The role of sentinel node detection techniques in vulvar and cervical cancer

The sentinel node is the first lymph node that receives the lymph drainage from the primary tumour. The pathological status of the sentinel node should reflect the histopathology of the entire regional lymph drainage area — both vulvar and cervical cancer spread through the lymphatic system. In gynaecological oncology recent studies have confirmed the utility of the sentinel node concept in vulvar and cervical cancer. Three techniques for sentinel node localisation are available. The preoperative lymphoscintigraphy and intraoperative handheld gamma probe detection require the administration of the technetium-99m-labelled colloid around the tumour. The other method is based on the injection of the patent blue dye — during the surgery of the sentinel node because of the dye uptake becomes visible. Following detection, the sentinel lymph node can be removed separately and assessed with ultrastaging and immunohistochemical staining. In the early stages of vulvar and cervical cancer the lymph nodes metastases rate is relatively low — in most cases lymphadenectomy is not necessary. The determination of the regional lymph nodes’ pathological status may limit the extent of the surgical treatment. The sentinel node detection rate is relatively high and depends on the applied technique. This technique may play an important role in the treatment of vulvar and cervical cancer. This paper describes the details of sentinel node identification and reviews the literature

Evaluation of sentinel node detection in vulvar cancer

BACKGROUND: In vulvar cancer, in a large portion of patients with early stages of the disease, the inguinal lymphadenectomy not only does not influence the overall survival and recurrence rate but may increase the incidence of complications. Sentinel lymph node (SN) detection is a promising technique for detecting groin lymph nodes, which may in future lead to less extensive use of surgical treatment. The aim of the study was to evaluate the feasibility of the sentinel node detection technique in patients with vulvar cancer. MATERIAL AND METHODS: Between the years 2003 and 2005, we performed intraoperative lymphatic mapping on 10 patients with planoepithelial vulvar cancer. In eight cases, vulvar lesion was localized centrally, around the clitoris. The extent of the surgery included radical vulvectomy with bilateral inguinal lymphadenectomy in nine cases and unilateral inguinal lymphadenectomy in one case. For the lymphatic mapping, we employed two detection methods: 99mTc-labelled radiocolloid (activity 35-70 MBq) and blue dye (3-5 ml). Both techniques were used in six cases (60%), blue dye only in three cases and radiocolloid only in one case. RESULTS: In each patient, we detected at least one sentinel lymph node. Sentinel nodes were localized in 14 of 19 operated groins (73.7%); a total of 25 SNs in all. The mean number of SNs for one groin was 1.78. Nodal metastases were found in four cases. In three cases, metastases were detected only in the SN. In one patient, two SNs with metastases were found in one groin and in the contralateral groin (without any SN) there was one unchanged node, which transpired to be metastatic. This can be explained by a complete overgrowth of neoplasm in the lymph node resulting in lymph flow stasis and disabling tracer uptake. In five cases, an SN was found only in one groin ó the first case is described above, in the second case the vulvar tumor was localized laterally, opposite to the groin without any SN. In the remaining three cases, we have used only one method of SN detection. CONCLUSIONS: Lymphatic mapping in vulvar cancer based on the combined detection technique is a highly accurate method after adequate training of the surgeons

The influence of depth of marker administration on sentinel node detection in cervical cancer

BACKGROUND: Regional lymph node surgical management is an integral part of cervical cancer therapy. In gynaecological oncology, recent studies have confirmed the utility of the sentinel node concept in vulvar and cervical cancer. The method of the marker’s administration is considered to play an important role in sentinel node detection. MATERIAL AND METHODS: 60 patients with cervical cancer (stage IB–IIA) underwent SLN detection during radical abdominal hysterectomy. The patients were randomly divided into two groups: the first group of 30 patients with 0.5–1cm deep marker injection, the second with sub-epithelial marker injection. Gamma-camera scanning, as well as hand-held probe detection was applied. RESULTS: All hot nodes visualised on lymphoscintigraphy were “hot” when using the hand-held gamma probe. Deep marker injection revealed a sentinel node in 27 patients (90%) on both sides, in 3 patients (10%) only on one side. Only 40 (67%) sentinel nodes were blue-stained. Sub-epithelial marker administration revealed a sentinel node on both sides in all 30 patients (100%). In 28 patients (93.3%) the sentinel nodes were radioactive and blue-stained, in one case not-blue stained on either side, in one case blue stained only on one side. CONCLUSIONS: The sentinel node detection rate in cervical cancer is relatively high and depends on the applied technique. The superficial administration of radiocolloid and the blue dye into the cervix provides a higher sentinel node detection rate than deep administration in cervical cancer patients

Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits.

The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals

Rabbit articular cartilage defects treated with cultured costal chondrocytes (preliminary report)

An attempt to repair articular cartilage defects by costal chondrocytes transplantation was made. A full-thickness defect in the rabbit's femoral patellar groove was artificially made. Cultured costal cartilage chondrocytes were then transplanted into the defects and covered with periosteal flaps. Empty defects were used as the control group. Animals were divided into two groups (five rabbits each). They were examined after four and twelve weeks from the day of transplantation, respectively. The reparative tissue was evaluated by macroscopic and histological examinations. The reparative tissues in defects with transplanted chondrocytes had an hyaline-like cartilage appearance and were firmly attached to the surrounding normal cartilage. No trace of newly formed bone was detected. The reparative tissues found in defects that were left empty had a fibrous character. They were loosely connected to the surrounding cartilage and were more compliant than tissues from transplanted defects. Considering these initial findings, the ease of surgical procedures during the harvesting of the costal cartilage and few interventions into the joint make the costal cartilage a promising source of chondrocytes for transplantation. However, this needs to be confirmed on a larger scale over a longer period of time

Determining Curie temperature of (Ga,Mn)As samples based on electrical transport measurements: low Curie temperature case

In this paper we show that the widely accepted method of the determination of Curie temperature (TC) in (Ga,Mn)As samples, based on the position of the peak in the temperature derivative of the resistivity,completely fails in the case of non-metallic and low-TC unannealed samples. In this case we propose an alternative method, also based on electric transport measurements, which exploits temperature dependence of the second derivative of the resistivity upon magnetic field.Comment: 5 pages, 3 figure

The presence of HER2 exon 20 insertion in patients with central nervous system metastases from non-small lung cancer — a potential application in classification for therapy

 WSTĘP: HER2 (ErbB2/neu) jest białkiem należącym do rodziny receptorów HER (EGFR, HER2, HER3 i HER4), posiadających w swej części wewnątrzkomórkowej aktywność kinazy tyrozynowej. Nadekspresja EGFR i HER2 występuje w wielu typach nowotworów, ale to mutacje w genach kodujących te receptory uwrażliwiają chorych na niedrobnokomórkowego raka płuca (NSCLC) na działanie inhibitorów kinaz tyrozynowych EGFR i HER2.MATERIAŁ I METODY: Wykorzystano technikę PCR oraz analizę długości fragmentów amplifikowanego DNA w celu zidentyfikowania u 150 chorych insercji 12 par zasad w obrębie eksonu 20 genu HER2 w przerzutach NDRP do mózgu.WYNIKI: W guzie z wykrytą mutacją HER2 nie stwierdzono mutacji EGFR ani BRAF. Insercja w eksonie 20 genu HER2 została wykryta u 77-letniego niepalącego mężczyzny chorego na niskozróżnicowanego raka gruczołowego (0,67% wszystkich chorych oraz 1,5% chorych na raka gruczołowego). U tego chorego nie zidentyfikowano innych nieprawidłowości genetycznych.WNIOSKI: W literaturze opisano, że u chorych posiadających mutację w genie HER2 mogą okazać się skuteczne inhibitory specyficzne w stosunku do kinaz tyrozynowych obu receptorów: EGFR i HER2 (np. afatynib). Dlatego też identyfikacja nowych mutacji kierujących w komórkach NSCLC wydaje się kluczem do właściwej kwalifikacji do terapii ukierunkowanych molekularnie. INTRODUCTION: HER2 (ErbB2/neu) is a member of the ErbB family of four structurally related receptors of tyrosine kinase activity. Overexpression of ErbB-1 (EGFR) and HER2 is found in many human cancers, but the presence of these genes mutations determines the effectiveness of EGFR and HER2 tyrosine kinase inhibitors in the therapy of non-small cell lung cancer (NSCLC).MATERIAL AND METHODS: To search for insertions of the HER2 gene in exon 20 in 150 brain metastases of non-small cell lung cancer patients, we used a PCR technique based on analysis of amplified DNA fragment lengths. We also compared the HER2 mutational status with clinicopathologic features and the presence of EGFR and BRAF mutations.RESULTS: HER2 mutation was present in one male, non-smoking patient with low differentiated adenocarcinoma (0.67% of all patients and 1.5% of patients with adenocarcinoma). The mutations of EGFR and BRAF genes were not found in HER2-mutated patient.CONCLUSIONS: The literature data suggests that patients with HER2 mutations may be sensitive to tyrosine kinase inhibitors of both EGFR and HER2 receptors (e.g. afatinib). Therefore, the identification of new driver mutations in NSCLC can improve the quality of patient care by enabling the use of correct molecularly targeted therapies

The Application of Real-Time PCR Technique to Detect Rare Cell Clones with Primary T790M Substitution of EGFR Gene in Metastases of Non-small Cell Lung Cancer to Central Nervous System in Chemotherapy Naive Patients

The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients

All-wurtzite (In,Ga)As-(Ga,Mn)As core-shell nanowires grown by molecular beam epitaxy

Structural and magnetic properties of (In,Ga)As-(Ga,Mn)As core-shell nanowires grown by molecular beam epitaxy on GaAs(111)B substrate with gold catalyst have been investigated.(In,Ga)As core nanowires were grown at high temperature (500 {\deg}C) whereas (Ga,Mn)As shells were deposited on the {1-100} side facets of the cores at much lower temperature (220 {\deg}C). High resolution transmission electron microscopy images and high spectral resolution Raman scattering data show that both the cores and the shells of the nanowires have wurtzite crystalline structure. Scanning and transmission electron microscopy observations show smooth (Ga,Mn)As shells containing 5% of Mn epitaxially deposited on (In,Ga)As cores containing about 10% of In, without any misfit dislocations at the core-shell interface. With the In content in the (In,Ga)As cores larger than 5% the (In,Ga)As lattice parameter is higher than that of (Ga,Mn)As and the shell is in the tensile strain state. Elaborated magnetic studies indicate the presence of ferromagnetic coupling in (Ga,Mn)As shells at the temperatures in excess of 33 K. This coupling is maintained only in separated mesoscopic volumes resulting in an overall superparamagnetic behavior which gets blocked below ~17 K.Comment: 37 pages, 8 figure