Vincenzo Di Crescenzo

Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review

BackgroundAnaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.MethodsThe study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.Results21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.ConclusionsMutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.

The serine protease HtrA1 is a novel prognostic factor for human mesothelioma

AIMS The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. MATERIALS & METHODS Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. RESULTS A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). CONCLUSION This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.

A simple technique to control placement of Dumon stent in subglottic tracheal stenosis

Airway stenting is the chosen treatment for patients affected by subglottic tracheal stenosis and unfit for surgery. Among the different types of prostheses, the Dumon stent is a valid option especially in patients without tracheotomy. Insertion is usually achieved by pushing the stent off from a loader using a prosthesis pusher. If the stent is expelled below the stenosis, rigid forceps grasping the proximal end of the stent retract it above the stenosis. However, in difficult cases such as rigid stenosis with a luminal diameter smaller than the profile of the stent, such a manoeuvre may be difficult in non-expert hands. Thus, we proposed a simple and safe technique to facilitate the placement of a Dumon stent. We passed a long thread from outside to the inside of the stent. After the dilatation of the stenosis, the stent was pushed and, if needed, easily retracted with the thread into the proper position to ensure airway patency and to avoid migration. In addition, our procedure could be useful also to rapidly remove the stent if its size turned out to be inaccurate for the stenosis. With such a simple method we successfully treated 7 consecutive patients affected by complex subglottic stenosis and unfit for surgery.

An unusual case of primary choriocarcinoma of the lung

Choriocarcinoma is a germ cell tumor containing syncytiotrophoblastic cells and secreting human Beta-HCG. Primary choriocarcinoma of the lung is extremely uncommon. The prognosis of this tumor is extremely poor, despite surgical and chemotherapeutic treatment. We report a surgically treated case of choriocarcinoma in a 37-year-old woman who came to our attention because of a isolated lung lesion. The tumor was successfully resected. Chemotherapy was started 2 months after thoracic surgery and consisted of bleomycin, etoposide, and cisplatin. At 1-year follow-up the patient is alive in good condition. The hCG level is actually normal.

The influence of body mass index and weight loss on outcome of elderly patients undergoing lung cancer resection.

BACKGROUND The aim of the study was to evaluate the influence of nutritional status on outcome of elderly patients resected for lung cancer. MATERIALS AND METHODS A total of 117 consecutive patients aged ≥ 70 years undergoing lung cancer resection were enrolled. In addition to routine preoperative evaluations, other variables such as body mass index, weight loss, serum albumin, lymphocytes, and transferrin were counted. According to the body mass index value, patients were divided into Group A (≤ 18.5, underweight) and Group B (> 18.5) and risk factors for morbidity and mortality were analyzed. RESULTS Group A and Group B counted 21 and 96 patients, respectively. The mean age was 74.9 ± 2.6; body mass index of Group A was significantly lower than that of Group B (16.7 ± 1.3 vs. 23.5 ± 1.7, respectively, p < 0.0001). On multivariate analysis, significant risk factors for complications were pneumonectomy (p = 0.001), stage (p = 0.006), predictive postoperative flow expiratory volume in 1 second (ppoFEV1%) (p = 0.003), and coronary disease (p = 0.04) and significant risk factors for early mortality were pneumonectomy (p = 0.0002), ppoFEV1% (p < 0.0001), BMI (0.02), and weight loss (0.007). The median survival time of Group A and Group B was 41 versus 54 months, respectively (p = 0.1). However, body mass index of less than 18.5 (p = 0.01) and weight loss of > 5% before operation (p = 0.01) were independent risk factors for 1 year mortality. CONCLUSIONS In elderly patients, malnutrition was a significant additional risk factor for early death. Nutritional assessment should be included in the routine preoperative selection. In malnourished patients, nutritional support before and after operation and a careful postdischarge care might be beneficial, but it should be corroborated by further prospective studies.

Quantitative assessment of emphysematous parenchyma using multidetector-row computed tomography in patients scheduled for endobronchial treatment with one-way valves

OBJECTIVES To investigate the role of volume quantitative assessment using multidetector-row computed tomography to select patients scheduled for endobronchial one-way valves treatment. METHODS Twenty-five consecutive patients (15 with heterogeneous emphysema and 10 with giant emphysematous bulla) undergoing endobronchial valves treatment were enrolled. All patients were studied pre- and postoperatively with standard pulmonary functional tests and quantitative volume assessment of target lobe and entire lung. Emphysematous parenchyma was obtained applying density thresholds of -1.024/-950 Hounsfield units. Among different subtype of patients, we evaluated: (i) the differences between preoperative versus postoperative data; (ii) the correlation between functional and volumetric quantification changes and (iii) the critical threshold value of volumetric quantification of the target lobe in close association with clinical effects. RESULTS Among heterogeneous emphysematous and giant emphysematous bulla patients, a significant improvement of flow-expiratory volume in 1 s (from 36.9 ± 15.3 to 43.9 ± 10.4; P = 0.01; and from 35.8 ± 6.0 to 47.5 ± 7.9; P < 0.0001, respectively); and of forced vital capacity (from 41.9 ± 5.9 to 47.3 ± 9.3; P = 0.0009 and from 40.7 ± 5.9 to 48.8 ± 4.9; P = 0.0002, respectively); and a significant reduction of residual volume (from 185 ± 14 to 157 ± 14.7; P = 0.005; and from 196 ± 13.5 to 137 ± 21; P < 0.0001, respectively) and of total lung volume (from 166.7 ± 13 to 137 ± 18 ; P = 0.0003, and from 169 ± 15 to 134 ± 18; P < 0.0001, respectively) were seen after treatment. The volumetric measurements showed a reduction of volume of the treated lobe among heterogeneous emphysematous patients (from 1448 ± 204 to 1076 ± 364; P = 0.0008); and in those with giant emphysematous bulla (from 1668 ± 140 to 864 ± 199; P < 0.0001). The entire lung and target lobe volume changes were inversely correlated with change in forced expiratory volume in 1 s in patients with heterogeneous emphysematous (r = -0.7; P = 0.0006; and r = -0.7; P = 0.0009, respectively) and giant emphysematous bulla (r = -0.8; P = 0.001; and r = -0.7; P = 0.009, respectively). Among patients with heterogenous emphysematous and giant emphysematous bulla, the value of sensitivity and specificity were 66.6 and 83%, respectively (for a volumetric qunatification >1.5239), and of 60 and 100%, respectively (for a volumetric qunatification >1.762). CONCLUSIONS Our study showed that the volumetric quantification adds further informations to the routine evaluation for optimizing the selection of patients scheduled for endobronchial valve treatment.

Cytological diagnosis of thyroid nodules in Hashimoto thyroiditis in elderly patients

BackgroundLong standing Hashimoto Thyroiditis (HT) causes shrinking and atrophy of the thyroid, but may also lead to diffuse enlargement of the gland and/or formation of nodules. These nodules should be differentiated from papillary thyroid carcinoma (PTC) and primary thyroidal non-Hodgkin lymphoma (PTL), which are possible complications of HT, and require pre-surgical diagnoses and different treatments.This study focuses on the role of fine-needle cytology (FNC) in the clinical surveillance and pre-surgical diagnosis of HT with diffuse and nodular enlargement of the gland in elderly patients.MethodsThirty-four elderly patients (≥ 65 yrs) with HT and diffuse or nodular enlargement of the thyroid underwent ultrasound (US)-guided FNC. Smears were routinely stained and evaluated; additional passes were used for flow cytometry (FC) assessment of lymphoid infiltrate in 6 cases.ResultsThe cytological diagnosis was HT in 12 cases with prevalence of Hurtle cells in 2 cases, PTC in 1 case and PTL in 2 cases. FC assessed the reactive, non-lymphomatous nature of the lymphoid infiltrate in 5 cases and demonstrated light chain restriction, hence the lymphomatous nature of the lymphoid infiltrate in 2 cases of PTL.ConclusionsFNC plays a key role in the clinical surveillance and pre-surgical diagnosis of diffuse enlargement and nodular presentation of HT in elderly patients. FNC can correctly diagnose HT, PTC and PTL indicating the need for surgery and its extension in suspicious or neoplastic cases, leaving other cases to the medical treatment and clinical surveillance.

Early cytological diagnosis of extranodal stage I, primary thyroid Non-Hodgkin lymphoma in elderly patients. Report of two cases and review of the literature

BackgroundPrimary thyroid lymphomas (PTLs) account for 5% of thyroid malignant tumors and often develop in patients with Hashimoto Thyroiditis (HT). Fine-needle cytology (FNC) is widely used in the diagnosis of thyroid nodules, including those arising in HT. Two PTL cases in HT elderly patients are here described and discussed.MethodsFNC was performed in rapidly enlarged thyroid nodules of 2 elderly patients under ultrasound (US) control. FNC was used to prepare conventional cytologic smears, immunocytochemistry (ICC) and flow cytometry (FC) assessment of cell populations.ResultsThe above cases were diagnosed as well differentiated, small B-cell and diffuse large B-cell thyroid lymphomas, respectively, by means of FNC. The histological diagnoses were mucosa-associated non Hodgkin lymphoma (MALT) and diffuse large B-cell lymphoma (DLBCL), confirming FNC diagnoses, and patients were treated accordingly.ConclusionsFNC diagnosis of PTL is reliable and accurate; it may be conveniently used in the clinical practice since it provides indications for appropriate therapeutic procedures or diagnostic surgery, and avoids to treat benign nodules.

The value of matrix metalloproteinase-9 and vascular endothelial growth factor receptor 1 pathway in diagnosing indeterminate pleural effusion.

OBJECTIVES Our aim was to determine the diagnostic value of the matrix metalloproteinase-9/vascular endothelial grow factor receptor-1 pathway in differentiating pleural effusions (PE) of varying origin. METHODS In the last two years, 55 consecutive patients with exudative PE have been enrolled. In all patients, we measured PE levels of vascular endothelial grow factor receptor-1 (VEGFR-1) in soluble form, through enzyme-linked immunosorbent assay (ELISA) (results expressed in pg/ml) and western blot, and of matrix metalloproteinase-9 (MMP-9), through ELISA (results expressed in ng/ml). The values recorded were then statistically compared with the etiologic diagnosis of the PEs. RESULTS Between the PEs analysed, 40 were found to be malignant and 15 to be benign. VEGFR-1 in soluble form (sVEGFR-1) was significantly higher in malignant than in benign effusions (P < 0.0001), using ELISA; the same was shown by the western blot analysis method. MMP-9 levels results also indicated significantly more malignant than benign effusions (P < 0.0001). VEGFR-1 in soluble form showed a sensitivity and specificity of 92% and 93%, respectively, (cut-off value >852; AUC: 0.9) in predicting the malignant nature of a PE. Sensitivity and specificity of MMP-9 in predicting the malignant nature of a PE were, respectively, 95% and 73% (cut-off value >639; AUC: 0.8). In the pleural fluids, the values of the two markers were significantly related to each other (r = 0.5; P < 0.0001). Eighteen patients with malignancies, diagnosed by pleural biopsy, had negative cytological findings. Of these patients, sixteen (89%) presented elevated levels of both markers. CONCLUSIONS Our data suggest that the VEGFR-1/MMP-9 pathway is significantly increased in malignant-rather than in benign-pleural effusions; thus, the measurement of their levels in the pleural effusion could be useful, throughout the diagnostic work-up, to select which cases would warrant a pleural biopsy.

Migration of surgical clips through a right lobectomy stump mimicking an asthmatic syndrome

The mechanical stapler is routinely used in thoracic surgery practice to attend resection of bronchus and vessels. Herein, we reported a very rare complication as the migration of a titanium surgical clip through a right lobectomy stump. One year after the procedure, the patient complained of persistent cough. A misdiagnosis of asthma was made and she treated for 6 months with bronchodilators, corticosteroid and antihistaminic without success. Thus, patient re-referred of our unit. No clinical signs of infection as fewer, productive cough, dyspnea were present. The laboratory exams were within normal value including white cells. CT scan revealed no abnormalities. Bronchoscopy demonstrated a healed upper bronchus stump without evidence of an actual, open bronchopleural fistula but with clips apparently working their way into the airway, with approximately half of the clip visible within the lumen. The side of the clips that would be open before closure by the surgeon formed the leading edge of the clips visible in the lumen. The clips were successfully removed during flexible bronchoscopy with a forceps usually used for biopsy. After the procedure, the cough disappeared. The endoscopy check after 3 months showed a normal bronchial stump without evidence of fistula.