[When a metastasis hides another]. / Quand une métastase en cache une autre.

Breast cancer is one of the leading causes of death in women. There are many different entities, both morphologically and immuno-histochemically or genomically. Intra-tumour heterogeneity can be defined in time (temporal heterogeneity) and in space (spatial heterogeneity) and is influenced by both internal and external factors, such as genetics, epigenetics, host response, possible treatments or the tumour microenvironment. The detailed analysis of these multiple interactions could help to develop new therapeutic targets.

Le cancer du sein est l'une des premières causes de décès chez les femmes. Il existe de nombreuses entités différentes, tant sur le plan morphologique que sur le plan immuno-histochimique ou encore génomique. L'hétérogénéité intra-tumorale peut être définie dans le temps (hétérogénéité temporelle) et dans l'espace (hétérogénéité spatiale) et influencée par des facteurs tant internes qu'externes tels que la génétique, l'épigénétique, la réponse de l'hôte, les éventuels traitements administrés, ou encore le micro-environnement tumoral. L'analyse approfondie de ces multiples interactions pourrait aider à développer de nouvelles cibles thérapeutiques.

Paracetamol: A Review of Guideline Recommendations.

Musculoskeletal pain conditions are age-related, leading contributors to chronic pain and pain-related disability, which are expected to rise with the rapid global population aging. Current medical treatments provide only partial relief. Furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are effective in young and otherwise healthy individuals but are often contraindicated in elderly and frail patients. As a result of its favorable safety and tolerability record, paracetamol has long been the most common drug for treating pain. Strikingly, recent reports questioned its therapeutic value and safety. This review aims to present guideline recommendations. Paracetamol has been assessed in different conditions and demonstrated therapeutic efficacy on both acute and chronic pain. It is active as a single agent and is additive or synergistic with NSAIDs and opioids, improving their efficacy and safety. However, a lack of significant efficacy and hepatic toxicity have also been reported. Fast dissolving formulations of paracetamol provide superior and more extended pain relief that is similar to intravenous paracetamol. A dose reduction is recommended in patients with liver disease or malnourished. Genotyping may improve efficacy and safety. Within the current trend toward the minimization of opioid analgesia, it is consistently included in multimodal, non-opioid, or opioid-sparing therapies. Paracetamol is being recommended by guidelines as a first or second-line drug for acute pain and chronic pain, especially for patients with limited therapeutic options and for the elderly.

Recurrent cardiac intimal sarcoma misdiagnosed as a myxoma or malignant transformation of a cardiac myxoma?

Cardiac intimal sarcoma is extremely rare and aggressive primary malignant cardiac tumors. Here, we reported the case of a young man initially operated for a tumor of the left atrium, causing a dynamic obstruction of the mitral valve and (mis-)diagnosed as a myxoma at the histopathological analysis. Patient presented a local recurrence at 3 months and was reoperated. Pathology revealed this time the presence of an intimal sarcoma. Patient received adjuvant chemotherapy. Despite a good local control, the 1-year follow-up positron emission tomography scan revealed the presence of a metastasis in the left adrenal gland that was surgically resected. This article aims to highlight the risk of misdiagnosis in case of cardiac tumors, the hypothetical concept of malignant transformation of a cardiac myxoma, the aggressive course of the extremely rare cardiac intimal sarcoma, and the therapeutic modalities available to treat this pathology.

Pancreatic Neuroendocrine Neoplasm Associated with a Familial MAX Deletion.

Most pancreatic neuroendocrine neoplasms (pNEN) occur sporadically but they can also occur as part of multiple endocrine neoplasia type 1 (MEN1). MAX was originally described as an inherited pheochromocytoma-paraganglioma risk gene, but also has recently been implicated in pituitary tumorigenesis. Here we describe the first case of a pNEN associated with an inherited MAX gene deletion in a family with endocrine tumors. The patient was a male carrier of an intragenic exon 3 deletion inherited from his father who had recurrent pheochromocytomas and a macroprolactinoma. The patient underwent screening and hormonal studies but no pheochromocytoma-paraganglioma, pituitary or renal tumors were identified. However, abdominal magnetic resonance imaging (MRI) identified a 1 cm lesion in body of the pancreas. The lesion was hyperintense on T2-weighted signal, and there was hyperfixation of the tumor on 68Ga-DOTANOC PET-CT images. No biochemical evidence of pancreatic hormone excess was identified. Following a guided biopsy, a pathological diagnosis of a low grade pNEN was made and immunohistochemistry showed loss of MAX nuclear staining. Genetic analysis of the tumor tissue indicated copy number neutral loss of heterozygosity consistent with uniparental disomy. This is the first reported case of a MAX deletion associated pNEN and strengthens the argument that MAX may represent an inheritable multiple endocrine neoplasia risk gene. Further analysis of germline and somatic MAX mutations/deletions in large cohorts of unexplained NEN cases could help clarify the potential role of MAX in NEN etiology.

[(18)F]FPRGD2 PET/CT imaging of integrin αvß3 levels in patients with locally advanced rectal carcinoma.

PURPOSE: Our primary objective was to determine if [(18)F]FPRGD2 PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [(18)F]FPRGD2 and [(18)F]FDG uptake, to evaluate the correlation between posttreatment [(18)F]FPRGD2 uptake and tumour microvessel density (MVD) and to determine if [(18)F]FPRGD2 and FDG PET/CT could predict disease-free survival. METHODS: Baseline [(18)F]FPRGD2 and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 ± 8 years) with LARC before starting any therapy. A posttreatment [(18)F]FPRGD2 PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). RESULTS: All LARC showed uptake of both [(18)F]FPRGD2 (SUVmax 5.4 ± 1.5, range 2.7 - 9) and FDG (SUVmax 16.5 ± 8, range 7.1 - 36.5). There was a moderate positive correlation between [(18)F]FPRGD2 and FDG SUVmax (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [(18)F]FPRGD2 SUVmax and the TRG (Spearman's r = -0.37, p = 0.037), and a [(18)F]FPRGD2 SUVmax of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [(18)F]FPRGD2 PET/CT scan the response index, calculated as [(SUVmax1 - SUVmax2)/SUVmax1] × 100 %, was not associated with TRG. Post-treatment [(18)F]FPRGD2 uptake was not correlated with tumour MVD. Neither [(18)F]FPRGD2 nor FDG uptake predicted disease-free survival. CONCLUSION: Baseline [(18)F]FPRGD2 uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the specificity was too low to consider its clinical routine use.

Intrapericardial bronchogenic cyst adherent to the ascending aorta.

Bronchogenic cysts arise from an abnormal budding of the ventral diverticulum of the foregut or the tracheobronchial tree during embryogenesis. Pericardial location of these cysts is very rare. We describe a case of a young asymptomatic woman with an intrapericardial cystic mass compressing the right heart. Because of severe adhesions of the mass to the ascending aorta and to the right coronary artery, these structures were injured during surgical resection requiring the replacement of the ascending aorta and a coronary artery by-pass graft. Only the histopathologic findings provided the final diagnosis.

Consequences of pneumoperitoneum on liver ischemia during laparoscopic portal triad clamping in a swine model.

BACKGROUND: Portal triad clamping (PTC) may be required during laparoscopic liver resection to limit blood loss. The aim of this study was to test in a swine model the hypothesis that during laparoscopic PTC, increased intraperitoneal pressure may alter hepatic vein reverse circulation, inducing a more severe hepatic ischemia compared with PTC performed in laparotomy. METHODS: Fifteen pigs were randomized into three groups: laparoscopy (1 h of pneumoperitoneum at 15 mmHg and 3 h of surveillance), open PTC (1 h PTC through laparotomy and 3 h of reperfusion), and laparoscopic PTC (1 h PTC with 15 mmHg pneumoperitoneum and 3 h of reperfusion). PTC was performed under mesenteric decompression using a veno-venous splenofemoral bypass. Hepatic partial oxygen tension and microcirculatory flow were continuously measured using a Clarke-type electrode and a laser Doppler flow probe, respectively. Liver consequences of PTC was assessed by right atrium serum determination of transaminases, creatinine, bilirubin, INR, and several ischemia/reperfusion parameters, drawn before PTC (T0), before unclamping (T60), and 1 (T120) and 3 h after reperfusion (T240). Histology was performed on T240 liver biopsies. RESULTS: Compared with open PTC, laparoscopic PTC produced a more rapid and more severe decrease in hepatic oxygen tension, indicating a more severe tissular hypoxia, and a more severe decrease in hepatic microcirculatory flow, indicating a decrease in hepatic backflow. At T240, the laparoscopic PTC livers suffered from a higher degree of hepatocellular damage, shown by higher transaminases and increased necrotic index at pathology. CONCLUSIONS: These results indicate that in this pig model, laparoscopic PTC induces a more severe liver ischemia, related to decreased hepatic oxygen content and decreased hepatic backflow. If confirmed by clinical studies, these results may indicate that caution is necessary when performing prolonged PTC during laparoscopic hepatic resection, particularly in cirrhotic or steatotic livers.