Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease.

This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials in ROC? The historical definition of using platinum-free interval (PFI) to categorise patients as having platinum-sensitive/resistant disease was replaced by therapy-free interval (TFI). TFI can be broken down into TFIp (PFI), TFInp (non-PFI) and TFIb (biological agent-free interval). Additional criteria to consider include histology, BRCA mutation status, number/type of previous therapies, outcome of prior surgery and patient reported symptoms. (ii) What are the control arms for clinical trials in ROC? When platinum is considered the best option, the control arm should be a platinum-based therapy with or without an anti-angiogenic agent or a poly (ADP-ribose) polymerase (PARP) inhibitor. If platinum is not considered the best option, the control arm could include a non-platinum drug, either as single agent or in combination. (iii) What are the endpoints for clinical trials in ROC? Overall survival (OS) is the preferred endpoint for patient cohorts with an expected median OS < or = 12 months. Progression-free survival (PFS) is an alternative, and it is the preferred endpoint when the expected median OS is > 12 months. However, PFS alone should not be the only endpoint and must be supported by additional endpoints including pre-defined patient reported outcomes (PROs), time to second subsequent therapy (TSST), or time until definitive deterioration of quality of life (TUDD).

Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral microenvironment.

Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype.

A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors.

BACKGROUND: Epigenetic aberrations lead to chemotherapy resistance; hence, their reversal by inhibitors of DNA methylation and histone deacetylases may overcome it. PATIENTS AND METHODS: Phase II, single-arm study of hydralazine and magnesium valproate added to the same schedule of chemotherapy on which patients were progressing. Schedules comprised cisplatin, carboplatin, paclitaxel, vinorelbine, gemcitabine, pemetrexed, topotecan, doxorubicin, cyclophosphamide, and anastrozole. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow, acetylators, and magnesium valproate at 40 mg/kg, beginning a week before chemotherapy. Response, toxicity, DNA methylation, histone deacetylase activity, plasma valproic acid, and hydralazine levels were evaluated. RESULTS: Seventeen patients were evaluable for toxicity and 15 for response. Primary sites included cervix (3), breast (3), lung (1), testis (1), and ovarian (7) carcinomas. A clinical benefit was observed in 12 (80%) patients: four PR, and eight SD. The most significant toxicity was hematologic. Reduction in global DNA methylation, histone deacetylase activity, and promoter demethylation were observed. CONCLUSIONS: The clinical benefit noted with the epigenetic agents hydralazine and valproate in this selected patient population progressing to chemotherapy' and re-challenged with the same chemotherapy schedule after initiating hydralazine and valproate' lends support to the epigenetic-driven tumor-cell chemoresistance hypothesis (ClinicalTrials.gov Identifier: NCT00404508).

Treatment guidelines in ovarian cancer.

National and international specialists have met with the aim of writing down the guidelines for the treatment of epithelial ovarian cancer (in the Spanish Castilian language). These guidelines are based on the International Consensus that was published in English in the Annals of Oncology in 2005. This condition is the leading cause of death from gynaecological cancer in western countries. Its low rate of survival, barely 30% at 5 years, is above all due to late diagnosis and inappropriate surgery, so emphasis is put on these aspects. After describing the methodology for early detection and a scheme of surgical diagnostic procedures in view of the staging of an ovarian mass, the following therapeutic strategies will be recommended: cytoreductive surgery together with platinum chemotherapy under normal conditions, and also in the case of relapse. Likewise, very recent models of treatment focused on molecular targets are presented, and a broad section on methodology of clinical assays. As for this, co-operation among groups is crucial in order to make the conclusions of these studies valid for the development of new therapies.

Treatment guidelines in ovarian cancer

National and international specialists have met with the aim of writing down the guidelines for the treatment of epithelial ovarian cancer (in the Spanish Castilian language). These guidelines are based on the International Consensus that was published in English in the Annals of Oncology in 2005. This condition is the leading cause of death from gynaecological cancer in western countries. Its low rate of survival, barely 30% at 5 years, is above all due to late diagnosis and inappropriate surgery, so emphasis is put on these aspects. After describing the methodology for early detection and a scheme of surgical diagnostic procedures in view of the staging of an ovarian mass, the following therapeutic strategies will be recommended: cytoreductive surgery together with platinum chemotherapy under normal conditions, and also in the case of relapse. Likewise, very recent models of treatment focused on molecular targets are presented, and a broad section on methodology of clinical assays. As for this, co-operation among groups is crucial in order to make the conclusions of these studies valid for the development of new therapies (AU)

Elevated CA125 level associated with Meigs' syndrome: case report and review of the literature.

Meigs' syndrome is the association of ovarian fibroma, pleural effusion, and ascites. Meigs' syndrome with marked elevation of CA125 is an unusual clinical condition reported in 27 cases in the literature. The patient was a 46-year-old woman with right pleural effusion, ascites, ovarian tumor, and CA125 level of 1808 U/mL. Tomography revealed ascites and bilobate pelvic tumor of approximately 25 cm. The diagnosis of advanced epithelial ovarian cancer was considered, and the patient was treated with chemotherapy. Three chemotherapy schemes were applied due to the total lack of response in tumor volume; however, CA125 decreased to 90 U/mL. Thus, surgery was performed with resection of 25 cm of the left ovarian tumor, with intact capsule and without implants; the result of histopathologic analysis was fibroma. Postoperative CA125 was 11 U/mL. Patients with elevated CA125 and ascites cytology positive for malignancy must be cautiously treated due to the possibility of false positives, even if the probability is low. Therefore, minimally invasive surgery for biopsy collection must be considered. Although the association between ovarian tumor, pleural effusion, ascites, and marked elevation of CA125 is highly indicative of epithelial ovarian cancer, Meigs' syndrome must be considered in the differential diagnosis.

Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature.

BACKGROUND: Secretory carcinoma (SC) of the breast is a rare and indolent tumor. Although originally described in children, it is now known to occur in adults of both sexes. Recently, the tumor was associated with the ETV6-NTRK3 gene translocation. CASE PRESENTATION: A 52-year-old male was diagnosed with secretory breast carcinoma and underwent a modified radical mastectomy. At 18 months the tumor recurred at the chest wall and the patient developed lung metastases. He was treated concurrently with radiation and chemotherapy without response. His tumor showed the ETV6-NTRK3 translocation as demonstrated by fluorescent in situ hybridization (FISH). CONCLUSION: SC is a rare slow-growing tumor best treated surgically. There are insufficient data to support the use of adjuvant radiation or chemotherapy. Its association with the ETV6-NTRK3 fusion gene gives some clues for the better understanding of this neoplasm and eventually, the development of specific therapies.

The role of pretherapeutic laparoscopy in the selection of treatment for patients with gastric carcinoma: a proposal for a laparoscopic staging system.

BACKGROUND: A pretherapeutic staging system to design nonoperative or neoadjuvant treatments in gastric cancer is required. In this study, a simple staging system based on laparoscopic findings to define a treatment algorithm was developed. METHODS: A retrospective cohort study was conducted of 151 patients allocated into four stages based on laparoscopic findings. The depth of tumor invasion and the presence of metastasis based on laparoscopic findings were used to construct these stages. Laparoscopic findings were compared with histopathology. RESULTS: An excellent agreement of the laparoscopy-defined depth of invasion and the surgical pathology standard was found (weighted kappa 0.85). The likelihood ratios for a positive and negative laparoscopic diagnosis of metastasis were 40.4 and 0.015, respectively (98.5% sensitivity, 97.6% specificity). Those for positive and negative diagnosis of resectability were 2.6 and 0.03, respectively (98.4% sensitivity, 62% specificity). The laparoscopic stages presented significant prognostic value. Two-year survival was 93%, 69%, 60%, and 17%, respectively. Surgical resection was possible in 100%, 100%, 49%, and 12%, respectively. CONCLUSIONS: The proposed laparoscopic staging system is a simple and reproducibLe way for selection of a suitable therapy. It allows for adequate stratification of the main risk factors in the setting of clinical trials evaluating preoperative treatments.

Neoadjuvant chemotherapy with P-ELF (cisplatin, etoposide, leucovorin, 5-fluorouracil) followed by radical resection in patients with initially unresectable gastric adenocarcinoma: a phase II study.

BACKGROUND: Gastric cancer is the most frequent gastrointestinal cancer in Mexico. Only 33% of cases are resectable. Our aim was to determine the activity and toxicity of the cisplatin, etoposide, leucovorin, and 5-fluorouracil combination in initially unresectable tumors and to determine its ability to permit resection. METHODS: Sixty patients with unresectable gastric adenocarcinoma were treated with cisplatin 80 mg/m2, etoposide 80 mg/m2, leucovorin 25 mg/m2, and 5-fluorouracil 800 mg/m2 by central intravenous catheter for 4 consecutive days. Two courses of this combination were followed by surgical resection. RESULTS: The overall response rate was 36.8% (20 partial responses and one complete response). By using logistic regression analysis, the tumor, node, and metastasis stage (risk ratio, 2.04; 95% confidence interval, 1.03-4.02; P = .039) was identified as the response determinant to chemotherapy. Major toxicity was grade 3 or 4 neutropenia in 67% of patients. Ten resections were performed (17.5%); five were curative and five palliative. Operative morbidity and mortality rates were 40% and 10%, respectively. The median length of survival was 7.46 and 13.3 months for nonresponders and responders, respectively (P = .011). CONCLUSIONS: The cisplatin, etoposide, leucovorin, and 5-fluorouracil combination is active in advanced gastric cancer and the toxicity level is acceptable. This treatment permits a 17.5% resection rate in previously unresectable tumors. A randomized trial of surgery vs. neoadjuvant chemotherapy plus surgery is warranted.

[Prognostic factors in 793 cases of gastric cancer in an oncologic referral center]. / Factores pronósticos en 793 casos de cáncer gástrico en un centro de referencia oncológico.

OBJECTIVE: To describe the 12-year experience with Gastric Cancer (GC), with special emphasis in prognostic factors. BACKGROUND: GC is the most common gastrointestinal malignancy and is the second cause of cancer-related mortality in Mexico. Poor results have been reported, and new treatments have not improved the life expectancy. The available information regarding GC in our country is limited. METHODS: Retrospective cohort study of 793 patients with gastric adenocarcinoma treated in an oncologic referral center in Mexico City. Demographic and clinical data, and the results of surgical treatment are presented. Survival curves by TNM stage and other prognostic factors are described. RESULTS: Sixty two percent of the patients presented in stage IV, with a median survival of 8.6 months. Only 33% of the whole group underwent surgical resection. One hundred and sixty two subtotal, 86 total and 12 proximal gastrectomies were performed, 74% with curative intention and in 26% for palliation. Operative morbidity and mortality were 23.3% and 10.9%, respectively. The multivariate analysis showed that the independent prognostic factors were TNM stage (Risk ratio 1.49; 95% CI 1.26-1.76; p < 0.0001), operative morbidity (RR 6.05; 95% IC 3.74-9.7; p < 0.0001), seralbumin (RR 1.26; 95% CI 1.03-1.5; p < 0.03), age (RR 1.01; 95% CI 0.9-1.02; p < 0.057), type of lymphadenectomy (RR 1.59; 95% CI 0.97-2.59; p < 0.06) and gastrectomy performed (RR 1.9; IC 95% 0.9-4.2; p < 0.06). CONCLUSION: The TNM staging system was the most important prognostic factor. The high rate of GC in advanced stages affects directly the results. Better survival may be expected if the relative frequency of stages I and II increase. Endoscopy is warranted to patients with dispeptic symptoms who present no response to treatment or recurrence. Our experience reflects the importance of this health problem in México.

[Cancer of the anal canal]. / Cáncer de canal anal.

Anal carcinoma is a rare malignant tumor, It occurs in only 0.02% of all malignant neoplasms. In Mexico, the incidence is of 1.5%, and only 0.18% belong to the anal canal. In recent years it has been reported an increased incidence of this tumor due to the association with the human papilloma virus in HIV positive patients. The most common histological forms are the epidermoid and the cloacogenic carcinomas. The most relevant prognostic factors are the size of the tumor and the presence of lymph node metastasis. Surgery has been the traditional form of treatment but the combined use of chemotherapy and radiotherapy seems to have the best results and surgery is reserved for local recurrences or palliation. A review of our experience at the National Institute of Cancer at Mexico city with the management of this tumor was performed. Thirty-four patients with the diagnosis of carcinoma of the anal canal were included of which none of them received previous treatment or have the diagnosis of AIDS. Patients were divided in four groups according to the form of treatment (surgery, radiation, and chemoradiation either with 5FU-MMC or 5FU and CDDP). The group that received chemotherapy with 5FU and CDDP combined with radiotherapy had the best results in terms of clinical response, survival and toxicity. The size of the tumor and the presence of lymph node metastasis are the prognostic factors that influence in survival: tumor smaller than 5 cm without lymph node metastasis have the best prognosis (p: 0.01 and p: 0.00004). Epidermoid carcinoma have a better prognosis than cloacogenic carcinoma (p: 0.07).

Misoprostol prophylaxis for high-dose chemotherapy-induced mucositis: a randomized double-blind study.

From April 1993 to September 1993, 15 patients with lymphoid or solid neoplasms underwent 16 non-cryopreserved peripheral stem cell transplantation courses using the ICE (ifosfamide, carboplatin, etoposide) program. They were randomized in a double-blind clinical trial to received oral misoprostol or placebo for mucositis prophylaxis. The active drug or placebo administration began jointly with chemotherapy at day -4 and was continued until day 16. The mucositis incidence and severity was significantly higher in patients who received misoprostol. We found no differences regarding myelosuppression, infections or other chemotherapy complications. Our results do not support the use of oral misoprostol as administered in this study, for high-dose chemotherapy-induced mucositis prophylaxis.

[Dyshemopoietic anemias (AD) (myelodysplastic syndromes). Retrospective analysis of 40 cases from the Instituto Nacional de la Nutrición Salvador Zubirán (INNSZ)]. / Anemias dishemopoyéticas (AD) (síndromes mielodisplásicos). Análisis retrospectivo de 40 casos del Instituto Nacional de la Nutrición "Salvador Zubirán" (INNSZ).

40 patients with DMPS were studied and diagnosed at the INNSZ during 1980-1985. Eighteen were males and twenty two females; age average of 55.7 years (17-82), with 72.5% over 50 years old. Their distribution according to the FAB classification was: 55% type I, 10% type II, 27.5% type III, 2.5% type IV and 5% type V. All of them had an anemic syndrome and 47.5% had bled, 52.5% had pancytopenia; there was anemia and thrombocytopenia in 32.5%, anemia and leukopenia in 7.5%, and anemia only in 7.5%. The bone marrow was normocellular in 42.5%, hypercellular in 40% and hypocellular in 17.5%, 45% of the patients survived; 22% achieved a complete remission (CR) and 9 patients (22.5%) died of causes related to DMPS. The rest was lost to follow up.