[Malformations of the anterior chest wall]. / Malformations de la paroi thoracique antérieure.

INTRODUCTION: Pectus excavatum or funnel chest is the most common anterior chest wall deformity seen in children and adults. The sternal depression appears to be caused by overgrowth of the costal cartilages, also the cause of the less common deformities: pectus carinatum (pigeon breast) and pectus arcuatum. BACKGROUND: Usually the overgrowth involves the third to seventh costal cartilages but it can be more or less extensive. The cardiopulmonary functional consequences are insignificant in the protrusional deformities and inconsistent in pectus excavatum and the indications for surgery are mainly cosmetic. VIEWPOINT AND CONCLUSIONS: The procedural modalities are guided by morphological study of the CT scan. We describe a surgical technique that comprise subperichondrial excision of all deformed costal cartilages followed by transverse sternotomy to correct the sternal deformity, anteriorly in the case of pectus excavatum and posteriorly for pectus carinatum and arcuatum. As the perichondrial sheaths are totally preserved they are sutured in continuous layers to give a shortening effect. In the case of pectus excavatum the sternum is then secured anteriorly for about 6 months by a retrosternal metallic strut in an overcorrected position. The partially resected seventh cartilages are then sutured to the xiphoid. Other surgical techniques are described, including modified Ravitch's procedure, modelling osteochondroplasty, prosthetic reconstruction and Nuss's procedure. Results of the more important series are reported and discussed.

Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer.

Proteases contribute to tumor invasion and metastasis via their potential to degrade basement membranes and extracellular matrix. Our aim was to compare the level of several proteases: urokinase-type plasminogen activator (u-PA), matrix metalloproteinase 2 (MMP-2; 72-kDa type IV collagenase, also known as gelatinase A), MMP-11 [also known as stromelysin 3 (STR3)], and cathepsins B and L in resected non-small cell lung cancer. Between June 1996 and March 1998, samples of lung tumor tissues were taken from 119 surgically treated patients. Thirty out of the 119 tumor samples were matched with corresponding adjacent normal tissue. u-PA was measured by a commercially available immunoluminometric assay. Metalloproteinases and cathepsins have been evaluated at the RNA level by Northern blot and quantified with a PhosphorImager. Expression of these proteases was compared to the following clinicopathological parameters: pathological diagnosis, tumor size, exposure to asbestos, radiotherapy, neo-adjuvant chemotherapy, tumor-node-metastasis stage, lymph node involvement, presence of metastasis. u-PA, MMP-2, MMP-11/STR3, and cathepsin B were significantly increased in tumor (the tumor:normal ratio was on average increased by 5.4-, 2.2-, 83.5-, and 2.2-fold, respectively). The tumor:normal ratio of MMP-11/ STR3 was found to be significantly linked to the lymph node involvement (P < 0.05). Our results suggest that several proteases are involved in the invasive potential of non-small cell lung cancer and that the quantification of MMP-11/ STR3 could represent an useful prognostic marker.

Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer.

The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor, a potent mitogen for epithelial cells that also promotes cell motility and invasiveness. We have studied the changes of c-met gene expression that occur during the progression of colorectal tumors. Sixteen adenomas, 123 primitive carcinomas, and 25 liver metastases were examined. In several instances it was possible to compare same-patient samples of normal colon mucosa against primary tumor and primary carcinoma against synchronous metastasis. The expression of the c-met gene was increased from 5- to 50-fold in about 50% of tumors, at any stage of progression, and in 70% of liver metastases. Overexpression was associated with amplification of the c-met gene in only 10% of carcinomas, but in 8 of 9 metastases examined. These data suggest that overexpression of the c-met oncogene contributes a selective growth advantage to neoplastic colorectal cells at any stage of tumor progression. Moreover, amplification appears to give a further selective advantage for the acquisition of metastatic potential.

Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal carcinoma: implications for prognosis.

Molecular markers can improve staging and predict aggressive clinical behavior in esophageal cancer, thus helping to define appropriate therapeutic protocols and to identify patients who will benefit from surgery. We therefore characterized, by Northern blot and/or immunohistochemistry, the relative expression of three effectors involved in the invasion, angiogenesis, and dissemination of tumor cells in esophageal cancer versus nontumoral mucosae: (a) stromelysin-3 (ST3), a member of the metalloproteinase family; (b) basement membrane 40/secreted protein acidic and rich in cysteine (BM-40/SPARC), an extracellular matrix-associated protein involved in angiogenesis; and (c) the hepatocyte growth factor receptor MET, which triggers the scattering of epithelial cells. Results were analyzed in relation to clinicopathological parameters (cpTNE) including tumor size (T), lymph node status (N), periesophageal tissue invasion (E), disease recurrence, and overall survival. The ST3, BM-40/SPARC, and MET genes were found to be overexpressed in tumor samples compared to control mucosa. BM-40/SPARC and MET mRNA levels were not linked to any one of the cpTNE, indicating that this overexpression occurs at an early stage of neoplastic progression. In contrast, ST3 expression, identified by immunohistochemistry in fibroblastic cells surrounding neoplastic islets, correlated with tumor size and periesophageal tissue invasion. Of the 36 patients studied, those with high ST3 levels had shorter disease-free survival than those with low levels, but there was no relationship between the cpTNE and disease recurrence or survival. Our study demonstrates that ST3, BM-40/SPARC, and MET are involved in different steps of esophageal carcinogenesis and that ST3 overexpression is a marker of aggressive clinical behavior. We conclude that in esophageal cancer, ST3 might help to assess survival and the risk of recurrence after surgical resection.

Morphologic characterization of isolated bovine early preantral follicles during short-term individual in vitro culture.

To provide new insights in the molecular mechanism controlling preantral follicular development and to unravel the needs to support in vitro follicular development of early-stage preantral follicles (PAFs), there is a need for alternative in vitro bovine follicle culture methods. In this study, we aimed to characterize follicular dynamics using an IVC system of isolated and individually cultured bovine early PAFs during 10 days to generate individual follicle follow-up data. Preantral follicles (<50 µm) were isolated from slaughterhouse ovaries and cultured individually for 10 days. Individual follicle morphology, growth, survival, quality, and cell proliferation were evaluated in time by combining noninvasive and invasive assessment methods. The PAFs were light microscopically evaluated during culture to assess follicular dynamics, stained with neutral red to determine follicle viability, stained with 4',6-diamidino-2-phenylindole and terminal deoxynucleotidyl transferase dUTP nick end labeling to evaluate cell proliferation and follicle quality, and processed for histologic evaluation to assess follicle morphology. On the basis of their morphology, follicles were subdivided in three categories, with category 1 follicles showing the best morphologic features. On Day 0, only category 1 follicles were selected, but follicle categories were reassigned on evaluation Days 1, 2, 4, 7, or 10. Although 67% of the follicles survived 10 days of IVC, the number of follicles exhibiting a normal morphology decreased significantly from Day 7 onward and the apoptotic index increased significantly from Day 10. Both category 1 and 2 follicles showed a significant increase in follicular diameter (Day 10: 21.80 ± 0.86 and 11.82 ± 0.80, respectively). This increase in follicular diameter showed to be correlated with an increase in the total cell number. In conclusion, this culture system showed to support follicular development until Day 10, although the proportion of follicles showing normal morphologic features and the follicular quality decreased after 10 days of IVC. Follicles maintaining their category 1 morphologic features over time seem to be of a better quality and show a higher developmental competence as compared to category 2 and 3 follicles.

Necrosis- and apoptosis-related Met cleavages have divergent functional consequences.

Upon activation by its ligand hepatocyte growth factor/scatter factor, the receptor tyrosine kinase Met promotes survival, proliferation, and migration of epithelial cells during embryogenesis. Deregulated Met signaling can also promote cancer progression and metastasis. Met belongs to the functional family of dependence receptors whose activity switches from pro-survival to pro-apoptotic during apoptosis upon caspase cleavage. Although apoptosis resistance is a hallmark of cancer cells, some remain sensitive to other cell death processes, including necrosis induced by calcium stress. The role and fate of Met during necrotic cell death are unknown. Following treatment with calcium ionophores, cell lines and primary cells undergo necrosis, and the full-length Met receptor is efficiently degraded. This degradation is achieved by double cleavage of Met in its extracellular domain by a metalloprotease of the A disintegrin and metalloproteinase (ADAM) family and in its intracellular domain by calpains (calcium-dependent proteases). These cleavages separate the Met extracellular region from its kinase domain, thus preventing Met activity and its potential pro-survival activity. Although the intracellular fragment is very similar to the fragment generated by caspases, it displays no pro-apoptotic property, likely because of the presence of the last few amino acids of Met, known to inhibit this pro-apoptotic function. The fragments identified here are observed in lung tumors overexpressing the Met receptor, along with fragments previously identified, suggesting that proteolytic cleavages of Met are involved in its degradation in tumor tissues. Thus, Met is a modulator of necrosis, able to protect cells when activated by its ligand but efficiently degraded by proteolysis when this process is engaged.

Extinction-ratio-independent method for chirp measurements of Mach-Zehnder modulators.

The authors describe a general method to extract the frequency chirping of Mach-Zehnder modulators based on direct measurements of the output spectrum. This method is independent of the modulator extinction ratio and allows measurement of the intrinsic chirp parameter to an accuracy of 5%.

Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas.

Lung adenocarcinomas are heterogeneous clinically and histologically. Expression of the mucin genes was analyzed as a molecular marker of glandular cytodifferentiation in primary lung adenocarcinomas. Expression was correlated with histopathologic subtypes of World Health Organization classification with the aim of investigating the histogenesis of primary lung adenocarcinomas. Thirty-four primary lung adenocarcinomas were examined by in situ hybridization for mucin gene expression (MUC1-4, MUC5AC, MUC5B, MUC6-7) and by immunohistochemistry for MUC5AC and MUC5B apomucin expression. Mucinous bronchioloalveolar carcinoma (BAC) had a homogeneous pattern of mucin gene expression different from those of other types of lung adenocarcinoma, involving secreted mucins (MUC5AC, MUC5B, and MUC6) and membrane-bound mucins (MUC1, MUC3, and MUC4). Non-BAC adenocarcinoma and mucinous BAC aberrantly expressed mucin genes MUC3, and MUC3 and MUC6, respectively, which are undetectable in normal fetal and adult lung. Our results show the particular phenotype of mucin gene expression in mucinous type of BACs and the heterogeneous expression of respiratory and nonrespiratory mucins in the other types. This finding supports the theory of a common progenitor cell with the potential of multicellular differentiation. From a practical point of view, the aberrant expression of MUC3 and MUC6 could serve as a diagnostic marker in the management of the mucinous type of bronchioloalveolar carcinomas. HUM PATHOL 32:274-281.

Arterial embolization for bleeding pseudocysts complicating chronic pancreatitis.

OBJECTIVES: To evaluate the efficacy of arterial embolization (EMB) in the management of bleeding pancreatic pseudocysts or pseudoaneurysms and to assess the possible indication for secondary surgery. DESIGN: Retrospective review with a mean follow-up of 60 months (range, 18-125 months). SETTING: Tertiary care center, university hospital. PATIENTS: The medical records of 14 patients who were referred to the hospital with bleeding pancreatic pseudocysts and/or pseudoaneurysms related to chronic pancreatitis, between 1983 and 1994, were reviewed. The clinical presentation was major bleeding in 10 patients (gastrointestinal or intraperitoneal) and chronic signs in 4. INTERVENTION: Celiac and superior mesenteric angiography with EMB attempt in all patients. MAIN OUTCOME MEASURES: The immediate effect on bleeding and the long-term safety of arterial EMB. RESULTS: Embolization failed in 3 patients and surgery was needed (1 patient died). Embolization was successful in 11 patients, but 2 complications occurred (duodenal necrosis and aortic thrombosis) (1 patient died). Among the 10 patients whose bleeding stopped, an intentional pancreatectomy was performed 4 times (all patients are alive). The 6 other patients did not undergo a further pancreatic operation due to unfavorable local or general condition. None of them had recurrent bleeding, 3 of them died later of extrapancreatic diseases. Overall, early mortality was 14%, with deaths occurring only in unsuccessful or complicated EMB cases. CONCLUSIONS: The immediate effectiveness of arterial EMB is undeniable but depends on the expertise of the radiologist. When EMB is successful, further surgery should be reserved for patients in good general condition who have other complications of chronic pancreatitis that are not amenable to minimally invasive techniques.

Retroperitoneal approach and endoscopic management of peripancreatic necrosis collections.

OBJECTIVE: To review the results of the different modalities of treatment of acute necrotizing pancreatitis that have been used by a single team during a 6-year period to assess the technique and indications of an endoscopic method of retroperitoneal drainage that is routinely performed for the management of peripancreatic necrosis. DESIGN AND SETTING: Retrospective study of 53 patients in a tertiary care center. RESULTS: All patients had signs of peripancreatic necrosis on initial computed tomography scan, 20 patients experienced organ failure during the first 7 days of the disease, and bacterial contamination was proved in 22 (56%) of 39 samples of peripancreatic necrosis. Methods of treatment included supportive therapy alone (group 1), percutaneous drainage (group 2), endoscopic retroperitoneal drainage (group 3), and laparotomy and transperitoneal drainage (group 4). Mortality and mean hospital stay were as follows: group 1, 0% and 23 days; group 2, 20% and 89 days; group 3, 10% and 62 days; and group 4, 33% and 86 days. Percutaneous drainage was beneficial in only 3 cases of sterile collection. Two local complications were related to the method of endoscopic drainage. Primary laparotomy was not routinely performed except in patients with an intraperitoneal complication. Overall mortality was 13.2%; mortality was significantly higher in patients with an infected necrosis (32%). CONCLUSIONS: The use of endoscopic retroperitoneal drainage seemed to be a significant factor in the observed improvement by providing a reliable drainage of the peripancreatic areas and avoiding the opening of the peritoneal cavity. This surgical approach is not exclusive and may be combined with a secondary laparotomy when needed. The preferred indications of this method are heterogeneous collections of necrosis with bacterial contamination.

Perforation of Barrett's ulcer: a challenge in esophageal surgery.

BACKGROUND: Barrett's ulcer, which develops within Barrett's esophagus, is frequently responsible for bleeding. Perforation is a rare complication constituting a great challenge for diagnosis and management. METHODS: Three personal cases and 31 published reports of perforated Barrett's ulcer were reviewed retrospectively. The site of perforation, clinical presentation, management, and outcome were assessed. RESULTS: The clinical presentation proved to be heterogeneous and was determined by the site of perforation: this was the pleural cavity (20% of cases), mediastinum (20%), left atrium (16.6%), tracheobronchial tract (13.3%), aorta (13.3%), pericardium (10%), or pulmonary vein (6.6%). Early esophagectomy and esophageal diversion-exclusion were the most frequent procedures, and overall mortality was 45%. CONCLUSIONS: The poor prognosis of perforated Barrett's ulcer should be improved by earlier diagnosis and adequate emergent operation. Although early esophagectomy constitutes the recommended procedure, esophageal diversion-exclusion, which allows control of both sepsis and bleeding, is also of interest.

Postpneumonectomy interatrial right-to-left shunt: successful percutaneous treatment.

This report describes the case of a 67-year-old man in whom atrial right-to-left shunt developed after a right pneumonectomy, leading to dyspnea with severe arterial desaturation. Transcatheter occlusion of the patent foramen ovale was successfully performed using a buttoned device. Review of literature and mechanisms of these atrial right-to-left shunts are discussed.

Long-term cardiovascular consequences of undiagnosed intralobar pulmonary sequestration.

We report the case of a patient with a congenital aortic valve stenosis associated with a long-term undiagnosed intralobar pulmonary sequestration. The important blood flow through the aberrant artery led to progressive congestive heart failure and severe hemoptysis at the age of 25 years. We demonstrate the regression of cardiac symptoms and left ventricular diameter after surgical resection of the sequestration.

A unique congenital mediastinal malformation.

We report a case of a 35-year-old patient presenting with a unique asymptomatic malformation associating extralobar pulmonary sequestration communicating with a bronchogenic cyst of the esophageal wall via the aortopulmonary window, dextroisomerism, and complete agenesia of the left pericardium. Despite computed tomography (CT) scan and magnetic resonance imaging (MRI), the diagnosis could not be established before left thoracotomy. The sequestrated lobe and bronchogenic cyst were then successfully resected.

Resection of adrenal metastases from non-small cell lung cancer: a multicenter study.

BACKGROUND: In recent case reports and limited series, adrenalectomy was recommended for an isolated adrenal metastasis from non-small cell lung cancer (NSCLC). METHODS: We retrospectively studied patients with a solitary adrenal metastasis from NSCLC who had undergone potentially curative resection in eight centers. RESULTS: Forty-three patients were included. Their adrenal gland metastasis was discovered synchronously with NSCLC in 32 patients, and metachronously in 11. It was homolateral to the NSCLC in 31 patients and contralateral in 12 (p < 0.01). Median survival was 11 months, and 3 patients survived more than 5 years. There was no difference between the synchronous and metachronous groups regarding recurrence rate or survival. Survival was not affected by the homolateral location of the metastasis, the histology of the NSCLC, TNM stage, any adjuvant and neoadjuvant treatment, or, in the metachronous group, a disease-free interval exceeding 6 months. CONCLUSIONS: We confirm the possibility of long-term survival after resection of isolated adrenal metastasis from NSCLC, but no clinical or pathologic criteria were detected to identify patients amenable to potential cure.

Randomized controlled trial of a synthetic sealant for preventing alveolar air leaks after lobectomy.

BACKGROUND: The intraoperative application of synthetic surgical lung sealant (SLS) to surfaces leaking air or at risk of air leaks has been advocated to reduce alveolar air leaks (AAL) after lobectomy. METHODS: This study was designed to investigate the effectiveness of SLS in reducing AAL in patients considered intraoperatively to have moderate to severe AAL, after all conventional measures to reduce such leaks had been used. Over 17 months, 124 patients undergoing standard lobectomy were randomized to standard closure of parenchymal surgical sites, with or without SLS. RESULTS: In treated patients, the mean numbers of intraoperative AAL after application of SLS were significantly smaller than in untreated patients (38.5 mL versus 59.9 mL, p = 0.0401). Postoperatively, the mean time to last observable AAL was shorter in the treated group (33.7 hours versus 63.2 hours, p = 0.0134) and the mean percentage of patients free of AAL at days 3 and 4 was smaller (87% versus 58.5%, p = 0.002). However, the occurrence of incomplete lung expansion after drain removal, and the length of the postoperative hospital stay due to prolonged AAL, were not different. In the treatment group, 4 patients developed localized empyema and incomplete lung expansion without bronchopleural fistula 7, 12, 15, and 20 days, respectively, after operation. In these 4 patients, inserted chest tubes drained infected sealant. CONCLUSIONS: Surgical lung sealant may be a useful adjunct to conventional techniques for reducing moderate and severe AAL after lobectomy, but its use seems to increase the risk of postoperative empyema.

Adrenalectomy for a solitary adrenal metastasis from lung cancer.

BACKGROUND: Several case reports have shown that patients with truly solitary adrenal gland metastases can undergo resection with long-term survival. METHODS: We assessed consecutive patients with operable or operated non-small cell lung cancer in whom the presence of a unilateral solitary adrenal metastasis was confirmed histologically. Synchronous homolateral adrenal metastases were resected at the same time as the non-small cell lung carcinoma through a transphrenic approach. Synchronous contralateral or metachronous adrenal metastases were resected through an elective approach. RESULTS: Of 598 patients with operable or operated non-small cell lung carcinoma, 11 had a unilateral solitary adrenal gland metastasis and underwent adrenalectomy with no additional mortality or morbidity. One patient died of late postoperative complications and 7 patients died of other distant metastases between 4 and 24 months after adrenalectomy. Two patients are still alive and free of recurrent disease and 1 patient is still alive with brain metastasis 66, 6, and 10 months, respectively, after adrenalectomy. CONCLUSIONS: In the absence of selection criteria to identify the subgroup of patients who will benefit from surgical resection, we suggest the resection of synchronous lesions in patients without N2 involvement and the careful selection of patients with metachronous adrenal metastases according to the evolution of their disease.

A pilot study of adjuvant hepatic arterial infusion chemotherapy, associating 5-fluorouracil and leucovorin, after resection of colorectal cancer liver metastases.

We initiated a pilot study of adjuvant hepatic arterial infusion chemotherapy (AHAIC) using 5-fluorouracil (5-FU) and leucovorin. Hepatic arterial infusion ports were placed in 15 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen consisted of a weekly infusion of 5-FU (12 mg m 2 per day) and leucovorin (200 mg m 2 per day) for 12 months. The mean follow-up was 22 months (range 3-62 months, SD 21-37 months). There were no clinical or biological complications related to chemotherapy, except for sharp epigastric burns in four patients immediately after 5-FU infusions. Catheter irreversible occlusions led to early cessation of the treatment in three patients. Four of the 15 evaluable patients developed recurrent disease. The site of relapse was the liver in two patients and extra-hepatic sites in the two remaining patients. Three of these four patients died of their recurrent disease. These results suggest that 5-FU and leucovorin can be combined for AHAIC in a long duration regimen with a very low rate of side-effects. This protocol could be safely employed in a prospective randomized study in combination with 5-FU systemic infusions.

Physical motion in dreams: one measure of three theories.

As a normal psychological event, dreaming is an object of fascination and of conflicting explanation. In biopsychological terms, this article compares 3 explanations of 1 salient feature of dream cognition. Physical movement can be measured in dream reports, can be understood in physiologic terms, and can provide a focus for comparing dream theories. In addition, dreamed motion may have functional importance. The authors discuss dream motor data that conflict with Freud's explanation of dream movement and with a distributed activation explanation but coincide with an activation-synthesis hypothesis. Because physiologic models of sleep intersect with physiologic models of psychopathology, this approach may be relevant to psychopathological dreaming.

Processing and characterization of the low density lipoprotein receptor in the human colonic carcinoma cell subclone HT29-18: a potential pathway for delivering therapeutic drugs and genes.

Low density lipoprotein (LDL) processing has been investigated in the subcloned human colonic carcinoma cell line HT29-18. LDL binding at 4 degrees C was a saturable process in relation to time and LDL concentration. The Kd for LDL binding was 11 micrograms/ml. ApoE-free HDL3 or acetylated LDL did not significantly compete with 125I-LDL binding, up to 500 micrograms/ml. 125I-LDL binding was decreased by 70% in HT29-18 cells preincubated for 24 hours in culture medium containing 100 micrograms/ml unlabelled LDL. Ligand blotting studies performed on HT29-18 homogenates using colloidal gold labelled LDL indicated the presence of one autoradiographic band corresponding to an apparent molecular weight of 130 kDa, which is consistent with the previously reported molecular weight of the LDL receptor in human fibroblasts. At 37 degrees C, 125I-LDL was actively internalized by HT29-18 cells and lysosomal degradation occurred as demonstrated by the inhibitory effect of chloroquine. LDL uptake and degradation by HT29-18 cells also resulted in a marked decrease in endogenous sterol synthesis. These data demonstrate that the HT29-18 human cancerous intestinal cells are able to specifically bind and internalize LDL, and that LDL processing results in down-regulation of sterol biosynthesis. Thus, intestinal epithelial cells possess specific LDL receptors that can be exploited to accomplish drug delivery and gene transfer via the receptor-mediated endocytosis pathway.