Mismatch repair protein expression and intratumoral budding in rectal cancer are associated with an increased pathological complete response to preoperative chemoradiotherapy: A case-control study.

AIM: To determine whether the association of rectal adenocarcinoma with a defective-mismatch repair system (dMMR) was associated with a pathological complete response (pCR) to preoperative chemoradiotherapy. METHODS: A case-control study was designed with the aim of determining if patients with rectal adenocarcinoma with dMMR had an associated high pCR rate in response to neoadjuvant chemoradiotherapy (nCRT). RESULTS: Seventy-two cases with pCR were compared against 144 controls without pCR. Across 216 cases, the mean age was 56.8 years, 140 (64.8%) were men, and 63 (29.2%) demonstrated the dMMR system. The pCR was associated with G1 tumors, dMMR, the absence of vascular invasion, and low tumor budding in the pretreatment biopsy. In a multivariant analysis, the factors associated with pCR were dMMR (OR: 2.61; 95%CI: 1.355-5.040, P = 0.004) and a low degree of tumor budding (OR: 2.52; 95%CI: 1.366-4.894, P = 0.025). CONCLUSION: We found an independent association between dMMR and a low rate of tumor budding, with a higher rate of pCR, in the basal biopsies of patients with rectal carcinoma subjected to nCRT.

Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy.

We evaluated the association between epithelial-mesenchymal transition (EMT)-derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 ± 10 years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty-six percent of the patients were positive for human papilloma virus. Median progression-free survival (PFS) was 6.6 months (95% confidence interval [CI]: 4.0-9.1, whereas overall survival (OS) was 30.0 months (95% CI: 11-48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P = 0.002), epidermal growth factor receptor (EGFR) (P = 0.001), and TWIST2 (P = 0.001) expression levels, as well as a tumor size <6 cm (P = 0.02), influenced OS. Changes in TWIST2 levels and loss of E-cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P = 0.0001), as those with loss of E-cadherin (P = 0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E-cadherin: median 14 months, 95% CI: 3-24; negative EGFR + positive E-cadherin: median 31 months, 95% CI: 14-NA; P = 0.02.). The presence of EMT markers was associated with proliferative and pro-angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer.

The safety of drug treatments for cervical cancer.

INTRODUCTION: The treatment of some early-stage and most locally advanced disease cervical cancer patients consists of concurrent chemoradiation, while almost all with advanced disease require palliative chemotherapy. AREAS COVERED: This review is aimed to analyze the safety issues emerging from trials of chemoradiation for early-stage high-risk disease and locally advanced stages, as well as safety issues of trials of palliative chemotherapy for advanced disease. Safety issues on fertility preservation are also discussed. EXPERT OPINION: Cisplatin chemoradiation produces higher toxicity as compared to radiation alone, yet it is well-tolerated. Further advances would require (i) the development of more effective and tolerated combination chemoradiation regimens, (ii) demonstration of the efficacy and tolerability of adjuvant chemotherapy after cisplatin chemoradiation, and (iii) incorporation of targeted therapies into radiosensitizing regimens. A major problem continues to be the population of patients with advanced disease. The recent incorporation of bevacizumab into chemotherapy regimens represents a step forward; however, toxicity as well as economic issues may impede its wide acceptance worldwide. Preserving fertility in young women with cervical cancer is an issue that must be fully addressed. In this setting, neoadjuvant chemotherapy seems to increase fertlity rate without compromising oncological outcomes.

A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer.

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m(2) as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m(2)) or cisplatin (50 mg/m(2)) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were 163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.

Emerging drugs for the treatment of cervical cancer.

INTRODUCTION: Worldwide, most cervical cancer (CC) patients require the use of drug therapy either adjuvant, concurrent with radiation or palliative. AREAS COVERED: This review briefly discusses the current achievements in treating CC with an emphasis in emerging agents. EXPERT OPINION: Concurrent cisplatin with radiation and lately, gemcitabine-cisplatin chemoradiation has resulted in small but significant improvements in the treatment of locally advanced and high-risk early-stage patients. So far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and encouraging results in a Phase II study. In advanced disease, cisplatin doublets yield median survival rates not exceeding 14 months. The first Phase III study of bevacizumab, added to standard chemotherapy cisplatin- or non-cisplatin-containing doublet, has shown significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. The characterization of the mutational landscape of CC and developments of novel targeted therapies may result in more effective and individualized treatments for CC. The potential efficacy of knocking down the key alterations in CC, E6 and E7 human papilloma virus oncoproteins must not be overlooked.

New molecular targets against cervical cancer.

Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Major advances but still insufficient achievements in the treatment of locally advanced and high-risk early stage patients have occurred in the last decade with the incorporation of concurrent cisplatin with radiation and, lately, gemcitabine added to cisplatin chemoradiation. Despite a number of clinical studies incorporating molecular-targeted therapy as radiosensitizers being in progress, so far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and shown encouraging results in a Phase II study. In advanced disease, cisplatin doublets do not have a great impact on the natural history of the disease with median survival rates not exceeding 13 months. The first Phase III study of bevacizumab, added to cisplatin or a non-cisplatin-containing doublet, showed significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. Characterization of the mutational landscape of cervical cancer has already been initiated, indicating that, for now, few of these targetable alterations match with available agents. Progress in both the mutational landscape knowledge and developments of novel targeted therapies may result in more effective and individualized treatments for cervical cancer. The potential efficacy of knocking down the key alterations in cervical cancer - E6 and E7 human papillomavirus oncoproteins - must not be overlooked.

Follow-up consultations for cervical cancer patients in a Mexican cancer center. Comparison with NCCN guidelines.

PURPOSE: This study aimed to determine the patterns of follow-up visits for cervix cancer in a national cancer center in Mexico. MATERIALS AND METHODS: The National Cancer Institute of Mexico is cancer center with 119 beds that mostly cares for an underserved and socially disadvantaged population. The medical records of cases of cervical cancer that had at least one year of clinical follow-up after being in complete response at the end of primary treatment were analyzed. We recorded the numbers of total and yearly follow-up visits and these were compared with the number of follow-up visits recommended by the National Comprehensive Cancer Network 2013, version 2 for cervical cancer. RESULTS: Between March and June 2007, the medical records of 96 consecutive patients were reviewed. Twenty (21%) of these met inclusion criteria and were selected. In the first year the median number of visits was 11 (4-20). In the ensuing years, 2nd, 3rd, 4th and 5th, the number of analyzed patients remaining in follow-up decreased to 17, 14, 13 and 9 respectively. There were 462 follow-up visits to primary treating services (Gynecology Oncology, Radiation Oncology and Medical Oncology) as compared to 220 suggested by the NCCN guidelines (X2 test p<0.0001). There were 150 additional visits to other services. CONCLUSIONS: Our results suggest that in our institution there is an overuse of oncological services by cervical cancer patients once treatment is completed.

Hydralazine-valproate: a repositioned drug combination for the epigenetic therapy of cancer.

INTRODUCTION: DNA methylation (DNMTi) and histone deacetylase inhibitors (HDACi) are in development for cancer therapy. So far, four epigenetic drugs are approved for myelodysplastic syndrome (MDS) and cutaneous T-cell lymphoma (CTCL). The combination of hydralazine-valproate (TRANSKRIP(™)) is being repositioned as an oral DNMT and HDAC inhibitor. AREAS COVERED: Brief discussion on the current status of epigenetic drugs and studies published on the preclinical and clinical development of the hydralazine-valproate combination. EXPERT OPINION: Drug repositioning is a strategy for prompt and cost-efficient drug discovery. There is evidence that combining DNMTi with HDACi would be more efficacious than administering each agent on its own. Hydralazine-valproate is safe when used alone or in combination with chemotherapy or chemoradiation. The fact that both drugs are orally administered is another advantage over current epigenetic drugs. This combination is promising but larger studies are needed. Among these, the randomized Phase III trials in advanced and in locally advanced cervical cancer combined with chemotherapy and cisplatin-radiation respectively, would eventually confirm its efficacy. Studies on MDS and CTCL would also eventually prove the efficacy of hydralazine valproate so that in the coming years hydralazine-valproate could have a role in cancer epigenetic therapy.

New pharmacotherapy options for cervical cancer.

INTRODUCTION: Cervical cancer is the fourth leading cause of cancer death in females worldwide. Incorporation of chemotherapy to radiation in locally advanced disease and molecular targeted therapy for advanced disease has increased survival; nevertheless, there is room for further improvement. AREAS COVERED: This review aims to discuss major recent advances in the treatment of invasive cervical cancer from randomized Phase III trials and ongoing late-stage developments. EXPERT OPINION: Combination chemotherapy concurrent with radiation plus adjuvant chemotherapy has demonstrated better survival rates as compared to standard cisplatin chemoradiation and ongoing Phase III trials would eventually confirm these findings. Gemcitabine and paclitaxel are the most evaluated agents added to cisplatin chemoradiation and in the adjuvant setting. Further survival gains combining classical cytotoxics will be limited by toxicity, hence, novel antitumor drugs; in particular angiogenesis inhibitors must be evaluated to increase the efficacy of current chemoradiation regimens. In advanced disease, modest survival gains were recently achieved with cisplatin doublets as compared to single agent cisplatin. Bevacizumab added to standard chemotherapy has for the first time demonstrated that targeted agents are valuable in the treatment of advanced cervical cancer. Ongoing Phase III trials for cervical cancer are limited reflecting the shortage of promising molecules and the need to increase research efforts for this disease.

A randomized comparison of cisplatin and oral vinorelbine as radiosensitizers in aged or comorbid locally advanced cervical cancer patients.

OBJECTIVE: Chemoradiation with cisplatin is considered the standard of care for patients with locally advanced cervical cancer; however, cisplatin could be difficult to use in aged patients or patients with comorbidities such as diabetes mellitus and blood hypertension; hence, it is important to investigate nonplatinum drugs for radiosensitization. In addition, oral cytotoxics may overcome the drawbacks of intravenous infusions and could be of easier administration. METHODS: In this small randomized trial, we tested cisplatin against oral vinorelbine as radiosensitizers in these patients. A total of 39 patients 65 years or older or diabetic and hypertensive patients of any age were randomized to cisplatin or oral vinorelbine at 40 mg/m² or 60 mg/m², respectively. Both drugs were administered weekly for 6 courses during pelvic external-beam radiotherapy and brachytherapy radiation. Efficacy and safety were assessed. RESULTS: Nineteen patients received oral vinorelbine, and 20 patients received cisplatin. The median cumulative dose to point A was 80.8 Gy for both groups, and the overall treatment time was 48 (42-54) and 50 (43-55) days for vinorelbine and cisplatin groups, respectively. Patients in both arms received a median of 5 applications of chemotherapy. Treatment was well tolerated in both arms. The most frequent toxicity in both arms was lymphopenia grades 2 and 3. At a median follow-up time of 16 months (4-19), there were no differences in either progression-free survival or overall survival between groups. CONCLUSIONS: Our results suggest that these patient populations can safely be treated with either cisplatin or navelbine as radiosensitizers; however, a larger randomized study is needed to demonstrate the noninferiority of oral vinorelbine as an easier and practical alternative for radiosensitization in cervical cancer.

Emerging drugs for cervical cancer.

INTRODUCTION: There is a shortage of therapeutical agents for invasive cervical cancer in late stages of development; however, a number of promising molecules are currently in early phases of development. AREAS COVERED: This review briefly discusses the current achievements in treating cervical cancer with an emphasis in emerging agents based on a literature search on pubmed and related sites for cervical cancer information. This is not a systematic review. EXPERT OPINION: In advanced disease, modest survival gains have been achieved with cisplatin doublets. Contrariwise, chemoradiation has increased survival rates in locally advanced disease, but there is still room for improvement. Anti-vascular endothelial growth factor and anti-epidermal growth factor receptor monoclonal antibodies are promising molecules that are at present in late-phase development, but a high number of miscellaneous agents are in early development. Strong experimental bases support that the 'Achilles' heel' of cervical cancer are the HPV-E6/E7 oncogenes. Unfortunately, agents aimed at targeting these cervical cancer-driven players are found in very early development; hence, major research efforts must be focused on developing technological strategies for their effective targeting using nucleic acid-based vehicles for safe and effective delivery to cancer cells as well as accelerating the search for small-molecule inhibitors of E6/E7 themselves or their interacting cellular proteins.

F18-FDG-PET/CT in the evaluation of patients with suspected recurrent or persistent locally advanced cervical carcinoma.

BACKGROUND: Cervical cancer (CC) represents the second most common neoplasm and the third cause of death by cancer among women. Recurrent or persistent disease depends on the clinical stage, but can be as high as 70%. Positron emission tomography/computed tomography (PET/CT) is an image study that can detect increased glucose uptake in tumor tissues. MATERIAL AND METHODS: PET/CT was performed in patients with confirmed CC, who had been previously treated, who developed suspected symptoms of recurrence or persistent disease with or without evidence of disease on a CT scan. Sensitivity, specificity, predictive values from PET/CT, and CT scan were evaluated. RESULTS: Sixteen patients with a mean age of 47.2 years were included in the study from April 2007 to June 2008. Thirteen patients (81.2%) were symptomatic. PET/CT was positive in 14/16 (85.7%), of these, 12 True positive (TP) and two, False positive (FP); meanwhile another two cases were True negative (TN) (12.5%). Cervix, retroperitoneal, iliac, obturator, and mediastinal lymph nodes were the most common anatomic sites detected by PET/CT. Mean number of anatomic sites with high Fluoro-deoxy-D-glucose (FDG) uptake was two sites (range 1-7 sites). PET/CT and CT scan had 100 and 91.7% sensitivity, respectively. Specificity for both was 50%. Positive predictive value (PPV) was 85.4 and 84.6%, respectively. Negative predictive value (NPV) was 100 and 66%, respectively, and accuracy was 88 vs. 81%, respectively. CONCLUSIONS: PET/CT has the capability for detecting recurrent or persistent cervical cancer; it detects increased metabolic activity mainly in primary site or lymph nodes. Further PET/CT evaluation is required to confirm the real impact of this study on the early detection of CC recurrence.

Pharmacokinetic evaluation of gemcitabine hydrochloride for the treatment of cervical cancer.

INTRODUCTION: Cervical cancer is the third most prevalent cancer in females worldwide. When advanced, the disease requires primary radiation concurrent with chemotherapy. However, chemotherapy alone is the standard treatment for recurrent/persistent/metastatic disease. AREAS COVERED: Areas covered in this review include the treatment of advanced cervical cancer with gemcitabine as radiosensitizer, either alone or in combination with cisplatin. The use of gemcitabine for recurrent/persistent/metastatic cervical cancer is also reviewed. EXPERT OPINION: Statistically significantly better survival rates are achieved with cisplatin doublets against cisplatin alone, in the management of recurrent/persistent/metastatic cervical cancer. The choice of the cisplatin doublet with paclitaxel, vinorelbine, gemcitabine and topotecan arms should be based on physician preference, pre-existing morbidity and patient-related factors. In advanced disease, a recently reported Phase III trial establishes the novel regimen of concurrent gemcitabine plus cisplatin and external radiation, followed by brachytherapy and two adjuvant 21-day cycles of gemcitabine plus cisplatin, as significantly improving survival outcomes when compared with the current standard of care. The increased acute toxicity of this regimen is clear; however, this should not deter its incorporation into clinical practice, in that the toxicity is predictable and manageable; nevertheless, the occurrence of late toxicity and survival at longer follow-up time are reasonable concerns in this regimen.

Primary malignant melanoma of the uterine cervix treated with ultraradical surgery: a case report.

Primary melanomas of the uterine cervix are rare tumors with no more than 60 cases reported in the world literature. Poor prognosis is considered for the neoplasia itself as well as for diagnostic tardiness. There is no standard treatment; however, radical surgery is the treatment cornerstone. Our aim was to present the case of a 34-year-old woman with a primary malignant melanoma in the uterine cervix with affectation of the posterior face of the vagina without metastasis. Total infraelevator pelvic exenteration and adjuvant radiotherapy was performed. The patient was under surveillance for 8 years of followup without evidence of local or distant disease. The majority of case reports found suggests radical hysterectomy as the treatment indicated for these patients. Notwithstanding this, survival is very short when patients are treated in this manner. Based on our results and on those reported in the literature, we propose initial treatment with total pelvic exenteration as optimal management for this neoplasia in its initial form.

A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

Pharmacotherapy options for locally advanced and advanced cervical cancer.

Cervical cancer continues to be a significant health burden worldwide. Globally, the majority of cancers are locally advanced at diagnosis; hence, radiation remains the most frequently used therapeutic modality. Currently, the value of adding cisplatin or cisplatin-based chemotherapy to radiation for the treatment of locally advanced cervical cancer is strongly supported by randomized studies and meta-analyses. Nevertheless, despite these significant achievements, therapeutic results are far from optimal; thus, novel therapies need to be investigated. A recent, randomized, phase III trial has shown for the first time that combination chemotherapy with cisplatin and gemcitabine concurrently with radiation improves parameters of survival over cisplatin alone and establishes a new standard for the management of locally advanced cervical cancer. On the other hand, advanced disease, presenting either as an International Federation of Gynecology and Obstetrics (FIGO) stage IVB or as persistent or recurrent to primary therapy without local curative options, remains a devastating group of diseases with no options other than palliative chemotherapy. Recent results from the GOG (Gynecologic and Oncologic Group)-204 study demonstrate that cisplatin-doublets with paclitaxel, vinorelbine, gemcitabine or topotecan only produce small improvements in survival, although with different toxicity patterns; hence, patient-related factors are important when choosing any one of these regimens. The role of targeted therapies both in locally advanced and advanced disease is promising, but still at an investigational stage.

Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

Vulvar fibroadenoma: a common neoplasm in an uncommon site.

Vulvar fibroadenomas are sporadic lesions informed in the literature and a controversy about origin has been discussed widely. We report a case of a 19 years old woman with a large slow growing mass in the right labia majora with the final diagnosis of fibroadenoma with mammary tissue surrounding it and positive hormone receptors. In this case, we support the origin in ectopic mammary tissue.

Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients.

BACKGROUND: A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT) and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy. METHODS: In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients. In the standard treated patients, EBRT-CT was followed by one or two intracavitary Cesium (low-dose rate) applications within 2 weeks of finishing external radiation to reach a point A dose of at least 85 Gy. In the surgically treated patients, radical hysterectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling were performed within 7 weeks after EBRT-CT. Response, toxicity and survival were evaluated. RESULTS: A total of 80 patients were analyzed. The patients receiving EBRT-CT and surgery were matched with the standard treated cases. There were no differences in the clinicopathological characteristics between groups or in the delivery of EBRT-CT. The pattern of acute and late toxicity differed. Standard treated patients had more chronic proctitis while the surgically treated had acute complications of surgery and hydronephrosis. At a maximum follow-up of 60 months, median follow-up 26 (2-31) and 22 (3-27) months for the surgery and standard therapy respectively, eight patients per group have recurred and died. The progression free and overall survival are the same in both groups. CONCLUSION: The results of this study suggest that radical hysterectomy can be used after EBRT-CT without compromising survival in FIGO stage IB2-IIB cervical cancer patients in settings were brachytherapy is not available. A randomized study is needed to uncover the value of surgery after EBRT-CT.

Serous adenocarcinoma of the fallopian tube, associated with verrucous carcinoma of the uterine cervix: a case report of synchronic rare gynecological tumors.

BACKGROUND: Synchronous gynecological tumors are rare; it is even rarer to find the rarest of gynecological tumors that of the fallopian tube, together with a histological sub-type as rare as verrucous cervix. CASE PRESENTATION: We report a synchronic fallopian tube adenocarcinoma and a verrucous cervical cancer. A 85-year-old woman with postmenopausal genital hemorrhage, endometrial biopsy was reported as squamous metaplasia, an exploratory laparotomy was performed finding a tubal tumor diagnosed as adenocarcinoma, a staging procedure was performed. Final staging revealed IB1 cervical carcinoma and IA G3 fallopian tube carcinoma. Adjuvant treatment with chemotherapy was not accepted by the patient. The patient has remained in follow-up, and at 9 months, there has been no documented evidence of recurrent disease. CONCLUSION: Reasons for our presentation of this work are: first, due to the rarity of these, and second, because of the usefulness of possessing a case report for establishing a norm for later behavior with respect to treatment of these patients.