[Rythmic-pathology: the French national pathology network for thymic epithelial tumours]. / Rythmic-Pathologie : le groupe français de relecture des tumeurs épithéliales thymiques du réseau clinique Rythmic.

Epithelial thymic tumours are rare and sometimes difficult to classify. Since 2010, the French National Cancer Institute supports a French national network, called Rythmic, devoted to the treatment of these tumours through regional and national multidisciplinary conferences using the web. All the tumours are secondarily reviewed by a French pathology national network for classification and staging. This review focuses on the presentation of the Rythmic network, and mainly to the Pathology review process.

Tracheal glomus tumor: a multidisciplinary approach to management.

A 66-year-old man presented with acute respiratory distress due to a tracheal tumor involving the posterior wall of the upper trachea, with nearly complete airway obstruction. Partial debulking of the tumor's endoluminal component, via rigid bronchoscopy and yttrium-aluminum-perovskite laser, allowed timely and effective airway restoration. The diagnosis was benign tracheal glomus tumor. Two weeks later, elective tracheal sleeve resection with end-to-end anastomosis allowed complete resection of the lesion. No tumor recurrence was found at 21-month follow-up. We describe the multidisciplinary management of this extremely rare tracheal tumor, and review its features.

Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model.

OBJECTIVE: Although aspiration pneumonitis is a severe complication in patients hospitalized in intensive care units, its pathogenesis is poorly understood. The aim of this study was to determine whether the intensity of lung injury and inflammation developing after aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid. DESIGN: In vitro study on human gastric juice and randomized controlled animal study. SETTING: Research laboratories of academic institutions. SUBJECTS: Male New-Zealand white rabbits. INTERVENTIONS: Proinflammatory activity of gastric juice from 17 intensive care unit patients and 12 controls undergoing elective surgery was measured based on a target cell activation assay. Two gastric juices from intensive care unit patients with similar pH but differing for their in vitro proinflammatory activity (high and low) were further instilled into the trachea of ventilated rabbits. Lung function, mechanics, pathology, leukocyte infiltration, and local cytokine levels were measured after 6 hrs. MEASUREMENTS AND MAIN RESULTS: Gastric juice from intensive care unit patients, even buffered at pH 7.4, stimulated human type II-like A549 epithelial cells to up-regulate intercellular adhesion molecule-1 and interleukin-8, significantly more than juice obtained in controls. Gastric juice from an intensive care unit patient supporting high proinflammatory activity in vitro also induced a more severe and persistent drop in PaO2/FIO2 and respiratory system compliance in ventilated rabbits, a worse histologic score, higher lung lavage concentrations of inflammatory cells, interleukin-8 (p < 0.01), and growth-related oncogene-alpha (p < 0.01) than one fluid with low proinflammatory activity. CONCLUSION: Gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high proinflammatory activity is more "toxic" to the lung than one with low proinflammatory activity in a ventilated rabbit model, an effect that is independent of pH and particulate matter content.

High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas.

BACKGROUND: Alterations in HDACs gene expression have been reported in a number of human cancers. No information is available concerning the status of HDACs in pancreatic cancer tumors. The aim of the present study was to evaluate the expression levels of members of class I (HDAC1, 2,, 3), class II (HDAC4, 5, 6, and 7), and class III (SIRT1, 2, 3, 4, 5, and 6) in a set of surgically resected pancreatic tissues. METHODS: Total RNA was isolated from 11 pancreatic adenocarcinomas (PA): stage 0 (n = 1), IB (n = 1), IIB (n = 6), III (n = 1), IV (n = 2), one serous cystadenoma (SC), one intraductal papillary mucinous tumor of the pancreas (IMPN), one complicating chronic pancreatitis (CP), and normal pancreas (NP) obtained during donor liver transplantation. Moreover, six other control pancreatic were included. HDACs gene expression was conducted using quantitative real-time polymerase chain reaction (qPCR). Protein expression levels were analyzed by Western blot and their localization by immunohistochemistry analyses of cancer tissues sections. RESULTS: Remarkably, 9 of the 11 PA (approximately 81%) showed significant increase of HDAC7 mRNA levels. In contrast to PA samples, message for HDAC7 was reduced in CP, SC, and IMPN specimens. The Western blot analysis showed increased expression of HDAC7 protein in 9 out of 11 PA samples, in agreement with the qPCR data. Most of the PA tissue sections examined showed intense labeling in the cytoplasm when reacted against antibodies to HDAC7. CONCLUSION: The data showed alteration of HDACs gene expression in pancreatic cancer. Increased expression of HDAC7 discriminates PA from other pancreatic tumors.

High-frequency percussive ventilation attenuates lung injury in a rabbit model of gastric juice aspiration.

OBJECTIVE: To test the effects of high-frequency percussive ventilation (HFPV) compared with high-frequency oscillatory ventilation (HFOV) and low-volume conventional mechanical ventilation (LVCMV), on lung injury course in a gastric juice aspiration model. DESIGN: Prospective, randomized, controlled, in-vivo animal study. SETTING: University animal research laboratory. SUBJECTS: Forty-three New Zealand rabbits. INTERVENTIONS: Lung injury was induced by intratracheal instillation of human gastric juice in order to achieve profound hypoxaemia (PaO2/FIO2< or =50). Animals were ventilated for 4h after randomization in one of the following four groups: HFPV (median pressure 15cmH2O); LVCMV (VT 6mlkg(-1) and PEEP set to reach 15cmH2O plateau pressure); HFOV (mean pressure 15cmH2O); and a high-volume control group HVCMV (VT 12ml kg(-1) and ZEEP). MEASUREMENTS AND RESULTS: Static respiratory compliance increased after the ventilation period in the HFPV, LVMCV and HFOV groups, in contrast with the HVCMV group. PaO2/FIO2 improved similarly in the HFPV, LVCMV and HFOV groups, and remained lower in the HVCMV group than in the three others. Lung oedema, myeloperoxidase and histological lung injury score were higher in the HVCMV group, but not different among all others. Arterial lactate markedly increased after 4h of ventilation in the HVCMV group, while lower but similar levels were observed in the three other groups. CONCLUSION: HFPV, like HFOV and protective CMV, improves respiratory mechanics and oxygenation, and attenuates lung damage. The HFPV provides attractive lung protection, but further studies should confirm these results before introducing HFPV into the clinical arena.

A rare cause of an endobronchial tumour in children: the role of interventional bronchoscopy in the diagnosis and treatment of tumours while preserving anatomy and lung function.

An 11-year-old girl was referred to our institution with complete obstruction of the left main stem bronchus by an endoluminal mass and was successfully treated by a combination of laser and mechanical debulking. Coring of the mass both allowed histological diagnosis (inflammatory myofibroblastic tumour) and definitive treatment with no recurrence after 3 years of follow-up. This case report emphasizes the major role of interventional bronchoscopy in the management of tumoural obstruction in children in whom benign conditions are frequent. Interventional bronchoscopy, which is minimally invasive when compared to surgery, in the vast majority of cases allows a precise diagnosis as it provides large samples of tissue removed during coring; in some cases it can be curative by itself and preserves lung parenchyma and function.

Pancreatic cancer and pancreaticoduodenectomy in elderly patient: morbidity and mortality are increased. Is it the real life?

BACKGROUND/AIMS: The aim of this study was to compare post-operative outcomes of two groups of patients aged more or less than 70 years old METHODOLOGY: From January 1990 to January 2006, 150 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinomas (PA) were reviewed at the Department of Digestive Surgery of University Hospital. Twenty five patients Group A> or =70 and Group B<70 years old, were well matched for gender, diagnosis, body mass index, American Society of Anesthesiologists (ASA) score, and texture of pancreatic parenchyma. RESULTS: There was no intraoperative death. Mean operative hospital and intensive care unit stays were in Group A, B: 21+/-9; 4.5+/-8 vs. 19+/-7; 3+/-3 NS respectively. There were four deaths in A and no death in B at three months of hospital discharge. More patients had complications in Group A (56% vs 36% NS). Medical complications seem to be more frequent in Group A (40%vs 12% NS). The median survivals were 20 and 27 months for A and B, respectively. CONCLUSION: We observed an increased rate of morbidity and mortality in patients aged more than 70 years.

Hemodynamics in experimental gastric juice induced aspiration pneumonitis.

OBJECTIVE: To characterize hemodynamic changes during experimental aspiration pneumonitis, paying special attention to echocardiographic assessment. DESIGN AND SETTING: Animal study in a university-based research laboratory. SUBJECTS: Fourteen mechanically ventilated New Zealand white rabbits INTERVENTIONS: We instilled 1 ml/kg human gastric juice (mean pH: 4.1+0.2) intratracheally. Hemodynamic and respiratory parameters were measured every hour for 4 h, associated with a transthoracic echocardiography. MEASUREMENTS AND RESULTS: Lung injury occurred within 1 hour with a marked decrease in PaO(2)/FIO(2) and an increase in plateau pressure; after this initial drop the ratio remained stable throughout the experiment. Seven rabbits experienced only a mild to moderate alteration in lung oxygenation function as defined by a PaO(2)/FIO(2) ratio above 200 (group A), while the other seven developed a severe alteration with a ratio below 200 (group B). At the end of the experiment pH and cardiac output were lower in group B than in group A. Using a PaO(2)/FIO(2) threshold value of 150, pH, mean arterial pressure, and cardiac output were lower in the animals with the more severe hypoxemia. Neither left nor right ventricular dysfunction occurred during the experiment, and no animal experienced circulatory failure CONCLUSION: Experimental aspiration pneumonitis after intratracheal infusion of human gastric juice is characterized by a stable fall in PaO(2)/FIO(2). Animals with the most severe lung injury experienced a lower systemic arterial pressure, cardiac output, and metabolic acidosis without circulatory failure or cardiac dysfunction.

[Retroperitoneal non-secreting paraganglioma. Apropos of a case]. / Paragangliome non sécrétant rétropéritonéal. A propos d'une observation.

Paragangliomas are rare tumors arising from extraadrenal chromaffin cells. These tumors are most commonly found in the adrenal gland but other locations are possible. A 79-year-old woman with abdominal pain underwent computed tomography (CT scan). Surgery was indicated because of the increase in the size of the tumor. Histopathological examination revealed a non secreting paraganglioma in the left retroperitoneum. Paragangliomas are rare neuroendocrine tumors. They have a greater potential for malignancy than pheochromocytomas due to metastases or local recurrence making surgical excision the treatment of choice.

Glut-1 intensity and pattern of expression in thymic epithelial tumors are predictive of WHO subtypes.

OBJECTIVES: Glucose-transporter-1 (Glut-1) may be a useful marker for differentiating B3 thymomas and thymic carcinomas. Since the literature is limited, we undertook a study to evaluate its diagnostic value in a series of thymic epithelial tumors. MATERIALS AND METHODS: Glut-1 expression was studied by the group of pathologists linked to the French national oncological network RYTHMIC. Immunostaining was performed on a whole section of one paraffin block in a series of 92 successive surgical specimens. Patterns (focal, zonal, diffuse) and intensity of Glut-1 expression were assessed and compared with WHO histological subtypes. RESULTS: Expression was mainly restricted to epithelial cells. Immature T-lymphocytes were negative. A diffuse, moderate or strong staining was observed in most thymic carcinomas (15/16). In B3 thymomas (10/11) and in B3 thymomas borderline to thymic carcinomas (5/6), a moderate to strong zonal staining was observed at distance from vessels and fibrous septa. This pattern sometimes created the aspect of an anastomosing network in large cellular lobules. In B1 thymomas, immunostaining highlighted foci of medullary differentiation (7/8). B2 thymomas (n=25) were heterogeneous, with a spectrum of patterns ranging between those of B1 and B3 thymomas. Type A thymomas (n=5) mostly presented a weak positivity but one aggressive case showed zonal moderate/strong positivity. Most AB thymomas (15/17) showed weak to moderate immunostaining in spindle cell areas. In micronodular thymomas (n=3), epithelial cells and B-lymphocytes were weakly positive while follicular dendritic cells were strongly highlighted. One metaplastic thymoma displayed diffuse and moderate positivity. CONCLUSION: Glut-1 expression globally depended on histological subtypes and the staining patterns (diffuse or zonal) were different between thymic carcinomas and type B3 thymomas. A comparative study of Glut-1 expression in atypical versus conventional type A thymomas appears warranted. Otherwise, restriction to epithelial cells makes likely a correlation with clinical assessment of glucose uptake in lymphocyte-poor tumors.

Cytology-based treatment decision in primary lung cancer: is it accurate enough?

Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007-2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies.

Recurrent dedifferentiated liposarcoma of mediastinum involving lung and pleura.

We report a case of primary recurrent mediastinal dedifferentiated liposarcoma with unusual long-term survival. A woman who complained of dyspnea showed on imaging features a bulky posterior mediastinal mass which was completely excised and initially misdiagnosed as an angiomyolipoma. She recurred 15 months later and histological examination showed a dedifferentiated liposarcoma. Resection was incomplete and the patient received adjuvant therapy. Eight years later a second recurrence occurred in the right pleura and lung. The patient died three months later.