Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report.

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan-Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.

Screen-detected multiple primary lung cancers in the ITALUNG trial.

Occurrence of multiple primary lung cancers (MPLC) in individuals undergoing low-dose computed tomography (LDCT) screening has not been thoroughly addressed. We investigated MPLC in subjects recruited in the ITALUNG randomized clinical trial. Cases of cytologically/histologically proven MPLC detected at screening LDCT or follow-up CT were selected and pathologically re-evaluated according to the WHO 2015 classification. Overall 16 MPLC were diagnosed at screening LDCT (n=14, all present at baseline) or follow-up CT (n=2) in six subjects (4 in one subject, 3 in two and 2 in three subjects), representing 0.43% of the 1,406 screenees and 15.8% of the 38 subjects with at least one screen-detected primary lung cancer. MPLC included 9 adenocarcinomas in three subjects and a combination of 7 different tumour histotypes in three subjects. MPLC, mostly adenocarcinomas, are not uncommon in smokers and ex-smokers with at least one LDCT screen detected primary lung cancer.

Gorham-Stout Disease Management during Pregnancy.

Gorham-Stout Disease (GSD) is a rare lymphatic disorder affecting children or young adults with no predilection of sex. It is generally associated with vanishing bone osteolytic lesions, thoracic and abdominal involvement, and diffuse pulmonary lymphangiomatosis. Chylous effusions and chylothorax, consequent to the abnormal proliferation of lymphatic vessels, may induce respiratory failure with a high mortality risk. Extrapulmonary alterations may include chylous ascites, lymphopenia, and destructing bone disease for overgrowth of lymphatic vessels. Here, we report the case of a young woman who developed a severe and recalcitrant GSD with persistent unilateral chylothorax during pregnancy. The complex management of this patient during and after pregnancy was discussed and compared with literature data to contribute to the definition of a correct diagnostic and therapeutic approach to this rare lymphatic disease.

Does videomediastinoscopy with frozen sections improve mediastinal staging during video-assisted thoracic surgery pulmonary resections?

BACKGROUND: To assess if video-mediastinoscopy (VM) with frozen sections (FS) combined with a video-assisted thoracic surgery major pulmonary resection (VMPRS) is able to improve VATS mediastinal intraoperative staging. METHODS: From June 2012 to March 2015 a total of 146 patients underwent VMPRS lymphadenectomy. NCCN guidelines were followed for pre-operative staging, including VM with FS in 27 patients (19%). Procedural time, dissected nodal stations, complications related to VM and VATS lymphadenectomy and definitive histology, were evaluated. RESULTS: Operative time for VATS resection with VM (group 1) and VATS pulmonary resection alone (group 2) was 198±64 vs. 167±43 min (P=0.003). Mean/median numbers of dissected nodal stations were 4.93±1.1/5 (range, 4-8) in group 1 and 3.25±0.5/5 (range, 3-8) in group 2 (P<0.001). Group 1 vs. group 2 right-sided lymphadenectomy (n=86) was performed at station 2R/4R in 18 (90%) and 46 (69.7%); at station 3a/3p in 14 (51.8%) and 22 (31%); at station 7 in 18 (90%) and 44 (66.7%); at station 8/9 in 11 (55%) and 24 (36.4%) respectively. On the left side (n=60) group 1 vs. group 2 lymphadenectomy resulted at station 4 in 6 (85.7%) and 38 (71.7%); at station 5/6 in 6 (85.7%) and 26 (49%); at station 7 in 6 (85.7%) and 33 (62.3%), and at station 8/9 in 1 (14.3%) and 18 (34%). There were no early deaths and recurrent laryngeal nerve palsy occurred in 1 (0.8%) in group 2. Pathological upstaging (pN1; pN2) was found in 5 patients (17%) in group 1, and 13 (11%) in group 2 (P=0.23). About FS (n=29), formal paraffin histology resulted in 0% of both, false negative and false positive results. CONCLUSIONS: Based on our experience, the combination "VM with FS followed by VMPRS in sequence", seems to be effective and offers an alternative approach to improve intraoperative mediastinal staging.

Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma.

AIMS AND BACKGROUND: A number of immunohistochemical markers have been suggested as useful in the positive diagnosis of epithelioid mesothelioma. The most widely used mesothelioma markers are thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1. Numerous investigations have demonstrated their variable sensitivity and specificity in differentiating epithelioid mesothelioma from lung adenocarcinoma. However, data on the expression of these markers in other types of lung carcinomas are very limited. We evaluated the expression of these markers in a series of 172 primary carcinomas of the lung and in 75 epithelioid pleural mesotheliomas. RESULTS: Thrombomodulin expression was found in squamous cell carcinomas (71%), small cell lung carcinomas (11%), adenocarcinomas (4%), large cell carcinomas (50%), large cell neuroendocrine carcinomas (25%) and in sarcomatoid carcinomas (10%). Calretinin expression was common in small cell lung carcinomas (44%) and large cell neuroendocrine carcinomas (25%), less common in squamous cell carcinomas (20%), rare and focal in adenocarcinomas (4%) and sarcomatoid carcinomas (10%). Cytokeratin 5/6 was expressed in most of the squamous cell carcinomas (94.5%). Immunoreactivity was also found in large cell carcinomas (50%), sarcomatoid carcinomas (30%) and rarely in adenocarcinomas (4%). D2-40 was consistently expressed in squamous cell carcinomas (42%). Focal immunoreactivity was found in adenocarcinomas (3%). WT-1 was focally present in one (2%) squamous cell carcinoma. CONCLUSIONS: These results indicate that some of the most commonly used mesothelioma markers may react with different types of primary lung carcinomas. These data should be taken into consideration especially when dealing with small biopsy fragments and poorly differentiated tumors.

Preliminary results of the influence of the in vivo use of a lymphatic dye (patent blue v) in the surgical treatment of Crohn's disease.

INTRODUCTION: Recently, the lymphatic vessels has been considered to play a key role in the pathophysiology and, consequently, in the treatment of Crohn's disease (CD). The aim of this study is to show that the evaluation of lymphatic anomaly might be a useful tool in the recognition of the pathological involvement of the intestinal wall in CD. MATERIAL AND METHODS: Fourteen patients with CD who underwent surgical treatment for distal ileum critical stenosis were prospectively evaluated. During surgery, 0.05 to 0.1 mL of Patent Blue V was injected into the subserosal layer of the antimesenteric edge of ileum and colon. The intestinal section was performed just beneath the outflow of the vital dye where it seemed to be normal (≤2 minutes), as a index of healthy intestinal wall. A comparison between the lymphatic alterations and the macroscopic aspects was performed. RESULTS: Out of 14 patients, 13 were electively operated on, whereas 1 was treated in emergency. In 8 patients (57%), laparoscopic approach was chosen in the first instance. One patient needed laparotomic conversion. When comparing the Patent Blue V outflow time with the macroscopic and microscopic evidence of CD, we found an absolute integrity of the intestinal wall with an outflow ≤2 minutes. Mean follow-up was 110 months with a recurrence rate of 14%. CONCLUSION: We can conclude that this method may be of utility to distinguish between normal and diseased intestine in CD. The possible consequences in postsurgical recurrences of this evidence are critical.

Long-term changes to in vitro preserved bioengineered human trachea and their implications for decellularized tissues.

Bioengineered tissues created for transplant will be expected to survive and contribute to function over the lifetime of the individual. To evaluate potential intrinsic changes and degradation of the extracellular matrix of decellularized human tissue scaffolds, human decellularized tracheas were evaluated over a one year period in vitro. Human tracheas were decellularized and stored for one year in phosphate-buffered saline at 4 °C in the presence of antibiotics and anti-mycotics, and their structural, mechanical, and angiogenic properties compared to baseline values. Results showed that stored human decellularized tracheas were increasingly degraded resulting in a loss of extracellular matrix architecture - in particular of collagenous and elastic fiber structure -and decreased mechanical and angiogenic properties. The mechanical alterations of the extracellular matrix but not the deterioration and microstructure were not improved by using a natural cross-linking agent. These findings demonstrate that human decellularized tracheas, stored for one year in phosphate-buffered saline solution at 4 °C, would not meet the demands for a tissue engineering matrix and likely would not yield a suitable graft for lifelong implantation. The degradation phenomenon observed in vitro may be further enhanced in vivo, having clinical relevance for tissues that will be transplanted long-term and this should be carefully evaluated in pre-clinical settings.

Diffuse cystic lung disease of unexplained cause with coexistent small airway disease: a possible causal relationship?

Diffuse "true" cystic lung disease is rare, and the specificity of high-resolution computed tomography (HRCT) has reduced the need for biopsy. We present 5 patients with similar clinical and HRCT features of cystic lung disease that were sufficiently atypical to warrant surgical lung biopsies that showed coexistent small airway diseases (SAD). There were 4 female patients and 1 male patient with a mean age of 43 years. All were never smokers. Four had symptoms such as dyspnea (1), cough (2), or both (1). HRCTs showed variably sized thin-walled cystic airspaces without zonal distribution, some with prominent vessels in their walls. One case was unilateral. Surgical lung biopsy showed cystic change comprising localized loss of alveolar density with coexistent SADs [chronic bronchiolitis (n=2), eosinophilic bronchiolitis, probable asthma (n=1), and diffuse idiopathic neuroendocrine cell hyperplasia (n=2)]. Two patients who were tested for Birt-Hogg-Dube-related gene mutations proved negative, and all lacked other features of Birt-Hogg-Dube. We hypothesize that chronic damage to small airways may lead to cystic degeneration in a minority of patients. Precedents in relation to Sjogren syndrome and hypersensitivity pneumonitis raise the possibility of a causal association between pathologies in these 2 anatomic compartments, although HRCT data in relation to common SADs indicate that this would be a rare phenomenon. The driving factor remains unknown.

Biomechanical and angiogenic properties of tissue-engineered rat trachea using genipin cross-linked decellularized tissue.

In this study, the obtainment and characterization of decellularized rat tracheal grafts are described. The detergent-enzymatic method, already used to develop bioengineered pig and human trachea scaffolds, has been applied to rat tracheae in order to obtain airway grafts suitable to be used to improve our knowledge on the process of tissue-engineered airway transplantation and regeneration. The results demonstrated that, after 9 detergent-enzymatic cycles, almost complete decellularized tracheae, retaining the hierarchical and mechanical properties of the native tissues with strong in vivo angiogenic characteristics, could be obtained. Moreover, to improve the mechanical properties of decellularized tracheae, genipin is here considered as a naturally derived cross-linking agent. The results demonstrated that the treatment increased mechanical properties, in term of secant modulus, without neither altering the pro-angiogenic properties of decellularized airway matrices or eliciting an in vivo inflammatory response.

Development of bioengineered human larynx.

To date, only two human laryngeal allotransplants have been reported and, although they were successful, both patients required life-long immunosuppression. A bioengineered human larynx could represent a possible alternative to allotransplantation. Human larynxes were decellularized enzymatically to obtain acellular matrices. Histological and molecular analysis demonstrated that all cellular components and nuclear material were removed. SEM showed that decellularized matrices retained the hierarchical structures of the native larynx, and mechanical tests demonstrated that the decellularization did not significantly impaired the biomechanically properties of the obtained matrices. Immunohistochemical staining found residual angiogenic factors after decellularization, and CAM analysis demonstrated that acellular laryngeal scaffolds induce a strong in vivo angiogenic response. Using a decellularization method, we are now able to obtain, in a short and clinically useful time, natural bioengineered laryngeal scaffolds which could be use for partial or total implantation in humans.

Epidermal growth factor receptor and K-RAS mutations in 411 lung adenocarcinoma: a population-based prospective study.

Targeting the epidermal growth factor receptor has played a central role in advanced non-small cell lung cancer research, treatment, and patient outcomes over the last several years; however, a number of questions about this approach remain to be addressed. Through the Istituto Toscano Tumori and the Italian Association of Women Against Lung Cancer Project, we collected 411 lung adenocarcinomas from several clinical centers in Tuscany. Mutations were assessed by sequencing exons 18-21 of the epidermal growth factor receptor gene, and by restriction fragment length polymorphism analysis of codons 12 and 13 of the K-RAS gene. Epidermal growth factor receptor mutations (12.6%) were more frequently observed in females (p<0.0001), in non-smokers (p=0.005), and in the presence of bronchioloalveolar features (p=0.0004). K-RAS mutations (17.9%) were more frequent in males (p=0.0007) and were associated with smoking habits (p=0.005). Epidermal growth factor receptor and K-RAS mutations were mutually exclusive (p=0.001). We focused on 21 female patients with advanced/metastatic lung adenocarcinoma who received gefitinib 250 mg/day (expanded access) or erlotinib 150 mg/die as second/third-line therapy; partial response was associated with classic epidermal growth factor receptor mutations (p=0.006) and with a non-smoking history (p=0.02). None of the female patients with partial response and/or stable disease showed K-RAS alterations. Although the data obtained in our study have yet to be analyzed and confirmed with a larger number of patients treated with tyrosine kinase inhibitors, they should provide useful information for targeted therapy, in particular for non-smoking female lung cancer patients.

Skin metastasis from typical carcinoid tumor of the lung.

Carcinoids are neuroendocrine tumors that may arise within any organ, although they are more commonly found in the gastrointestinal tract and in the bronchopulmonary tract. They are generally characterized by an indolent clinical course but may in some instances metastatise to regional lymph nodes or to distant sites. We herein describe a rather infrequent case of a 60-year-old man with a skin metastasis from a typical carcinoid of the lung. We discuss the histopathological and immunohistochemical features in the context of previous literature and comment issues related to difficulties in the differential diagnosis. Dermatopathologists should be familiar with the metastatic carcinoid profile in order to avoid potential misdiagnoses and to properly address the patient management when the skin metastasis represents the first manifestation of an internal disease.

Liver angiogenesis as a risk factor for hepatocellular carcinoma development in hepatitis C virus cirrhotic patients.

AIM: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. METHODS: One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies. RESULTS: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (chi(2) = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: chi(2) = 1.41; P = 0.2351; PCNA: chi(2) = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD < or = 4 (P = 0.0006). No relationship was found between MIB1 or PCNA and MVD (MIB-1 r(2) = 0.00007116, P = 0.9281; PCNA: r(2) = 0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION: Liver angiogenesis has a role for in HCV-related liver carcinogenesis and for defining patients at higher risk.

h-caldesmon, calretinin, estrogen receptor, and Ber-EP4: a useful combination of immunohistochemical markers for differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.

Distinguishing between epithelioid peritoneal mesothelioma and papillary serous carcinomas involving the peritoneum may be very difficult, owing to overlapping morphologic features. Immunohistochemistry may facilitate establishing a correct diagnosis, but, as no single antibody has demonstrated absolute sensitivity and specificity for either mesothelioma or serous carcinoma, the differential diagnosis is based mainly on the combined use of several markers. The purpose of this study was to ascertain the sensitivity and specificity of a series of mesothelial markers [including more recently investigated antigens such as h-caldesmon (h-CD) and D2-40] and, using receiver operating characteristic curve analysis, to identify a selected appropriate panel of antibodies for differentiating between epithelioid peritoneal mesothelioma and serous papillary carcinoma of the ovary. Fifteen cases of epithelioid peritoneal mesothelioma and 40 cases of papillary serous carcinoma of the ovary (25 primary and 15 metastatic to the peritoneum) were immunostained for h-CD, D2-40, calretinin, cytokeratin 5/6, thrombomodulin, estrogen and progesterone receptors (ER and PR), Ber-EP4, B72.3, CA19-9, and CD15. h-CD and calretinin showed the highest sensitivity (100%), followed by D2-40 (93.3%) and cytokeratin 5/6 (93.3%); thrombomodulin had the lowest sensitivity (60%). h-CD and thrombomodulin had the best specificity (95%) for mesothelioma, followed by calretinin (87.5%), D2-40 (80%), and cytokeratin 5/6 (72.5%). Among carcinoma markers, ER and Ber-EP4 demonstrated the highest sensitivity (95%) followed by B72.3 (72.5%), PR (65%), CA19.9 (60%), and CD15 (45%). The specificity of the nonmesothelial markers was 100%, except for Ber-EP4 (93.3%). The relationship between the values of sensitivity and specificity of each marker using receiver operating characteristic analysis permitted the identification of h-CD, calretinin, ER, and Ber-EP4 as the markers with the best performance in differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.

Clear cell sarcoma of the ileum: report of a case and review of literature.

Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile and with morphological features resembling those of melanoma. CCS has been rarely described in other locations other than the soft tissues, including the gastrointestinal tract. In this study, we report a case of CCS arising in the ileum of a 31-year-old woman. Histologically, the tumor involved the entire thickness of the intestinal wall. Tumor cells were polygonal or fusiform, with clear or eosinophilic cytoplasm, arranged in a uniform nested to fascicular growth pattern. Immunohistochemical studies revealed strong positivity for vimentin and S-100 protein. HMB-45, Melan-A, tyrosinase, cytokeratins, EMA, smooth muscle actin, CD34, CD31, CD117, CD99, synaptophysin, chromogranin A, CD56, and NSE were negative. Fluorescence in situ hybridization analysis demonstrated the presence of a t(12;22)(q13;q12) translocation, the diagnostic hallmark of CCS of soft parts. The present case, together with a detailed review of the literature on this topic, demonstrates that the gastrointestinal tract is a possible site of CCS of soft tissues and that making a reliable diagnosis of this tumor requires cytogenetic or molecular diagnostic investigations.

Prognostic variability among nonsmall cell lung cancer patients with pathologic N1 lymph node involvement. Epidemiological figures with strong clinical implications.

BACKGROUND: Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement. METHODS: The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection. RESULTS: The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor. CONCLUSIONS: N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.

Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma.

Approximately 30% of patients with lymph node (LN)-negative colorectal carcinoma (CRC) die of tumor recurrence, which can be related to the presence of tumor cells in LNs not detected by conventional histopathologic analysis. However, the prognostic significance of occult cancer cells still remains uncertain. We evaluated the incidence and the prognostic significance of occult cancer cells in LNs from 395 consecutive patients with curatively resected stage IIA CRC using immunohistochemistry for cytokeratin 20. Immunostained tumor cells were categorized as micrometastases (MCMs) or isolated tumor cells (ITCs) according to the American Joint Committee on Cancer criteria. The detection rates were compared with the clinicopathologic characteristics of the patients and with cancer-specific survival. The median follow-up time was 128 months. Micrometastases were detected in 39 patients (9.9%), whereas ITCs were found in 112 (28.4%), for an overall frequency of 38.2%. None of the clinicopathologic parameters examined was correlated with the presence of occult cancer cells. Patients with ITCs and those with negative LNs showed a similar survival rate (77.7% and 78.3%, respectively), whereas patients with MCMs had a lower survival rate (64.1%). At the univariate analysis, MCMs, tumor growth pattern, extent of tumor spread, and Crohn's-like lymphoid reaction influenced the survival rate significantly. Nevertheless, at the multivariate analysis, only the pattern of tumor growth and the extent of tumor spread were independent prognostic factors. The detection of immunostained tumor cells in the LNs of patients with stage IIA CRC occurs relatively frequently but has no significant effect on prognosis.

hERG1 channels in human esophagus: evidence for their aberrant expression in the malignant progression of Barrett's esophagus.

Ion channels regulate a broad range of cellular activities. Alteration in ion channel function has been reported in different human pathologies, such as cardiac, neuromuscular, autoimmune diseases, and cancer. We investigated the expression of hERG1 K+ channels in the human upper gastrointestinal tract, focusing our attention on the lower esophagus. In particular, we analyzed by both Reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) endoscopic samples obtained from normal subjects, from patients suffering from gastroesophageal reflux, associated or not with esophagitis, and from patients affected by Barrett's esophagus (BE), that is, intestinal metaplasia. None of the normal samples, nor those from patients with gastro-esophageal reflux symptoms and reflux esophagitis expressed the hERG1 protein. On the other hand, 69% of patients with BE expressed hERG1. Since BE is a preneoplastic lesion, dysplasias (Ds) and adenocarcinomas (ADKs) arising on a previously diagnosed BE were also analyzed, and all the samples showed a high expression of the hERG1 protein. The surveillance of patients with BE showed that 89% of those who later developed ADKs displayed hERG1 expression. Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.

h-Caldesmon, a useful positive marker in the diagnosis of pleural malignant mesothelioma, epithelioid type.

Although a large number of immunohistochemical markers that can facilitate the differential diagnosis between epithelioid pleural mesothelioma and lung adenocarcinoma involving the pleura have proven to be valuable, no single antibody has demonstrated absolute sensitivity and/or specificity in making this distinction. Using immunohistochemical analysis with h-caldesmon, a specific marker for smooth muscle tumors, we examined 70 cases of epithelial mesotheliomas and 70 cases of lung adenocarcinomas. In addition, immunohistochemistry for muscle markers, such as desmin, alpha-smooth-muscle actin, muscle-specific actin, myoglobin, myogenin, myosin, and MyoD-1, was performed on all mesothelioma cases. Reactivity for h-caldesmon was obtained in 68 (97%) of the 70 epithelial mesotheliomas, but in none of the adenocarcinoma cases. All mesothelioma cases were found to be negative for the other muscle markers examined. We conclude that h-caldesmon is a highly sensitive and specific marker and suggest its inclusion in the immunohistochemical panel for the differential diagnosis of epithelioid mesothelioma versus lung adenocarcinoma.