[Primary testicular NK/T cell lymphoma. Case report and review of literature]. / Linfoma de células T/NK primario de testículo. Caso clínico y revisión de la literatura.

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Association of p16 and Ki-67 with Risk of Recurrence in Previously Treated Cervical High-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: Our main objective was to assess the association between the markers p16 and Ki-67 and recurrence of disease in patients previously treated for cervical high-grade squamous intraepithelial lesion (HSIL). DESIGN: This is a case-control study at the National Cancer Institute conducted between 2005 and 2015. Of the patients with a pathologically confirmed diagnosis of HSIL, 107 cases were selected. They were divided into 2 groups: 28 cases with recurrence after treatment and a control group of 79 patients without recurrence. We identified clinical, pathological, and treatment variables. METHODS: Two experienced pathologists performed immunohistochemical analysis of biomarkers; they agreed on their interpretation, and we calculated the odds ratios (ORs) associated with recurrence. For group comparisons, we used the Wilcoxon signed-rank, χ2, or Fisher's exact test, depending on the type of variable. We conducted logistic regression models to estimate ORs and determine the factors associated with recurrence. The recurrence-free period was defined as the time frame between conization and either recurrence of disease or the last date the patient was seen. We used Kaplan-Meier plots to visualize survival curves and log-rank tests to compare the curves. We established a p value <0.05 as statistically significant. RESULTS: After pathologists performed immunohistochemical analysis, they achieved an agreement level of 83.7% for p16 and 60% for Ki-67. We did not find an association between recurrence and either p16 expression (p = 0.69) or the percentage of Ki-67 expression (p = 0.71). The recurrence-free period analysis did not reveal a difference in p16 expression (p = 0.57) nor in the percentage of Ki-67 expression in the 3-tiered scale (p = 0.56). LIMITATIONS: Our main limitation was a reduced sample size. CONCLUSION: We found no association between p16 and Ki-67 positivity and the risk of recurrence in previously treated HSIL.

New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors.

The value of SATB2 in the differential diagnosis of intestinal-type mucinous tumors of the ovary: primary vs metastatic.

Primary mucinous adenocarcinomas of the ovary are a diagnostic challenge because their histologic and immunohistochemical features usually overlap with metastatic tumors. SATB2 is a recently identified protein with restricted expression in the glandular cells lining the lower gastrointestinal tract. The aim of this study is to examine the differential expression of SATB2 in primary and metastatic tumors of the ovary. Mucinous ovarian tumors of intestinal type were retrieved from the pathology files of the Instituto Nacional de Cancerología de México. A double reading of the hematoxylin and eosin-stained slides was performed to confirm the diagnosis, and a detailed review of the clinical chart was performed to define the primary origin of the tumor (ovarian vs metastatic). Immunohistochemical staining for CK20, CDX2, and SATB2 was performed and evaluated by 2 gynecopathologists. A total of 106 mucinous tumors were identified, 26 of which were considered to be metastatic, and 80 of which were primary ovarian tumors. All of the primary tumors that were not associated with cystic teratomas were negative for SATB2, and the 4 that were associated with a teratoma were positive for SATB2. All 20 of the metastatic tumors of the colon and appendix were positive for CK20, and 4 were positive for CK7. In addition, all 20 of these tumors were positive for SATB2, and 19 were positive for CDX2. SATB2 appears to be a useful marker for the diagnosis of primary vs metastatic mucinous intestinal-type neoplasms and is highly sensitive in detecting lower gastrointestinal tract metastasis.

[Primary ovarian carcinosarcoma. Report of eight cases]. / Carcinosarcoma primario de ovario. Reporte de ocho casos.

BACKGROUND: The carcinosarcoma, or Mixed Mullerian Malign Tumors, represent 1% of malignant ovarian neoplasm, they are formed by a component epithelium and another mesenquimal malignant both. OBJECTIVE: Report the experience of the Ginecological Department of the Instituto Nacional de Cancerología (Mexico) in the treatment of patients with ovarian carcinosarcoma or primary malignant of the ovary. METHODS: A retrospective of 8 cases of carcinosarcoma primary of ovary at National Institute of Cancerology, from January, 2005 to December, 2008. RESULTS: The carcinosarcoma or Mixed Mullerian Malign Tumors appeared in 4.1% of all the malignant primary tumors of ovary, the clinical initial presentation was with pain and abdominal expansion both in 62.5% and mass palpable and bled vaginal in 25% of the patients. In 2/8 (25%) patients there was achieved a residual tumor minor of 1cm, in 4/8 (50%) cases one administered chemotherapy. In 3/8 (37.5%) they were kept free of disease in the follow-up of 42 months, 1/8 (12.5%) with stable disease and 4/8 (50%) they died for disease. CONCLUSIONS: Ovarian carcinosarcoma is a rare tumor, the clinical of this neoplasm is aggressive, usually presenting in advanced stages, with a poor prognosis with existing medical treatment.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases. Cases of invasive endocervical adenocarcinoma from 12 institutions were reviewed, and clinical/pathologic features assessed: patients' age, tumor size, DOI, differentiation, lymph-vascular invasion, lymph node metastases, recurrences, and stage. Cases were classified according to a new pattern-based system into Pattern A (well-demarcated glands), B (early destructive stromal invasion arising from well-demarcated glands), and C (diffuse destructive invasion). In total, 352 cases (FIGO Stages I-IV) were identified. Patients' age ranged from 20 to 83 years (mean 45), DOI ranged from 0.2 to 27 mm (mean 6.73), and lymph-vascular invasion was present in 141 cases. Forty-nine (13.9%) demonstrated lymph node metastases. Using this new system, 73 patients (20.7%) with Pattern A tumors (all Stage I) were identified. None had lymph node metastases and/or recurrences. Ninety patients (25.6%) had Pattern B tumors, of which 4 (4.4%) had positive nodes; whereas 189 (53.7%) had Pattern C tumors, of which 45 (23.8%) had metastatic nodes. The proposed classification system can spare 20.7% of patients (Pattern A) of unnecessary lymphadenectomy. Patients with Pattern B rarely present with positive nodes. An aggressive approach is justified in patients with Pattern C. This classification system is simple, easy to apply, and clinically significant.

[Plasmoblastic lymphoma initially recognized as ovarian tumor]. / Presentación inicial de un linfoma plasmablástico como tumor ovárico.

Plasmablastic lymphoma is an uncommon B-cell lymphoma representing <3% of all non-Hodgkin lymphoma associated with human immunodeficiency virus infection. It displays a distinctive affinity for extranodal presentation in the oral cavity. The case of a plasmablastic lymphoma present in the ovary, cervix and soft thigh tissues of a 27-year-old woman with human immunodeficiency infection is reported.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

Antimetastatic effect of epigenetic drugs, hydralazine and valproic acid, in Ras-transformed NIH 3T3 cells.

INTRODUCTION: Metastasis involves the accumulation of genetic and epigenetic alterations leading to activation of prometastatic genes and inactivation of antimetastatic genes. Among epigenetic alterations, DNA hypermethylation and histone hypoacetylation are the focus of intense translational research because their pharmacological inhibition has been shown to produce antineoplastic activity in a variety of experimental models. AIMS: This study aimed to evaluate the antimetastatic effect of the DNA-methylation inhibitor, hydralazine, and the histone deacetylase inhibitor, valproic acid. METHODS: NIH 3T3-Ras murine cells were treated with hydralazine and valproic acid to evaluate their effects upon cell proliferation, cell motility, chemotaxis, gelatinase activity, and gene expression. Lung metastases were developed by intravenous injection of NIH 3T3-Ras cells in BALB/c nu/nu mice and then treated with the drug combination. RESULTS: Treatment induced a growth-inhibitory effect on NIH 3T3-Ras cells, showed a trend toward increased gelatinase activity of MMP2 and MMP9, and inhibited chemotaxis and cell motility. The combination led to a strong antimetastatic effect in lungs of nude mice. CONCLUSION: Hydralazine and valproic acid, two repositioned drugs as epigenetic agents, exhibit antimetastatic effects in vitro and in vivo and hold potential for cancer treatment.

Linfoma de células T/NK primario de testículo. Caso clínico y revisión de la literatura

Natural killer/T cell lymphomas chiefly involving the midline facial structures including the nasal cavity or nasopharyns are a relatively rare type of non-Hodgkin's lymphoma. Apart from the upper respiratory tract, the disease occasionally presents in certain extranodal sites, such as the central nervous system, skin, gastrointestinal tract, or testes. We report a case of natural killer NK/T cell lymphoma as a testicular tumor in a 36-year-old man with a history of progressive swelling of his right testicle. Histologically, the testicular mass showed a diffuse infiltrate of medium-sized and atypical large lymphoid cells with angiocentric infiltration and areas of coagulative necrosis. Immunohistochemical studies demonstrated tumor cells staining positively with CD3, TIA-1, and Granzyme B. The Epstein-Barr virus genoma was detected by in situ hybridization. There were no abnormal findings in the nasal and nasopharyngeal regions. Classified as stage IEA, the patient received involved-field irradiation to contralateral testis (45 Gy), followed by systemic chemotherapy with a combination regimen ofL-asparaginase, methotrexate and dexamethasone. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Unusual case of subcutaneous angiosarcoma metastatic to the ovary.

The ovaries are common sites for metastatic disease, however, the most frequent ones are carcinomas. Metastatic sarcomas are very rare in ovary and most of them arise from genital tract. We present the case of a 33-year-old woman with subcutaneous angiosarcoma who had metastatic disease to the ovary resulting in acute abdominal pain. Discussion of the case and a review of the literature are presented.

Primary retroperitoneal mucinous cystadenocarcinoma: report of two cases.

BACKGROUND: Retroperitoneal cystadenocarcinomas are rare lesions, the majority of cases presented as one-patient reports. METHODS: We present two cases of retroperitoneal cystadenocarcinoma, both in women of reproductive age: one with aggressive behavior, and the remaining case, with a more indolent clinical evolution. RESULTS: One case presented as pelvic tumor, was treated with surgical resection of the disease, but manifested with recurrent disease a few months later despite use of chemotherapy. The second case involved a patient with diagnosis of abdominal tumor; during laparotomy, a retroperitoneal tumor was found and was totally removed. At follow-up, the patient is disease-free with no other treatment. CONCLUSION: The behavior and treatment of retroperitoneal cystadenocarcinoma are controversial. We suggest aggressive surgery including radical hysterectomy and bilateral salpingoopherectomy with adjuvant chemotherapy in these cases.

[A woman with a pure seminoma and a contralateral intratubular germinal neoplasm. A case report]. / Mujer con seminoma puro y neoplasia intratubular germinal contralateral. Informe de un caso.

BACKGROUND: Androgen insensitivity syndrome is an X-linked disorder, and is characterised by a female phenotype in a chromosomally male individual. It usually occurs in puberty with primary amenorrhoea or as an inguinal tumour in a female infant. In recent years, it is often also diagnosed in fertility clinics in adulthood. OBJECTIVE: The case is presented of a pure seminoma in a woman with the reference diagnosis of inguinal hernia. CLINICAL CASE: A 53 year old woman, who was operated on in 2014 due to a nodule in left groin. Androgen insensitivity syndrome was corroborated, and histopathology reported it as a right testicular seminoma. DISCUSSION: The importance of early diagnosis is discussed, highlighting the consequences of misdiagnosis, and question whether these patients have been adequately treated in the past. The risk of malignant transformation of an undescended testicle increases with age, thus gonadectomy should be performed after puberty, and in some cases hormone replacement therapy.

Satellitosis and CD117 immunohistochemical expression correlates with poor outcome in thick vulvar melanoma.

BACKGROUND: Melanoma of the vulva is the second most common vulvar cancer after epidermoid carcinoma. Patients suffering from this disease usually present with a late-stage disease with a poor prognosis. The prognostic factors reported in previous studies are not homogeneous and the clinical/pathogenic role of c-KIT expression is not clear. Breslow staging currently is the most accurate predictor factor. METHODS: A clinicopathological study with literature review was performed to identify predictors of prognosis and survival in melanoma of the vulva and investigated the expression of c-KIT (by immunohistochemistry) in 10 patients from the National Institute for Cancer Research (Mexico City). RESULTS: The 10 patients enrolled were all older women with delayed presentation, high-stage disease and limited response to treatment. Five patients (50%) were found to have c-KIT expression; 4 of them recurred (P=0.01), and ultimately 3 died (P=0.038). We identified satellitosis and c-KIT expression as prognostic predictors for death. CONCLUSIONS: We conclude that c-KIT expression is a valuable predictor of prognosis and survival, especially in thick (>4 mm) melanomas.

Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.

Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer.

BACKGROUND: Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells. RESULTS: PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRalpha gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor. CONCLUSION: The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.

Carcinosarcoma of the pancreas arising in a mucinous cystic neoplasm.

We report a carcinosarcoma of the pancreas in a 67-year-old woman who presented with nausea, vomiting, and painless jaundice. A work-up demonstrated a well-circumscribed mass in the head of the pancreas. After pylorus-preserving pancreaticoduodenectomy, the tumor was found to be grossly yellow, and it compressed the common bile duct and pancreatic duct. Histological examination of the neoplasm showed a 4.0 x 4.0 x 3.0-cm mucinous cystadenocarcinoma with invasive poorly differentiated carcinoma, well-differentiated squamous cell carcinoma, and sarcomatous stroma invading into the duodenum. There was no evidence of nodal metastasis (pT3N0M0). Immunohistochemical studies showed that the epithelial cells stained positive for cytokeratin 7, cytokeratin AE1/3, cytokeratin monoclonal antibody 5.2, epithelial membrane antigen, M-carcinoembryonic antigen, and low-molecular-weight kininogen, and the sarcomatous component was immunoreactive with vimentin. The patient had an uneventful recovery, but died 4 months later of rapidly progressive metastatic disease to the liver and peritoneum. To the best of our knowledge, this is the second case of carcinosarcoma with invasive epithelial and sarcomatous areas in the background of a mucinous cystic neoplasm of the pancreas.

Prognostic significance of pathological response after neoadjuvant chemotherapy or chemoradiation for locally advanced cervical carcinoma.

BACKGROUND: Cisplatin-based chemoradiation is the standard of care for locally advanced cervical cancer patients; however, neoadjuvant modalities are currently being tested. Neoadjuvant studies in several tumor types have underscored the prognostic significance of pathological response for survival; however there is a paucity of studies in cervical cancer investigating this issue. METHODS: Four cohorts of patients with locally advanced cervical carcinoma (stages IB2-IIIB); included prospectively in phase II protocols of either neoadjuvant chemotherapy with 1) cisplatin-gemcitabine, 2) oxaliplatin-gemcitabine, 3) carboplatin-paclitaxel or 4) chemoradiation with cisplatin or cisplatin-gemcitabine followed by radical hysterectomy were analyzed for pathological response and survival. RESULTS: One-hundred and fifty three (86%) of the 178 patients treated within these trials, underwent radical hysterectomy and were analyzed. Overall, the mean age was 44.7 and almost two-thirds were FIGO stage IIB. Pathological response rates were as follows: Complete (pCR) in 60 cases (39.2%), Near-complete (p-Near-CR) in 24 (15.6 %) and partial (pPR) in 69 cases (45.1%). A higher proportion rate of pCR was observed in patients treated with chemoradiotherapy (with cisplatin [19/40, 47.5%]; or with cisplatin-gemcitabine [24/41, 58.5%] compared with patients receiving only chemotherapy, 6/23 (26%), 3/8 (37.5%) and 8/41 (19.5%) for cisplatin-gemcitabine, oxaliplatin-gemcitabine and carboplatin-paclitaxel respectively [p = 0.0001]). A total of 29 relapses (18.9%) were documented. The pathological response was the only factor influencing on relapse, since only 4/60 (6.6%) patients with pCR relapsed, compared with 25/93 (26.8%) patients with viable tumor, either pNear-CR or pPR (p = 0.001). Overall survival was 98.3% in patients with pCR versus 83% for patients with either pNear-CR or pPR (p = 0.009). CONCLUSION: Complete pathological response but no Near-complete and partial responses is associated with longer survival in cervical cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

[Laparoscopic radical trachelectomy for preservation of fertility in early cervical cancer. A case report]. / Traquelectomía radical laparoscópica para preservación de la fertilidad en cáncer de cérvix etapa temprana. Reporte de un caso.

BACKGROUND: Radical hysterectomy is the standard treatment for patients with early-stage cervical cancer. However, for women who wish to preserve fertility, radical trachelectomy is a safe and viable option. OBJECTIVE: To present the first case of laparoscopic radical trachelectomy performed in the National Cancer Institute, and published in Mexico. CLINICAL CASE: Patient, 34 years old, gravid 1, caesarean 1, stage IB1 cervical cancer, squamous, wishing to preserve fertility. She underwent a laparoscopic radical trachelectomy and bilateral dissection of the pelvic lymph nodes. Operation time was 330minutes, and the estimated blood loss was 100ml. There were no intraoperative or postoperative complications. The final pathology reported a tumour of 15mm with infiltration of 7mm, surgical margins without injury, and pelvic nodes without tumour. After a 12 month follow-up, the patient is having regular periods, but has not yet tried to get pregnant. No evidence of recurrence. CONCLUSIONS: Laparoscopic radical trachelectomy and bilateral pelvic lymphadenectomy is a safe alternative in young patients who wish to preserve fertility with early stage cervical cancer.

A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes.

BACKGROUND: The antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer. METHODS: Hydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARbeta, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the "normally methylated" sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria. RESULTS: Hydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150 mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation. CONCLUSION: Hydralazine at doses between 50 and 150 mg/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation.