In vitro characterization of Trichophyton rubrum and T. mentagrophytes biofilms.

Dermatophytes are fungi responsible for a disease known as dermatophytosis. Biofilms are sessile microbial communities surrounded by extracellular polymeric substances (EPS) with increased resistance to antimicrobial agents and host defenses. This paper describes, for the first time, the characteristics of Trichophyton rubrum and T. mentagrophytes biofilms. Biofilm formation was analyzed by light microscopy, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) as well as by staining with crystal violet and safranin. Metabolic activity was determined using the XTT reduction assay. Both species were able to form mature biofilms in 72 h. T. rubrum biofilm produced more biomass and EPS and was denser than T. mentagrophytes biofilm. The SEM results demonstrated a coordinated network of hyphae in all directions, embedded within EPS in some areas. Research and characterization of biofilms formed by dermatophytes may contribute to the search of new drugs for the treatment of these mycoses and might inform future revisions with respect to the dose and duration of treatment of currently available antifungals.

Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment.

Cryptococcosis is an important systemic mycosis and the third most prevalent disease in human immunodeficiency virus (HIV)-positive individuals. The incidence of cryptococcosis is high among the 25 million people with HIV/acquired immunodeficiency syndrome (AIDS), with recent estimates indicating that there are one million cases of cryptococcal meningitis globally per year in AIDS patients. In Cryptococcus neoformans, resistance to azoles may be associated with alterations in the target enzyme encoded by the gene ERG11, lanosterol 14α-demethylase. These alterations are obtained through mutations, or by overexpressing the gene encoding. In addition, C. gattii and C. neoformans present a heteroresistance phenotype, which may be related to increased virulence. Other species beyond C. neoformans and C. gattii, such as C. laurentii, have been diagnosed mainly in patients with immunosuppression. Infections of C. albidus have been isolated in cats and marine mammals. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth, which is also related with increased resistance to antifungal agents. Therefore, there is a great need to search for alternative antifungal agents for these fungi. The search for new molecules is currently occurring from nanoparticle drugs of plant peptide origin. This article presents a brief review of the literature regarding the epidemiology of cryptococcosis, as well as fungal resistance and new alternatives for treatment.

Microwave irradiation as an alternative method for disinfection of denture base acrylic resins.

AIM: This study evaluated the effect of microwave irradiation as an alternative method for disinfection of different types of denture base acrylic resins. METHODS: Twenty-four samples for each conventional, microwaved and characterized heat-cured acrylic resin were made and subjected to sterilization with ethylene oxide for the groups: 1) irradiated samples; 2) non-irradiated samples; and 3) samples without yeast. Each group was subdivided according to inoculation with C. albicans, C. dubliniensis and C. tropicalis. The samples were inoculated with 100 µL of inoculum of each species of Candida and later placed in an incubator at 37 °C for 1 hr to perform the first adhesion. After this time, each well was supplemented with sterile media and the plate was once again taken to a stove for incubation at 37 °C for 6 hr. The samples were immersed in 100 mL of sterile water and irradiated with microwave at 650 W for 3 min. Control samples were considered as the non-irradiated group. After incubation for 48 hr, irradiated and non-irradiated samples were subjected to a digital colony counter. RESULTS: Control group (non-irradiated) showed microbial growth for resins and the means of ufc/mL were without statistically significant differences. Microwave irradiated samples (experimental group) promoted no viable colonies for all Candida species and types of acrylic resins. The means of ufc/mL were without statistically significant differences. CONCLUSION: Microwave irradiation was an effective method for disinfection of the acrylic resins inoculated with C. albicans, C. dubliniensis and C. tropicalis.

Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis.

BACKGROUND: The efficacy of neoadjuvant chemotherapy before surgery (NCS) has not been well-established in FIGO stage IB1 to IIA cervical cancer when compared with primary surgical treatment (PST). Thus, we performed a meta-analysis to determine the efficacy of NCS in patients with FIGO stage IB1 to IIA cervical cancer when compared with PST. METHODS: We searched Pubmed, Embase and the Cochrane Library between January 1987 and September 2010. Since there was a relative lack of relevant randomized controlled trials (RCTs), we included 5 RCTs and 4 observational studies involving 1784 patients among 523 potentially relevant studies. RESULTS: NCS was related with lower rates of large tumor size (≥4 cm) (ORs, 0.22 and 0.10; 95% CI, 0.13-0.39 and 0.02-0.37) and lymph node metastasis (ORs, 0.61 and 0.38; 95% CI, 0.37-0.99 and 0.20-0.73) than PST in all studies and RCTs. Furthermore, NCS reduced the need of adjuvant radiotherapy (RT) in all studies (OR, 0.57; 95% CI, 0.33-0.98), and distant metastasis in all studies and RCTs (ORs, 0.61 and 0.61; 95% CI, 0.42-0.89 and 0.38-0.97). However, overall and loco-regional recurrences and progression-free survival were not different between the 2 treatments. On the other hand, NCS was associated with poorer overall survival in observational studies when compared with PST (HR, 1.68; 95% CI, 1.12-2.53). CONCLUSIONS: Although NCS reduced the need of adjuvant RT by decreasing tumor size and lymph node metastasis, and distant metastasis, it failed to improve survival when compared with PST in patients with FIGO stage IB1 to IIA cervical cancer.

Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options.

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drug-resistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options.

Adhesion of Histoplasma capsulatum to pneumocytes and biofilm formation on an abiotic surface.

The pathogenic fungus, Histoplasma capsulatum, causes the respiratory and systemic disease 'histoplasmosis'. This disease is primarily acquired via inhalation of aerosolized microconidia or hyphal fragments of H. capsulatum. Evolution of this respiratory disease depends on the ability of H. capsulatum yeasts to survive and replicate within alveolar macrophages. It is known that adhesion to host cells is the first step in colonization and biofilm formation. Some microorganisms become attached to biological and non-biological surfaces due to the formation of biofilms. Based on the importance of biofilms and their persistence on host tissues and cell surfaces, the present study was designed to investigate biofilm formation by H. capsulatum yeasts, as well as their ability to adhere to pneumocyte cells. H. capsulatum biofilm assays were performed in vitro using two different clinical strains of the fungus and biofilms were characterized using scanning electron microscopy. The biofilms were measured using a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium-hydroxide (XTT) reduction assay. The results showed that both the H. capsulatum strains tested were very efficient at adhering to host cells and forming biofilm. Therefore, this is a possible survival strategy adopted by this fungus.

Biodegradation and abrasive wear of nano restorative materials.

The purpose of this study was to evaluate the biomechanical degradation of two nanofilled restorative materials (a resin-modified glass ionomer, Ketac N100 and a composite, Filtek Z350), compared with conventional materials (Vitremer and TPH Spectrum). Twenty specimens obtained from each material were divided into two storage groups (n=10): relative humidity (control) and Streptococcus mutans biofilm (biodegradation). After 7 days of storage, roughness values (Ra) and micrographs by scanning electron microscopy (SEM) were obtained. In a second experimental phase, the specimens previously subjected to biodegradation were fixed to the tooth-brushing device and abraded via toothbrushes, using dentifrice slurry (mechanical degradation). Next, these specimens were washed, dried, and reassessed by roughness and SEM. The data were submitted to repeated measures three-way analysis of variance (ANOVA) and Tukey tests (p<0.05). There was statistically significant interaction among factors: material, storage (humidity/biofilm), and abrasion (before/after). After biodegradation (S mutans biofilm storage), Ketac N100 presented the highest Ra values. Concerning bio plus mechanical challenge, TPH Spectrum, Ketac N100, and Vitremer presented the undesirable roughening of their surfaces, while the nano composite Filtek Z350 exhibited the best resistance to cumulative challenges proposed. The degraded aspect after biodegradation and the exposure of fillers after mechanical degradation were visualized in micrographs. This study demonstrated that the nanotechnology incorporated in restorative materials, as in composite resin and resin-modified glass ionomer, was important for the superior resistance to biomechanical degradation.

Favorable clinical behavior in young ovarian carcinoma patients: a rationale for conservative surgery?

The objective of this study was to analyze prognostic factors and epidemiologic data in young women with invasive epithelial cancer (YWEOC). Forty consecutive cases were selected from our database, treated according to current standards. A control group with older patients (>40 years) was created using concurrent cohort technique (n= 114). Median follow-up was 95 months in YWEOC and 84 months in elder patients. They were grouped by FIGO stages, histologic type, and tumor grade. Oncologic family history was compared in both cohorts. Survival was calculated using Kaplan-Meier curves. Chi-square, log rank test, uni- and multivariate analyses were used for statistical comparison. Family history was obtained in 25 of 40 of YWEOC, and 7 had first-line relatives with hematologic tumors, while this was observed in 1 of 80 of the elder patients (OR 9.8; 1.2-74.7). Due to these findings, a <40-years control healthy group selected from the gynecology office was rated and when compared with YWEOC, statistically significant differences were observed (OR 39.2; 4.5-338). Tumors were more differentiated, compared to the elder group (G(1): 68% vs 7%, P < 0.0001); stage I was more frequent (70% vs 19%, P < 0.0001) as well as mucinous and endometroid histologic types (P < 0.03). Survival was higher among younger patients (81% vs 35%, P < 0.0001) and decreased by decade, especially after 41 years. In advanced cases, optimal cytoreduction was more frequently performed, and survival was significantly higher. Multivariate analysis revealed that the only independent prognostic factor was residual disease in both groups. Age is not an independent prognostic factor for ovarian cancer but it has a different biologic behavior. An interesting association with hematologic tumors was observed, suggesting another pathway for ovarian cancer oncogenesis.

Metastases to the uterine cervix from a gastric carcinoma presenting with obstructive renal failure: a case report.

Metastases to the uterine cervix are infrequent(1-3). Except for cases of endometrial primary carcinoma, the most common origin of neoplastic dissemination to the uterine cervix is the ovary, followed by the breast(1,2). Primary gastrointestinal tumors are rare, and in most of these cases cervical metastases are associated with adnexal bilateral masses (Krukenberg's tumors)(1).

Carcinoma celular renal y colitis ulcerosa / Renal cell carcinoma and ulcerative colitis

No disponible

Hydrogen breath test with D-xylose for celiac disease screening is as useful in the elderly as in other age groups.

Up to one fifth of celiac disease patients are diagnosed after the age of 60. The hydrogen breath test with D-xylose as substrate (xylose-BT) has proved useful for the diagnosis of adult celiac disease. Our aim was to determine the potential influence of age-related intestinal mucosal changes on the reliability of this test. We reviewed the results of the xylose-BT in 50 patients with clinical celiac disease in whom the diagnosis was confirmed by histology. A control group of 53 patients with various diarrheal disorders and without jejunal mucosal atrophy at biopsy was similarly studied. Both celiac patients and controls were divided into adults (age < or = 60 years) and elderly (age >60 years). Seven of the 50 celiacs and 8 of the 53 controls were in the elderly category (P = NS). In the celiac disease group, no differences were observed between the elderly and adult patient subgroups for basal H2 excretion (22.4 +/- 42 vs 9.7 +/- 11 ppm), delta increase (56 +/- 43 vs 53 +/- 36 ppm), or area under the curve (7,452 +/- 5,546 vs 6,739 +/- 5,951 ppm x min). The false negative rate was similar for celiac adult (7/43) and elderly (2/7, P = ns) patients. Sensitivity of the xylose-BT was 0.83 in adults and 0.71 in the elderly, and specificity 0.51 in adults and 0.50 in the elderly. In conclusion, the results of the xylose-BT in celiac patients are not influenced by age. The xylose-BT is as valuable a tool for the screening of celiac disease in the elderly as it is in younger patients.

Neoadjuvant chemotherapy in gynecologic oncology.

The use of neoadjuvant chemotherapy in conjunction with surgery in squamous carcinoma of the uterine cervix can reduce the surgical treatment extent (to be confirmed) in small-volume tumors (diameter < 4 cm) and increase overall survival and disease-free interval in localized median-volume tumors (< or = 8 cm) and improve the quality of life of patients with large, locally advanced tumors, due to longer disease-free period. These issues have yet to be completely resolved (three randomized trials have confirmed these data), but in the meantime, neoadjuvant chemotherapy could be used as an alternative treatment in locally advanced tumors or large localized tumors. It is necessary to use high-dose chemotherapy to achieve a good tumor response and satisfactory "down-staging." Surgical treatment after neoadjuvant chemotherapy seems to be the most appealing option, especially in patients with poor response to chemotherapy. The proper extension of surgery after neoadjuvant chemotherapy is an unexplored matter for the gynecologic oncologist, and no trial has been developed to address this issue, but it seemingly must be performed according to the initial size and extension of the tumor (prior to neoadjuvant chemotherapy) despite the tumor response to it.

Pancreatitis and haemobilia due to arterioportal fistula after percutaneous liver biopsy resolved by selective arterial embolization.

Haemobilia and arterioportal fistula are uncommon complications secondary to percutaneous liver biopsy. We report the case of a patient who developed haemobilia and subsequently acute pancreatitis as a result of a liver biopsy. Selective hepatic angiogram showed an arterioportal fistula. Transcatheter arterial embolization successfully occluded the fistula. The patient remained asymptomatic 4 months later. We review the published literature concerning acute pancreatitis associated with haemobilia and draw conclusions for management of similar cases in the future.

Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge.

OBJECTIVE: The aim of this study was to analyze diagnostic criteria, response to chemotherapy, rate and site of relapse, and overall survival (OS) in neuroendocrine cervical carcinoma. METHODS: Twenty patients were included. Stage was Ia(2) in 1 case, Ib(1) in 4, Ib(2) in 4, II in 5, IIIb in 2, IVa in 2, and IVb in 2. Patients with stage Ib(2) or greater received neoadjuvant chemotherapy (NCH). Eighteen patients were operated on. Immunohistochemistry was performed on the surgical specimens. Statistical analysis included the Kaplan-Meier method and the chi(2) and log-rank tests. RESULTS: The response to NCH was <50% in 2/13 cases (15.3%), >50% in 9/13 (69.4%), and complete in 2/13 (15.3%). Cytokeratin was positive in 17/18 cases, neuron-specific enolase in 15/18, chromogranin in 9/18, and synaptophysin in 8/18. Tumor was pure in 12 cases. Two cases had simultaneous ovarian carcinoma. Positive nodes were observed in 9/20 pts (45%). Tumors <4 cm had no recurrences. Pure tumors >4 cm had distant relapses (6/11). Mixed tumors >4 cm had 2/6 pelvic and 3/6 lung metastases. OS was 39%. When the initial tumor volume was <4 cm OS was 76%, and it was 18% for tumors >4 cm (P < 0.05). OS was 58% when the residual tumor after NCH was <2 cm and 21% when it was >2 cm (P < 0.05). When the tumor was pure OS was 54% and 19% when it was mixed (P < 0.05). OS was 72% among pts with negative nodes and 11% for those with positive nodes (P < 0.01). CONCLUSIONS: (1) Stage IV was frequent (20%); (2) Response to NCH was high; (3) The pattern of relapse differs for mixed tumors; (4) For tumors <4 cm outcome is similar to that of squamous carcinoma.

[Clinical relevance of immunoglobulin A deficiency in celiac disease]. / Prevalencia y repercusión clínica de la deficiencia de inmunoglobulina A en la enfermedad celíaca.

BACKGROUND: To determine the prevalence of the IgA deficiency in patients with celiac disease and its influence on the presentation and evolution of celiac disease. PATIENTS AND METHOD: 47 patients with clinical and histological diagnosis of celiac disease were included. Seric immunoglobulin levels were determined in all patients. RESULTS: Five patients presented a low level of IgA (IgA-deficient group) and 42 patients presented normal levels (non-IgA-deficient group). The age and the relation male/female were similar between both groups. Presentation, clinical manifestations, analytic data of intestinal malabsorption, and the radiologic pattern were also similar between both groups of patients. There were bronchiectasies in two out of 5 IgA-deficient patients and in only one out of 42 non-IgA- deficient patients (p < 0.05). None of the IgA-deficient group showed complications due to the celiac disease, meanwhile 3 non-IgA deficient patients developed intestinal lymphoma (p = NS). CONCLUSIONS: The IgA deficiency is frequently associated to celiac disease. This association does not seem to influence in a significant way the presentation or the evolution of celiac disease.

Laparoscopically assisted Schauta operation: learning experience at the Gynecologic Oncology Unit, Buenos Aires University Hospital.

OBJECTIVES: The aim of this study was to show the learning experience of the employment of laparoscopic lymphadenectomy followed by a Schauta operation to treat patients with cervical carcinoma at a university hospital and to evaluate the feasibility, complications, hospital stay, delay in return to work, and overall survival of this procedure. METHODS: Between June 1, 1993, and December 30, 1997, 56 patients were selected. Surgical treatment began with a pelvic laparoscopic lymphadenectomy followed by a Schauta operation. Patients were staged according to FIGO criteria (Ia2, 10 cases; Ib1, 33 patients; Ib2, 8 cases; IIa, 3 cases; and IIb, 2 patients). Patients had a follow-up of 47 months. Overall survival was calculated with Kaplan-Meier tables. RESULTS: The procedure was not completed in 9 pts, in 5 cases among the first 20 pts that were entered on the trial due to technical problems and in 4 due to extracervical spread of disease (2 with gross laparoscopically unresectable lymph node metastases, 1 with parametrial infiltration, and 1 with rectovaginal septum involvement). In the 47 pts in which the procedure could be completed, the laparoscopic approach was done in 102 min and the vaginal part in 165 min. There were 4 complications: 1 ureteral injury, 1 abscess of the ischiorectal fossa, 1 hematoma of the Schuchardt incision, and 1 case of leg edema. The mean number of resected nodes was 17. Among the 47 cases in which the surgical procedure was completed, overall survival was 100% for Stage Ia, 88% for Ib1, and 85% for Ib2 after a mean follow-up of 4 years. Four pts have relapsed and died; 3 were stage Ib1 and the other was stage Ib2. They had pelvic recurrences. CONCLUSIONS: This surgery is secure and has an excellent outcome, so it can be considered a valid approach for the treatment of patients with cervical carcinoma, but in our hands, 20 cases were needed to obtain the minimum skill needed to perform it.

Laparoscopic staging in locally advanced cervical carcinoma: A new possible philosophy?

OBJECTIVES: The aim of this study was to evaluate the feasibility and efficacy of designing the therapeutic management of each patient, morbidity, and mortality using laparoscopic staging in locally advanced cervical carcinoma and to establish the standard procedure for a "complete" staging. METHODS: From July 10, 1995, to June 30, 1998, 98 pts were included. Clinical staging was performed according to FIGO's criteria (22 Ib2; 38 IIb; 25 IIIb; and 6 IV). The Quetelet index was calculated for each patient. Forty-nine pts were submitted to a previous CT scan. Surgical steps for a complete staging were: (1) peritoneal washings for cytology; (2) whole abdominal cavity exploration, with a biopsy of all suspicious lesions; (3) exploration of the vesicocervical and rectovaginal septums with a biopsy of suspicious areas; (4) bilateral pelvic lymphadenectomy and, when macroscopically positive, paraaortic lymphadenectomy. RESULTS: Eighty-four of 91 pts were evaluable. The average duration for the procedure was 108 min, and blood loss was less than 200 cc. Hospitalization time ranged from 24 to 48 h. The average number of resected pelvic nodes was 18.5 (9-31). Positive nodes were found in 38 cases; 19 pts had unresectable positive nodes. Paraaortic dissection was performed in 26 cases and 11 cases were positive. When tumor was <5 cm, 8/32 (25%) lymphadenectomies were positive; when it was >5 cm, 30/52 (58%) were positive. Thirty-eight of 49 pelvic CT scans were reported to be normal (18/38 had positive nodes) and 11/49 suspicious (6/11 had positive nodes). Tumor invasion of the vesicocervical space or of the anterior parametrium was found in 23/84 patients. The rectovaginal septum was positive in 10 cases. Four of 84 patients (4.7%) presented with intraperitoneal spread. Only one trauma to the vena cava occurred at the time of the Verres needle insertion and two postoperative lymphoceles were observed. All patients began curative treatment within 3 to 7 days. CONCLUSIONS: This method is feasible, complications are infrequent, and subsequent treatment is not delayed.

Neoadjuvant chemotherapy followed by radical hysterectomy and postoperative adjuvant chemotherapy in the treatment of carcinoma of the cervix uteri: long-term follow-up of a pilot study.

OBJECTIVE: The aim of the study was to determine if ACH given after NCH followed by RH could decrease the incidence of distant metastases in patients with locally advanced carcinoma of cervix uteri. MATERIAL: 56 pts (34 Ib, 18 IIb, 4 IIIb) with confirmed diagnosis of squamous cervical cancer were enrolled in this phase II trial. The methodology used was: 1) Figo clinical staging; 2) Ultrasonographic determination of tumor volume in < or > 4 cms; 3) V.B.P. scheme: cis-platinum 50 mg/m2/day 1; vincristine 1 mg/m2/day 1; bleomycin 25 mg/m2/days 1-2-3 (3 courses with 10 days interval); 4) Clinical and sonographic tumor response evaluation following U.I.C.C. response criteria; 5) Radical hysterectomy; 6) Pathological risk factor evaluation; 7) ACH with P.M.C. (cis-platinum 50 mg/m2, methotrexate 30 mg/m2, cyclophosphamide 500 mg/m2) 3 courses every 21 days; 8) Comparison and location of recurrences with a neoadjuvant group (NCH + RH + RT to whole pelvis), and with a control group treated with conventional radiotherapy were done. For statistical analysis the Chi-Square was used and D.F.S. and overall survival (O.S.) were calculated according to the Kaplan Meier and Log Rank Test. RESULTS: After a median follow-up of 75 months (range 42-108), O. S. for stage Ib was 88%, Stage IIb 78%, and 50% for IIIb. The recurrences were 12% (4/34) for Stage Ib (3 local and 1 distant); 28% for IIb (5/18) (4 pelvic and 1 distant); 50% (2/4) for IIIb (2 pelvic recurrences). When residual tumor volume was < 2 cm in the surgical specimen (n=39) there were 4 recurrences (3 pelvic and 1 distant), and 7 (6 pelvic and 1 distant) for tumors > 2 cm. (p<0.01 for pelvic recurrences). For the stage Ib with residual tumor <2 cm (n=14) there were no pelvic recurrences and only 1 distant. Comparing for Stage Ib with previous tumor volume >4 cm of the ACH Group (n=17) with a classical NCH (n=51) and control (n=51) groups, there were observed 2 (11.7%) pelvic and 1 (5,8%) distant relapses for the 1st Group, 3 (5.9%) pelvic and 3 (5.9%) distant relapses for the 2nd, and 11 (21.6%) pelvic and 5 (9.8%) distant relapses for the 3rd Group. From the comparison of locally advanced tumors (Stages IIb + IIIb) of ACH group (n=22), with a Stage IIIb surgically removed of classical NCH group (n=38) and with a control group of conventional RT (n=51), there were observed 6 (27%) pelvic and 1 (4.5%) distant relapses for the 1st Group, 4 (11%) pelvic and 7 (18.4%) distant relapses for the 2nd, and 31 (60.7%) pelvic and 5 (9.8%) distant for the 3rd one. CONCLUSION: ACH after NCH + RH could be used for stage Ib with tumor volume > 4 cm, with complete clinical response or residual tumor < 2 cm. The results of this group of tumors suggest the importance of going on phase III trials comparing NCH+RH alone vs. NCH+RH+ACH. ACH could also be used to try to obtain better control of distant metastases in Stages IIb and IIIb. In these cases radiotherapy to the whole pelvis must not be excluded.