Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

A new model outperforming RPA and DS-GPA scores for individualized survival prediction of patients following whole brain irradiation for brain metastasis.

PURPOSE: Survival after whole brain radiation therapy (WBRT) in patients with multiple brain metastases (BM) is currently predicted by group-based scoring systems with limited usability for decision. We aimed to develop a more relevant individualized predictive model than Radiation Therapy Oncology Group - Recursive Partitioning Analysis (RTOG-RPA) and Diagnosis - Specific Graded Prognostic Assessment (DS-GPA) for patients with limited life-expectancy. METHODS: Based on a Discovery cohort of patients undergoing WBRT, multivariable piecewise Cox regression models with time cut-offs at 1 and 3 months were developed to predict overall survival (OS). A final parsimonious model was defined, and an external validation cohort was used to assess its discrimination and calibration at one, six, and 12 months. RESULTS: In the 173-patient Discovery cohort, the majority of patients had primary lung cancer (56%), presence of extracranial disease (ECD) (75%), Eastern Cooperative Oncolgy Group - Performance Status (ECOG-PS) score 1 (41%) and no intracranial hypertension (ICH) (74%). Most patients were classified as the RPA class II (48%). The final piecewise Cox model was based on primary site, age, ECD, ECOG-PS and ICH. An external validation of the model was carried out using a cohort of 79 patients. Individualized survival estimates obtained with this model outperformed the RPA and DS-GPA scores for overall survival prediction at 1-month, 6-months and 12- months in both Discovery and Validation cohorts. A R/Shiny web application was developed to obtain individualized predictions for new patients, providing an easy-to-use tool for clinicians and researchers. CONCLUSION: Our model provides individualized estimates of survival for poor prognosis patients undergoing WBRT, outperforming actual scoring systems.

Psychological and physical impact in women treated for breast cancer: Need for multidisciplinary surveillance and care provision.

PURPOSE: Cancer survivors often experience adverse physical and psychosocial effects. Fear of recurrence is a difficulty very commonly reported in post-cancer life. The primary objective of this study was to describe post-cancer supportive care needs in patients treated for breast cancer. PATIENTS AND METHODS: In this monocentric observational study, cancer survivors aged≥18years, diagnosed with breast cancer and treated in 2017 (cohort A) and in 2015 (cohort B) were administered a post-cancer needs questionnaire, and the Fear of Cancer Recurrence Inventory (severity subscale). RESULTS: The study included 139 patients. Pain (51.9%), fatigue (51.9%), weight gain during treatment (35.1%), psychological difficulties (20.5%), and difficulties in marriage and sexual life (13.1%) were the complaints in the post-cancer period. There were no differences between the two cohorts. The severity subscale of the Fear of Cancer Recurrence Inventory showed 35.8% patients with a score>13. The fear of recurrence was a source of social difficulties, psychological disorders, and difficulties in marriage and sexual life. CONCLUSIONS: Not only FCR, but also issues such as fatigue, pain, psychological difficulties, and difficulties in marriage and sexual life all call for a psycho-oncological follow-up. Clinical and radio-senological surveillance is essential, but it absolutely must be accompanied by a multidisciplinary follow-up, with central importance to psychological care.

[Extracting a foreign body from the nasal fossa without an ENT specialist]. / Extraction d'un corps étranger de la fosse nasale sans recours au spécialiste.

Foreign bodies in the nasal fossa are frequent and generally occur in children. In developing countries, access to an ENT specialist can be difficult or impossible. The authors describe several extraction techniques with special emphasis on those best suited to areas with limited access to specialist facilities. Using illustrations, a step-by-step description of the so-called "hook" technique is given. This simple technique allows successful removal of a foreign body from the nasal fossa in almost all cases.

[Venous malformations of the parotid in adults. Report of two cases and review of the literature]. / Les malformations veineuses de la parotide chez l'adulte. A propos de deux cas et revue de la littérature.

Parotid vascular malformation in the adult is a very rare and benign tumor; only 47 cases were described in the world literature. This vascular malformation, mostly of venous origin is, on the opposite of the clinical, histological and evolution features of parotid hemangiomas in children, which are more frequent. Some clinical and radiological elements are pathognomonic allowing preoperative diagnosis. We present 2 cases of intraparotid venous malformation in adults, and based on an exhaustive study of the world literature discuss frequency, diagnosis and treatment of this disease.

[Evaluation of transcutaneous electrostimulation in the management of post-tonsillectomy pain in adults]. / Evaluation de l'électrostimulation transcutanée dans la prise en charge des douleurs post-amygdalectomie chez l'adulte.

Transcutaneous electrical nerve stimulation (TENS), has been known for many years, especially in neurosurgery for the treatment of chronic pain syndromes. The authors report the results of the use of this technique in 45 adults feeling acute pain after tonsillectomy. Spontaneous pain and odynophagia were both studied. TENS was effective in 40 out of 45 patients, with full control or significant decrease of the pain. This harmless treatment appears to be attractive and needs larger studies.

[Mucocutaneous leishmaniasis in otorhinolaryngology]. / La leishmaniose cutanéo-muqueuse en ORL.

The authors present a case of mucocutaneous Leishmaniasis of the nose in a patient originally from French Guiana and review the characteristics of this parasitic disease and its importance in the differential diagnosis of lethal midline granuloma. Beyond the exotic pathology of this case, the review of the literature indicates that with the present extension of concomitant leishmaniasis and Hids, authentic autochtonal leishmaniasis may be responsible for otolaryngologic manifestations. The increased prevalence of leishmaniasis associated with AIDS, as well as the presence of mucosal lesions, seems to be underestimated.

Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion.

Oxygenated free-radicals appear to play a prominent role in mediating damage associated with gastrointestinal diseases. Production of reactive oxygen metabolites in ischemia-reperfusion involves oxidases found in resident phagocytic cells and microvascular and mucosal epithelial cells. Platelet activating factor (PAF), a phospholipid associated with inflammatory disorders, has been shown to both prime and amplify the release of superoxide anion and hydrogen peroxide from polymorphonuclear neutrophils and macrophages stimulated by FMLP or PMA. To further elucidate the involvement of free radicals in intestinal damage and the potential role of PAF in their production, we examined the effect of superoxide dismutase (SOD) and BN 52021 (ginkgolide B) on ischemia-reperfusion induced damage in the small intestine. The study involved 32 Sprague-Dawley rats (100-200 g) divided into four groups. Three of these groups were subjected to occlusion of the mesenteric artery 30 mins followed by 24 h reperfusion. On 2 groups SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) were administered 45 mins before arterial occlusion. Following the 24 h reperfusion, the rats were sacrificed after overnight fasting. The jejunum and ileon were removed and fixed for morphological examination. Lesions in the small intestine were quantified. The results showed extensive necrosis, hemorrhage, oedema and neutrophil invasion in the jejunal and ileal mucosa. This injury was significantly reduced by SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) pretreatment. In conclusion, free-oxygenated radicals appear to mediate reperfusion damage in the small intestine and PAF appears to be involved in the genesis of these toxic products. Thus, SOD and BN 52021 may be considered as protectors against ischemic disorders.

[Involvement of arterial vessels in the blood supply to adenomas of the human pituitary, functional implications]. / La participation de vaisseaux artériels à l'irrigation sanguine des adénomes de l'hypophyse humaine, implications fonctionnelles.

Among 190 human pituitary adenomas investigated, 140 contained arterial blood vessels (nearly 75 percent). In 160 adenomas (PRL-, GH-secreting or nonfunctioning tumors) arterial vessels were present in 80 to 90 percent of the cases, whereas in 30 corticotropic adenomas (Cushing's disease), 5 only contained arterial vessels. According to data of the literature and to our own findings, such vessels should originate from the anterior pituitary itself or from the surrounding structures (trabecular, interlobar, capsular arteries). This arterial blood supply could appear even at the microadenoma stage and increase as the tumor growths. Consequently, the blood from portal origin will be diluted or excluded, so that tumor cells would escape from hypothalamic control.