One Step Nucleic Acid Amplification (OSNA) positive micrometastases and additional histopathological NSLN metastases: Results from a single institution over 53 months.

INTRODUCTION: The role of sentinel lymph node micrometastases on histopathological analysis is controversial in axillary staging and management in clinically node negative breast cancer. Long-term studies addressing the clinical relevance of occult breast cancer in sentinel lymph nodes based on molecular analysis are lacking. One Step Nucleic Acid Amplification (OSNA), a highly sensitive assay of cytokeratin 19 mRNA, is used intra-operatively for the detection of lymph node macro- and micrometastases in breast cancer. AIM: The aim of this study is to review the rate of micrometastases and further histopathological NSLN metastases, in our unit following the introduction of OSNA in Guildford. METHODS: Data was collected prospectively from the period of introduction 01/12/2008 to 31/05/2013. All patients eligible for sentinel lymph node biopsy were offered OSNA and operations were performed by the consultant breast surgeons. Presence or absence of micro-metastases depends on the agreed cut-off point on the amplification curve. On detection of micrometastases (+) and positive but inhibited (i+) metastases, a level 1 axillary clearance (ANC) was performed and for a macrometastasis (++), a level 3 ANC was carried out. RESULTS: 66% of the patients had negative SLN (n = 672) and 34% (n = 336) had positive sentinel lymph nodes who had further axillary surgery. Of these, 45% (n = 152/336) had macrometastases, 40% (n = 136/336) had micrometastases and 15% (48/336) had positive but inhibited results. There was no difference in the patient demographics and tumour characteristics in the various positive SLN groups. In patients with micrometastases, 15% (20/136) had further positive NLSNs and a further 6% (8/136) had >4 overall positive nodes (SLN + NSLN) thus requiring adjuvant supraclavicular/chest wall radiotherapy (p < 0.05). 25% of node positive patients had further NLSN metastases (85/336) and in these patients, the ratio of positive SLN/harvested SLN (+SLN/SLN) is constant at 1:1. This shows the likelihood of further positive NSLNs if all the harvested lymph nodes are positive. This linear trend is present in both micro-and macrometastases, thus correlating with the size and number of NSLN metastases. CONCLUSION: Our study reflects the tumour burden of NSLNs based on the molecular analysis of the SLN. OSNA has the potential to accurately identify axillary micrometastases. Micro-metastases are important as some of the patients with micrometastases had overall four positive nodes [SLN + NSLN] (criteria for radiotherapy in the absence of other adverse clinicopathological features). Also, our study highlights certain factors that predict the NSLN metastases, pending validation by further prospective long-term data. This will allow accurate calculation of the axillary tumour burden, particularly in patients with micro-metastases.

Results of a national training programme in sentinel lymph node biopsy for breast cancer.

BACKGROUND: New Start, a structured, validated, multidisciplinary training programme in sentinel lymph node biopsy (SLNB), was established to allow the introduction and rapid transfer of appropriate knowledge and technical skills to ensure safe and competent practice across the UK. METHODS: Multidisciplinary teams attended a theory/skills laboratory course, following which they performed 30 consecutive SLNBs, either concurrently with their standard axillary staging procedure (training model A) or as stand-alone SLNB (training model B). SLNB was performed according to a standard protocol using the combined technique of isotope ((99m) Tc-labelled albumin colloid) and blue dye. An accredited New Start trainer mentored the first five procedures in the participant's hospital, or all 30 if stand-alone. Validation standards for model A and B were a localization rate of at least 90 per cent. In addition, for model A only, in which a minimum of ten patients were required to be node-positive, a false-negative rate (FNR) of 10 per cent or less was required. RESULTS: From October 2004 to December 2008, 210 SLNB-naive surgeons, in 103 centres, performed 6685 SLNB procedures. The overall sentinel lymph node (SLN) localization rate was 98·9 (95 per cent confidence interval 98·6 to 99·1) per cent (6610 of 6685) and the FNR 9·1 (7·9 to 10·5) per cent (160 of 1757). The FNR was related to nodal yield, ranging from 14·8 per cent for one node and declining to 9·7, 6·6, 4·7 and 4·1 per cent for two, three, four and more than four SLNs respectively. No learning curve was identified for localization or FNR. CONCLUSION: The programme successfully trained a wide range of UK breast teams to perform safe SLNB and suggested that a standard injection protocol and structured multidisciplinary training can abolish learning curves.

Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Ideally, intraoperative sentinel lymph node (SLN) analysis in breast cancer should be automated, have high concordance with extensive histopathology, and be applicable in any hospital setting. A prospective multicentre evaluation of the one-step nucleic acid amplification (OSNA) automated molecular diagnostic system of SLN analysis was undertaken. METHODS: Intraoperative examination of SLNs from 204 patients with breast cancer was performed by OSNA at four sites in the UK. Half of each SLN was assessed by OSNA (for cytokeratin 19 mRNA) and the remaining half was paraffin embedded for intensive histological examination at ten levels. Discordant cases were reanalysed by further molecular biological techniques and by additional histological examination of all remaining nodal material to ascertain whether the discordance was due to an uneven distribution of metastases, known as tissue allocation bias (TAB). RESULTS: After exclusion of samples affected by TAB, the overall concordance rate for OSNA versus histopathology was 96.0 per cent, with a sensitivity of 91.7 per cent and a specificity of 96·9 per cent. The median time to process a single SLN was 32 (range 22-97) min, and that for two nodes 42 (30-73) min. CONCLUSION: OSNA enables accurate automated intraoperative diagnosis and can be used successfully in different UK hospitals. When the SLN is shown to be positive, the patient can undergo immediate axillary clearance under the same anaesthetic rather than having a delayed second procedure.

[Clinical results and prospects for the use of phenosanic acid in patients with focal epilepsy]. / Klinicheskie rezul'taty i perspektivy primeneniya fenozanovoi kisloty u vzroslykh patsientov s fokal'noi epilepsiei.

OBJECTIVE: To study the efficacy and safety of using a new original synthetic antioxidant - phenosanic acid as an adjunct therapy in patients with focal epilepsy. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy and safety of phenosanic acid as an adjunct therapy to basic antiepileptic drugs in 120 patients with focal epilepsy. Primary purpose: to study the dynamic of seizure frequency. Secondary purposes: to study the dynamic of seizure-free days, the dynamics of bilateral tonic-clonic seizures, the results of questionnaires and scales (General Dynamics Assessment, Visual Analogue Scale (VAS), Quality of Life in Epilepsy (QOLIE-31-P), European Quality of Life Questionnaire (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Frontal Asstssment Battery (FAB), Mini-Mental State Examination (MMSE)). RESULTS: Phenosanic acid (Dibufelon) showed statistically significant benefit over placebo in the primary indicator of efficacy (reduction in the frequency of epileptic seizures by at least 50%) and in the secondary indicators. The drug was safe and well tolerated by the patients. CONCLUSION: The addition of phenosanic acid (Dibufelon) to base antiepileptic drugs seems to be perspective because of its positive effect on reducing the number of epileptic seizures, as well as on comorbid disorders in the emotional and cognitive spheres.

Melanoma sentinel node biopsy and prediction models for relapse and overall survival.

BACKGROUND: To optimise predictive models for sentinal node biopsy (SNB) positivity, relapse and survival, using clinico-pathological characteristics and osteopontin gene expression in primary melanomas. METHODS: A comparison of the clinico-pathological characteristics of SNB positive and negative cases was carried out in 561 melanoma patients. In 199 patients, gene expression in formalin-fixed primary tumours was studied using Illumina's DASL assay. A cross validation approach was used to test prognostic predictive models and receiver operating characteristic curves were produced. RESULTS: Independent predictors of SNB positivity were Breslow thickness, mitotic count and tumour site. Osteopontin expression best predicted SNB positivity (P=2.4 × 10⁻7), remaining significant in multivariable analysis. Osteopontin expression, combined with thickness, mitotic count and site, gave the best area under the curve (AUC) to predict SNB positivity (72.6%). Independent predictors of relapse-free survival were SNB status, thickness, site, ulceration and vessel invasion, whereas only SNB status and thickness predicted overall survival. Using clinico-pathological features (thickness, mitotic count, ulceration, vessel invasion, site, age and sex) gave a better AUC to predict relapse (71.0%) and survival (70.0%) than SNB status alone (57.0, 55.0%). In patients with gene expression data, the SNB status combined with the clinico-pathological features produced the best prediction of relapse (72.7%) and survival (69.0%), which was not increased further with osteopontin expression (72.7, 68.0%). CONCLUSION: Use of these models should be tested in other data sets in order to improve predictive and prognostic data for patients.

[The risk of suicidal behavior in patients with epilepsy]. / Risk razvitiia suitsidal'nogo povedenia u bol'nykh épilepsiei.

AIM: To study a role of psychopathological and social factors in the development of suicidal behavior in patients with different forms of epilepsy. MATERIAL AND METHODS: One hundred and nineteen patients with epilepsy, 57 men and 62 women, mean age 40.7±0.54 years, were studied using neurological and psychiatric examinations, along with a large battery of scales for assessment patient's state and suicidal behavior. RESULTS AND CONCLUSION: Clinical and psychological risk factors for suicidal behavior as well as for motivation of suicide prevention are identified. The formation of psychopathology determines the model of personality changes associated with epilepsy and the patients' response to social exclusion and stigma that lead to suicide.

[Brivaracetam in the treatment of patients with epilepsy]. / Brivaratsetam v lechenii bol'nykh épilepsiei.

The newest antiepileptic drug (AED) brivaracetam (Briviac, UCB Pharma) (BRV) was approved in the Russian Federation in 2017 as an adjuvant therapy for the treatment of partial seizures with/without secondary generalization in adults and adolescents over 16 years old with epilepsy. This review contains the data of BRV preclinical studies, pharmacokinetic profile and the results of comparative study of BRV and LEV. The results of main studies of efficacy and tolerability with pooled analysis as well as data from meta-analysis are presented. The authors present conclusions of the Russian leading epileptologists on perspectives of using BRV in different populations of epileptic patients. The use of BRV is able to provide long-term efficacy in terms of seizure control, is well tolerated, keeps quality of life and social activity of people with epilepsy.

Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer.

Parathyroid hormone-related protein (PTHrP) is known to be a causative factor in humoral hypercalcemia of malignancy. A polyclonal rabbit antiserum directed against the amino-terminal region of the protein and immunoperoxidase methods have been used to locate the presence of PTHrP in a series of 102 consecutive invasive breast tumors removed surgically from normocalcemic women. Positive PTHrP staining was detected in 60% of the tumors but not in the accompanying normal breast tissue. Positive staining was related to the progesterone receptor status of the tumor (P = 0.039) and to the prognostic index of the patient (P = 0.046) and not to estrogen receptor status, patient age, tumor size, histological grade, or nodal status.

Splenorenal Arterial Bypass: Description of Technique and Case Example in an Instance of Renal Revascularization during Adrenalectomy for Adrenocortical Carcinoma.

We present a patient with a 16 cm adrenocortical carcinoma that underwent a left adrenalectomy en bloc with resection of the involved segment of the left renal artery. A splenectomy and splenorenal bypass was performed to revascularize the left kidney. To our knowledge, this is the first instance in the literature of a splenorenal arterial bypass being reported for renal revascularization during an extirpative oncologic procedure. A 64-year-old male patient, with history significant for adrenocortical carcinoma, status post prior right adrenalectomy with partial right nephrectomy, presented for an elective left adrenalectomy. Preoperative work-up revealed an 11.4 × 13.2 × 16 cm left adrenal mass, most consistent with an adrenocortical carcinoma. At the time of surgery, the mass was found to be intimately adherent to the aorta at the takeoff of the left renal artery. Moreover, the left renal artery appeared to be coursing directly through the mass. The involved segment of the left renal artery was resected en bloc with the tumor. Because of concerns for a small and likely poorly functioning right renal remnant, a decision was made to attempt to salvage the left kidney. This was accomplished by performing a splenectomy and constructing a splenorenal bypass. Serial Duplex Doppler renal ultrasound studies were obtained over the first three postoperative days and demonstrated improved arterial waveforms. Serum creatinine reached a peak level of 3.76 mg/dL on postoperative day 3, and then began to slowly trend down to 3.37 mg/dL on the day of discharge (postoperative day7).

[Russian experience of lacosamide (vimpat) usage in treatment of uncontrolled focal epilepsy]. / Rossiiskii opyt primeneniya lakosamida (vimpat) pri lechenii patsientov s nekontroliruemoi fokal'noi epilepsiei.

Many patients with epilepsy receive treatment in polytherapy. Selection of antiepileptic drugs (AEDs) for the combination should be carried out in accordance with the principles of rational polytherapy, taking into account the mechanism of action, pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs. Along with levetiracetam, gabapentin, vigabatrin and pregabalin, lacosamide (LCM) shows superior PK profile in rating of all AED and can be combined with any of them. The goal of this study was to evaluate efficacy and tolerability of LCM in patients with uncontrolled partial onset seizures (POS) in routine clinical practice. METHODS: 181 patient's charts from 14 sites in Russia have been analyzed in retrospective manner. Patients 16 years old and older with POS with or without secondary generalization were included. Documented observation period of up to 12 months after initiation or until discontinuation of LCM therapy. Primary effectiveness variables was retention at Observational Point 3 (approximately 12 months). Other variables were: percentage change from historical baseline in seizure frequency, 50% and 75% treatment response and seizure-free status at the Observational Points 1, 2 and 3 (approximately 3, 6 and 12 months) and incidence and reason of treatment discontinuation. RESULTS: retention rate was high with 89.5% after 12-month observation. The development of seizure frequency showed a continuous decrease in terms of 50%, 75% treatment respond rates and seizure free status. A total of 5 adverse drug reactions leading to discontinuation of LCM therapy were recorded in 5 of 181 patients (2.8%) during the observation period. The high retention rate observed in this retrospective chart review is assumed to indicate a good tolerability and effectiveness of an adjunctive LCM treatment in patients with uncontrolled partial epilepsy in Russia.

Role of routine preoperative lymphoscintigraphy in sentinel node biopsy for breast cancer.

Sentinel node biopsy (SNB) is rapidly emerging as the preferred technique for nodal staging in breast cancer. When radioactive colloid is used, a preoperative lymphoscintiscan is obtained to ease sentinel lymph node (SN) identification. This study evaluates whether preoperative lymphoscintigraphy adds diagnostic accuracy to offset the additional time and cost required. 823 breast cancer patients underwent SNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99 mTc-nanocolloid and Patent Blue V injected peritumourally. The SNB was followed by standard axillary treatment at the same operation. Preoperative lymphoscintigraphy was performed around 3 h after the radioisotope injection. Preoperative lymphoscintigraphy revealed SNs in 593 (72%) of the 823 patients imaged. SN visualisation on lymphoscintigraphy was less successful in large tumours and tumours involving the upper outer quadrant of the breast (P=0.046, P<0.001, respectively). Lymphoscintigraphy showed internal mammary sentinel nodes in 9% (62/707) patients. The SN was identified intraoperatively in 98% (581) patients who had SN visualised on preoperative lymphoscintigraphy, with a false-negative rate of 7%. In patients who did not have SN visualised on preoperative lymphoscintigraphy, the SN was identified at operation in 90% (204) patients, with a false-negative rate of 7%. The SN identification rate was significantly higher in patients with SN visualised on preoperative lymphoscintigraphy (P<0.001). SN identification rate intraoperatively using the gamma probe was significantly higher in the SN visualised group compared with the SN non-visualised group (95% vs. 68%; chi square (1 degrees of freedom (df)) P<0.001. There was no statistically significant difference in the false-negative rate and the operative time between the two groups. A mean of 2.3 (standard deviation (SD) 1.3) SNs per patient were removed in patients with SN visualised on preoperative lymphoscintigraphy compared with 1.8 (SD 1.2) in patients with no SN visualised on lymphoscintigraphy (P<0.001). Although SN visualisation on preoperative lymphoscintigraphy significantly improved the intraoperative SN localisation rate, SN was successfully identified in 90% of patients with no SN visualisation on lymphoscintigraphy. Given the time and cost required to perform routine preoperative lymphoscintigraphy, these data suggest that it may not be necessary in all cases. It may be valuable for surgeons in the learning phase to shorten the learning curve and in patients who have increased risk of intraoperative failed localisation (obese or old patients). A negative preoperative lymphoscintiscan predicts the inability to localise with the hand-held gamma probe. Therefore, if the SN is not visualised on lymphoscintigraphy then the addition of intraoperative blue dye is recommended to increase the likelihood of SN identification.

T1 G1 NO ER positive breast cancer--adjuvant therapy is needed.

AIMS: To assess the outcome of treating patients with excellent prognosis (T1 G1 N0 ER +ve) breast cancers with breast conserving surgery alone. METHODS: One hundred and twenty-one women with grade 1, node negative, ER+ tumours, smaller than 20 mm who were treated by breast conserving surgery alone between 1991 and 2000. Margin width was always at least 5 mm. The following were recorded: local recurrence (LR), distant recurrence, new contra-lateral primaries and death. Recurrence rates were then compared to those in the largest series. RESULTS: One hundred and twenty-one women were followed up for a median of 68 months. Fourteen developed further breast cancer in the same side and eight new cancers in the contra-lateral breast. There was one case of distant metastasis and no deaths. Local recurrence rate was significantly higher than other studies (p=0.006). CONCLUSIONS: Although there is no detrimental effect on survival after this length of follow-up, the omission of radiotherapy and tamoxifen appears to increase the probability of LR. Patients with T1 G1 N0 ER+ breast cancer treated by breast conserving surgery should be offered both radiotherapy and tamoxifen.

Hepatic resection for breast cancer metastases.

INTRODUCTION: Hepatic resection is an established modality of treatment for colorectal cancer metastases. Resection of breast cancer liver metastases remains controversial, but has been shown to be an effective treatment in selected cases. This study reports the outcome of 8 patients with liver metastases from breast cancer. PATIENTS & METHODS: 8 patients with liver metastases from previously treated breast cancer were referred for hepatic resection between September 1996 and December 2002. Six were eligible for liver resection. The mean age was 45.8 years. The resections performed included 1 segmentectomy and 5 hemihepatectomies of which one was an extended hemihepatectomy. One patient had a repeat hepatectomy 44 months after the first resection. RESULTS: There were no postoperative deaths or major morbidity. The resectability rate was 75%. Follow-up periods range from 6 to 70 months with a median survival of 31 months following resection. There have been 2 deaths, one died of recurrence in the residual liver at 6 months and one died disease-free from a stroke. Of the remaining 4 patients, 1 has had a further liver resection at 44 months following which she is alive and 'disease-free' at 70 months. The one patient with peritoneal recurrence is alive 49 months after her liver resection with 2 patients remaining disease-free. CONCLUSION: Hepatic resection for breast cancer liver metastases is a safe procedure with low morbidity and mortality.

Late leakage of saline-filled breast prosthesis.

Twenty-four women with breast cancer have had postmastectomy submuscular reconstruction with a valved inflatable prosthetic mammary implant. In four cases (16.6%) spontaneous deflation occurred between seven and 12 months after reconstruction.

Cytogenetic findings in a case of nodular fasciitis of the breast.

We report the cytogenetic findings in a case of nodular fasciitis of the breast. The abnormalities found in all 11 metaphases available for analysis were -2, -2, -13, der(15)t(2;15)(q31;q26), + der(?) t(?;2), + mar1, + mar2. Other consistent abnormalities were also identified. Fluorescence in situ hybridization (FISH) was used to confirm the origin of some of the chromosomes. A large acrocentric chromosome was confirmed to be derived from chromosome 15 with chromosome 2 material translocated onto the q arm. The metacentric der(?)t(?;2) was demonstrated to have part of chromosome 2 on the q arm. No other chromosome 2 material was found. Eight of 11 cells were tetraploid and had two copies of a del(6)(q16q24).

Intramammary sentinel nodes in early breast cancer: can we find them and do they matter?

Intramammary nodes identified using the sentinel node biopsy technique can play an important prognostic role in early breast cancer. Two cases of intramammary nodes found by sentinel node biopsy are discussed from the Guildford perspective.

Hepatic metastases in adenoid cystic carcinoma of the submandibular gland.

We present a case of adenoid cystic carcinoma of the submandibular gland resulting in metastases to the liver, nine years following initial presentation.

Angiosarcoma arising in a patient with Maffucci syndrome.

Maffucci syndrome comprises multiple enchondromas together with cutaneous haemangiomas. Review of the literature shows a 15-20% incidence of sarcomatous change in one or more of the enchondromas. Malignancy arising from the vascular component, however, has only been reported in one case. We present a further case where a patient with Maffucci syndrome presented with multifocal angiosarcoma.

Chondrosarcoma arising in an osteochondroma: an unusual cause of an abdominal mass.

Secondary chondrosarcomas are rare tumours, which can develop in up to 2% of patients with single osteochondromas. The rarity of presentation of these tumours to the general surgeon can lead to difficulty and delay in diagnosis. We describe such a tumour presenting as an abdominal mass and discuss the appropriate investigations necessary to establish the diagnosis and plan subsequent management.