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Highlights • Indications for the surgical correction of pectus excavatum. • Pectus excavatum repair was proposed by Ravitch in 1949. • The goal is to remove abnormal rib cartilage in a more anatomic manner. • A case of bilateral pectoralis muscle flap transposition during modified Ravitch procedure. • Significant reduction in late complications and better functional and aesthetic outcomes., Background Indications for the surgical correction of pectus excavatum include functional/physiological, cosmetic, and psychosocial reasons. The most popular open technique for pectus excavatum repair was proposed by Ravitch in 1949 as an open approach that requires partial resection of the costal cartilage, xiphoid excision, and osteotomy of the sternum. The goal is to remove abnormal rib cartilage while preserving the perichondrium, allowing regrowth of the rib cartilage to the sternum in a more anatomic manner. Operative technique. We present a case of bilateral pectoralis muscle flap transposition during a modified Ravitch procedure is presented herein. Conclusion: This approach allows for a significant reduction in late complications and improves both functional and aesthetic outcomes.

// Valentina Masciale 1 , * , Giulia Grisendi 2 , * , Federico Banchelli 3 , * , Roberto D’Amico 3 , Antonino Maiorana 4 , Pamela Sighinolfi 4 , Alessandro Stefani 1 , Uliano Morandi 1 , Massimo Dominici 2 , * and Beatrice Aramini 1 , * 1 Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 2 Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 3 Center of Statistic, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy 4 Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy * Co-first/last authors Correspondence to: Beatrice Aramini, email: beatrice.aramini@unimore.it Keywords: immunophenotype; cancer stem cells; cancer stem-like cells; non-small cell lung cancer (NSCLC); target therapy Received: February 08, 2020 Accepted: April 03, 2020 Published: April 28, 2020 ABSTRACT Objectives: Several studies demonstrated that aldehyde dehydrogenase (ALDH) and CD44 are the most considered cancer stem cells (CSC) markers. However, a comparison between ALDH high cells and CD44+ cells have been previously described with no significant correlation. Indeed, the aim of the present research is to identify a superficial marker able to match with ALDH high cells population in freshly isolated human lung cancer cells. Materials and Methods: This cross-sectional study analyzed the expression of ALDH high/low cells and the positivity for CD44 and epithelium cell adhesion molecule (EPCAM) antigens in surgical lung cancer tissues. The main approach was a cytofluorimetric analysis of ALDH expression and positivity for CD44/EPCAM on primary cell population obtained from 23 patients harboring NSCLC. Results: There was a highly positive correlation between the expressions of ALDH high and CD44+/EPCAM+ cells, with a Pearson’s correlation coefficient equal to 0.69 (95% CI 0.39–0.86; P = 0.0002), and Spearman’s correlation coefficient equal to 0.52 ( P = 0.0124). The average paired difference between the expression of ALDH high and CD44+/EPCAM+ cells was very close to 0, being 0.1% (SD 2.5%); there was no difference between these subpopulations in terms of means (95% CI = –1.0; 1.2%, P = 0.8464). These results highlight a strong similarity between ALDH high and CD44+/EPCAM+ cells. Conclusions: Our study is the first attempt which identifies a high correlation between the ALDH high and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.

IntroductionLung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30–55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC).MethodsThis cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDHhigh (CSC) and ALDHlow (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDHhigh and ALDHlow populations were then assessed and compared.ResultsSurgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDHhigh cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients.ConclusionsOur study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages.

Background: Primary angiosarcoma of the lung is a very aggressive rare malignant disease resulting in a severe prognosis (1). This type of cancer represents about 2% of all soft tissue sarcomas and has a high rate of metastasis through the hematogenous route. For the rarity of this malignant vascular tumor it is still challenging to set a diagnosis (1). The diagnostic features that have thus far been considered include primarily clinical and radiological findings. In some cases, immunohistochemical characteristics based on the most common markers used in pathology have been described. The aim of this report is to present two cases of angiosarcoma of the lung in which the aldehyde dehydrogenase (ALDH) marker was analyzed by immunohistochemistry. Methods: We report two cases of angiosarcoma of the lung in patients underwent lung surgery at our Unit. In addition to the standard histopathological analysis for this disease, immunohistochemistry using an ALDH1A1 antibody was performed in both of the cases. For ALDH quantification, a semi-quantitative method based on the positivity of the tumor cells was used: 0 (25–50%), 3 (>50–75%), 4 (>75%). Results: One patient with recurrent lung disease survived, achieving complete remission after chemo- and radiotherapy. The second patient died of recurrent disease within 5 years of diagnosis. ALDH1A1 was evaluated in both of these cases using an immunohistochemistry scoring system based on the positivity for this marker. The scores were consistent with the patients’ clinical outcomes, as the lower (score 1) was observed in the patient with the better clinical outcome, while the higher (score 3) was seen in the patient with the worse outcome. Conclusion: Our data suggest that ALDH may be an important clinical marker in angiosarcoma of the lung. Although further studies need to be performed in a larger cohort of patients, we believe that, if the results will be confirmed, ALDH1A1 may be used to stratify patients in terms of prognosis and for targeted therapy.

Background: Inflammatory myofibroblast tumor (IMT) is a rare tumor with obscure etiopathogenesis in which different inflammatory cells and myofibroblastic spindle cells are seen histologically. Although the majority of these neoplasms have a benign clinical course, the malignant form has also been reported. The gold standard is surgical treatment for complete removal. Our report describes a 50-year-old woman who underwent surgery for IMT of the lung. The aim is to determine whether cancer stem cells may be present in IMT of the lung. Methods: In April 2018, the patient underwent surgery for tumor mass asportation through lateral thoracotomy. The histology of the tumor was consistent with IMT of the lung. The ALDEFLUOR assay, after tissue digestion, was used to identify and sort human lung cancer cells expressing high and low aldehyde dehydrogenase (ALDH) activity. SOX2, NANOG, OCT-4, and c-MYC positivity were additionally determined by immunohistochemistry. Results: The specimen contained 1.10% ALDHhigh cells among all viable lung cancer cells, which indicates the population of cancer stem cells is not negligible. Immunohistochemically assessed cell positivity for ALDH1A1, SOX2, NANOG, OCT-4, and c-MYC, which are considered as lung cancer stem-like cells markers. Conclusion: For the first time, we demonstrated the presence of cancer stem cells in a case of IMT of the lung. This finding may provide a base for considering new pathological and molecular aspects of this tumor. This perspective suggests further studies to understand the possibility of developing recurrence depending on the presence of cancer stem cells.

Highlights • Vacuum-assisted closure is a well-established technical resource for treating complicated wounds. • In cases of suspicion of bone infection, VAC therapy is not enough to prevent bar removal. • Multiple surgical debridement sessions are mandatory before wound closure in cases of infection. • We present a case of surgical wound dehiscence with hardware exposure. • After VAC therapy and surgical debridement, the bilateral pectoralis muscle flap mobilization has been used., Introduction Multiple surgical debridement sessions are mandatory before wound closure in cases of infection after a modified Ravitch procedure for pectus excavatum. Vacuum-assisted closure (VAC) is a well-established technical resource for treating complicated wounds; however, in cases of suspicion of bone infection, this approach is not enough to prevent bar removal. Presentation of the case We present a case of surgical wound dehiscence with hardware exposure in a patient who had undergone chondrosternoplasty for pectus excavatum. Several sessions of debridement (three) and VAC were applied every time. The final result was achieved without the necessity to remove the hardware; however, to avoid the risk of infection, a bilateral pectoralis muscle flap mobilization was performed as the final step after the surgical wound revisions, although this approach is suggested to be used during the modified Ravitch procedure. This approach allows for a significant reduction in late complications and improves morphological outcomes. Discussion In summary, the pectoralis muscle flap transposition is very useful not only for aesthetical results but also in combination with multiple surgical revisions for conservative management in case of wound infection during a modified Ravitch procedure. In our case, this technique was adopted after accurate care of the wound and before the final closure, which helps to maintain good vascularization and a very satisfying result. Conclusion It is important to consider this approach during the modified Ravitch procedure, not only for better aesthetical results but also to prevent infections or wound dehiscence at the level of the bar.

Background: Lung cancer stem cells (CSCs) share many characteristics with normal stem cells, such as self-renewal and multipotentiality. High expression of aldehyde dehydrogenase (ALDH) has been detected in many tumors, particularly in the CSC compartment, and it plays an important role in tumor proliferation, metastasis, and drug resistance. CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumors. The aim of this study was to isolate and analyze cancer stem-like cells from surgically removed specimens to compare lung adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma. Methods: The ALDEFLUOR assay was used to identify and sort ALDHhigh and ALDHlow human lung cancer cells following tissue digestion. Fluorescence-activated cell sorting analysis for CD44 was performed with tumor cells. Quantitative real-time PCR was performed to assess the expression of SOX2 and NANOG as stemness markers. ALDH1A1 expression was additionally determined by immunohistochemistry. Anchorage-independent ALDHhigh cell growth was also evaluated. ALDHhigh ADENO and SQUAMO cells were cultured to analyze spheroid formation. Results: All specimens contained 0.5–12.5% ALDHhigh cells with 3.8–18.9% CD44-positive cells. SOX2 and NANOG relative expression in ALDHhigh compared to ALDHlow cells in ADENO and SQUAMO was analyzed and compared between the histotypes. Immunohistochemistry confirmed the presence of ALDH1A1 in the sections. SOX2 and NANOG were expressed at higher levels in the ALDHhigh subpopulation than in the ALDHlow subpopulation only in ADENO cells, and the opposite result was seen in SQUAMO cells. In vitro functional assays demonstrated that ALDHhigh cells exhibited migration capacity with distinct behaviors between ALDHhigh spheres in ADENO vs. SQUAMO samples. Conclusions: Our results highlight the importance of a better characterization of cancer stem-like cells in ADENO and SQUAMO histotypes. This may suggest new differential approaches for prognostic and therapeutic purposes in patients with non-small-cell lung cancer.

Background: Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches. Methods: In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALD Hhigh cells. Fluorescence-activated cell sorting (FACS) analyses for CD3+, CD4+, and CD8+ TILs were performed in combination with immunohistochemistry evaluation. Results: Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6–25% positive cells. Conclusions: We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer.

Introduction and importance Mediastinal paragangliomas are rare neuroendocrine tumors that originate from extra-adrenal paraganglia, occasionally secreting catecholamines. Nonfunctional mediastinal paragangliomas present nonspecific clinical and radiological features and represent a diagnostic challenge. Case presentation A 53-year old woman presented with cough and dyspnea increasing over time. CT-scan and ultrasonography showed a large vascularized cervico-mediastinal mass, consistent with an intrathoracic ectopic goiter. Preoperative angiography showed a blood supply from neck vessels. The lesion was completely removed through a cervical approach. The diagnosis of paraganglioma was a histological surprise. The patient is alive without recurrence 30 months after surgery. Clinical discussion When preoperatively diagnosed, the treatment of choice of a mediastinal paraganglioma is surgical excision. However, a preoperative diagnosis of mediastinal paraganglioma is difficult to obtain, especially in cases of nonfunctional lesions. Distinction between an intrathoracic goiter and a nonfunctional paraganglioma can be extremely difficult and, given the rarity of the latter, an ectopic goiter is suspected in first instance. CT-scan and ultrasonography are of little use in the differential diagnosis. However, scintigraphy with 123I-metaiodobenzylguanidine can be an useful diagnostic tool when a paraganglioma is suspected. In case of vascularized cervico-mediastinal mass, such as paragangliomas or intrathoracic goiter, preoperative angiography should be performed to study the blood supply and orient the surgical approach. Conclusion Although uncommon, paragangliomas should be considered in the differential diagnosis of mediastinal masses, especially when an ectopic goiter is suspected., Highlights • Clinical diagnosis of mediastinal nonfunctioning paragangliomas is challenging. • Mediastinal paragangliomas can mimic intrathoracic goiters. • If a clinical suspicion of paraganglioma is raised, 123I-MIBG can be useful. • In case of a vascularized cervico-mediastinal mass, an angiography is recommended. • Angiography can detect the blood supply and guide the surgical approach.

Background Elastofibroma dorsi (ED) is a benign soft-tissue tumor of the chest wall located near the tip of the scapula. Clinical presentation includes swelling, pain and impairment of shoulder movements. The present literature relies only on few small case series. The aim of this study was to analyze the surgical management of ED, focusing on the debated topics regarding preoperative evaluation, operative technique, post-operative outcome and follow-up. Methods We conducted a single-center retrospective cohort analysis of patients operated for ED between 2003 and 2018. Diagnostic techniques were ultrasonography (US), computed tomography (CT-scan) and magnetic resonance imaging (MRI). CT-scan represented our preferred imaging study for preoperative assessment. Surgery was proposed for symptomatic and/or large lesions. Marginal excision through a muscle-sparing approach was performed. An open-door follow-up policy was adopted. All clinical, radiological, perioperative and pathological variables were matched in a univariate analysis. A multivariate analysis was performed to investigate risk factors for postoperative complications. Correlations analysis between radiological and pathological measurements of elastofibroma was conducted. Results Seventy elastofibromas were excised in 59 patients. Mean age was 59 years and female prevalence was 59%. All elastofibromas were completely resected with no recurrence. Postoperative complications rate was 17%. Complications were mild in most cases. At the univariate analysis, patients with body mass index (BMI) >25 had a longer operative time (P=0.048), patients on antiplatelet medications experienced a prolonged drainage time (P=0.006) and a higher rate of complications (P=0.038); the occurrence of complications resulted in prolonged drainage time (P=0.047) and length of stay (P=0.023). A BMI ≤25 was the only independent risk factor for postoperative morbidity (OR 8.71, P=0.024). CT-scan showed the highest correlation with pathological size (r=0.819), US the lowest (r=0.421). Conclusions Marginal resection through a muscle-sparing approach is safe and effective for the treatment of ED. CT-scan can be adequate for preoperative assessment. Giving the benign nature of the lesion and the absence of recurrence after complete resection, an open-door follow-up may be appropriate.

Introduction and importance Pleomorphic carcinoma of the lung is a rare malignant epithelial tumor. Due to its rarity, its clinicopathological characteristics are not clear, and there is no defined therapeutic path for this type of tumor. Case presentation We retrospectively analyzed the medical and pathological reports of 8 patients who underwent surgical resection for pleomorphic carcinoma between 2007 and 2010. Clinical discussion Eight patients were analyzed (7 males and 1 female, mean age 60). All patients underwent CT scans, and the average diameter of the nodules was 56 mm. Four patients were also investigated with FDG-PET with hypermetabolic activity in all four cases. In four patients, the carcinomatous component was adenocarcinoma (all with sarcomatoid component of spindle cell and giant cell carcinoma), although in two patients, it was squamous cell carcinoma (one with spindle cell and one with giant cell). In the two remaining patients, one showed a non-small cell carcinoma with giant cell carcinoma, and the other was a non-small cell carcinoma and squamous cell carcinoma with spindle and giant cell carcinoma. All cases were treated with surgical resection. Only two patients underwent neoadjuvant chemotherapy. At the time of data analysis, only one patient treated with neoadjuvant chemotherapy was alive. Conclusion The prognosis for these patients with a diagnosis of pleomorphic carcinoma undergoing surgery is generally better than those not treated with surgical resection, however the survival remains poor. Although with low number of patients, our research would suggest to consider neoadjuvant chemotherapy an appropriate approach for improving the outcomes before surgery., Highlights • Pleomorphic carcinoma of the lung • Rare malignant epithelial tumor • Clinicopathological characteristics unclear • Not defined therapeutic path • Neoadiuvant chemotherapy improves the prognosis.

BackgroundThe notion that smoking cannabis may damage the respiratory tract has been introduced in recent years but there is still a paucity of studies on this subject. The aim of this study was to investigate the relationship between cannabis smoking, pneumothorax and bullous lung disease in a population of operated patients.Methods and findingsWe performed a retrospective study on patients operated on for spontaneous pneumothorax. Patients were divided into three groups according to their smoking habit: cannabis smokers, only-tobacco smokers and nonsmokers. Cannabis lifetime exposure was expressed in dose-years (1d/y = 1 gram of cannabis/week for one year). Clinical, radiological and perioperative variables were collected. The variables were analyzed to find associations with smoking habit. The impact of the amount of cannabis consumption was also investigated by ROC curves analysis. Of 112 patients, 39 smoked cannabis, 23 smoked only tobacco and 50 were nonsmokers. Median cannabis consumption was 28 dose/years, median tobacco consumption was 6 pack/years. Cannabis smokers presented with more severe chronic respiratory symptoms and bullous lung disease and with a higher incidence of tension pneumothorax than both tobacco smokers and nonsmokers. Cannabis smokers also developed a larger pneumothorax, experienced prolonged postoperative stay and demonstrated a higher incidence of pneumothorax recurrence after the operation than nonsmokers did. The risk of occurrence of chronic respiratory symptoms and bullous lung disease in cannabis smokers was dose-related.ConclusionsCannabis smoking seems to increase the risk of suffering from respiratory complaints and can have detrimental effects on lung parenchyma, in a dose-dependent manner. Cannabis smoking also negatively affected the outcome of patients operated for spontaneous pneumothorax. A history of cannabis abuse should always be taken in patients with pneumothorax. There may be need for a specific treatment for pneumothorax in cannabis smokers.

Pectus excavatum (PE) is the most common congenital chest wall deformity, affecting 1 to 8 in 1,000 live births.1 Indications for the surgical correction of congenital chest wall deformities include functional/physiological, cosmetic, and psychosocial reasons. Palpitations, exertional dyspnea, fatigue, and chest pain are commonly reported symptoms attributed to pectus deformities.2 Many patients report exercise intolerance and increasing limitations in physical activity, which they attribute to their chest deformity. Some patients with PE have been shown to suffer a dynamic restrictive pulmonary process.3 Pectus deformities are often associated with body image issues, especially in patients in their teenage years, and these issues can predispose patients to psychological distress. Surgical repair of pectus deformities was shown to improve both physical limitations and psychosocial well-being in children.3–5 The most common surgical approaches for PE treatment are the modified Ravitch technique and the minimally invasive Nuss technique.4–6 The first technique for PE repair was proposed by Ravitch in 1949 and is an open technique that requires partial resection of the costal cartilage, xiphoid excision, and osteotomy of the sternum.6 Multiple modifications to this procedure have been proposed over time, such as the placement of a metal strut to support the sternum, which is removed within 6 months to 1 year. It was not until nearly half a century later that an alternative surgical option was devised and published.7,8 The goal of the Ravitch procedure is to remove abnormal rib cartilage while preserving the perichondrium, allowing regrowth of the rib cartilage to the sternum in a more anatomic fashion. Other key elements in the operation include performing a sternal osteotomy to allow redirection of the sternum and stabilization of the sternum with a metal bar, when necessary. A modification of the established Ravitch procedure, which is applied to treat symmetric as well as asymmetric forms of PE and carinatum, was established. It requires exposure of the sternum and ribs, removal of abnormal cartilage, and fixation of the sternum in a proper anatomical position with 2 metal bars, 1 inserted into the sternum (Kirschner nail) and 1 perpendicularly (Rush wire) fixed between the bilateral corresponding ribs and the xiphoidal process. The metal bars are left in place for at least a year and then are removed with a second operation. Results have shown this technique to be effective in correcting the deformity but at the expense of a quite invasive and long-lasting surgical procedure associated with 7–10 days of hospitalization and resulting in a long scar on the anterior portion of the chest. Physical activity is also severely restricted for several months as the costal cartilage slowly grows back together. Furthermore, this procedure is associated with a 15%–20% complication rate according to different series.9 A number of complications that can be classified as immediate and late-stage may affect open sternochondroplasty. These complications include hemothorax and pneumothorax, infection, seroma, hardware dislocation, exposure, and eventually inadequate correction or deformity recurrence.9 Early complications may be prevented or solved in most instances (at the expense of a reoperation); however, late complications, such as soft tissue thinning, skin breakdown with hardware exposure, hardware dislocation, and inadequate sternocostal healing, may severely compromise the outcome, posing a relevant clinical challenge (Table ​(Table11). Table 1. Complications of Open Sternochondroplasty

Highlights • Calcified nodules in a goiter are often found when performing an ultrasound of the neck. • Analysis of different calcification patterns could contribute to discriminating between nodules. • Mixed pattern calcifications is not so frequent and not interpreted. • We believe that a better radiologic evaluation setting of thyroid nodules needs to be performed., Background Calcified nodules are often found in a goiter when performing an ultrasound of the neck. An analysis of different calcification patterns could contribute to discriminating between nodules with a lower malignancy risk and those with a higher malignancy risk. In certain cases, the results of a simple cytological analysis of a nodule are not specific enough to be completely trusted. Case presentation We present the case of a goiter with a mixed calcification pattern, including a type of calcification that is strongly associated with a malignant diagnosis, for which a completely benign diagnosis was determined. Conclusion We believe that further studies examining a combination of ultrasound (US) and computed tomography (CT) scan presentations of thyroid nodules need to be performed.

Highlights • The differential diagnosis between pneumothorax and giant bulla is not straightforward. • We emphasized how to differentiate between giant bulla and pneumothorax. • The complexity to differentiate induces to make mistakes in diagnosis and in treatment decision. • Chest CT is mandatory in case of the impossibility to understand the radiological findings., Background The differential diagnosis between pneumothorax and giant bullae is thought to be straightforward but sometimes poses a challenge. Case presentation We present a case of a 54-year-old Caucasian man with a giant emphysematous bulla who underwent surgical resection. He had no smoking history and had previous pneumonia episodes. The surgery was free of complications, without air leaks, and he showed good ventilation of the lung. Discussion The main complications of bullae are pneumothorax, infection and hemorrhage. Pneumothorax is a serious complication in patients with compromised lung function. Therefore, it is very important to carefully distinguish bullae from pneumothorax to avoid iatrogenic pneumothorax in patients with bullous disease. Conclusion We emphasize how to differentiate between giant bullae and pneumothorax utilizing history, physical examination, and radiological studies, including computed tomography (CT) scan.

Lung neuroendocrine cells tumor (NET) classification and diagnosis, particularly for typical and atypical carcinoids, are complicated by a variable natural history and nonspecific symptoms. Mechanisms for the development and progression of well-differentiated lung NETs are still unclear. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and impact on prognosis. One of the main unclear point is the definition of these cells’ composition. In fact, it is known that carcinoids are mainly constituted by neuroendocrine cells. Aim of our report is to show for the first time the presence of a high percentage of cancer stem cells (CSCs) in an atypical carcinoid. The ALDEFLUOR assay was used to identify and sort ALDH(high) and ALDH(low) human lung cancer cells following tissue digestion. SOX2 was additionally determined by immunohistochemistry. All specimens contained the 53.10% of ALDHhigh cells among all viable lung cancer cells, which indicates that more than half of the entire tumor cell population was composed by CSCs. As expected also in immunohistochemistry, about a half of the nuclei of the cells were positive for SOX2. We strongly support the hypothesis of the presence of cancer stem-neuroendocrine cells (CSCs-NETs) as subpopulation in these types of tumors.

Highlights • A multinodular goiter in an HIV-positive with lipodystrophy, buffalo hump and taurine neck. • Needle aspiration biopsy was difficult to use to determine the presence of lipodystrophy. • The goiter was with retrosternal engagement and the ovalization of the tracheal lumen. • Surgical treatment was necessary due to the presence of dyspnea during exercise. • Importance of the perioperative teamwork, in particular to the patient positioning., Background The authors present a case of multinodular goiter in an HIV-positive patient affected by lipodystrophy with particular accumulation of adipose tissue in the region of the neck and trunk. Case presentation The patient, a 53-year-old man, presented with multinodular struma with partial retrosternal engagement, as well as multiple thyroid nodules increasing in size; some of the nodules had suspicious characteristics on ultrasound. Needle aspiration biopsy was difficult to use to determine the presence of lipodystrophy; however, even in the absence of cytology, surgical treatment was necessary due to the presence of dyspnea during exercise, the dimension of the goiter with retrosternal engagement, and the ovalization of the tracheal lumen. The patient underwent total thyroidectomy by anterior cervicotomy with particular attention to patient positioning because of the buffalo hump and taurine neck. Histological examination was positive for adenomatous hyperplasia with outbreaks of papillary microcarcinoma. Conclusions The aim of this case report was to highlight the importance of the perioperative teamwork, with particular attention to patient positioning before surgery, as well as professional collaboration and experience among the operators.

Highlights • Renal cell carcinoma (RCC) is the most frequent type of renal tumor in adults. • RCC is able to metastasize through the blood system and lymphatic system. • Metastases from RCC to the bones are often of the osteolytic type. • The sternal metastatic site for RCC is a rare site and it often begins as pain., Background There are few papers published on sternal metastasis from renal cell carcinoma. The unifying element is the operability of the sternal metastasis if it is the only site of metastasis, on the operability of the primary site of the tumor and on the patient’s health conditions. Presentation of the case We present a case of a 66-years-old man undergone sternal resection for a large painful metastasis. He was previously undergone left nephrectomy for clear cells carcinoma. En bloc resection of the sternal manubrium and right clavicle was performed, a Gore-Tex mesh was placed. Histology confirmed metastasis of kidney clear cells carcinoma. Patient was discharged with no complications and no pain. Chest CT at six months follow up was negative for recurrence. Discussion and conclusion We highlighted the importance of surgery as possible first-line treatment in symptomatic large sternum metastasis. Therefore, prospective studies should be considered to confirm our strategy.

Case Presentation A 72-year-old man underwent endoscopic resection of a 10-mm polypoid sessile lesion of the rectum. Histologic examination found a well-differentiated, low-grade (G1), neuroendocrine tumor. A thoracoabdominal CT scan was performed for staging purposes. The chest CT scan revealed a so-called cannonball-like distribution of multiple rounded nodules, with well-defined margins, ranging from 0.5 to 5 cm, scattered in both lungs (Figs 1A, 1B). The abdominal CT scan showed no abnormalities. A recent colonoscopy showed no evidence of malignancy. No prior chest imaging was available and the patient had never complained of respiratory symptoms. The patient was a former smoker, with a smoking history of 20 pack-years. He had a history of hypertension, mild stenosis of both carotid arteries, and benign prostatic hypertrophy. He reported the presence of long-standing multiple cutaneous hemangiomas on the trunk and face and a larger hemangiomatous lesion on his left lower limb, which was previously investigated by color Doppler ultrasound imaging. All these lesions were reported as unaltered and unchanged since early infancy.

Congenital cystic adenomatoid malformations are lung anomalies usually detected prenatally or in newborns and infants. Type 1 congenital cystic adenomatoid malformations appears as a multicystic lesion, with cysts up to 2 cm in diameter, or as a single large cyst. In the latter case, when detected in adults, the preoperative diagnosis is challenging because congenital cystic adenomatoid malformations can be confused with other more common lesions. We describe two cases of uniloculated type 1 congenital cystic adenomatoid malformation in adults. In both cases, the preoperative clinical diagnosis was missed and the patients were surgically treated with lung-sparing cyst resections.

Vacuum-Assisted Closure (VAC) in association to flap reconstruction is a well-established approach for treating complicated wounds. The authors present a case of soft-tissue breakdown with hardware exposure in a patient treated with modified Ravitch procedure for pectus excavatum. VAC therapy was applied in association to multiple debridement procedures and final flap closure. This was achieved without the need for hardware removal, thus maintaining adequate skeletal fixation. To our knowledge this approach has not yet been described into the literature after sternochondroplasty procedure. Aggressive debridement and VAC therapy before final closure may represent a new, conservative method for managing surgical complications after sternochondroplasty procedures.

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.

Background: The prevention of recurrence after a first episode of primary spontaneous pneumothorax (PSP) remains a debated issue. The likelihood of recurrence based on the presence of blebs and bullae detected on high-resolution computed tomography (HRCT) imaging is controversial. Methods: We evaluated patients conservatively treated for PSP who underwent chest HRCT scan in a single-institution retrospective longitudinal study. Absolute risk values and positive and negative predictive values of recurrence based on HRCT findings were the primary end points. Results: We analyzed 176 patients. Ipsilateral and contralateral recurrence developed in 44.8% and 12% of patients, respectively. The risk of recurrence was significantly related to the presence of blebs or bullae, or both, at HRCT. The risk of ipsilateral recurrence for patients with or without blebs and bullae was 68.1% and 6,1%, respectively (positive predictive value, 68.1%; negative predictive value, 93,9%). The risk of contralateral pneumothorax for patients with or without blebs and bullae was 19% and 0%, respectively (positive predictive value, 19%; negative predictive value, 100%). The risk of ipsilateral recurrence was directly related to the dystrophic severity score: recurrence risk increased by up to 75% in patients with bilateral multiple lesions. Multivariate analysis showed that a positive HRCT was significantly related to ipsilateral recurrence. Conclusions: The presence of blebs and bullae at HRCT after a first episode of PSP is significantly related to the development of an ipsilateral recurrence or a contralateral episode of pneumothorax. Further studies are needed to validate the dystrophic severity score in the selection of patients for early surgical referral. © 2013 The Society of Thoracic Surgeons.

Primary lung tumors arising in pulmonary sequestration is an exceptional event, usually consisting of common histologic types. On the other hand, malignant perivascular epithelioid cell (PEComatous) tumors with deposition of melanin pigment have never been reported in the lung so far. In this study, we report a challenging case of a 34-year-old man presented with recurrent hemoptysis and CT scan detection of a pulmonary mass at the left lower lobe, vascularized by aberrant communication with the left diaphragmatic artery. After surgical resection, we documented a malignant PEComatous tumor (characterized by TFE3 expression and high mitotic rate) that had arisen in the context of an extralobar sequestration.

Pulmonary sarcomatoid carcinoma (PSC) is a very rare subtype of non-small cell lung cancer (NSCLC). The aim of this study was to clarify the pathologic characteristics and long-term survival after surgical treatment in patients with PSC.From January 2003 to December 2013, we retrospectively reviewed the clinical findings, surgical notes, and pathologic and follow-up data from 148 consecutive patients who underwent curative resection for PSC in 5 institutions. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used.Mean age and male to female ratio were 66.6 ± 9.9 years and 120:28, respectively. Surgical resection (pneumonectomy in 8 patients, bilobectomy in 132 patients, and sublobar resection in 8 patients) was complete in 142 cases (96%). At pathologic evaluation, 36 patients (24%) had stage I, 69 patients (47%) had stage II, 33 patients (22%) had stage III, and 10 patients (7%) had stage IV disease. A "biphasic tumor" (PSC with an NSCLC component) was observed in 77 patients (52%). We detected a high rate of vascular emboli in the surgical specimens (overall, 68%; 57% in pathologic stage I tumors), whereas lymphatic emboli were found in 30% of cases (5% of pathologic stage I tumors). Overall median and 5-year long-term survival (LTS) was 19 months and 12.6% (LTS, 16.3% in pathologic stage I), respectively. Distant recurrences frequently occurred after surgical treatment (81%), even in pathologic stage I tumors that underwent R0 resection (62%). Multivariable survival analysis identified R+ resection (hazard ratio [HR],12.3; 95% confidence interval [CI], 3.67-41.28; p0.0001), advanced pathologic stage (HR, 5.75; 95% CI, 2.55-12.98; p 0.0001), and the presence of vascular emboli (HR, 1.67; 95% CI, 1.05-2.67; p = 0.0327) as independent negative prognostic factors.PSCs have very aggressive behavior and high metastatic potential even in early stages. R+ resection, pathologic TNM status, and the presence of vascular emboli are independent prognostic factors.

IntroductionPrognostic evaluation of bronchioloalveolar carcinoma (BAC) from a homogenous population of Caucasian patients.MethodsRetrospective analysis of resected BAC reclassified according to the 2004 World Health Organization classification of lung tumors. Analyzed variables are clinicoradiologic presentation, histologic subtypes, stage, epidermal growth factor receptor (EGFR) and HER2/neu immunohistochemical expression, EGFR exons 18, 19, and 21 mutations, K-RAS exon 2 mutation. Univariate and multivariate analyses of survival were performed.ResultsOf 40 patients analyzed, EGFR and HER2/neu expression were detected in 72% and 20%, respectively. HER2/neu expression significantly characterized mucinous BAC (46% versus 7%; p = 0.014). EGFR mutations were identified in 17% (30% in nonmucinous BAC and none in mucinous BAC; p = 0.083). K-RAS mutations were found in 42.5% (92% in mucinous BAC versus 18% in other types; p < 0.0001). Early stages (IA+IB) nonmucinous BAC had excellent prognosis: 5 years overall survival of 91% (100% for stage IA). Sixty six percent (4 of 6) of patients with multifocal disease died (two mucinous BAC and one nonmucinous BAC with recurrent disease). Seventy one percent (5 of 7) of patients with pneumonic-like tumor (all mucinous BAC) died of recurrent/progressive disease. Stage (p = 0.004) and histologic classifications (p = 0.035) resulted as independent prognostic factors at multivariate analysis.ConclusionsEarly stage nonmucinous BAC has excellent prognosis, whereas mucinous BAC presents a poor prognosis. Locally advanced nonmucinous BAC has a poor prognosis: the diagnosis of nonmucinous BAC in large tumors should be interpreted with caution given the possible presence of invasive areas in incompletely sampled tumor. Coexpression of EGFR and HER2/neu in mucinous BAC could be considered for future trials on target therapies even in Caucasian population.

BACKGROUND: Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. METHODS AND FINDINGS: By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. CONCLUSIONS: Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM. ispartof: PLoS One vol:11 issue:2 ispartof: location:United States status: published

Objectives Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. Materials and methods CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage I–II lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. Results CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, pÂ=Â0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, pÂ=Â0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank pÂ=Â4.2Â×Â10−5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28–46%, log-rank pÂ=Â0.0011) Conclusions The molecular prognostic score stratifies early-stage, resected lung cancer patients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions.

Objective: The aim of this study was to investigate the effectiveness, safety and appropriate mode of administration of intrapleural talc for pleurodesis, in the treatment of malignant pleural effusion (MPE). Methods: Prospective not randomized trial was conducted to compare thoracoscopic talc poudrage (TP) with tube thoracostomy and talc slurry (TS) for the local control of malignant pleural effusion. Both procedures were previously standardized; 6 g of talc was administered for each procedure. Only the patients with lung re-expansion after drainage entered the study. Patients at high risk for general anaesthesia, poor general conditions and short life-expectancy received talc slurry through a chest tube, at the bedside. All the other patients underwent videothoracoscopic talc poudrage,with a pneumatic atomizer, under general anaesthesia. Morbidity, 30-day freedom from recurrence and long-term results were assessed and the two groups were compared. Results: One hundred and nine patients entered the study (72 TP, 37 TS). Sixty-three patients in the TP group (87.5%) and 27 in the TS group (73%) had an immediate successful pleurodesis (p = 0.049); 53 patients (88.3%) and 16 patients (69.6%) had a successful pleurodesis 90 days after the procedure; 59 patients (81.9%) and 23 patients (62.2%), respectively, had a life-long pleural symphysis (p = 0.023). Adverse effects were generally mild: chest pain (36.1% in TP patients, 48.6% in TS patients) and fever (38.8% and 35.1%, respectively) were the more common but the difference was not significant between the two groups. We observed neither acute respiratory failure nor mortality due to the procedure. Conclusions: Our study confirms that intrapleural talc carries good results in the treatment of malignant pleural effusion. TP was significantly more effective than TS; both methods were safe but TS had a higher incidence of thoracic pain during the procedure. Talc pleurodesis should be offered to every patient with MPE, apart from terminally ill ones, provided that a satisfying lung re-expansion has been achieved. TP should be performed whenever possible; otherwise, a slurry bedside procedure will be worthwhile, even in patients with low performance status (PS), though poorerresults have to be expected. A careful selection is essential to define the proper technique.

We report a rare case of malignant pleural mesotheliomapresentingclinically with pneumotho ax and histologically with an exclusiveintrapulmonary lepidic growth. Neither intrathoracic nodules norpleural thickening were found. The patient subsequently experiencedacute abdominal painwith peritonitis and intestinal occlusion byperitoneal mesothelioma. The morphologic clues leading to the correct diagnosis of mesothelioma with prominent intrapulmonary growth are briefly discussed.

OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS: We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Objective: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. Methods: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. Results: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. Conclusions: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies. Q 2005 Elsevier B.V. All rights reserved.

Double strand RNA (dsRNA) species were previously thought to be a ‘junk DNA’ equivalent are related to endogenous retroviral elements (ERV) inserted into the human genome. Genomic integration sites and blocking of these processes have been well documented in HIV and Hepatitis C related diseases. Viral integration into human genome has been shown in a range of solid tumors, but mechanisms less understood. The detection of dsRNA in the research setting has been largely limited to cell line models and controlled transfections. To better characterize function significance of ERV and interactions at the cellular level, we outline efforts to detect and quantify such viral genomic elements with a focus on archival clinical samples in the commonly stored paraffin block. Tissue blocks issues with clinical and biochemical documented viral infection and associated viral cytopathic changes were selected from the Department of Pathology and Biorepository and standard 4 micron sections were prepared. Two (2) commercially available antibodies raised to dsRNA fragments (J2 and K1 antibodies) were directly compared by chromogenic and immunofluorescent methods. In addition, downstream biomarkers as identified by literature searches include RIG-1 and IRF 7 as moderate probable success and MDA-5 and STAT 1 as higher level success. Correlative analysis of downstream pathway markers with labeling results of dsRNA antibodies suffers from lack of sensitive measures of dsRNA fragments as opposed to the downstream cellular pathway markers. This lack of concordance likely reflects the short nature of dsRNAs in decade old paraffin tissue and/or differences in abundance. Future work will focus on developing more sensitive probes or IF probe signal amplification. Prediction of distant recurrence-free survival in resectable lung adenocarcinoma

Spontaneous pneumothorax represents a rare and potentially severe complication of Wegener's granulomatosis. A 31-year-old man with Wegener's granulomatosis on immunosuppressive therapy was admitted for a right massive spontaneous pneumothorax. After chest drainage he presented with a prolonged air leak that required a surgical treatment. Histologic findings did not reveal any necrotizing granulomatous vasculitis, but only subpleural fibrous tissue. We hypothesize that pneumothorax could be related to the subpleural fibrous retraction induced by immunosuppressive therapy.

Methods: From January 1989 to October 1993, at the Department of Cardio-Thoracic Surgery of the University of Modena, 806 patients underwent thoracotomy and curative pulmonary resection for non small-cell lung cancer. Eighty five patients were 70 years old or older (mean 73.4 years, range 70-88). There were 78 males (91.7%) and 7 females (8.3%). This population was compared to 130 younger patients (under 70 years old), treated during the same period and with similar features with respect to the type of resection, sex, histology, grading and staging. Lobectomy was the procedure of preference in both groups. Results: As regards postoperative mortality and overall complications, no significant differences were noted between the two groups of patients (two younger patients died and 43.8% had postoperative complications; one patient of the older group died and 55.2% had postoperative complications), but in the older ones a higher incidence of cardiovascular complications was found (P < 0.01). With respect to the long-term survival (follow-up 12-70 months), no significant difference was found between the two groups. Conclusion: Such findings show that pulmonary resection for bronchogenic cancer is feasible and justified in patients more than 70 years old, even if a higher incidence of cardiovascular complications may occur: a careful preoperative selection ought to be performed and lobectomy should be preferred..

Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1–3glucan, β1–3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA.

Open techniques represent a valid repair option for severe asymmetric pectus excavatum in adults. The use of metal supports is recommended to reduce the risk of recurrence. A wide variety of metal supports have been proposed, with pre-, trans- or retrosternal fixation. A novel open technique using titanium bars fixed to the ribs with clips has been recently introduced (STRATOS™ system) for chest wall reconstruction, rib fracture fixation and chest wall malformation repair. We employed this technique in two adult patients with severe asymmetric pectus excavatum: after sternal mobilization, one bar is passed below the body of the sternum and secured with clips bilaterally to two ribs. In the first case, the results remained excellent 5 years after surgery. In the second case, the initial results were satisfying but the bar ruptured after 30 months: removal of the bars and clips was performed and a subsequent recurrence of the deformity occurred. The experiences reported in literature are still too limited to draw firm conclusions about the use of the STRATOS™ system in pectus excavatum repair, but it seems that the use of two bars may reduce the risk of rupture. At present, we are the only ones who reported long-term results.

Background: Video-assisted thoracoscopic surgery (VATS) and thoracotomy are the main surgical options for treating parapneumonic empyema. The choice of either operation depends on many preoperative features, including the patient's condition, clinical and radiologic findings, and pleural fluid characteristics. The identification of the combination of those preoperative findings that will allow surgeons to select the appropriate approach for a successful operation (VATS or thoracotomy) could be of great interest in clinical settings. Methods: We retrospectively reviewed a series of 97 patients who had undergone successful VATS or thoracotomy for parapneumonic empyema; in all cases, the operation had begun through VATS and was changed to a thoracotomy if a complete decortication was needed. Preoperative clinical, radiologic, and laboratory features were compared between the two groups to search for differences that might serve as predictive factors for either operation. Perioperative findings were also analyzed. Results: The operation was accomplished by VATS in 40 patients (41%), and conversion to thoracotomy was necessary in 57 (59%). Significant predictive factors for conversion were a prolonged delay from diagnosis to operation, the presence of fever and of pleural thickness on computed tomography (CT) images. The 25 patients who presented with these three features were cured by thoracotomy. The operative time and postoperative complication rate were significantly higher for the thoracotomy patients. Conclusions: Some preoperative features can help the surgeon to better select patients for the appropriate operation. Delayed operation, fever, and pleural thickness can be used to predict the likelihood of conversion to thoracotomy. © 2013 The Society of Thoracic Surgeons.

Rationale Clusterin expression may change in various human malignancies, including lung cancer. Patients with resectable non-small cell lung cancer (NSCLC), including adenocarcinoma, have a poor prognosis, with a relapse rate of 30–50% within 5 years. Nuclear factor kB (Nf-kB) is an intracellular protein involved in the initiation and progression of several human cancers, including the lung. Objectives We investigate the role of clusterin and Nf-kB expression in predicting the prognosis of patients with early-stage surgically resected adenocarcinoma of the lung. Findings The level of clusterin gradually decreased from well-differentiated to poorly differentiated adenocarcinomas. Clusterin expression was significantly higher in patients with low-grade adenocarcinoma, in early-stage disease and in women. Clusterin expression was inversely related to relapse and survival in both univariate and multivariate analyses. Finally, we observed an inverse correlation between Nf-kB and clusterin. Conclusions Clusterin expression represents an independent prognostic factor in surgically resected lung adenocarcinoma and was proven to be a useful biomarker for fewer relapses and longer survival in patients in the early stage of disease. The inverse correlation between Nf-kB and clusterin expression confirm the previously reported role of clusterin as potent down regulator of Nf-kB.

Background Non Small Cell Lung Cancer (NSCLC) is the major cause of cancer related-death. Many patients receive diagnosis at advanced stage leading to a poor prognosis. At present, no satisfactory screening tests are available in clinical practice and the discovery and validation of new biomarkers is mandatory. Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-ToF-MS) is a recent high-throughput technique used to detect new tumour markers. In this study we performed SELDI-ToF-MS analysis on serum samples treated with the ProteoMiner™ kit, a combinatorial library of hexapeptide ligands coupled to beads, to reduce the wide dynamic range of protein concentration in the sample. Serum from 44 NSCLC patients and 19 healthy controls were analyzed with IMAC30-Cu and H50 ProteinChip Arrays. Results Comparing SELDI-ToF-MS protein profiles of NSCLC patients and healthy controls, 28 protein peaks were found significantly different (p < 0.05), and were used as predictors to build decision classification trees. This statistical analysis selected 10 protein peaks in the low-mass range (2-24 kDa) and 6 in the high-mass range (40-80 kDa). The classification models for the low-mass range had a sensitivity and specificity of 70.45% (31/44) and 68.42% (13/19) for IMAC30-Cu, and 72.73% (32/44) and 73.68% (14/19) for H50 ProteinChip Arrays. Conclusions These preliminary results suggest that SELDI-ToF-MS protein profiling of serum samples pretreated with ProteoMiner™ can improve the discovery of protein peaks differentially expressed between NSCLC patients and healthy subjects, useful to build classification algorithms with high sensitivity and specificity. However, identification of the significantly different protein peaks needs further study in order to provide a better understanding of the biological nature of these potential biomarkers and their role in the underlying disease process.

N1 non-small-cell lung cancer has heterogeneous prognosis in relation to node descriptors. There is no agreement on the ideal type of resection. A new classification of N1 descriptors was proposed in the 7th edition of the TNM staging system. A retrospective study was conducted on 384 patients with T1-T3N1 non-small-cell lung cancer who underwent complete pulmonary resection. The prognostic role of N1 descriptors according to the current and new staging systems and type of resection was investigated. The 5-year survival rate was 46%. Involvement of hilar node stations, multiple stations, and multiple nodes were poor prognostic factors (5-year survival, 33%, 21%, and 30%, respectively), as well as involvement of the hilar zone and multiple zones (5-year survival, 27% and 23%, respectively). Pneumonectomy showed significantly better survival rates compared to lobectomy or bilobectomy (5-year survival, 60% vs. 29%). Multivariate analysis showed that the number of N1 zones and type of resection were independent prognostic factors. Patients with hilar nodal, multiple-level, or multiple-zone involvement had poor prognosis. Standard lobectomy remains the procedure of choice, but in cases of fixed nodes in the hilar zone, sleeve resection or even pneumonectomy should be considered.

Adipose-derived mesenchymal stromal/stem cells (AD-MSC) may offer efficient tools for cell-based gene therapy approaches. In this study, we evaluated whether AD-MSC could deliver proapoptotic molecules for cancer treatment. Human AD-MSCs were isolated and transduced with a retroviral vector encoding full-length human tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a proapoptotic ligand that induces apoptosis in a variety of human cancers but not normal tissues. Although several studies have documented the antitumor activity of recombinant human TRAIL, its use in vivo is limited by a short half-life in plasma due to a rapid clearance by the kidney. We found that these limitations can be overcome using stably transduced AD-MSC, which could serve as a constant source of TRAIL production. AD-MSC armed with TRAIL targeted a variety of tumor cell lines in vitro, including human cervical carcinoma, pancreatic cancer, colon cancer, and, in combination with bortezomib, TRAIL-resistant breast cancer cells. Killing activity was associated with activation of caspase-8 as expected. When injected i.v. or s.c. into mice, AD-MSC armed with TRAIL localized into tumors and mediated apoptosis without significant apparent toxicities to normal tissues. Collectively, our results provide preclinical support for a model of TRAIL-based cancer therapy relying on the use of adipose-derived mesenchymal progenitors as cellular vectors. Cancer Res; 70(9); 3718–29. ©2010 AACR.

Retrospective evaluation of long-term functional results of surgical treatment of chronic pleural empyema. Two different surgical procedures (debridement vs. decortication) and approaches (VATS vs. thoracotomy) were analyzed. Three end-points were considered: short-term surgical results, short- and long-term radiological results, clinico-functional long-term results. Fifty-one debridement (52% VATS, 48% thoracotomy) and 68 decortication were performed. Postoperative mortality and morbidity were 1.5% and 24%, respectively. Older age (70 years old) had worse postoperative morbidity (P=0.048). Video-assisted thoracic surgery (VATS) debridement had lower postoperative hospital stay (P=0.006) and shorter duration of chest drainage (P=0.006). The infectious process was resolved in all patients. All patients presented a postoperative radiological improvement, 63 patients (60%) with a complete pulmonary re-expansion. Sixty patients (58%) referred a complete respiratory recovery. VATS debridement had a greater improvement in subjective dyspnea degree (P=0.041). The long-term spirometric evaluation was normal in 58 patients (56%). Age70 years old resulted the only variable associated to poor long-term results (FEV(1)%60% and/or MRC gradeor = 2) at multivariate analysis. Surgical treatment of pleural empyema achieves excellent long-term respiratory outcomes. VATS is associated to less postoperative mortality and shorter postoperative hospital stay. In elderly patients, postoperative morbidity could be higher and long-term functional improvement less warranted.

The current WHO classification of lung tumors recognizes bronchial typical carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites. Symptoms are usually related to local compression and obstruction of the bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome, Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy are useful in the preoperative staging. Only selected cases can be treated endoscopically with laser resection. The complete surgical resection remains the only therapy with curative intent in the majority of patients. Parenchyma-sparing resections are indicated whenever possible. Overall survival after surgery is excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status and type of resection seem not to affect prognosis. Local relapse can be treated successfully with surgery, whereas distant metastases have a poor prognosis even after chemotherapy.

The current TNM staging system for non-small cell lung cancer subdivides stage IA and IB according to a tumor size threshold of 3 cm. Some authors have suggested that tumor size behaves as a continuous, but the optimal diameter thresholds to be adopted remain debated.We conducted a retrospective study on 548 patients who underwent a complete surgical resection at our institute for stage IA and IB non-small cell lung cancer according to the current TNM staging system. Univariate and multiaviate analysis of overall and disease-specific survival were performed.Stage IA had an overall 5 years survival of 67% and a 5 years disease-specific survival of 85%. Stage IB had an overall 5 years of 49% and 5 years disease-specific survival of 53%. Tumors2 cm had a significantly better survival than tumorsor =2 cm (overall survival: p=0.007; disease-specific survival: p=0.026), as well as tumors ranging from 2 to 5 cm in comparison with larger ones (overall survival: p=0.031; disease-specific survival: p=0.013). No significant difference was found between groups ranging from 2 to 5 cm. Tumors of 2-5 cm had 57% higher probability of death in comparison with tumors2 cm and tumors5 cm had a probability of death 60% higher than tumor of 2-5 cm. Age and tumor size (two thresholds diameter classification) resulted independent variables at multivariate analysis.the definition of T factor in the staging system of non-small cell lung cancer should consider two cutoffs according to tumor size. Two and 5 cm represent appropriate thresholds diameters that define subgroups with significant different prognosis.

Summary Objective Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. Patients and methods The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan–Meier method, and compared by the log rank test. Results There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p = 0.001 log-rank test on Kaplan–Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p = 0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. Conclusion large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease.

Purpose Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets. Patients and Methods We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRα, PDGFRβ, and Met. Results LCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRα in 60.2%, PDGFRβ in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (≥ 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001). Conclusion Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide–based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRα, PDGFRβ, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.