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A radical hysterectomy with pelvic lymph node dissection is the standard operative treatment in patients with diagnosed IB-IIA degree by FIGO 2018 invasive uterine cervix carcinoma. A concept and technique of radical hysterectomy was created at the end of the 19th Century based on the then knowledge on the progression of neoplasms. In the space of years, in order to limit the scale of side effects, subsequent modifications of the radical hysterectomy technique appeared, however still on the basis of the same model of the neoplasm’s propagation concerning the accidental infiltration of surrounding tissues promoted by reduced mechanical resistance. In 2003 Prof. M. Hockel was the first to present a new concept of radical hysterectomy, which originated in the studies on the local development of the tumour. In comparison with the other methods of radical surgery, radical hysterectomy involving tissue morphogenesis (total mesometrial resection – TMMR) by M. Hockel with therapeutic lymph node dissection (tLND), apart from the maintenance of the oncologic efficacy range with concomitant conservation of the vegetative innervation, allows the improvement of a therapeutic index in tumours with unfavourable prognostic factors, at the same time generating a small number of post-operative complications. It should also be noted that the fundamental feature distinguishing tLND-assisted TMMR from the classic radical hysterectomy is a possibility to avoid a supplementary radiotherapy with no effect on future outcomes.

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT. Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB–IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1–L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m2, 5–6 cycles, 1 day per cycle, plus 45–50 Gy external-beam radiotherapy delivered in 1·8–2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920. Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm3 (IQR 20–40) and median minimal dose to 90% of the clinical target volume (D90%) was 90 Gy (IQR 85–94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20–64), actuarial overall 5-year local control was 92% (95% CI 90–93). Actuarial cumulative 5-year incidence of grade 3–5 morbidity was 6·8% (95% CI 5·4–8·6) for genitourinary events, 8·5% (6·9–10·6) for gastrointestinal events, 5·7% (4·3–7·6) for vaginal events, and 3·2% (2·2–4·5) for fistulae. Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies. Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems. © 2021 Elsevier Ltd

EgeUn###, Aim:The aim of this study is to investigate the accuracy of dose distributions calculated by the BrachyDose Monte Carlo (MC) code in heterogeneous media for high-dose-rate (HDR) brachytherapy and to evaluate its usability in the clinical brachytherapy treatment planning systems.Materials and methods:For dose comparisons, three different dose calculation algorithms were used in this study. Namely, BrachyDose MC code, Eclipse TG-43 dose calculation tool and Acuros®BV model-based dose calculation algorithm (MBDCA). Dose distributions were obtained using any of the above codes in various scenarios including 'homogenous water medium scenario', an 'extreme case heterogeneous media scenario' and clinically important 'a patient with a cervical cancer scenario'. In the 'extreme case, heterogeneous media scenario', geometry is a rare combination of unusual high-density and low-density materials and it is chosen to provide a test environment for the propagation of photons in the interface of two materials with different absorption and scattering properties. GammaMed 192Ir Model 12i Source is used as the HDR brachytherapy source in this study. Dose calculations were performed for the cases where there is either a single source or five sources planted into the phantom geometry in all homogenous water phantom and extreme case heterogeneous media scenarios. For the scenario a patient with a cervical cancer, dose calculations were performed in a voxelized rectilinear phantom, which is constructed from a series of computed tomography (CT) slices of a patient, which are obtained from a CT device.Results:In homogeneous water phantom scenario, we observed no statistically significant dose differences among the dose distributions calculated by any of the three algorithms at almost every point in the geometry. In the extreme case heterogeneous media scenario, the dose calculation engines Acuros®BV and BrachyDose are agreed well within statistics in every region of the geometry and even in the points close to the interfaces of low-density and high-density materials. On the other hand, the dose values calculated by these two codes are significantly different from those calculated by the TG-43 algorithm. In the 'a patient with a cervical cancer scenario', the calculated D2cc dose difference between Acuros®BV and BrachyDose codes is within 2% in the rectum and 11% for the bladder and sigmoid. There was no meaningful difference in the mean dose values between MBDCAs in the bone structures.Conclusions:In this study, the accurate dose calculation capabilities of the BrachyDose program in HDR brachytherapy were investigated on various scenarios and, as a MC dose calculation tool, its effectiveness in HDR brachytherapy was demonstrated by comparative dose analysis. © Cambridge University Press 2019.

El cáncer de cuello uterino es una neoplasia maligna frecuente en las mujeres, que se disemina hacia pulmones, ganglios linfáticos supraclaviculares, hígado y hueso como metástasis a distancia. La resultante es mala y la supervivencia varía de 3 a 6 meses. Se presenta un caso de paciente de 67 años de edad con antecedente de carcinoma de células escamosas de cuello uterino estadio IIB hacía 5 años tratada con cirugía más radio-quimioterapia, quien presentó alteraciones de la marcha, cefalea y vómitos. Las imágenes de resonancia magnética revelaron múltiples lesiones con aumento de edema perilesional hipointensas en T1 e hiperintensas en T2. La paciente murió una semana después del diagnóstico. Los hallazgos de la necropsia demostraron carcinoma de células escamosas pobremente diferenciado de origen en cuello uterino. Cervical cancer is a frequent malignancy of women that spreads to lungs, supraclavicular lymph nodes, liver, and bones as distant metastasis. Prognosis is poor and survival varies from 3 to 6 months. We report the case of a 67-yearold woman with history of squamous cell carcinoma of cervix stage IIB 5 years ago treated with surgery plus radio-chemotherapy who presented walking impairment, headache and vomiting. Cranial magnetic resonance imaging revealed multiple lesions with increasing perilesional edema, T1-hypointense and T2-hyperintense. The patient died one week after the diagnosis. Necropsy findings showed poorly differentiated carcinoma of cervical origin.

Background Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrast-enhanced (DCE) MRI to assess the microvascular density (MVD), interstitial fluid pressure (IFP), and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study. Methods Four patient-derived xenograft (PDX) models of squamous cell carcinoma of the uterine cervix (BK-12, ED-15, HL-16, and LA-19) were subjected to Gd-DOTA-based DCE-MRI using a 7.05 T preclinical scanner. Parametric images of the volume transfer constant (K trans) and the fractional distribution volume (v e) of the contrast agent were produced by pharmacokinetic analyses utilizing the standard Tofts model. Whole tumor median values of the DCE-MRI parameters were compared with MVD and the fraction of hypoxic tumor tissue, as determined histologically, and IFP, as measured with a Millar catheter. Results Both on the PDX model level and the single tumor level, a significant inverse correlation was found between K trans and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological v e values (v e > 1.0). None of the DCE-MRI parameters were related to MVD or IFP. Conclusions DCE-MRI may provide valuable information on the hypoxic fraction of squamous cell carcinoma of the uterine cervix, and thereby facilitate individualized patient management. Electronic supplementary material The online version of this article (10.1186/s12967-017-1331-4) contains supplementary material, which is available to authorized users.

Metastasis to the mandibular condyle and cervical spine in oncologic patients is rare, and clinicians should therefore be alert if patients present with such suspicious lesions for further clinical and pathological examinations. A 58-year old female patient with uterine cervical cancer initially presented with mild left condylar dysfunction. CT-imaging revealed a progressive osteolytic lesion of the left condyle and at the same time CT-scans revealed an osteolytic lesion of the cervical spine. Further metastatic bone lesions were ruled out. An incisional biopsy of the left condyle revealed metachronous metastasis from the uterine cervical carcinoma. Based on clinical and radiological examinations the patient underwent surgery with total alloplastic replacement of the temporomandibular joint (TMJ) and in a second surgical approach stabilization of the cervical spine. Suspicious symptoms with TMJ dysfunction in conjunction with osteolytic lesions of the maxillofacial skeleton in oncologic patients should be addressed quickly to prevent further diagnostic delay. Surgical resection of metastatic lesions should be considered as a palliative treatment option in selected patients.

Background Primary analyses of a study in young women aged 16–26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. Methods We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16–26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. Findings Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0–99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. Interpretation The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. Funding Merck and Co, Inc. © 2017 Elsevier Ltd

Erdogan, Kivilcim Eren/0000-0002-4951-8703; kilic bagir, Emine/0000-0002-1447-1060; Celik, Betul/0000-0001-9731-9939; Tatli Dogan, Hayriye/0000-0003-4318-2775; Cakir, Asli/0000-0003-0128-6947 WOS: 000414649400006 PubMed: 28272675 Objective: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. Material and Method: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. Results: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells/Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. Conclusion: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 39 - N° 2 - p. 102-115

Resume Les auteurs rapportent la survenue, chez une femme de 37 ans, d’une metastase osseuse occipitovertebrale d’un carcinome epidermoide invasif du col de l’uterus, confirmee histologiquement, decouverte trois mois apres le cancer du col, traitee par radiotherapie locale puis chimiotherapie generale. La radiotherapie a ete efficace sur les douleurs, meme si elle n’a pas modifie les images IRM. La chimiotherapie a ete entreprise. Mais des metastases ganglionnaires, une extension des lesions locales sont survenues et la patiente est decedee a peine plus d’une annee apres la decouverte de la metastase osseuse. Une revue de la litterature est faite a l’occasion de cette localisation exceptionnelle de metastases d’un cancer du col uterin.

Resume L'enregistrement prospectif des complications aigues et tardives des traitements des cancers du col uterin est un devoir indissociable de la publication des resultats du controle local et de la survie. En raison de la diversite des classifications et des glossaires utilises, la comparaison des resultats des differentes series est souvent difficile. Le glossaire franco-italien semble actuellement l'echelle la mieux adaptee, a condition qu'elle evolue afin de tenir compte de l'impact des complications sur la qualite de vie. Les principaux facteurs predictif des complications et independants du traitement sont les antecedents d'interventions chirurgicales abdominales et/ou pelviennes. Les complications engendrees par la chirurgie varient en frequence et en gravite en fonction de la voie d'abord et de l'importance de l'elargissement aux tissus periuterin. Les causes connues des complications postradiques sont l'augmentation des doses et des volumes d'irradiation externe et de curietherapie ainsi que l'augmentation du debit de dose de la curietherapie de bas debit de dose. La diminution significative du taux des complications severes au cours des 15 dernieres annees a surtout ete obtenue grâce aux ajustements individuels de la planification de la radiotherapie. L'association de radiotherapie et de chimiotherapie concomitante est recemment devenue un standard de traitement pour les stades precoces de pronostic defavorable et pour les stades localement avances. La toxicite a long terme de cette association demande a etre documentee par un suivi rigoureux des patientes. Les methodes d'optimisation developpees lors des traitements par irradiation exclusive doivent rester la reference, car l'adjonction d'une chimiotherapie ne doit pas tenter de compenser une mauvaise planification de la radiotherapie externe et de la curietherapie.

Resume La curietherapie est une etape fondamentale dans le traitement des patientes atteintes de cancer du col de l'uterus. Elle permet une augmentation significative des taux de controle local et de survie. Sa realisation doit se situer le plus pres possible de la fin de la radiotherapie externe, en cas d'irradiation exclusive, de facon a ne pas augmenter l'etalement au-dela de 53 jours. Les donnees techniques et dosimetriques caracterisant la curietherapie de bas debit de dose et exprimees generalement a l'aide des recommandations de l'ICRU 38 ont permis d'augmenter le taux de controle local et de diminuer celui de complications. Ces donnees sont moins bien connues pour les autres types de debit. La place de la curietherapie interstitielle reste mal definie dans les formes etendues et son benefice potentiel se fait vraisemblablement au prix d'une elevation du taux des complications. L'interet de la chimiocurietherapie necessite des investigations cliniques complementaires, meme si la chimioradiotherapie est devenue un standard dans les stades de pronostic defavorable.

Resume La technique chirurgicale de reference dans le traitement des cancers du col uterin de stades Ib et Il est la colpohysterectomie par laparotomie avec resection de la totalite du parametre. Neanmoins, il est possible de realiser chez les patientes ayant une tumeur de pronostic tres favorable une resection partielle du parametre, voire une chirurgie conservatrice de l'uterus et/ou des annexes. La lymphadenectomie est un geste diagnostique, pronostique, mais aussi probablement therapeutique. Elle doit concerner les ganglions pelviens mais aussi lomboaortiques chez les patientes ayant une tumeur de gros volume. L'exenteration pelvienne est le traitement de reference des recidives centropelviennes isolees chez les patientes jeunes. Des techniques chirurgicales recentes de reconstruction permettent de diminuer la morbidite et d'ameliorer la qualite de vie des patientes.

Imaging of uterine cervix carcinoma has evolved during the last decade. Recent developments in magnetic resonance imaging have expanded the role of MRI in evaluating the pathology of uterine cervix carcinoma. MRI is now the modality of choice for tumor staging, evaluating tumor response to treatment, diagnosing recurrences and for evaluating pregnant patients. MRI images will soon be used to calculate dosimetry for brachytherapy with matching and fusion software.

Objective : To quantify first-pass enhancement of cervix carcinoma using fast dynamic MRI. To assess the accuracy of dynamic contrast-enhanced colour-coded MRI for determining tumour invasion into surrounding pelvic tissues. Methods : Gadolinium enhanced dynamic MRI at one image every 2 s was performed in 47 patients with cervical carcinoma and five controls. First-pass contrast enhancement of cervix carcinoma and surrounding pelvic tissues was quantified. Automated colour-coded images were constructed using the dynamic parameters slope, amplitude and timing of enhancement. Of 47 patients, 28 underwent surgery and colour coded images were correlated with histological findings. Results : First-pass contrast enhancement imaging of cervix carcinoma required a temporal resolution of dynamic MRI of one image every 3–4s. Cervix carcinoma firstpass was more rapid and intense than that of other pelvic tissues ( P P >0.05). Binary colour coding, however, was not reliable for tumour delineation or for accurate assessment of tumour invasion into the parametria or the bladder wall. Overestimation of the extent of tumour invasion occurred in 15, 16 and nine out of 28 patients, respectively, using amplitude, slope and timing of enhancement as parameters. Conclusion : Dynamic contrast-enhanced colour-coded MRI of cervix carcinoma has limited value for assessing the extent of tumour spread and tumour staging.

SummaryFibrinogen has been detected in ME-180 human uterine cervix carcinoma cells, and synthesis of fibrinogen by ME-180 cells has been measured using [35S] L-methionine incorporation. Expression of mRNA for the B|3-chain of the fibrinogen in ME-180 cells has been identified by PCR-assisted mRNA amplification. The AΑ-, BΒ-, and Γ-chains of fibrinogen synthesized by ME-180 cells were chemically and immunologically identical to those of plasma fibrinogen. These findings suggest that fibrinogen is present and synthesized in ME-180 human uterine cervix carcinoma cells, and that fibrinogen plays a role in these malignant tumor cells.

Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG.We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes.All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels.Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Caso clínico: Se presenta el caso clínico de una paciente de 70 años con coroiditis serpiginosa y carcinoma de cérvix uterino. Discusión: La etiología de la coroiditis serpiginosa es desconocida pero lesiones similares han sido descritas en asociación con lupus eritematoso sistémico, linfoma no Hodgkin, enfermedad de Crohn, sarcoidosis, tuberculosis, infección por virus del herpes, hepatitis autoinmune y carcinoma pulmonar. Case report: We report the case of a 70-year-old patient with serpiginous choroiditis and uterine cervix carcinoma. Discussion: The etiology of serpiginous choroiditis is unknown, but similar lesions have been described in association with systemic lupus erythematosus, non-Hodgkin lymphoma, Crohn's disease, sarcoidosis, tuberculosis, herpes virus infection, autoimmune hepatitis and lung carcinoma.

Crystals of the [SbBr3(MMBZT)2] (1) complex (MMBZT = N-methyl-2-mercaptobenzothiazole) were grown from acetonitrile/methanol of the filtrate derived from the reaction between 3-methyl-2-mercaptobenzothiazole (MMBZT) in methanol, with antimony(III) bromide in acetonitrile. The crystal structure of 1 (C16H14Br3N2S4Sb) was determined by X-ray diffraction at 100(2) K, in space group P-1, with a = 10.738(2) A, b = 11.387(3) A, c = 11.439(3) A, α = 62.764°, β = 63.36(2)°, γ = 85.074(2)°, and Z = 2. The geometry around the metal center of complex 1 is square pyramidal, with two sulfur atoms from thione ligands and three bromide anions around Sb(III). Complex is monomer. The equatorial plane is formed by two sulfur and two bromide atoms in complex, in a cis-S, cis-Br arrangement. The in vitro cytotoxicity against leiomyosarcoma cells (LMS) of antimony(III) bromide complexes with thioamide ligands with formulae: [SbBr3(MMBZT)2] (1), [SbBr3(TU)2] (2), [SbBr3(MMI)2] (3), {[SbBr2(MBZIM)4]+·[Br]−·H2O} (4), {[SbBr2(μ 2-Br)(MMBZIM)2]2} (5), {[SbBr2(μ 2-Br)(EtMBZIM)2]2·MeOH} (6), {[SbBr3(μ 2-S-tHPMT)(tHPMT)] n } (7), {[SbBr2(μ 2-Br)(PYT)2) n } (8), {[SbBr2(μ 2-Br)(MTZD)2] n } (9), and {[SbBr5]2−[(PMTH2 +)2]} (10) (where TU = thiourea, MMI = methylimidazole, MBZIM = 2-mercaptobenzimidazole, MMBZIM = 2-mercapto-5-methyl-benzimidazole, EtMBZIM = 5-ethoxy-2-mercaptobenzimidazole, tHPMT = 2-mercapto-3,4,5,6-tetrahydro-pyrimidine, PYT = 2-mercaptopyridine, MTZD = 2-mercapto-thiazolidine, and PMTH = 2-mercaptopyrimidine) were evaluated. Complex 8 shows the strongest activity against LMS cells with IC50 value 1.7 ± 0.1 μΜ. The results are compared with their activity against human cervix carcinoma cell lines. Complexes 1, 6–9 were also tested for their inhibitory activity upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase. Computational studies using multivariate linear regression and considering biological results (50% inhibitory concentration, IC50) as dependent variables derived a theoretical equation for IC50 values of the complexes studied. The calculated IC50 values are compared adequately with the experimental inhibitory activity of the complexes measured.

Background: HIV-infected individuals have heightened cancer risk. With the advent of highly active antiretroviral therapy (HAART), the frequency of some AIDS-defining cancers (ADC) has decreased although certain non-AIDS-defining cancers (NADC) are becoming more frequent. Cancers among HIV-infected individuals in Latin American and the Caribbean have not yet been carefully studied. Methods: Cancer cases among the Caribbean, Central and South American network for HIV Research (CCASAnet) cohort were identified reviewing clinical records and pre-existing databases. Results: There were 406 cancers reported: 331 ADC (224 Kaposi sarcomas and 98 non Hodgkin lymphomas). Most frequent NADC (n = 75) were Hodgkin lymphoma and skin cancers. Seventy-three percent of NADC and 45% of ADC were diagnosed >1 year after HIV diagnosis. Fifty-six percent of ADC occurred before HAART start. Median time from HAART start until cancer diagnosis was 2.5 years for NADC and 0.5 years for ADC (P =

We synthesized the novel seco cyclopropa[c]pyrrolo[3,2-e]indole (CPI) bisalkylators and evaluated their antitumor activity. Among these derivatives, 11a (AT-760), in which the two seco 3-methoxycarbonyl-2-trifluoromethyl CPI (MCTFCPI) moieties are connected with a 3,3‘-(1,4-phenylene)bisacryloyl group, was found to exhibit more potent cytotoxicity and antitumor activity against HeLaS3 human uterine cervix carcinoma cells and Colon 26 adenocarcinoma cells, respectively, than 8 (bizelesin, U-77,779). It also appeared that compound 11a exhibits improved in vivo efficacy in the human colon CX-1 model when compared to either compound 8 or mitomycin C (MMC). Efficacious doses for 11a were found to be 2-fold lower than those for 8.

Introduction: The aim of this phase II study was to evaluate response and toxicity of a prolonged chemoradiation regimen in patients with locally advanced cervical cancer. Patients and Methods: Three cycles of concomitant chemotherapy were used with cisplatin (20 mg/m2, 2-hour intravenous infusion, days 1-4) and 5-fluorouracil (1000 mg/m2, 24-hour continuous intravenous infusion, days 1-4) administered at weeks 1, 5, and 9 of radiotherapy. In combination, radiotherapy was delivered to a planning target volume (PTV) defined as the CTV (clinical target volume) plus 8 mm. The CTV was defined as follows: gross tumor volume, upper half of the vagina (if not involved) or the whole vagina (if clinically involved), uterus, obturator nodes, external iliac nodes, internal iliac nodes, and the presacral nodes (cranial to S2). The prescribed dose to the PTV was 50 Gy, 2 Gy/fraction (ICRU 62) delivered in 25 fractions with a 2-week break at 20Gy and 40 Gy (split-course technique). Early and late toxicity was assessed according to the RTOG and RTOG/ EORTC toxicity scales. Perioperative toxicity was evaluated according to the Chassagne classification of surgical complications. Results: A total of 25 patients were included in this study. Median age was 52 years (range, 28-69). Clinical stage was: IB2-II: 19 patients (76%), III-IVA: 6 patients (24%). All patients completed the prescribed dose of chemoradiation and were evaluated 4 weeks after the end of treatment. Complete and partial clinical local response was observed in 4 and 19 patients, respectively (totaling 92% of clinical responses). About 32% of patients experienced grade 3 to 4 toxicity, in particular, grade 3 or 4 hematological toxicity was observed in 7 patients and 1 patient developed grade 3 genitourinary toxicity. No patients developed grade 3 gastrointestinal toxicity or skin toxicity. Of total, 22 patients (88%) underwent radical hysterectomy. Seven patients (28%) showed a complete response (CR) to treatment, and 7 patients (28%) showed microscopic residual disease (=PR), totaling 14 patients (56%) complete/partial microscopic responses. Perioperative morbidity was higher than reported in historical controls especially in terms of tissue fibrosis (64%) and perioperative urinary toxicity (14%). Actuarial 2-year local control, disease-free survival, and overall survival were 65.5%, 61.8%, and 80.8%, respectively. Conclusion: A prolonged treatment with more chemotherapy courses does not improve tumor response and increases the risk of perioperative complication. This treatment regimen, considering the low incidence of acute gastrointestinal toxicity, might be tested in the adjuvant setting. © 2010 by Lippincott Williams & Wilkins.

Cellular hypoxia is a cause of radioresistance. The oxygen tension (pO2) in normal tissues and in tumours can be measured by polarography. In this feasibility study we have measured the tissue pO2 of 10 patients suffering from uterine cervix carcinoma, using the Eppendorf histograph. The measurements were performed at the time of the brachytherapy after external radiotherapy. The machine was found to be reliable and no adverse effect was noted. The mean pO2 values in tumours were lower than those of normal tissues.

Fusion toxins are an emerging class of targeted therapeutics for the treatment of cancer. Diphtheria toxin-stem cell factor (DT-SCF) is one such novel fusion toxin designed to target malignancies expressing c-kit. Since, c-kit overexpression has been reported on many types of cancers, it appeared to be a reasonably good molecule to target. In the present study, we report construction, expression, purification, and characterization of DT-SCF. DT-SCF gene coding for 1-387 amino acids of diphtheria toxin, His-Ala linker, 2-141 amino acids of SCF was cloned into expression vector with C terminal His tag. The induced DT-SCF protein was exclusively expressed in insoluble fraction. Purification of DT-SCF was achieved by inclusion body isolation and metal affinity chromatography under denaturing and reducing conditions. Purified DT-SCF was renatured partially on-column by gradually reducing denaturant concentration followed by complete refolding through rapid dilution technique. Cell viability assay provided the evidence that DT-SCF is a potent cytotoxic agent selective to cells expressing c-kit. The novelty of this study lies in employing SCF as a ligand in construction of fusion toxin to target wide range of malignancies expressing c-kit. Efficacy of DT-SCF fusion toxin was demonstrated over a range of malignancies such as chronic myeloid leukemia (K562), acute lymphoblastic leukemia (MOLT4), pancreatic carcinoma (PANC-1), and cervical carcinoma (HeLa 229). This is the first study reporting specificity and efficacy of DT-SCF against tumor cells expressing c-kit. There was significant correlation (P?=?0.007) between c-kit expression on cells and their sensitivity to DT-SCF fusion toxin. � 2010 Springer Science+Business Media, LLC.

Purpose: Helicobacter pylori (H. pylori) is believed to play a role in several gynecological and obstetric pathologies since the cervical mucosa resembles the gastric environment. The microorganism is expected to infect the upper genital tract via the oral-genital and fecal-genital routes. Methods: We studied 35 cases with benign, ASCUS, ASC-H, LSIL and HSIL pap-smear results. The presence of H. pylori in the uterine cervix and active infection were investigated with the H. pylori stool antigen test. Biopsy specimens were stained with hemnatoxylin-eosin and Warthin-Starry stains to find H. pylori in cervical tissue. Seroprevalence was investigated by using ELISA for H. pylori IgG and IgA. Results: The H. pylori seroprevalence was 65.7%; further, 17.1% of the cases had an active infection. H. pylori was not found in the cervix or the cervicovaginal secretions. Conclusion: The cervix is not a reservoir for H. pylori, and the microorganism does not appear to be transmitted through the fecal-genital route.

Purpose: Evaluation of the association between perineural invasion (PNI) and predictive and prognostic factors in early-stage cervical carcinoma patients treated with surgery. Methods: Fifteen PNI (+) and 21 PNI (-) early-stage cervical carcinoma patients, primary treated by surgery, were evaluated retrospectively. Patients' complete blood counts and biochemistry tests, tumoral prognostic parameters. PNI status. postoperative treatment, recurrence and survival data were obtained from the records. Results: The percentage of mean depth of stromal invasion was significantly higher in the PNI (+) group (p 0.05) was significantly more prevalent in the PNI (+) group. Conclusion: PNI is closely related with stromal invasion in percentage, vaginal and uterine involvement and lymphatic invasion of the tumor.

The role of intracavitary irradiation in the treatment of uterine cervix carcinoma is well established, and over the years a number of different systems for intracavitary irradiation have been developed. To compare the clinical efficacy of different systems and to develop guidelines for the design of applicators with new sources such as americium-241, we present a dosimetric comparison of three systems: (a) the Morris system, a modified Stockholm technique; (b) the Henschke system; and (c) the Fletcher system. Using a computerized planning system, dose distributions with different configurations of each system were calculated. For each case, doses to point A, B, and a set of reference points representing bladder and rectum were also calculated. Also, the 60 Gy reference volumes, as defined by ICRU Report No. 38, 1985, were calculated for six different treatment regimens. These treatment regimens employ widely different combinations of whole pelvis external beam dose, split pelvis external beam dose, and intracavitary irradiation dose to achieve similar clinical outcomes for the treatment of various stages of cervix carcinoma. From this analysis we observe the following: (a) The Morris system produces a higher dose rate to point A (70 to 90 cGy/hr) compared to the Fletcher or Henschke system (50 to 70 cGy/hr); (b) the doses to point B relative to point A dose are about the same for all three systems at 28 to 32%; (c) the doses to reference rectum and bladder points relative to point A dose for clinically equivalent configurations are about the same for Fletcher and Henschke systems (58–65%) not including the effects of shields in the vaginal ovoids, and somewhat higher for the Morris system (72–79%); (d) the volume treated to a given dose rate by each intracavitary system alone is about the same; and (e) the 60 Gy volume depends critically upon the external beam whole pelvis dose, rising steeply as the external beam whole pelvis dose approaches 30 Gy. Since different groups have used widely different prescriptions of external beam whole pelvis dose, ranging from 0 to 50 Gy depending upon stage, the 60 Gy volumes for these various dose prescriptions are strikingly different. Because the Morris system uses lower values for the external beam whole pelvis dose than the others, its 60 Gy volume for the advanced Stage IIB and IIIB is 2 to 4 times lower than others. This choice makes the Morris system more conservative than others, probably resulting in slightly lower cure rates for the advanced stage disease.

Objective: Adenofibroma is a form of mixed mesodermal tumor in which epithelial and stromal components are benign, and usually arises in the endometrium of postmenopausal women. We report a case of lipoadenofibroma of the endometrium that appeared as an intracavitary mass, which is very unusual because endometrioid adenofibroma rarely contains mature adipose tissue, only the second such case described in detail. Case: An endometrial polypoid mass measuring 1,5 cm with maximum diameter was found incidentally during total abdominal hysterectomy for keratinizing large cell carcinoma of the cervix in a 60-year-old woman. The endometrial polypoid mass was found to be a lipoadenofibroma composed predominantly of collagenated fibrous stroma populated by cystically dilated and occasionally crowded glands lined with proliferative endometrium, intermingled with abundant mature adipose tissue. Conclusion: We suggest that uterine adenofibromas with lipomatous areas belong to the family of mixed tumor of Mullerian origin. We discuss the pathogenesis of this entity and review the previously documented similar cases. © 2008 Springer-Verlag.

Summary Objectives: A proof of principle study was conducted for microscopic tissue volume reconstructions using a new image processing chain operating on alternately stained large histological serial sections. Methods: Digital histological images were obtained from conventional brightfield transmitted light microscopy. A powerful nonparametric nonlinear optical flow-based registration approach was used. In order to apply a simple but computationally feasible sum-of-squared-differences similarity measure even in case of differing histological stainings, a new consistent tissue segmentation procedure was placed upstream. Results: Two reconstructions from uterine cervix carcinoma specimen were accomplished, one alternately stained with p16INK4a (surrogate tumor marker) and H&E (routine reference), and another with three different alternate stainings, H&E, p16INK4a, and CD3 (a T-lymphocyte marker). For both cases, due to our segmentation-based reference-free nonlinear registration procedure, resulting tissue reconstructions exhibit utmost smooth image-to-image transitions without impairing warpings. Conclusions: Our combination of modern nonparametric nonlinear registration and consistent tissue segmentation has turned out to provide a superior tissue reconstruction quality.

International audience; Therapeutic administration of the antiviral agent cidofovir with radiation markedly enhanced the antitumor effect of ionizing radiation in cells of two HPV18+ human cervical carcinoma cell lines. Although this potent radiosensitizing effect was associated with repression of the viral oncoproteins E6/E7 and restoration of TP53 as shown previously, additional mechanisms may be involved. In the present study, we investigated the antiangiogenic effect of the combination of cidofovir and radiation in cells of two HPV18+ cervical cancer cell lines, HeLa and ME180, and assessed the molecular mechanisms associated with the antiangiogenic effect observed. Cells were exposed to cidofovir (10 μg/ml) and irradiated (1-9 Gy). The angiogenic response was studied in vitro by a matrigel invasion assay. Modulations of E6, TP53 and VEGF mRNA and protein levels were studied by real-time RT-PCR, Western blot analysis and ELISA, respectively. Then a double RNA interference approach was used to analyze the connection between E6/TP53 and VEGF. The combination of cidofovir and radiation had a potent antiangiogenic effect. It induced E6 inhibition, restoration of TP53, and reduction of the proangiogenic phenotype of HPV18+ cells associated with VEGF inhibition. A siRNA strategy showed an anti-VEGF action of the combination mediated directly by E6 inhibition and TP53 restoration, since E6 siRNA inhibited VEGF whereas co-transfection with E6 and TP53 siRNA abrogated the anti-VEGF effect. This study showed that the combination of cidofovir with ionizing radiation has an antiangiogenic effect associated with VEGF inhibition subsequent to E6 inhibition and TP53 restoration. © 2006 by Radiation Research Society.

Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological malignancies. We present the case of a 70-year-old woman with uterine cervix carcinoma metastatic to the skin and treated with surgery and radiotherapy. The last relapse to the skin was complicated by the formation of an enterocutaneous fistula. This low-output fistula was treated with surgery and adequate supportive care. The treatment of enterocutaneous fistulas may be either invasive (surgical resection, surgical repair with corrective procedures or with myocutaneous flaps, colonic and/or urinary diversion, endoscopic treatments with metallic stents) or conservative (skin care and local disinfection, pouching of secretions, control of nutrition and electrolytes, TPN, antisecretory treatment with scopolamine or octreotide, and control of psychological conditions). Enterocutaneous fistulas associated with skin metastases are not commonly reported in the literature and may be successfully treated with surgery and supportive care in patients with good performance status and no evidence of further metastatic disease.