[Eosinophilia: from neoplastic disease to anguillulosis]. / Eosinophilie: de la néoplasie à l'anguillulose.

Hypereosinophilia (HE), defined as eosinophil count above 0.5 G/l in the peripheral blood. Most cases are secondary to other diseases. Etiological diagnosis remains complex especially as causes of HE vary across the population. Allergic diseases and parasitic infections are the predominant causes. However up to 10% of HE are secondary to tumors. Here, we describe a case of HE initially attributed to a breast cancer that turn out to be due to an angillulosis acquired just before the diagnosis of the tumor.

Grading the neuroendocrine tumors of the lung: an evidence-based proposal.

Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.

Resection of giant typical carcinoid tumor with cardiopulmonary bypass support.

Carcinoids, defined as well-differentiated neuroendocrine tumors, are classified as typical or atypical based on their microscopic pathological features. Typical carcinoids have a favorable prognosis after complete resection, with 10-year survival rates of up to 90%. We present the surgical strategy used to achieve a left pneumonectomy and the indications for cardiopulmonary bypass (CPB) support in a patient with a huge typical carcinoid tumor.

Advantages of multidetector-row CT with multiplanar reformation in guiding percutaneous lung biopsies.

PURPOSE: This study aimed to assess the usefulness of multiplanar reformations (MPR) during multidetector-row computed tomography (MDCT)-guided percutaneous needle biopsy of lung lesions difficult to access with the guidance of the native axial images alone owing to overlying bony structures, large vessels or pleural fissures. MATERIALS AND METHODS: MDCT-guided transthoracic needle biopsy (TNB) was performed on 84 patients (55 men and 29 women; mean age 65 years) with suspected lung neoplasm by using a spiral MDCT scanner with the simultaneous acquisition of six slices per rotation. We determined the site of entry of the 22-gauge Chiba needle on native axial images and coronal or sagittal MPR images. We took care to ensure the shortest needle path without overlying large vessels, main bronchi, pleural fissures or bony structures; access to the lung parenchyma as perpendicular as possible to the pleural plane; and sampling of highly attenuating areas of noncalcified tissue within the lesion. RESULTS: Diagnostic samples were obtained in 96% of cases. In 73 patients, lesions appeared as a solid noncalcified nodule <2 cm; 11 lesions were mass-like. In 22, the biopsy required MPR guidance owing to overlying ribs (18), fissures (2) or hilar-mediastinal location (2). CONCLUSIONS: MDCT MPR images allowed sampling of pulmonary lesions until now considered unreachable with axial MDCT guidance because of overlying bony structures (ribs, sternum and scapulae) or critical location (hilar-mediastinal, proximity to the heart or large vessels). Compared with the conventional procedure, the use of MPR images does not increase the rate of pneumothorax or the procedure time.

Effect of inducible FHIT and p53 expression in the Calu-1 lung cancer cell line.

Loss of FHIT expression and p53 mutations are critical events in the early stages of lung carcinogenesis. The restoration of Fhit function in FHIT-negative cancer cells has been reported to cause tumour suppression by inhibition of cell proliferation and/or activation of apoptotic pathways. However, the studies designed to elucidate the biological role of Fhit and its potential interaction with p53 have produced conflicting results. We investigated here the effects of the simultaneous restoration of FHIT and p53 in Calu-1 cells by using a hormone-inducible gene expression system. We demonstrate that the restoration of FHIT expression reinforces the anti-proliferative effect associated with the simultaneous replacement of p53. Indeed, a more pronounced inhibition of cell proliferation associated with an earlier and higher induction of p21(waf1) mRNA and protein expression was observed in Fhit/p53-expressing cells compared with cells expressing p53 alone. This effect was not due to Fhit-mediated up-regulation of p53 expression; in fact p53 protein was expressed at the same level in both FHIT-positive and FHIT-negative cell clones. Consistent with this result, Fhit did not affect the expression of MDM2, a protein known to interact directly with p53 and target p53 for proteolytic degradation, thus down-regulating its activity.

Endotracheal migration of a central venous catheter.

Subcutaneous infusion ports for prolonged central venous access are commonly used for drug administration and parenteral nutrition in a wide range of chronic diseases. The extensive use of these devices has to be balanced against its complications, some of which potentially life-threatening. We describe the case of a patient admitted to our unit with haemoptysis and cough. At bronchoscopy the tip of the central venous catheter was discovered protruding into the tracheal lumen. The catheter was pulled out from the subcutaneous pouch under simultaneous surgical control of the tracheal fistula orifice.

Disposition of voriconazole during continuous veno-venous haemodiafiltration (CVVHDF) in a single patient.

OBJECTIVES: To determine whether voriconazole dosage adjustment is required during continuous veno-venous haemodiafiltration (CVVHDF). METHODS: Voriconazole pharmacokinetics were studied in a critically ill patient under CVVHDF. The analysis was carried out for 12 h following a 6 mg/kg dose. Voriconazole concentrations were measured by HPLC in blood inlet and outlet lines and in dialysate. RESULTS: The total body clearance of voriconazole was 20.3 L/h, with a terminal half-life of 13.7 h and a distribution volume of 399 L. The estimated sieving coefficient was 0.53 and the filtration-dialysis clearance 1.2 L/h. CONCLUSIONS: CVVHDF does not significantly affect voriconazole disposition and requires no dosage adjustment.

Surgical outcome of combined pulmonary and atrial resection for lung cancer.

OBJECTIVES: The study was carried out to assess the short and long-term outcome of patients with non-small cell lung cancer infiltrating the left atrium treated by surgery. METHODS: We retrospectively collected the hospital files of twenty-three consecutive patients operated on between 1982 and 2001 in two units of Thoracic Surgery. Four patients received an induction regimen. Fourteen right pneumonectomies, 8 left pneumonectomies and 1 right inferior lobectomy were performed. No cardiopulmonary bypass was employed. RESULTS: In all patients the diagnosis of T4 atrial invasion was confirmed by pathological examination. A complete resection was achieved in nineteen patients (83%). With respect to nodal staging, there were 13 N0, 5 N1 and 4 N2 cases, respectively. Two deaths occurred during the one month postoperative period (9%). Three patients had postoperative atrial fibrillation. Two other patients had postpneumonectomy empyema without bronchopleural fistula and recovered, one after thoracoscopic debridement and the second after open window thoracostomy. Follow-up was completed on September 2002; only one patient was lost to follow-up. Median survival, excluding the perioperative mortality, was 20 months (range 4 - 62 months). The survival rate, calculated with the Kaplan-Meier method, was estimated as 63% at 1 year, 2 % at 3 years and 10% at 5 years. Using a Cox model analysis, lymph node stage and completeness of resection were not independent prognostic factors. CONCLUSIONS: In cases of NSCLC with left atrial invasion complete resection is technically feasible in most instances without cardiopulmonary bypass. The acceptable operative risk and the encouraging long-term survival observed in this series suggest that NSCLC invading the left atrium should not be systematically considered as a definitive contraindication to surgery.

Histological and immunohistochemical study of the bronchial stump with flap coverage in an animal model.

OBJECTIVE: The purpose of our study was to evaluate the healing process of the bronchial stump after pneumonectomy reinforced with different pedicled flaps in an animal model. The specimens were analyzed by means of histology and immunohistochemistry. MATERIALS AND METHODS: We have considered 45 New Zealand White male rabbits that underwent a left pneumonectomy under general anesthesia. Nine animals had no bronchial coverage and represented the controls. The other 36 rabbits were divided into three groups of 12 and had bronchial coverage with either diaphragmatic, intercostal or pericardial flaps. The histological examinations were performed on the animals sacrificed 7, 14 and 30 days after surgery. Immunohistochemical analyses were done on the specimens on postoperative day 7 and 14. On postoperative day 7, the specimens were examined for expression of proliferating cell nuclear antibody (PCNA) expression. On postoperative day 14, neoangiogenesis was measured by CD31 expression. The measurements of antibody expression were done with a computer-assisted morphometric count and analyzed with the t test. RESULTS: On postoperative day 14, standard histology showed more evident neoangiogenesis in the bronchial stump specimens covered with intercostal and diaphragmatic flaps compared to pericardial flaps and controls. The immunohistochemical evaluation of PCNA by morphometric computer-assisted analysis did not show any statistically significant differences among the groups. The CD31 morphometric count revealed a higher and statistically significant antibody expression in muscular flaps compared to pericardial flaps and controls. CONCLUSIONS: Our study showed that bronchial coverage with a pedicled muscular flaps promotes the production of new vessels and gives the possibilities to optimize the healing process of a bronchial stump after pneumonectomy.

[Volatile hydrocarbons in exhaled air: preliminary data on the characteristic profile associated with lung tumors]. / Idrocarburi volatili nell'aria esalata: dati preliminari sul profilo caratteristico associato con tumore polmonare.

The aim of this pilot study was to identify and quantify selected volatile organic compounds (VOCs), such as aliphatic and aromatic hydrocarbons in exhaled air from patients with non small cells lung cancer (NSCLC) as compared to healthy subjects, either smokers or non smokers. Exhaled air has been collected by repeated expirations in Tedlar bags. VOCs were sampled by solid phase micro-extraction (SPME) and analyzed by gascromatography/mass spectometry. NSCLC patients showed higher levels of pentane, 2-metilpentane, 2,4-dimetilheptane in the exhaled air as compared to smokers and non smokers. BTEX (benzene, toluene, etilbenzene and xylenes) concentrations were higher in smokers compared to other groups, whereas no differences were observed between subjects with NSCLC and smokers for heptane and octane. In summary, selected VOCs have sufficient diagnostic power to differentiate among the three groups we examined. These differences might be exploited to identify characteristic fingerprints of various lung diseases.

Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery.

BACKGROUND: The biological markers in non-small cell lung cancer (NSCLC) have been widely studied and encouraging results have shown that products of some oncogenes and other molecular markers can predict the aggressiveness of the disease and the outcome of the patients. METHODS: To verify the reliability of these prognostic markers we have studied retrospectively the expression of c-erbB-2 and 67Ki (growth regulation), p53 (cell cycle regulation and apoptosis), bcl-2 (apoptosis) and CD31 and CD34 (angiogenesis) in 78 patients operated on for NSCLC with curative intent between January 1987 and December 1988 and followed up for 10 years. For the determination of the biological markers we have used the ABC (Avidin-Biotin-Peroxidase complex) immunohistochemical method. The Cox regression model was used for the univariate and multivariate analysis. RESULTS: Nineteen patients (24%) were alive after 10 years and 59 (76%) died. The univariate analysis of the relationship between the 10-year survival and the expression of the markers was significant only for p53 (p=0.0097). Stratifying the patients according to the 3 histological subtypes (squamous cell carcinoma, adenocarcinoma and large cell undifferentiated carcinoma) the correlation between markers and survival pointed out that the only significant one was p53 (p=0.0459) in adenocarcinoma. In the same way considering the stages p53 was significant in stage IIIa (p=0.0357). The multivariate analysis emphasized that p53 was the only significant marker with respect to the 10-year survival (p=0.0091). Examining the histological groups significant was only p53 in adenocarcinoma (p=0.0192) and in large cell undifferentiated carcinomas (p=0.0290). This marker is also significant in pathological stage II (p=0.0271) and IIIa (p=0.0402). Apart from histology and staging the 10-year survival was 33% for p53 negative versus 10% for p53 positive. In patients with adenocarcinoma the 10-year survival was 40% for p53 negative and 6% for p53 positive. CONCLUSIONS: In conclusion our results emphasize the importance of p53 as a prognostic factor in 10-year survival in patients with adenocarcinoma and in stage II and IIIa.

Surgical treatment of primary and metastatic sternal tumours.

BACKGROUND: Primary and metastatic malignancies of the sternum are uncommon. Surgery that is the best treatment for the majority of primary sternal tumors, and arguably for metastatic lesions, has improved permitting us to perform wide resection and simultaneous reconstruction safely. METHODS: From January 1988 to December 1998 we treated 13 patients, 4 with primary chondrosarcoma and 9 with sternal metastasis, 5 breast cancer, 3 kidney cancer and 1 thyroid cancer. In 3 patients total sternectomy was performed and in 10 a partial sternectomy associated with resection of the anterior segment of the ribs in 7 cases and resection of the clavicle in 5 patients. Bone reconstruction was done in the majority of cases (5) with Marlex mesh with methylmethacrylate and in 3 cases rib grafts were used to strengthen a Vicryl mesh. The major pectoralis muscle was the most frequently used soft tissue, 9 of 12. RESULTS: Our postoperative mortality was 15%, 2 cases. The median overall survival was 48 months. All the primary tumours were alive after a mean follow-up of 34 months (range 4-84 months). While survival of the sternal metastasis was 24 months. CONCLUSIONS: Surgical resection and reconstruction of sternal lesions represent a basic step in the treatment of the primary tumors with encouraging survival results while in the metastatic lesions surgery can be a part of a multimodality approach with unsatisfactory results.

The bilobectomies for lung cancer.

BACKGROUND: The purpose of our retrospective study is to confirm that bilobectomy is a feasible operation with an oncological value. METHODS: From 1981 to 1998, 46 patients underwent bilobectomy for lung cancer. Eight upper and middle lobectomies (UML) and 38 middle and lower lobectomies (MLL) were performed. Intraoperative pneumoperitoneum was done in 11 MLL. We have considered operative mortality, postoperative complications, the persistence of drainage tubes and the length of hospital stay and the data were statistically compared with those relative to right lobectomies. Survival was estimated with the Kaplan-Meier method and the curves were compared with those of the right lobectomies and right pneumonectomies using the log-rank test. RESULTS: Overall morbidity was 43.4%. Mortality was 6.5%. Mean chest tube persistence was 7.8 days and mean hospital stay was 14 days. No statistical significance was found about these data comparing the UML and MLL separately and the bilobectomies with the right lobectomies. The pneumoperitoneum done in the MLL enabled a shorter hospital stay, statistically significant, in comparison with MLL without pneumoperitoneum. The overall 5-year survival rate was 38%. Considering the I and the II stages no statistical differences in survival were found considering the right lobectomies and right pneumonectomies. CONCLUSIONS: The bilobectomies can have a role in treatment of lung cancer that is equal to the other standard major resections.

Unusually located hydatid cysts miming a pulmonary tumor invaliding the spine.

Hydatid disease is a worldwide encountered zoonosis but at present very rare in Europe, liver and lungs being the most frequently involved sites. Bone involvement is very uncommon and the vertebral spine is the most common site of skeletal involvement (less than 1% overall). We report a case of vertebral hydatid disease with secondary pleuro-pulmonary involvement successfully treated by emergency spinal decompression followed by lung resection en bloc with chest wall and partial vertebrectomy.

Spontaneous intercostal pulmonary hernia.

A case of spontaneous intercostal pulmonary hernia as a result of vigorous coughing is reported in a 67-year-old man. The great majority of acquired pulmonary hernias are post-traumatic; rare cases are spontaneous, resulting from prolonged and/or repeated increased intrathoracic pressure. This hernia was successfully repaired with a polyglactin absorbable mesh and approximation of the ribs with heavy stitches. When required, surgical repair is the treatment of choice.

Biological variables in non-small cell lung cancer: comparison between immunocytochemical determination on fine needle aspirates from surgical specimens and immunohistochemical determination on tissue sections.

A number of biological and predictive markers of non-small cell lung cancer (NSCLC) have been sought, but these have so far been mainly evaluated on surgically resected specimens. Given that fine needle aspiration biopsy (FNAB) is being increasingly used in the diagnosis of NSCLC, its application could be extended to the immunocytochemical detection of biological parameters at the time of diagnosis before surgery. In order to assess the reliability of estimating biological markers on fine needle aspirates (FNAs) from NSCLC, the aim of this study was to compare Ki67 growth fraction, p53 and bcl-2 protein expression as revealed by the immuncytochemical assessment of FNAs obtained from surgical samples with the immunohistochemical results obtained from the corresponding histological sections. FNAs were performed on surgical specimens obtained from 29 NSCLC patients. Ki67, p53 and bcl-2 were cytologically and histologically evaluable in respectively 25, 27 and 19 cases. Concordance between FNAs and corresponding paraffin sections was 84% for Ki67, 93% for p53 and 95% for bcl-2. All of the specimens whose biological parameters were studied by immunocytohistochemistry also underwent flow cytometric DNA analysis of FNAs taken from fresh surgical specimens. Of the 29 cases, 22 were aneuploid and seven diploid. The S-phase fraction (SPF) was evaluable in 62% of cases. Comparison of SPF results on FNAs with Ki67 values evaluated on the corresponding histologic and cytologic specimens, revealed a significant correlation only with histology. Good reproducibility was also found in relation to the immunocytochemical results obtained on FNAs from different areas of the same tumour, showing that tumour heterogeneity does not affect the method. The concordance between the immunocytochemical and immunohistochemical results suggests that FNAB may be a reliable procedure for the biological characterization of NSCLC. Given its limited invasiveness, FNAB could be used in vivo for the preoperative assessment of biological parameters in patients with operable or metastatic NSCLC.

The modified "hemi-clamshell" approach for tumors of the cervicothoracic junction.

The anterior approaches proposed for treatment of the apical chest tumors (anterior transcervical, transmanubrial, and hemi-clamshell) have precise advantages and limits. To avoid these limits we have modified the hemi-clamshell with the resection of the first costal cartilage and the costoclavicular ligament. This allows a wider opening of the sternocostal flap, with safe control of the entire subclavian vessels as well as easier access to the T1 to T3 vertebral bodies and the posterior chest wall.

Pulmonary abnormalities in Cowden's disease.

Cowden's disease is an inheritable multiple neoplastic syndrome represented by benign and malignant lesions of skin, digestive tract, mucosae, breast and thyroid. The syndrome, first described by Lloyd and Dennis in 1963, includes benign lung lesions, described in the literature only as hamartomas. The unusual condition of our case consists of multiple and bilateral lipomatous lesions of the lung and of adipose colonic polyps, diagnosed respectively by video assisted mini-thoracotomy and by endoscopic biopsies.

A standard muscle-sparing utility thoracotomy for VATS procedures.

BACKGROUND: Improvements in surgical equipment have rendered video-assisted thoracic surgery (VATS) an effective device for thoracic surgeons and nowadays several intrathoracic diseases can benefit from this approach. This development has expanded potential use and recently the technical feasibility of major lung resections by VATS has been demonstrated. The authors present their experience with a standard muscle-sparing utility thoracotomy (UT) utilized for all VATS procedures, including major lung resections. METHODS: From November 1996 to October 1997, 30 patients were operated on. There were 22 males and 8 females (medium age 58 years; range 24-78). There were 13 anatomical lung resections (i.e.: 11 lobectomies, 1 left pneumonectomy, 1 segmental resection), 8 wedge resections, 3 lung biopsies, 2 debridements of pleural empyema, 2 mediastinal nodes biopsies, 1 esophageal resection for leiomyoma, 1 excision of benign mediastinal cyst. RESULTS: No mortality or major morbidity were recorded, as well as no rib fractures due to the rib spreader. Two patients suffered from prolonged air-leaks after respectively left upper lobectomy and lung biopsy and required prolonged chest drainage. Concerning anatomic major lung resections the medium hospital stay was 7.9 days and medium chest tube time was 5.6 days. The utility thoracotomy through the auscultatory triangle proved to be a safe approach and confirmed the technical feasibility of various type of surgical procedures with results comparable to standard open thoracotomy. Our data shows that VATS approach did not seriously affect the duration of hospital stay, chest tube time, the overall morbidity or lung function. CONCLUSIONS: As the real benefit of this approach remains controversial, the majority of the studies comparing the VATS approach to conventional muscle-sparing thoracotomy neither nor prospective nor randomized, and several parameters are difficult to evaluate in the literature further study are mandatory.