospective chart review was conducted on 140 patients with squamous cell carcinoma of the vulva treated between 1994 and 2006. Twenty-one patients were found to have groin recurrence. Median interval between primary treatment of vulvar cancer and groin recurrence was 7 months. Three patients refused any treatment, 3 received chemotherapy, 2 inguino-pelvic radiotherapy and 13 had resection of the groin recurrence. After surgery seven patients received irradiation of the groin and pelvis, and three patients received chemotherapy. One patient died following surgery; 19 patients died of disease with the median survival after diagnosis of inguinal recurrence of 9 months. Only one patient is alive without evidence of disease at 60 months following surgery. In univariate analysis, stage and grade at diagnosis, age and performance status at the recurrent disease, and the extent of residual tumour after resection of groin recurrence were predictors for survival. Groin recurrences from vulvar carcinoma carry a poor prognosis. Multi-modal treatment may result in a palliation of the disease, and a very limited number of patients have long-term survival.

Although uterine prolapse and carcinoma of the uterine cervix are not rare event, their association is very uncommon. An 86-year-old patient gravida 8, para 5 was admitted for vaginal bleeding from a uterine prolapse of 20 years of duration. On physical examination, a complete third-degree prolapsed uterus with an ulcerated lesion of 12 cm in maximum diameter involving both the anterior and posterior lips of the cervix was observed. Because of the poor performance status and high American Society of Anesthesiology scoring, the patient was admitted for a vaginal hysterectomy with upper vaginectomy in spinal anesthesia. However, she died of pulmonary embolism 20 days after surgery. A case of a cervical cancer with a complete uterine prolapse of 20 years of duration is reported. We believe that this case typically rare to see in a developed country might be a useful addition to the few published reports.

Background: The objective of this study was to evaluate feasibility, safety and clinical outcome of long-term therapy with topotecan (Hycamtin) in recurrent or persistent ovarian cancer. Patients and Methods: A retrospective chart review was conducted on all patients treated with topotecan (TPT) at the Department of Obstetrics and Gynecology, University of Bari, Italy between 1999 and 2007. Pertinent clinicopathologic information, response and toxicity following treatment with TPT were collected. TPT was given at a dosage ranging between 1.5 and 1.0 mg/m(2) every three to four weeks. All patients were evaluated for toxicity acording to the CTC and response according to the RECIST response criteria. Time to progression (TTP) was calculated from initiation of TPT treatment and start of the next chemotherapy regimen. Results: A total of 30 patients received TPT for at least eight cycles for recurrent ovarian (22), fallopian tube (3) or primary peritoneal carcinoma (5). A total of 432 cycles of chemotherapy were given, with an average of 14.4 cycles per patient (range 8-22). Dose reduction was necessary in 20 patients (66%). About half of the patients required blood transfusions and growth factors. Non hematologic toxicity was mild and manageable. Responses were observed in 16/30 patients (53%), the remaining having SD. Median time to treatment progression was 28 months (range 9-88). Conclusion: Long-term treatment with topotecan in recurrent/persistent ovarian cancer is feasible with limited evidence of cumulative toxicity. The results of this retrospective analysis suggest a potential role for late response and survival benefit for those patients without disease progression who continue topotecan therapy beyond six cycles of treatment.

Objective: Pelvic lymph nodes are the most common site of extrauterine spread in clinical early-stage endometrial cancer. International Federation of Gynecology and Obstetrics has mandated surgical evaluation of lymph nodes in endometrial cancer since 1988; however, the clinical impact of lymphadenectomy has never been addressed. Design: We reported a retrospective analysis in order to evaluate whether pelvic systematic lymph dissection improves overall and progression-free survival compared with no lymphadenectomy. Method: From 1991 through 2008, patients with endometrial carcinoma were evaluated using a log-rank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. Results: Of the 410 patients with a diagnosis of endometrial carcinoma, 390 underwent primary surgery. Of those who underwent surgery, 285 had endometrioid histology. One hundred and ninety (190) patients had surgery with no lymphadenectomy, whereas 95 had surgery with lymphadenectomy. Only 4 women revealed positive nodes. Median number of removed nodes was 14 in the lymphadenectomy group. The 5-year survival rate of 90% and 86% was achieved, respectively, for lymphadenectomy and no lymphadenectomy ( p¼0.501). Conclusions: Although systematic pelvic lymphadenectomy significantly improved surgical staging of women with clinical early-stage endometrial carcinoma by detecting a higher rate of patients with positive nodes, it did not improve overall survival.

Objectives: Aim of this study was to evaluate the effect of adjuvant therapy on the recurrence and on the overall survival in patients with early stage endometrioid adenocarcinoma of endometrium and lymphovascular space invasion (LVSI) treated with primary surgery. Methods: 48 patients with endometrioid adenocarcinoma of endometrium and LVSI were evaluated in this retrospective study. The Log-Rank test was used for statistical analyses and the Kaplan-Meyer method was used for time-to-event analysis. Results: 14 (29%) received radiotherapy as adjuvant therapy, whereas 34 (71%) did not received any adjuvant therapy. Between the patients who underwent adjuvant therapy, 4 (28%) developed a recurrence, the median time to recurrence was 26 months (8-53) and the median survival after recurrence was 56 months (29-120). 12(50%) patients who had not received any therapy relapsed, the median time to recurrence was 12 months (4-38) and the median survival after recurrence was 30 months (14-93). The analysis demonstrated that adjuvant therapy is not associated neither to a decreased in the occurrence of relapse (p=0,2), neither to an increase in survival (p=0,1). Conclusion: The administration of adjuvant radiotherapy in patients with recurrent endometrioid adenocarcinoma of early stage endometrial cancer and LVSI does not affect neither the occurrence of relapse, neither the overall survival.

BACKGROUND: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1alpha signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma. RESULTS: Given that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage. CONCLUSION: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Type I endometrial cancer (EC) is the most common form of EC, displaying less aggressive behavior than type II. The development of type I endometrial cancer is considered a multistep process, with slow progression from normal endometrium to hyperplasia, the premalignant form, and endometrial cancer as a result of an unopposed estrogenic stimulation. The role of mitochondria in type I EC tumor progression and prognosis is currently emerging. This review aims to explore mitochondrial alterations in this cancer and in endometrial hyperplasia focusing on mitochondrial DNA mutations, respiratory complex I deficiency, and the activation of mitochondrial quality control systems. A deeper understanding of altered mitochondrial pathways in type I EC could provide novel opportunities to discover new diagnostic and prognostic markers as well as potential therapeutic targets.

Objectives: It was the aim of this study to evaluate clinicopathological characteristics and prognostic factors of uterine leiomyosarcomas (LMS). Methods: Twenty-eight patients with uterine LMS were evaluated in this retrospective study. Their features and survival were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the patients was 52 years (range 25-74). Nine patients had a disease with a mitotic count <10/10 high-power fields. Twenty-one patients presented with stage I disease, 1 with stage II and 6 with stage IV. Twelve patients underwent total hysterectomy and bilateral salpingo-oophorectomy, 2 simple hysterectomy, 5 myomectomy and 9 more comprehensive surgical treatments. Adjuvant chemotherapy was administered to 16 patients, whereas chemoradiation was given only to 2 patients. Fifty percent presented with recurrence of the disease. The median overall survival was 46 months. Age, mitotic count, type of surgery, adjuvant therapy, recurrence and clinical response to chemotherapy were not found to affect survival, while the menopausal status and FIGO (International Federation of Gynecology and Obstetrics) stage were found to be prognostic factors. Conclusion: In our series, the menopausal state and FIGO stage were found to be prognostic factors related to survival. Copyright (C) 2011 S. Karger AG, Basel

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P &lt; 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

OBJECTIVE: The aim of this multicenter, retrospective study was to evaluate the efficacy and the safety of single agent Trabectedin (ET-743, Yondelis) in very heavily treated, relapsed ovarian cancer (ROC) patients. PATIENTS AND METHODS: Response to treatment was classified according to RECIST criteria. Progression-free (PFS), and overall survival (OS) were also assessed. RESULTS: 98 patients were analyzed (originally 67 platinum sensitive, and 31 platinum refractory/resistant). Median number of previous regimens was 4 (range: 1-6). In the whole population, overall response rate (ORR) was 27.5%; stable disease (SD) was observed in 33 patients (33.6%), and clinical benefit was achieved in 60 cases (61.2%). ORR was 38.6% in fully platinum sensitive population, and 26.1% in partially platinum sensitive patients. In platinum refractory/resistant disease, ORR was 12.9%. Overall, median PFS and OS were 5, and 13 months, respectively. Patients responding to Trabectedin showed a more favorable PFS (median = 9 months) than patients with SD (median = 6 months), or progression (median = 2 months). Median OS of responding patients was 18 months compared to 14 months in SD patients, and 9 months in progressing patients. Grade 3-4 neutropenia was observed in 17 (17.3%) patients. Transient and non-cumulative Grade 3-4 AST and ALT level elevation was found in 7 (7.1%), and 13 (13.3%) cases, respectively. There was 1 case of Grade 3, and 1 case of Grade 4 cardiac toxicity. CONCLUSIONS: Trabectedin, as a single agent, retains its efficacy in terms of rate of ORR and clinical benefit in heavily treated ROC patients, especially in the group of platinum sensitive disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Objectives: The aim of this study was to assess the accuracy of transvaginal sonography (TVS) in the preoperative staging of endometrial carcinoma, because accurate preoperative staging of the disease would assist in planning the optimal course of treatment. We investigated the ability to distinguish between cases with &lt; 50% and &gt; 50% myometrial invasion (FIGO Stage Ia -Ib vs. Stage Ic), and tumor extension to the cervical stroma (Stage IIb) according to the old FIGO classification. Methods: 140 women with pathologically-proven of endometrial cancer, referred to our istitution between 2007 and 2010, were included in this study. All underwent TVS examination about seven days before the surgical staging. Histological findings of myometrial and cervical stroma invasion were used as the reference standard. Results: The histological subtypes comprised 75% endometrioid adenocarcinoma, 9% serous papillary, 6% endometrioid villoglandular, 4% villoglandular, 3% adenosquamous and 3% clear cells; there were 60% well differentiate, 15% moderately differentiate and 25% poorly differentiate cancers. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for TSV in the evaluation of &lt; 50% myometrial infiltration were 82%,77%, 79%, 80% and 48%; of &gt; 50% myometrial infiltration were 86%, 90%, 86%, 90%, and 57%; for cervical invasion were 80%, 100%, 100%, 89% and 63%, respectively. Conclusion: The transvaginal sonography shows good accuracy in the staging of endometrial carcinoma. Our results support a potential role of TVS for the prediction of strome cervix infiltration of endometrial cancer.

No abstract available

Aims: We present this case to improve medical knowledge about unusual presentation of leiomyomas and about the diagnostical findings of examinations settled down per rectal way. We provide images and stress the importance of differential diagnosis based on imaging. Presentation of the Case: We report a case of a 26 years old nulliparous, with a leiomyoma developed on the posterior upper third of the vagina surgically removed. The patient came to our Unit with dysmenorrhea and menorrhagia and underwent physicalexamination and ultrasound scan. Both exams were executed per transrectal way because of her being a virgo. A Computed Tomography scan has been executed too. All the results pointed out the presence of a round-shaped, well delimitated, solid mass in posterior vaginal wall. Magnetic Resonance confirmed this diagnosis. Discussion: We widely discuss the symptomathologic cortege, the diagnostic iter based on imaging we settled down, the possible differential diagnosis, and surgical therapy performed. Concordance of imaging, negativity of tumor markers and general well-being status of the patient led to the diagnostical hypotesis of vaginal benign neoformation. These data excluded other diagnosis as endometriosis, uterine fibroma, primitive vaginal malignant tumor and metastasis of other-site primitive malignant neoplasia. The patient has been treated by surgical transvaginal excission therapy. Conclusion: US imaging and MR gives us the possibility to recognize a mass and to discern his nature and localization, thus to choose the best therapy in each case. Hystopathology still represent the gold standard in making a diagnosis in gynaecological oncology.