José Chanona-Vilchis

Primary retroperitoneal mucinous cystadenocarcinoma: report of two cases.

BackgroundRetroperitoneal cystadenocarcinomas are rare lesions, the majority of cases presented as one-patient reports.MethodsWe 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.ResultsOne 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.ConclusionThe behavior and treatment of retroperitoneal cystadenocarcinoma are controversial. We suggest aggressive surgery including radical hysterectomy and bilateral salpingoopherectomy with adjuvant chemotherapy in these cases.

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

BackgroundCisplatin-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.MethodsFour 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.ResultsOne-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).ConclusionComplete pathological response but no Near-complete and partial responses is associated with longer survival in cervical cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

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

BackgroundDespite 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.ResultsPDGF 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 PDGFRα 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.ConclusionThe 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.

Use of an orthovoltage X-ray treatment unit as a radiation research system in a small-animal cancer model.

BackgroundWe explore the use of a clinical orthovoltage X-ray treatment unit as a small-animal radiation therapy system in a tumoral model of cervical cancer.MethodsNude mice were subcutaneously inoculated with 5 × 106 HeLa cells in both lower limbs. When tumor volume approximated 200 mm3 treatment was initiated. Animals received four 2 mg/kg intraperitoneal cycles (1/week) of cisplatin and/or 6.25 mg/kg of gemcitabine, concomitant with radiotherapy. Tumors were exposed to 2.5 Gy/day nominal surface doses (20 days) of 150 kV X-rays. Lead collimators with circular apertures (0.5 to 1.5 cm diameter) were manufactured and mounted on the applicator cone to restrict the X-ray beam onto tumors. X-ray penetration and conformality were evaluated by measuring dose at the surface and behind the tumor lobe by using HS GafChromic film. Relative changes in tumor volume (RTV) and a clonogenic assay were used to evaluate the therapeutic response of the tumor, and relative weight loss was used to assess toxicity of the treatments.ResultsNo measurable dose was delivered outside of the collimator apertures. The analysis suggests that dose inhomogeneities in the tumor reach up to ± 11.5% around the mean tumor dose value, which was estimated as 2.2 Gy/day. Evaluation of the RTV showed a significant reduction of the tumor volume as consequence of the chemoradiotherapy treatment; results also show that toxicity was well tolerated by the animals.ConclusionResults and procedures described in the present work have shown the usefulness and convenience of the orthovoltage X-ray system for animal model radiotherapy protocols.

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

BackgroundGerm cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors.MethodsWe conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis.ResultsHistologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016), AFP ≥ 14.7 ng/mL (p = 0.0001), and hCG ≥ 25 mIU/mL (p = 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04). When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (p < 0.0001). VEGF expression was not associated with VD or hCG serum levels.ConclusionThis is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.

Endometrial stromal sarcomas: Immunoprofile with emphasis on HMB45 reactivity

OBJECTIVES We describe the morphologic and immunohistochemical features of 17 endometrial stromal neoplasms, 16 sarcomas, and one stromal nodule. METHODS We reviewed 35 cases interpreted as endometrial stromal neoplasms, but 17 high-grade endometrial stromal sarcomas (ESS) and one case of mixed endometrial sarcoma and leiomyosarcoma were excluded from the study. Data from the Surveillance Epidemiology and End Results program on low- and high-grade ESS for 1973 through 2003 were obtained. RESULTS One uterine primary ESS had collections of clear cells (20%), while a metastatic ESS contained predominantly clear cells (90%). CD10 (88.2%) and smooth muscle actin (70.5%) were the most common positive immunohistochemical markers. The latter marker was located in the cytoplasm in 47% of the ESS and in the nucleus in 23.5%, a previously unreported feature. HMB45 was detected in 23.5% of the ESS, which contrasts with the 2% reported by other authors. CONCLUSIONS The presence of clear cells and HMB45 reactivity does not justify the term perivascular epithelioid cell tumors for these neoplasms. Two of 17 patients with ESS died of metastatic disease. However, among 274 cases of ESS (all stages included) collected by the Surveillance Epidemiology and End Results Program of the National Cancer Institute during a 30-year period, the 10-year survival rate was 94%.

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.

Percutaneous interventional procedures with ultrasonographic guidance in patients with cancer

Background Percutaneous interventional procedures offer diagnostic, curative and palliative treatment options to patients with cancer. Ultrasound (US) is an alternative guiding technique for various procedures including biopsy oflung, spleen, soft tissue and bone, and procedures like tumor ablation and abscess drainages among others. US has advantages like versatility, availability, lesser cost and time, lack of ionizing radiation and contrast media exposure, and complete visualization of the needle track in real time. This is a description of the various interventional procedures performed at the Instituto Nacional de Cancerologia under US guidance, its technical success and complications.