Sites of Failure in Breast Cancer Patients with Extracapsular Invasion of Axillary Lymph Node Metastases: No Need for Axillary Irradiation?!

Background and Purpose:: Extracapsular spread (ECS) is frequent, but the specific sites of relapse are seldom given in the literature. In this study it was evaluated, if ECS might be an indicator for axillary irradiation. Patients and Methods:: After a retrospective review of pathology reports, the information about ECS was available in 254 lymph node-positive patients: ECS was absent in 34% (ECS-negative; n = 87) and present in 66% (ECS-positive; n = 167). All patients were irradiated locally, 78 patients got periclavicular and 74 axillary irradiation (median total dose: 50.4 Gy). 240/254 patients (94.5%) received systemic treatment/s. Mean follow-up was 46 months. Results:: The regional relapse rate was 4.6% without ECS versus 9.6% with ECS. The 5-year axillary relapse-free survival was 100% in ECS-negative and 90% in ECS-positive patients (p = 0.01), whereas corresponding values for periclavicular relapse-free survival (with ECS: 91% ± 4%; without ECS: 94% ± 3%; p = 0.77) and local relapse-free survival (with ECS: 86% ± 4%; without ECS: 91% ± 3%; p = 0.69) were not significantly different. χ2-tests revealed a high correlation of ECS with T-stage, number of positive lymph nodes and progesterone receptor status, comparisons with estrogen receptor, grade, or age were not significant. In multivariate analysis number of positive lymph nodes was solely significant for regional failure. Dividing the patients into those with one to three and those with four or more positive lymph nodes, ECS lost its significance for axillary failure. Conclusion:: ECS was accompanied by an enhanced axillary failure rate in univariate analysis, which was no longer true after adjusting for the number of positive lymph node

Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases.

BACKGROUND Breast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50. METHODS RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours. RESULTS All four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences. CONCLUSIONS RISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences

Expression profiling with RNA from formalin-fixed, paraffin-embedded material

<p>Abstract</p> <p>Background</p> <p>Molecular characterization of breast and other cancers by gene expression profiling has corroborated existing classifications and revealed novel subtypes. Most profiling studies are based on fresh frozen (FF) tumor material which is available only for a limited number of samples while thousands of tumor samples exist as formalin-fixed, paraffin-embedded (FFPE) blocks. Unfortunately, RNA derived of FFPE material is fragmented and chemically modified impairing expression measurements by standard procedures. Robust protocols for isolation of RNA from FFPE material suitable for stable and reproducible measurement of gene expression (e.g. by quantitative reverse transcriptase PCR, QPCR) remain a major challenge.</p> <p>Results</p> <p>We present a simple procedure for RNA isolation from FFPE material of diagnostic samples. The RNA is suitable for expression measurement by QPCR when used in combination with an optimized cDNA synthesis protocol and TaqMan assays specific for short amplicons. The FFPE derived RNA was compared to intact RNA isolated from the same tumors. Preliminary scores were computed from genes related to the ER response, HER2 signaling and proliferation. Correlation coefficients between intact and partially fragmented RNA from FFPE material were 0.83 to 0.97.</p> <p>Conclusion</p> <p>We developed a simple and robust method for isolating RNA from FFPE material. The RNA can be used for gene expression profiling. Expression measurements from several genes can be combined to robust scores representing the hormonal or the proliferation status of the tumor.</p

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months

A randomized controlled clinical and histopathological trial comparing excisional biopsies of oral fibrous hyperplasias using CO2 and Er:YAG laser

This study was conducted in order to compare clinical and histopathological outcomes for excisional biopsies when using pulsed CO laser versus Er:YAG laser. Patients (n = 32) with a fibrous hyperplasia in the buccal mucosa were randomly allocated to the CO (140 Hz, 400 μs, 33 mJ) or the Er:YAG laser (35 Hz, 297 μs, 200 mJ) group. The duration of excision, intraoperative bleeding and methods to stop the bleeding, postoperative pain (VAS; ranging 0-100), the use of analgesics, and the width of the thermal damage zone (μm) were recorded and compared between the two groups. The median duration of the intervention was 209 s, and there was no significant difference between the two methods. Intraoperative bleeding occurred in 100% of the excisions with Er:YAG and 56% with CO laser (p = 0.007). The median thermal damage zone was 74.9 μm for CO and 34.0 μm for Er:YAG laser (p < 0.0001). The median VAS score on the evening after surgery was 5 for the CO laser and 3 for the Er:YAG group. To excise oral soft tissue lesions, CO and Er:YAG lasers are both valuable tools with a short time of intervention and postoperative low pain. More bleeding occurs with the Er:YAG than CO laser, but the lower thermal effect of Er:YAG laser seems advantageous for histopathological evaluation

In einer Stomatologiesprechstunde diagnostizierte Mundschleimhautveränderungen. Eine Untersuchung klinisch-histopathologischer Befunde aus dem Jahre 2003

During 2003, a total of 258 new patients with oral soft tissue lesions were admitted at the Stomatology Service of the Department of Oral Surgery and Stomatology at the University of Berne. For the present study, 185 patients with clinically and histopathologically verified diagnoses were included. The following data was collected: prevalence of oral mucosal lesions, distribution of benign, precancerous and malign lesions in different age groups, and the concordance of the referral with the working diagnosis at the Stomatology Service. The most frequent pathological soft tissue findings were fibrous hyperplasias (n = 44) and oral lichen planus (n = 30). Precancerous lesions were present in 41 cases (30 patients with oral lichen planus, eleven oral leukoplakias), and ten patients had oral malignomas. Most lesions were found in patients between the age of 40 and 60 years. The referral diagnosis concurred in 36.6% (n = 67) of the cases with the definite diagnosis before initiation of treatment, the working diagnosis in 70% (n = 128) of the cases. Therefore, it can be concluded that a specialised Stomatology Service serves as a center of competence due to large numbers of patients/cases seen and treated, and the resulting high level of clinical experience of the staff. Moreover, it is important in the primary diagnosis of oral squamous cell carcinoma, in collaboration with the referring dentist in private practice.Im Verlauf des Jahres 2003 wurden 258 Patienten mit Mundschleimhautveränderungen in der Stomatologiesprechstunde der Klinik für Oralchirurgie und Stomatologie der Universität Bern aufgenommen. Für die vorliegende Untersuchung wurden bei 185 Patienten, bei denen die Diagnose klinisch und histopathologisch abgesichert wurde, folgende Daten erhoben: Prävalenz der oralen Mukosaläsionen, Häufigkeitsverteilung von benignen Veränderungen, Präkanzerosen und Malignomen nach Altersgruppen und die Übereinstimmung der Zuweisungs- mit der Arbeitsdiagnose in der Stomatologiesprechstunde. Die häufi gsten Schleimhautpathologien waren fibröse Hyperplasien (n = 44) und der orale Lichen planus (n = 30). Insgesamt wurden 41 Präkanzerosen (30 Patienten mit einem oralen Lichen planus, elf orale Leukoplakien) und zehn Malignome diagnostiziert. Die meisten stomatologischen Veränderungen wurden bei Patienten im Alter zwischen 40 und 60 Jahren vorgefunden. Die Zuweisungsdiagnosen stimmten in 36,6% (n = 67), die Arbeitsdiagnosen in 70% (n = 128) der Fälle mit der definitiven Diagnose vor Therapiebeginn überein. Es kann somit festgehalten werden, dass eine spezialisierte Stomatologiesprechstunde durch grosse Fall-/Patientenzahlen und damit einhergehender hoher klinischer Erfahrung der Behandler bei der Primärdiagnose des Mundhöhlenkarzinoms in Zusammenarbeit mit den zuweisenden Kollegen in der Privatpraxis eine wichtige Rolle einnimmt

[Intraoral lipoma in the region of the mental nerve--report of a case and review of the literature]

The intraoral lipoma is a benign, slowly growing, painless soft tissue neoplasia, which can cause esthetic or functional problems for the patient, depending on its size. All parts of the body can be affected, whereas the oral cavity is rarely involved. Clinically, the tumour often exhibits an exophytic growth pattern, a soft consistency, a broad base connected to the underlying tissue, and frequently has a reddish-yellowish colour. Instead of a superficial mucosal involvement, a deep localization in the soft tissues is also possible. Depending on the localization of the tumour, the diagnosis and the resulting therapy can turn out to be a challenge for the clinician. A clear differentiation to malign neoplasias of the fat tissues and other soft tissue expansions is essential. The following case report presents a female patient who is affected by a lipoma in the proximity of the mental nerve. The diagnostic work-up and resulting therapy including a review of the current literature are presented and discussed

Inverted ductal papilloma

Benign papillary lesions originating from the ductal epithelium of the minor salivary glands of the oral cavity include intraductal papilloma, inverted ductal papilloma (IDP) and sialadenoma papilliferum

Loss of pulp sensitivity and pain as the first symptoms of a Ewing's sarcoma in the right maxillary sinus and alveolar process: report of a case

This case report describes the diagnosis and treatment of a Ewing's sarcoma in the right maxillary sinus and alveolar bone of a 19-year-old female patient. The first clinical symptoms were a loss of sensitivity of the premolars and first molar in the right maxilla and acute pain located in the area of these teeth. Initially, the referring dentist had treated these findings as an acute apical periodontitis with root canal medication. Because swellings on the palatal and buccal aspects of the teeth occurred and could not be treated with incision and drainage, the dentist referred the patient. Cone-beam computed tomography revealed a proliferation of soft tissue in the right maxillary sinus, with a radiopaque material at the tip of the mesiobuccal root of the first molar and resorptive signs of the mesiobuccal and distobuccal roots of the first molar. The palatal cortical bone of the right alveolar process seemed to be intact. After explorative surgery with biopsies from the buccal, palatal, and sinus proliferation areas, the pathologist diagnosed the lesion as a Ewing's sarcoma. Treatment of the patient consisted of initial chemotherapy, hemimaxillectomy, and postsurgical chemoradiotherapy