Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation

International audienceAims: To correlate World Health Organization (WHO) grade, patient's outcome and presence of t(11;19) to histological tumor variants in 40 well characterized mucoepidermoid carcinomas (MECs) out of a series of 290 salivary gland carcinomas. Methods and Results: MECs were classified as classical based on the presence of equal proportions of the three cell types or the dominance (≥50%) of mucous cells beside at least one other cell type, and as variant if composed of ≥80% single cell type. Classical MECs were more common (n=23). Variant MECs had predominant squamoid (n=9), eosinophilic (n=5), or clear cell (n=3) morphology. 27 tumors were WHO grade 1, 3 grade 2 and 10 grade 3. The t(11;19) was detected in 82%, 35% and 0% of classical MEC, variant MEC and non-MEC, respectively. Classical MECs were significantly associated with age ≤60 years (p<0.001), grade 1 (p<0.001), and t(11;19) (p=0.003). Short overall survival was significantly associated with age >60 years (p=0.001) and UICC stage >I (p=0.031), residual tumor (p<0.001), tumor grade >1 (p=0.001) and squamoid variant (p=0.002) in Kaplan-Meier analysis. Conclusions: The results underscore the great histological diversity of MEC, the reproducibility of the WHO grading and the value of histological subtypes as an additional prognostic factor

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent

Alternatives to free flap surgery for maxillofacial reconstruction: focus on the submental island flap and the pectoralis major myocutaneous flap

Background Microvascular tissue transfer (MTT) has been established as the gold standard in oral- and maxillofacial reconstruction. However, free flap surgery may be critical in multimorbid elderly patients and after surgery or radiotherapy, which aggravate microsurgery. This study evaluates indications and outcome of the submental island flap (SMIF) and the pectoralis major myocutaneous flap (PMMF) as alternatives to the free radial forearm flap (RFF). Methods This retrospective study included 134 patients who had undergone resection and reconstruction with SMIF, PMMF, or RFF at our department between 2005 and 2020. The level of comorbidity was measured with the Age-adjusted Charlson comorbidity index (ACCI). Primary outcome variables were flap success, complications, wound dehiscence, surgery duration, as well as time at the ICU and the ward (hospitalization). Chi-square tests, t-tests, and ANOVA were performed for statistics. Results 24 SMIFs, 52 RFFs, and 58 PMMFs were included in this study. The flap types did not significantly differ in terms of flap success, complications, and healing disorders. The SMIF presented a success rate of 95.8% and was significantly more often used in elderly patients (mean age = 70.2 years; p < 0.001) with increased comorbidities than the PMMF (p < 0.01) and RFF (p < 0.001). SMIF reconstruction reduced surgery duration (p < 0.001) and time at the ICU (p = 0.009) and the ward (p < 0.001) more than PMMF and RFF reconstructions. PMMF reconstruction was successful in 91.4% of patients and was more frequently used after head and neck surgery (p < 0.001) and radiotherapy (p < 0.001) than SMIF and RFF reconstructions. Patients undergoing PMMF reconstruction more frequently required segmental jaw resection and had presented with advanced tumor stages (both p < 0.001). Nicotine and alcohol abuse was more frequent in the RFF and PMMF groups (both p < 0.001) than in the SMIF group. Conclusions The pedicled SMIF represents a valuable reconstructive option for elderly patients with increased comorbidity because of the shorter duration of surgery and hospitalization. On the other hand, the PMMF serves as a solid backup solution after head and neck surgery or radiotherapy. The rates of flap success, complications, and healing disorders of both pedicled flaps are comparable to those of free flap reconstruction

The Folded Radial Forearm Flap in Lip and Nose Reconstruction—Still a Unique Choice

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness

The Predictive Value of PITX2 DNA Methylation for High-Risk Breast Cancer Therapy: Current Guidelines, Medical Needs, and Challenges

High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the PITX2 (paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application of PITX2 as a predictive biomarker to personalize breast cancer management