István Sinkovics

Inguinal sentinel lymph node biopsy for staging anal cancer.

Background and Aims: The optimal treatment of clinically negative inguinal lymph nodes in patients with primary anal cancer has not yet been clearly defined. The presence of metastases in the inguinal lymph nodes is an adverse prognostic factor for anal cancer. In the present study the feasibility of sentinel lymph node biopsy (SLNB) for staging anal cancer was investigated. Patients and Methods: From September 1999 to March 2002, 8 patients with biopsy proven primary anal cancer underwent lymphoscintigraphy and dual-agent guided inguinal SLNB for nodal staging before starting multimodality treatment. Results: Inguinal SLNB was successful in all 8 patients (13 groins). A total of 20 hot and blue SLNs (mean 1,5 (1–2) per groins) were removed. In 2 patients (25 %) the SLN was positive for metastasis. Conclusions: Lymphoscintigraphy followed by dual-agent guided inguinal SLNB is technically feasible for staging patients with primary anal cancer. The detection of metastases in the removed sentinel lymph node(s) may alter the treatment and thus may improve the locoregional control and overall survival of these patients.

Relationship between sentinel lymph node status and regression of primary malignant melanoma

The prognostic significance of spontaneous regression of primary melanoma is a controversial issue. Studies on sentinel lymph node status and circulating tumour cells may represent a step towards a better understanding. The clinical details of 269 melanoma patients who underwent sentinel lymph node biopsy were analysed. Correlation was sought between the parameters of the primary tumour, particularly tumours showing a partial intermediate level of regression, and sentinel lymph node status. The presence of circulating tumour cells was studied by reverse transcription-polymerase chain reaction for tyrosinase messenger RNA preoperatively in 94 patients. Of the examined tumours, 27.8% showed histological features of a partial intermediate level of regression. Regressive tumours were localized predominantly on the trunk (P=0.006), were significantly thinner (P<0.0000) and were less frequently ulcerated (P=0.003) than tumours without regression. Moreover, the majority of regressive melanomas were of the superficial spreading type (P<0.0000) and their sentinel node status was more favourable (P=0.026). We demonstrated the presence of circulating tumour cells in five of 26 (19.2%) regressive and 19 of 68 (29.4%) non-regressive tumours. The difference was not significant (P=0.32). By multivariate analysis, however, the Breslow thickness and ulceration of the primary tumour were predictors of the sentinel lymph node status, in agreement with literature data. A partial intermediate level of regression of the primary tumour did not affect unfavourably the sentinel lymph node status in our study. We failed to demonstrate a significant relationship between the presence of circulating tumour cells and either primary tumour regression or the sentinel lymph node status.

Clinical significance of sentinel lymph node involvement in malignant melanoma.

In the period 1997–2002, sentinel lymph node (SLN) surgery was performed on 179 primary skin melanoma patients, one to two months after the removal of the primary. Staining with patent blue was combined with an isotope technique. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph node was followed, preferably within 2–3 weeks, by regional block dissection. In these cases interferon-α2 in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26÷177 patients (14.7%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p < 0.00001). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007 respectively). Comparison of the tumor thickness and positive SLN by discriminance analysis, yielded 81.7% and 79.9%, respectively for correct classification rates. Based on our study and data from the literature, we suggest SLN-positivity as equally strong poor prognosis factor for skin melanoma as the tumor thickness.

Optimal treatment of the axilla after positive sentinel lymph node biopsy in early invasive breast cancer. Early results of the OTOASOR trial

INTRODUCTION Sentinel lymph node biopsy alone has become an acceptable alternative to elective axillary lymph node dissection in patients with clinically node-negative early-stage breast cancer. Approximately 70 percent of the patients undergoing breast surgery develop side effects caused by the axillary lymph node dissection (axillary pain, shoulder stiffness, lymphedema and paresthesias). AIM The current standard treatment is to perform completion axillary lymph node dissection in patients with positive sentinel lymph node biopsy. However, randomized clinical trials of axillary dissection versus axillary irradiation failed to show survival differences between the two types of axillary treatment. The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment of the Axilla - Surgery or Radiotherapy) trial compares completion axillary lymph node dissection to axillary nodal irradiation in patients with sentinel lymph node-positive primary invasive breast cancer. METHOD Patients with primary invasive breast cancer (clinically lymph node negative and less than or equal to 3 cm in size) were randomized before surgery for completion axillary lymph node dissection (arm A-standard treatment) or axillary nodal irradiation (arm B-investigational treatment). Sentinel lymph node biopsy was performed by the radio-guided method. The use of blue-dye was optional. Sentinel lymph nodes were investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin staining. In the investigational treatment arm patients received 50Gy axillary nodal irradiation instead of completion axillary lymph node dissection. Adjuvant treatment was recommended and patients were followed up according to the actual institutional guidelines. RESULTS Between August 2002 and June 2009, 2106 patients were randomized for completion axillary lymph node dissection (1054 patients) or axillary nodal irradiation (1052 patients). The two arms were well balanced according to the majority of main prognostic factors. Sentinel lymph node was identified in 2073 patients (98.4%) and was positive in 526 patients (25.4%). Fifty-two sentinel lymph node-positive patients were excluded from the study (protocol violation, patients preference). Out of the remaining 474 patients, 244 underwent completion axillary lymph node dissection and 230 received axillary nodal irradiation according to randomization. The mean length of follow-up to the first event and the mean total length of follow-up were 41.9 and 43.3 months, respectively, and there were no significant differences between the two arms. There was no significant difference in axillary recurrence between the two arms (0.82% in arm A and 1.3% in arm B). There was also no significant difference in terms of overall survival between the arms at the early stage follow-up. CONCLUSIONS The authors conclude that after a mean follow-up of more than 40 months axillary nodal irradiation may control the disease in the axilla as effectively as completion axillary lymph node dissection and there was also no difference in terms of overall survival.

Immunohistochemistry and reverse transcriptase polymerase chain reaction on sentinel lymph nodes can improve the accuracy of nodal staging in breast cancer patients.

In this study the nodal staging sensitivity of sentinel lymph node biopsy (SLNB) with detailed pathological and molecular biological examination has been investigated and compared to that of axillary lymph node dissection (ALND) with routine histological evaluation. Sentinel lymph nodes (SLNs) were removed by the dual-agent injection technique in 68 patients with primary, clinically node-negative breast cancer. Forty-seven patients had negative SLNs according to hematoxylin and eosin (H&E) staining. These H&E-negative SLNs were serially sectioned and examined at 250 μm levels by anticytokeratin immunohistochemistry (IHC). In 14 patients the SLNs were also investigated by cytokeratin 20 (CK20) reverse transcriptase polymerase chain reaction (RT-PCR). SLNB with IHC increased the node-positive rate by 26% (by 40% in tumors less than or equal to 2 cm in size (pT1) and by 9% in tumors more than 2 cm but less than or equal to 5 cm in size (pT2)). The sensitivity of SLNB with IHC was superior to that of ALND with routine histology in pT1 tumors and identical in pT2 tumors. The concordance between histology and RT-PCR was only 21%, and in two of three cases with positive histological results RT-PCR was negative. In conclusion, SLNB with detailed pathological and/or molecular biological evaluation can improve the sensitivity of regional staging. ALND can probably be abandoned in patients with pT1 SLN-negative breast cancer. Further prospective studies are required to determine the clinical significance of these detailed SLN evaluation techniques, but at present these methods are still investigational.

[The potential role of SPECT/CT in the preoperative detection of sentinel lymph nodes in breast cancer].

Regional lymph node status is the most important prognostic factor in breast cancer. Sentinel lymph node biopsy is the standard method of axillary staging in early breast cancer patients with clinically negative nodes. Preoperative lymphoscintigraphy might support refining biopsy findings by determining the number and location of sentinel lymph nodes. In aged or overweight patients, in the presence of atypical or extra-axillary lymphatic drainage, non-visualized lymph nodes, or sentinel lymph nodes close to the isotope injection site, detection could be aided by a new, hybrid imaging tool: the single-photon emission computed tomography combined with computed tomography (3D SPECT/CT). For the first time in Hungarian language, authors overview the literature: all 14 English-language articles on the implementation of 3D SPECT/CT in sentinel lymph node detection in breast cancer are included. It is concluded that 3D SPECT/CT increases the success rate and quality of preoperative sentinel node identification, and is capable of providing a more accurate staging of breast cancer patients in routine clinical practice.

Nem tapintható tüdőgócok drót- és izotópjelölés segítségével történő minimálinvazív műtéti eltávolítása

INTRODUCTION Nowadays ever smaller, sub-centimetre lung nodules are screened and diagnosed. For these, minimally invasive resection is strongly recommended both with diagnostic and therapeutic purpose. AIM Despite many advantages of minimally invasive thoracic surgery, thorough palpation of the lung lobes and thus the localization of lung nodules are still limited. There are several options to solve this problem. From the possibilities we have chosen and tried wire- and isotope-guided lung nodule localization. MATERIALS AND METHODS In 2017, at the Thoracic Surgery Department of the National Institute of Oncology we performed wire- and isotope-guided minimally invasive pulmonary nodule resection in five patients. The diameter of the lung nodules was between 0.5 and 1.2 cm. The age of the patients was between 44 and 65 years and none of them had severe comorbidities, which meant low risk for complications. RESULTS We successfully performed the minimally invasive atypical resection in all cases. After the wire and isotope placement we found a 2-3 mm pneumothorax in one patient that did not need urgent drainage. In another patient we found that high amount of intraparenchymal bleeding surrounded the channel of the wire. During the operation, two wires were displaced when the lung collapsed, and in another case the mentioned bleeding got into the thoracic cavity and made it difficult to detect the nodule. In one case we resected the wire-guided lung tissue, but the isotope-guided lung nodule was below the resection line. CONCLUSION Both techniques could help to localize the non-palpable lung nodules. Based on our initial experiences, the isotope-guided method provides more details to estimate the exact depth of the nodule from the visceral surface of the pleura and we can avoid the unpleasantness of wire displacement. On the other hand, the production of the isotope requires a more developed infrastructure and the exact timing of the operation after the isotope injection is more strict. Orv Hetil. 2018; 159(34): 1399-1404.INTRODUCTION Nowadays ever smaller, sub-centimetre lung nodules are screened and diagnosed. For these, minimally invasive resection is strongly recommended both with diagnostic and therapeutic purpose. AIM Despite many advantages of minimally invasive thoracic surgery, thorough palpation of the lung lobes and thus the localization of lung nodules are still limited. There are several options to solve this problem. From the possibilities we have chosen and tried wire- and isotope-guided lung nodule localization. MATERIALS AND METHODS In 2017, at the Thoracic Surgery Department of the National Institute of Oncology we performed wire- and isotope-guided minimally invasive pulmonary nodule resection in five patients. The diameter of the lung nodules was between 0.5 and 1.2 cm. The age of the patients was between 44 and 65 years and none of them had severe comorbidities, which meant low risk for complications. RESULTS We successfully performed the minimally invasive atypical resection in all cases. After the wire and isotope placement we found a 2-3 mm pneumothorax in one patient that did not need urgent drainage. In another patient we found that high amount of intraparenchymal bleeding surrounded the channel of the wire. During the operation, two wires were displaced when the lung collapsed, and in another case the mentioned bleeding got into the thoracic cavity and made it difficult to detect the nodule. In one case we resected the wire-guided lung tissue, but the isotope-guided lung nodule was below the resection line. CONCLUSION Both techniques could help to localize the non-palpable lung nodules. Based on our initial experiences, the isotope-guided method provides more details to estimate the exact depth of the nodule from the visceral surface of the pleura and we can avoid the unpleasantness of wire displacement. On the other hand, the production of the isotope requires a more developed infrastructure and the exact timing of the operation after the isotope injection is more strict. Orv Hetil. 2018; 159(34): 1399-1404.

Modern diagnostics of breast cancer: nuclear medicine techniques

The authors discuss the role of nuclear medicine techniques in the modern diagnostics of breast cancer, including the methods currently used in Hungary and the future possibilities.