The prognosis of endometrial cancer (EC) is generally favorable, while lymph node status remains the most important prognostic factor. Sentinel lymph node mapping (SLNM) could help to find women in ...whom adjuvant therapy could be omitted. This review analyzes different techniques of injection and histopathologic elaboration of SLNM in EC. Results of studies on SLNM in ECs seem to be promising, but only a small series have been published so far. The studies are subdivided into three groups by the technique of injection (hysteroscopic, subserosal and cervical). Range of detection rate for SLNM varies from 45 to 100%. Hysteroscopic injection is not easy to learn; moreover, exact peritumoral injection in large tumors is often impossible. Subserosal administration of tracer is difficult during laparoscopic or robotic surgery. Cervical injection is quite a controversial technique because distribution of SLNs in ECs is different from cervical cancer; moreover, there is no large study using cervical injection with systematic pelvic and para-aortic lymphadenectomy.
Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the ...effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high‑resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression‑free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.
We studied the distribution of sentinel lymph nodes (SLNs) in vulvar cancer using blue dye and (99m)Tc radiocolloid and evaluated the techniques used, including the optimum timing of preoperative ...scintigraphy scans and its contribution to (99m)Tc SLN detection over that of the intraoperative handheld gamma probe. Fifty-nine women with squamous cell cancers <4 cm treated at our institution between December 2001 and December 2005 were included in this study. Blue dye alone was used in the first 16 women (group A) and the combination of (99m)Tc and blue dye was used on 43 women (group B). Of the 118 SLN detected in 82 groins, 83.9% (99) were sited in the superficial medial and intermediate inguinal chain, none were in superficial lateral groin, 16.1% (19) were deep femoral. The patient-specific SLN detection and false-negative rate in group B was 100% and 0%, compared to 68.8% (11/16 cases) and 6.3% (1/16) in group A. The optimum timing for preoperative lymphoscintigraphy scans was 45 min postinjection, but intraoperative use of the handheld gamma probe yielded 15% more "hot" nodes and allowed tailored placement of the lymphadenectomy incision. Eighty-four percent of SLNs were in the medial and intermediate region of the superficial inguinal chain, 16.1% were deep femoral. The combined use of (99m)Tc radiocolloid and blue dye was significantly superior at SLN detection than blue dye alone. (99m)Tc SLN detection using the intraoperative handheld probes was not enhanced by preoperative scintigraphy scans.
Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel ...effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases. In all tissue samples, transcript levels of the above target genes were assessed using quantitative real-time PCR. Gene expression levels were compared between particular tissue types and evaluated with regard to progression-free survival (PFS) and drug-resistance status of patients with metastases. Gene expression of
significantly increased and that of
decreased in the order control ovarian tissues - primary EOCs - metastases. High expressions of
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,
,
,
,
,
, and
genes were significantly associated with longer progression-free survival of patients. In intraperitoneal metastases, expression of all of these genes highly correlated and indicated prognostic profile. Transporters from the ABCA family, ABCG2, and ESR2 are involved mainly in lipid metabolism, membrane transport, and cell proliferation. These processes are thus probably the most important for EOC progression. Based on these results, we have proposed novel markers of ovarian carcinoma progression and metastatic spread which might be potentially useful as therapeutic targets. Their significance should be further explored on a larger independent set of patients.
Endometrial cancer incidence increases over the age of 65 and lymphadenectomy in these women is a morbid procedure. Sentinel lymph node (SLN) should avoid extensive lymphadenectomy in node negative ...patients. The aim of this prospective study is to determine the feasibility and usefulness of lymphatic mapping and SLN identification in the management of endometrial cancer.
From January 2004 to December 2007 101 women with endometrial cancer participated in the study. We injected Tc hysteroscopically, peritumorally 2 hours before laparotomy in 24 women. We applied Tc and blue dye subserously after laparotomy and before adhesiolysis in 67 women. Ten patients with metastatic disease in ovary, omentum, peritoneum, and bulky nodes were excluded from analysis.
We detected SLN in 12 women (50%) in hysteroscopic group and in 49 women (73.1%) in subserous group. We identified 133 SLNs in 61 women. We found 20 SLNs (15.0%) in supraobturator region, 78 (58.6%) in external iliac area, 11 (8.3%) in paraaortal area, 13 (9.8%) on common iliac artery, 8 (6.0%) in medial part of lateral parametrium, and 3 (2.3%) in presacral area.
Sentinel lymph node identification is a new strategy that can be used to examine nodal status with a high successful rate in breast, cervical, and vulvar cancer. Results in endometrial cancer are not as successful, however. In the future, it will be necessary to find optimal timing, the best route of application, and the "right" size of the Tc particles. Subserous application seems to be superior to hysteroscopic application.
The role of neoadjuvant chemotherapy (NAC) in "bulky" and locally advanced cervical cancer has been of interest for the last 25 years, and in many countries, NAC has become the standard of care. In ...the present paper, we review our 10 years' experience with high-dose-density NAC in cervical cancer management in 141 women (CervNAC I protocol). High-dose-density neoadjuvant chemotherapy and radical surgery has resulted in high clinical response rates and seems to be feasible in the management of stage IB bulky cervical cancer. Neoadjuvant chemotherapy reduces tumor volume and positivity of lymph nodes and thus minimizes the need for postoperative radiotherapy or chemoradiotherapy. Tumor size reduction and node negativity allows less radical surgical procedures such as modified radical hysterectomy or nerve-sparing radical hysterectomy. Early and especially late toxicity of our high-dose density chemotherapy is acceptable. Neoadjuvant chemotherapy followed by surgery represents a valid alternative to primary chemoradiotherapy in young and sexually active patients. Five-year survival in patients who underwent surgery in our study was 80.6%. Currently, 3 papers with 3 approaches have been published on NAC before fertility-sparing surgery. One of the limitations of fertility-preserving surgery is deep stromal invasion and tumors larger than 2 cm. The idea underlying NAC is to reduce the size of the cervical tumor to preserve fertility. In the present paper, we also review our experience with high-dose-density NAC in fertility-sparing surgery in 15 women (LAP3-NAC protocol).
p16(INK4a) immunoprofiles of non-precancerous and dysplastic squamous cervical lesions were defined and applied to the reclassification of atypical immature squamous metaplasia (AIM). The ...immunoexpression of cytokeratin 17 (CK 17) in AIM was also evaluated. Totally, 295 cervical cone biopsies representing squamous metaplasia, reactive changes, koilocytosis, flat condyloma, CIN I, CIN II, CIN III and AIM were subjected to p16(INK4a) immunohistochemistry. AIM cases were analyzed using CK 17 antibody. Typical p16(INK4a) immunoprofiles for the metaplastic, LSIL/HPV and HSIL phenotypes were recorded and used for the categorization of AIM into particular phenotype groups. Results were correlated with CK 17 immunoexpression. All CIN II and CIN III lesions, all but one case of CIN I and all flat condylomas overexpressed p16(INK4a). Other non-precancerous lesions, including koilocytosis, were predominantly negative. Contrary to the sporadic and focal immunostaining, diffuse positivity was associated with the dysplastic features of the lesion. CIN II and CIN III were characterized by a diffuse, strong/weak, full-thickness staining, whereas CIN I showed a heterogeneous diffuse/focal, weak/strong, lower half positivity. One third of AIM lesions may be reclassified as HSIL, one third as LSIL/HPV and one third shows metaplastic phenotype. All AIM cases with metaplastic and LSIL/HPV phenotypes expressed CK 17 diffusely, whereas focal positivity slightly prevailed in AIM with HSIL phenotype. We conclude that p16(INK4a) immunohistochemistry is a supporting method for the differential diagnosis of cervical lesions, which may be especially useful for the reclassification of AIM. The efficacy of CK 17 immunohistochemistry seems to be controversial for these purposes.
Surgical options in early cervical cancer Rob, Lukas; Robova, Helena; Chmel, Roman ...
International journal of hyperthermia,
09/2012, Letnik:
28, Številka:
6
Journal Article
Recenzirano
Cancer of the cervix is the second most common cancer in women worldwide and the fourth leading cause of cancer mortality in women. Early cervical cancer stage IB1 includes a broad range of disease ...from clinically undetectable microinvasive cancer to bulky tumours that infiltrated the entire cervix. This article reviews the literature about risk factors and surgical radicality and fertility-sparing surgery in early cervical cancer. The review evaluates selection criteria, preoperative management and the most frequent surgical procedures used for individually tailored surgery for cervical cancer.
The term vulvar intraepithelial neoplasia (VIN) introduced in 1986 incorporates 3 grades of usual VIN (u-VIN I-III) and the differentiated VIN (d-VIN). Although u-VIN is etiologically associated with ...the human papillomavirus (HPV) infection, d-VIN represents an alternative HPV negative pathway of vulvar carcinogenesis. In 2004, the u-VIN I category was abandoned and u-VIN II and III were merged. Further, an alternative Bethesda-like terminology scheme presenting the term vulvar intraepithelial lesion was proposed recently. To analyze the impact of HPV profiles of vulvar precancerous lesions for their classification and to assess the presumable efficacy of the prophylactic HPV vaccination, 269 vulvar excisions representing lichen sclerosus, lichen simplex chronicus, condylomata acuminata, d-VIN, all grades of u-VIN and squamous cell carcinomas were subjected to the HPV typing by use of GP5+/6+ polymerase chain reaction and reverse line blot hybridization. The results showed different HPV profiles, and also differing frequency of multiple-type HPV infection and the age structure in patients with u-VIN II and III. The biologic heterogeneity within the u-VIN II category was also demonstrated. u-VIN I was distinguished as a rare disorder associated with high-risk HPV infection. We conclude that the original VIN terminology proposed in 1986 seems to be appropriate for the classification of vulvar squamous dysplastic lesions. The spectrum of HPV types found in vulvar squamous cell carcinomas indicates that the efficacy of HPV vaccination in preventing vulvar cancer might be diminished in the studied population, because the recently developed prophylactic vaccines are targeted against a limited number of HPV types.
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