Inherited predisposition to malignant mesothelioma: germline BAP1 mutations and beyond.

Malignant mesothelioma (MM) is a rare aggressive neoplasm arising from mesothelial lining of body cavities, most commonly pleura and peritoneum. It is characterised by a poor prognosis and limited treatment options. A universally recognised risk factor for the development of MM is exposure to asbestos. However, evidence supporting a genetic susceptibility to the development of MM has been accumulating during the last decades. Intensive research for the identification of MM susceptibility genes has led to the discovery of BAP1 and to the definition of the so-called "BAP1-related tumour predisposition syndrome". Patients carrying germline BAP1 mutations have an increased risk for the early development of tumours, including MMs, uveal melanomas, cutaneous melanocytic lesions, clear cell renal cell carcinomas and basal cell carcinomas. Furthermore, pathogenic variants in tumour suppressor genes with a role in DNA repair have been recently described in families with clustered MM cases. These genetic alterations seem to confer exaggerate sensitivity to asbestos carcinogenic effect and, arguably, increased response to specific chemotherapeutic strategies. While the translational significance of BAP1 alterations is explored in the research field, the identification of families carrying germline BAP1 mutations is mandatory to start appropriate surveillance programs and guarantee the best clinical management to these patients.

Giant solitary fibrous tumors of the pleura: two case reports.

Solitary fibrous tumors of the pleura (SFTP) are rare neoplasms. We report two cases of giant SFTP treated by surgical resection. One of these was enormous (30 x 19 x 18 cm, weight: 4,050 g) and occupied the entire left pleural cavity with complete lung collapse and contralateral mediastinal shift. Both tumors were removed en bloc. The patients had no postoperative complications. Surgical treatment is curative in most patients; resection must be complete because of the possibility of recurrence and metastasis.

Role of diffusing capacity in predicting complications after lung resection for cancer.

BACKGROUND: The purpose of our study was to determine whether the assessment of the diffusing capacity of the lung for carbon monoxide (DL (CO)), together with the forced expiratory volume in 1 second (FEV (1)), could improve the selection of surgical patients. METHODS: The data of 76 patients undergoing major lung resection (pnemonectomy, bilobectomy or lobectomy) for non-small cell lung cancer were retrospectively studied. All patients were reviewed for age, sex, preexisting medical conditions, operative, and pathological findings and postoperative outcome. RESULTS: Univariate and multivariable logistic regression analysis showed that ppoFEV (1) and ppoDL (CO) were the only statistically significant predictors of pulmonary complications. In the group of patients with marginal ppoFEV (1) (between 30 - 40 %), ppoDL (CO) predicted pulmonary morbidity with a better accuracy ( P < 0.005) than ppoFEV (1) ( P > 0.05). Multiple regression analysis showed that pneumonectomy was the only statistical factor correlated with mortality ( P < 0.05). CONCLUSION: Our experience seems to suggest that ppoDL (CO) is a strong predictor of pulmonary complications after major lung resection, allowing a better surgical selection of the patients with compromised respiratory function.

Surgical strategies in cervico-mediastinal goiters.

AIM: We retrospectively studied clinical picture, diagnosis, treatment and complications of patients with cervico-mediastinal goiter who underwent surgery. METHODS: Sixty-three patients underwent surgical treatment for cervico-mediastinal goiter in the last 10 years. Thirty-two patients (50.8%) had cervico-mediastinal goiter, 24 patients (33.3%) had mediastino-cervical goiter and 7 patients (11.1%) had mediastinal goiter. Forty-seven cases were prevascular goiters and 16 were retrovascular goiters. We performed total thyroidectomy in 25 patients, subtotal thyroidectomy in 31 patients and in 7 cases the resection of residual goiter. In 50 patients we used a cervical approach, in 12 patients the cervical incision was combined with median sternotomy (6 in total) and in 1 patient with transverse sternotomy. RESULTS: Three patients (4.7%) died in the postoperative period (2 cardio-respiratory failure and 1 pulmonary embolism). The histologic study revelead 5 (7.9%) carcinomas. Postoperative complications were: dyspnea in 7 cases (11.1%), transient vocal cord paralysis in 5 patients (7.9%), temporary hypoparathyroidism in 6 patients (9.5%) and kidney failure in 1 case (1.6%). CONCLUSIONS: Cervicotomy is the approach of choice but in some limited cases (carcinoma, thyroiditis, retrovascular goiter, ectopic goiter) the sternotomy should be performed. Postoperative mortality and morbidity is very low, independent of surgical techniques.

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma.

BACKGROUND: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. METHODS: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. RESULTS: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. CONCLUSIONS: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.

Solitary muscle metastasis from lung carcinoma.

Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome. Limb muscle metastasis from lung cancer is extremely rare. We present a case of a 71-year-old man who presented with a solitary metastasis to his right lower limb two months after right upper lobectomy for lung cancer (stage: T2N0M0). Twenty-four months after surgical excision and chemotherapy he is alive without signs of neoplastic disease. We believe that a more aggressive approach might be considered for selected patients with solitary extracranial and extra-adrenal metastasis from lung cancer.

[Role of the surgeon in the treatment of small cell lung carcinoma]. / Ruolo del hcirurgo nel trattamento del carcinoma polmonare a piccole cellule.

Surgery has never played a precise and well consolidated role in the planned treatment of lung microcytoma (SCLC). The acknowledged therapeutic strategy associates local treatment (radiotherapy) with general treatment (chemotherapy). Exeresis is particularly indicated in limited or peripheral forms, followed by intensive polychemotherapy. Scintigraphy with octreotide may be used for the initial screening of patients with widespread disease. Another minor role played by surgery is in the treatment of neoplastic foci remaining after chemotherapy. In some cases the use of a radioguided method which, after intravenous injection of radiolabeled octreotide, allows the accumulation of somatostatin analog in neoplastic foci to be assayed intraoperatively using a manual probe, might help the surgeon to check the radical nature of the operation. In addition, octreotide can be used as a radiotherapeutic pharmacological agent or to enhance the efficacy of chemotherapy in microcytoma and other lung tumours with neuroendocrine differentiation.

[Role of radio-guided surgery with 111In-octreotide in the treatment of thoracic neoplasms]. / Ruolo della chirurgia radio-guidata con in-octreotide nel trattamento delle neoplasie toraciche.

The study evaluates the role of radio-guided surgery (RGS) with 111In-octreotide in the treatment of lung neoplasms. RGS with octreotide appears to be useful in surgery, above all during the intraoperative staging of the tumour; it can define with greater precision the extent of the resections extended towards the lung wall and ensure a radical approach in minimal lung resections.

[Pleural mesothelioma. A case report]. / Mesotelioma pleurico. Descrizione di un caso.

Malignant mesothelioma can be considered a rare neoplasm, very aggressive, chemo- and radio-resistant, characterized by high percentage of mortality and precarious quality of life. Surgery, radio- and chemo-therapy must be administered with articulate strategy and with realistic objective of palliation. Our experience can represent a model in this direction: we treated a patient with palliative surgery and following loco-regional and "maintenance" systemic chemotherapy with taxol at minimal efficacious dosage (135 mg/m2 every 3 weeks). After 27 months the patient is alive and with a good quality of life.

Crohn's disease in infancy: a case report.

Crohn's disease in infants is infrequent. We describe here the case of a baby girl born at the 33rd week of pregnancy, that underwent surgery at the age of 55 days for intestinal occlusion. This was found to be due to stenosis of the right colonic flexure associated with cecum, appendix and terminal ileum. Microscopic examination showed features consistent with Crohn's disease. Eleven years after surgery, followed by cortisone therapy, the patient shows normal growth and is asymptomatic.

[Preliminary experience with radioimmuno-guided surgery of primary neoplasms of the lung]. / Esperienze preliminari sulla chirurgia radioimmunoguidata delle neoplasie primitive del polmone.

BACKGROUND: Radioimmunoguided surgery (RIGS) can be a valid option in the management of lung cancer as well as neoplasms in other anatomic sites. METHODS: We evaluated the usefulness of radioimmunoguided surgery (RIGS) in the staging of primitive non small cell lung cancer. Intraoperatively, this technique can define the lymph nodes involvement and thus, the radicality of the resection. In the first stage of our study, we looked for the epitope TAG 72 in 45 patients with primary non small cell lung cancer. The epitope was found by immunochemistry in only 6 cases. The only one operable patient was injected with monoclonal antibody B 72.3, that was 125I-labelled. RESULTS: At the operation, the monoclonal antibody showed no selectivity for neoplastic cells. Neoplastic tissue and healthy tissue showed a similar detection of the monoclonal antibody both intraoperatively and at the histochemical study. Because of the problems related with this method--e.g. technical difficulties, excessive wasting of time and lack of imaging--we modified our strategy. In this second stage of our study we used fragments of murine anti-CEA monoclonal antibody F023C5. The protocol was performed in 11 patients with squamous cell lung cancer. In one patient operated on for an excavated cancer(not well-defined at the immunoscintigraphy) intraoperative detection was negative while the ex vivo counts were significant: the neoplastic tissue showed a radioactivity twice higher than healthy tissue. Furthermore, the RIGS found a small intraparenchimal lymph node that was seen neither by CT nor by immunoscintigraphy. CONCLUSIONS: Our data are still preliminary, but with improvement of the technique and the use of more specific monoclonal antibodies the RIGS could become a helpful method, able to improve the radicality of surgery for lung cancer.

[Pulmonary blastoma in adults]. / Blastoma polmonare dell'adulto.

Pulmonary blastoma is a rare tumor of the lung consisting of immature mesenchyma and epithelial structures that can mimic the structure of the embryonic lung. In this article, we report a case of pulmonary blastoma occurred in an adult individual. We review the literature concerning this rare neoplasm that includes less than one hundred cases reported. We also describe the pathologic features of this disease which is microscopically divided in two classes: 1) lesions composed solely of malignant gland of embryonic appearance (WDFA: Well-Differentiated Fetal Adenocarcinomas), and 2) lesions with biphasic appearance, containing both neoplastic glands and either adult sarcomatous or embryonic mesenchyme. The adult pulmonary blastomas are considered as an entity distinct from childhood blastomas. This condition may be frequently asymptomatic; if symptomatic, it show the same clinical picture of a mass in the lung impinging on bronchi or pleura; the most usual symptoms include cough, hemoptysis, and chest pain. Chest radiography typically shows a peripheral or central lung opacity without preference for any lobe. The prognosis is poor, due to the high incidence of metastasis. Histologic class and clinical findings can be of prognostic value in pulmonary blastoma. We believe that an early diagnosis is essential: in our case, this allowed a complete resection of the tumor and the patient is still alive without recurrence 3 years after the surgical treatment.

[Cystic adenomatoid malformation of the lung in an adult]. / Malformazione adenomatoide cistica del polmone in un adulto.

Congenital cystic adenomatoid malformation of the lung (CCAM) is characterized by an adenomatoid proliferation of bronchiole-like structures and cysts formation. The condition is most commonly found in newborns and children and it may be associated with other malformations; rarely, the presentation is delayed until adulthood. This paper presents a case of CCAM in a 62-year-old male, who presented with recurrent bacterial pneumonias and breathlessness one exertion. The chest X-rays and CT scan revealed a patchy opacity in the right lower pulmonary zone. Bronchoscopic examination was normal. At surgery, a mass involving the right lower and middle lobes, and enlargement of hilar lymph nodes were found. A bilobectomy was performed without complications. Examination of the gross specimen showed a lesion characterised by multiple small cysts, all less than 1 cm in diameter; they were lined predominately by columnar epithelium, occasionally by ciliated epithelium. Rare cysts were lined by foreign body giant cells. Elastic fibers and smooth muscle were present within the cysts wall. Peripherally, there were normal alveoli and bronchioli mixed with cysts, and plasmalymphocytic infiltrates. The final diagnosis was Stocker's Type II CCAM of the lung. CCAM of the lung is a rare development lesion of the lung and it has no sexual predilection. It is usually unilateral and sublobar or lobar in size, but occasionally it can be multilobar. Typical histologic feature of CCAM are adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands. Inflammatory changes are not found in infants, but may be present in adult patients. Based on the size of the cysts, CCAM may be classified into three different types: type I characterised by multiple cysts, over than 1 cm in diameter; type II with smaller cysts, less than 1 cm in diameter; type III that shows solid lesions composed of bronchiole-like structures. Type II is commonly found in childhood, but is occasionally seen in adult patients, as that one in our report. The insult probably occurs between 4th and 7th week of fetal life. The etiologic agent is unknown. The histologic diagnosis of CCAM is difficult in adult patient, perhaps because of supervening infections that sometimes distort the underlying diagnostic pathologic appearances and make them difficult to recognise, as happened in our case. From the clinical point of view, most of the lesions cause severe respiratory failure; in adult individuals the diagnosis is difficult, since there are very few relevant symptoms and signs. The patients can present with fever, recurrent infections, breathlessness and haemoptysis. The chest X-rays abnormalities are not specific and include homogeneous or multicystic opacities. Similarly, other diagnostic methods add no further useful informations. Surgical treatment is necessary also in adult patients, because of the risk of recurrent pulmonary infections and malignancies associated with CCAM. Lobectomy is the treatment of choice, but sometimes a larger resection is required, when the lesion involves more than one lobe.