Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG).

INTRODUCTION: Since 2010, the network of rare malignant tumors of the ovary (TMRG) was developed to optimize the management of patients, also allowing a histological second opinion of rare ovarian tumors. The aim of this work was to study the contribution of second opinion to improve histological diagnostic accuracy on ovarian rare malignant tumors included in the TMRG database. MATERIAL AND METHODS: Histological data of patients diagnosed with a rare ovarian tumor included in TMRG network over a one-year period (2018) were collected. Initial diagnoses were compared with second opinion from national gynecological pathologist experts. The modalities of histological second opinion requests were studied, as well as the histological characteristics of the tumors. The discordances were classified as minor (if the modification of histological diagnosis did not change patient management) and major (if the patient management can be modified). RESULTS: Of 1185 included patients, 937 matched the inclusion criteria. Full concordance between primary diagnosis and expert second opinion was reached in 611 cases (65,3%), minor discordance was seen in 114 (12,2%) and major discordance in 209 (22,3%) of cases. In systematic review requested by the network, 26% (n = 137) of cases were reported with a change in histological diagnosis, while the change concerned 44% (n = 186) of cases for a second opinion spontaneously requested by the initial pathologist. The discrepancies concerned all categories of ovarian tumors, with a majority of mucinous tumors (43% of major discordances), followed by stromal and sex-cord tumors (13.8% of major discordances) and clear cell tumors (12,4% of major discordances). CONCLUSION: This analysis confirms the diagnostic difficulty of ovarian tumors, due to their rarity and morphological heterogeneity. French pathologists are aware of these difficulties and spontaneously refer ovarian tumors with unusual histology for a second opinion and collaborate with rare tumor networks for systematic review.

Networking for ovarian rare tumors: a significant breakthrough improving disease management.

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.

Unexpectedly long half-life of metformin elimination in cases of metformin accumulation.

INTRODUCTION: In a study of the oral administration of a single dose of metformin to healthy participants, the estimated half-life (t½ ) for the elimination of the drug from erythrocytes was found to be 23.4 h (compared with 2.7 h for metformin in plasma). However, these pharmacokinetic indices have not been well defined in metformin accumulation. METHODS: We systematically reviewed all the data on plasma and erythrocyte metformin assays available in our centre. We then selected patients with a plasma metformin concentration ≥ 5 mg/l and in whom the metformin concentration had been remeasured once or more at least 5 days after admission. RESULTS: Twelve patients met the aforementioned criteria. All but one of these patients displayed generally severe lactic acidosis on admission (mean ± sd pH and lactate: 6.88 ± 0.35 and 14.8 ± 6.56 mmol/l, respectively) and 11 were treated with dialysis. The mean ± sd time interval between the first and last blood sample collections for metformin measurement was 8.3 ± 3.2 days (range 5-14 days). Five days after the first sample had been collected, metformin was still detectable in plasma and in erythrocytes in all patients. Metformin remained detectable for up to 13 days (both in plasma and in erythrocytes). The estimated mean terminal t½ for metformin in plasma and erythrocytes was 51.9 and 43.4 h, respectively. CONCLUSIONS: The prolonged elimination of accumulated metformin (even after dialysis therapy) challenges the traditional view that the drug clears rapidly because of a short half-life in plasma.

Magnetic resonance imaging and computed tomography in the assessment of mandibular invasion by squamous cell carcinoma of the oral cavity. Influence on surgical management and post-operative course.

INTRODUCTION: Preoperative evaluation of the bone for invasion by oral cavity squamous cell carcinoma remains challenging. The aim of our study was to compare the accuracy of MRI and CT in detecting mandibular invasion by oral squamous cell carcinoma of the oral cavity, with histologic results as the reference standard, and to assess the influence on surgical management and post-operative course. PATIENTS AND METHODS: Patients who were clinically suspected of having bone invasion from oral cavity carcinoma were retrospectively included. A single senior radiologist reviewed MRI images and CT-scans, independently, for the presence or absence of mandibular invasion. The different surgical procedures were compared in terms of length of hospital stay and occurrence of surgical complications. RESULTS: Histological mandibular invasion occurred in 9 of 35 patients (25.7%). None of the preoperative imaging tests failed to detect bone invasion which resulted in a sensitivity of 100% for both MRI and CT. CT had slightly higher specificity than MRI (61.9% and 57.1% respectively) in predicting bone invasion, but no statistically significant difference was found (P=0.32). Specificity of CT and MRI was higher in the edentulous group (75% and 625% respectively) than in the dentate group (53.8% both), although no statistically significant difference was found. The length of hospital stay was increased in the segmental resection group (25±14.5 days) compared to the marginal resection group (13±4.6 days; P=0.004) and to the hemimandibulectomy group (15±7.2 days; P=0.014). Occurrence of post-operative complications, across all categories, was increased in the segmental resection group (70%, n=7/10; P=0.006) compared to the marginal resection group (8.3%, n=1/12) and to the hemimandibulectomy group (23.1%, n=3/13; P=0.04). CONCLUSION: MRI and CT being equivalent in detecting mandibular invasion, we suggest MRI as single imaging technique in the preoperative assessment of oral cavity SCC. Specificity could be increased if combined with PET/CT, in order to reduce the number of unnecessary mandibular interruptions.