Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis.

In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC.

Increased carotid intima-media thickness in pre-pubertal children with constitutional leanness and severe obesity: the speculative role of insulin sensitivity, oxidant status, and chronic inflammation.

DESIGN: In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children. METHODS: Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2alpha), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound. RESULTS: hs-CRP was not different between lean and control subjects (P=0.45), while higher values were found in obese compared with lean and control children (P<0.001 and P<0.001 respectively). PGF-2alpha and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P<0.001; P<0.001; P<0.001 and obese P<0.001; P<0.001; P<0.001 respectively), while no differences were documented between lean and obese subjects (P=0.78, P=0.019, and P=0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (P=0.001; P=0.004), while no differences were documented between obese and lean subjects (P=0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2alpha (beta=0.641, P<0.001) and HOMA-IR (beta=0.307; P<0.001). CONCLUSIONS: Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.

A new polymorphism (Ser362Thr) of the L-myc gene is not associated with lung adenocarcinoma risk and prognosis.

The non-coding variation in the second intron of the L-myc gene, generating an EcoRI polymorphism, is associated with lung cancer risk and prognosis. We carried out sequence analysis of the L-myc gene in lung adenocarcinoma (ADCA) patients to identify functional polymorphisms and identified a new single nucleotide polymorphism (SNP) in the third exon of the gene causing a Ser362Thr conservative amino acid change in the C-terminus of the encoded protein. This polymorphism showed significant linkage disequilibrium with the L-myc EcoRI polymorphism located at 1751 bp distance. Genotyping of the Ser362Thr SNP in 220 Italian ADCA patients and in 230 general population controls revealed a similar low frequency (0.10-0.11) of the Thr allele in both groups. The multivariate odds ratio was 0.68 (95% confidence interval (CI) 0.38-1.22). In the ADCA patients, no significant association between the Ser/Thr polymorphism and survival was observed. Thus, the present results do not support candidacy of the L-myc Ser362Thr polymorphism for the functional polymorphism of the L-myc genomic region.

[The role of surgical therapy for esophageal microcytoma. Experience of there clinical cases and results analysis]. / Il ruolo della terapia chirurgica nel microcitoma dell'esofago. Esperienza di tre casi clinici ed analisi dei risultati.

Small cell carcinoma of the esophagus is a rare tumor. It was described for the first time in 1952 by McKeown and 200 cases have been reported till now. Because of its similarity with small cell carcinoma of the lung, the treatment of this tumor is controversial. In our Institute we treated three patients with small cell carcinoma of the esophagus. All subjects underwent subtotal esophagectomy with esophagogastroanastomosis through laparotomic and thoracotomic approach. Histologically, the tumor was classified as pure SCEC in one patient and mixed SCEC in the other two. The stage I and II patients received operation as single treatment. The two patients are alive and disease free 219 and 193 months after surgery. The third patient, classified at stage III, underwent postoperative chemotherapy but local and distant recurrence was observed 11 months after surgical resection. He was submitted to a second choice chemotherapy, but he died 24 months after the operation. The long-term survival observed in our two patients treated by surgery is the longest described in literature. Our experience seems to demonstrate that an early diagnosis and oncological radical resection, may be helpful in the long-term prognosis even in presence of a very aggressive neoplasm.

[Biphasic blastoma of the lung. Report of 4 consecutive cases and evaluation of long-term prognosis]. / Il blastoma bifasico del polmone. Report di 4 case consecutivi e valutazione della prognosi a distanza.

Pulmonary blastoma is a rare malignant disease and it can occur in adults and in children. In 1952, Barnard reported the first case classified as pulmonary embryoma while in 1961 Spencer reported the first case as pulmonary blastoma. Since then 200 cases were described in literature. Four patients with adult primary pulmonary blastoma were treated in our Institute. The tumor was right sided in all cases; it belonged to upper lobe in 1 patient, to middle in 1 and to lower in 2. The patients underwent middle lobectomy in 1 case, lower lobectomy in 2 and upper lobe typical segmentectomy in one (the subject previously operated for lung adenocarcinoma). Histology detected primary pulmonary biphasic blastoma in all the cases. In only one case it was associated with hilar lymph nodal metastases. She received adjuvant chemotherapy, but after 17 months she developed distant metastases and she died 22 months after operation. About the other 3 patients: one patient died 6 months after intervention for acute cardiac disease, while two subjects are still alive and disease free 158 and 70 months after surgery. Surgical resection, when radicality could be ensured, is considered the treatment of choice, in absence of other curative therapies. The analysis of our experience confirms surgery to be a good therapeutic choice permitting to obtain long term survivals. The patient, alive ten years after the operation, is one of the longest survival case for pulmonary blastoma reported in literature.

[Use of the skin-closure system Medizip in median sternotomy in oncological patients. Evaluation of results obtained in 30 patients]. / Utilizzo del dispositivo Medizip per la sutura cutanea in caso di sternotomia mediana in pazienti oncologici. Valutazione dei risultati ottenuti in 30 pazienti.

BACKGROUND: The authors evaluate effectiveness, safety and cosmetic results obtained using the new skin closing system Medizip. METHODS: At the Thoracic Surgery Department of the National Cancer Institute (Milan) between June 1999 and March 2001, in 30 patients who underwent median sternotomy for bilateral pulmonary wedge resections, Medizip a new skin-closing system to suture the sternal wounds has been used. Twenty patients were under 30 (66%) and 6 of the 10 remaining were females. The average age was 34.25+/-21.60 years, (median: 25, range: 12-72). It took about half a minute (average time: 30.00+/-10.54 seconds) to perform all the application manoeuvres. In order to better evaluate the cosmetic results obtained, a scale of three levels was created: level 1: very good, level 2: satisfactory, level 3: inadequate. RESULTS: Twenty-eight 20 cm-long zippers, one 25 cm-long and one 30 cm-long were employed. Medizip has been kept in site for 9.88+/-2.12 days on average (median: 9; range: 8-12). The time employed for each dressing was on average 70.00+/-21.35 seconds (median: 70, range: 46-128). No wound infections were observed even if all the patients were affected by neoplastic diseases and were immunocompromised because of lots of antiblastic treatments. The quick removal (few seconds) and the non-invasiveness of the disposal constitutes remarkable advantages. Using the criteria previously described, 26 patients at level 1 (87%), and 4 (13%) at level 2 were classified. CONCLUSIONS: Medizip is considered to be an effective skin-closure system easy and quick to handle, assuring very good cosmetic results, with non-invasive removal, particularly useful in pediatric patients and in young adults affected by neoplastic diseases undergone to a lot of combined treatments.

A particular case with long-term follow-up of rare malignant hemangiopericytoma of the lung with metachronous diaphragmatic metastasis.

The authors report the case of a woman with a primary hemangiopericytoma of the lung and successive metachronous diaphragmatic metastasis treated with surgery only according to the patient's decision. The patient was first submitted to left lower lobectomy with resection of diaphragm and three ribs en-bloc for pulmonary sarcoma. One year later, a chest computed tomography (CT) scan showed a small lesion above the diaphragm on the left side. She refused the proposed operation and returned fifteen months later with a new thorax CT, and told us that she had in the meantime become pregnant and given birth. A rethoracotomy to remove the metastatic diaphragmatic tumor was performed. Chemotherapy with anthracycline and iphosphamide was proposed, but the patient again refused therapy for fear of side effects impairing another pregnancy. Currently, the patient is alive and disease-free, 68 months after the first treatment. The authors emphasize the long-term follow-up obtained with surgery alone in this kind of rare sarcoma.

Major surgery in lung cancer in elderly patients? Risk factors analysis and long-term results.

BACKGROUND: In the Oncological Thoracic Surgery Department of the Istituto Nazionale Tumori of Milan a retrospective study was performed on lung cancer patients 70 years old or more with the aim of evaluate the role of surgical treatment and to analyse long-term results. METHODS: In our Institute from January 1988 to December 1993, 151 lung cancer patients 70 years old or more underwent surgery for lung cancer. One hundred and twenty-six of them (83%) were males and 25 were females (17%), the average age was 73.09+/-2.91 years (median: 77; range: 70-82). All the subjects were completely staged preoperatively. In order to establish operability criteria, we considered some selection parameters. Patients general conditions were evaluated using Karnofsky score accepting only the ones with 70% or more for surgery, all the cases performed cardio-respiratory functional evaluation. Patients with: a) FEV1 <60% of predicted value or FEV1 <1 l; b) PaO2 <60 mmHg e PaCO2 >40 mmHg were excluded from surgery. RESULTS: The operations performed were: 23 pneumonectomies, 6 bilobectomies, 93 lobectomies, 13 segmentectomies and 16 wedge resections. Eight cases were submitted to thoracectomy in association to pulmonary resection. Peroperative mortality was 3% and morbidity was 10%. Histological examination showed 69 adenocarcinomas, 65 squamous carcinomas, 4 large cells carcinomas, 4 typical carcinoids, 5 small cells carcinomas, 2 mucoepidermal carcinomas and 2 adenosquamous carcinomas. Eighty-six patients were classified at stage I, 38 at stage II, 24 at stage III and 3 at stage IV (multifocal disease). The actuarial 4-years global survival predicted with Kaplan Meier method was 40%, in particular it was 75% for stage I patients. CONCLUSIONS: In case of resectable primary pulmonary neoplasm, surgery represents the first choice therapy; patient's age doesn't seem to be an absolute contraindication, but it has to be evaluated with biological and not with age criteria. Using adequate selection criteria, it's possible to obtain, in patients older than 70 years, long-term survivals that don't seem to differ from global survivals.

Gastrobronchial fistula repair followed by esophageal leak--rescue by transesophageal drainage of the pleural cavity.

A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia was diagnosed six years after an esophagectomy with gastric pull-up. After failed surgical repair, an uncontained esophagopleural leak developed. Fistula closure was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became dislodged. Transesophageal drainage was positioned endoscopically through the suture-line defect and led to closure of the leak after 10 days.

Video-assisted thoracoscopic surgery for diagnosis, staging, and management of lung cancer with suspected mediastinal lymphadenopathy.

The aim of this report was to evaluate the effectiveness of video-assisted thoracoscopic surgery (VATS) in staging, diagnosis, and treatment of lung cancer. Fifty-two patients were scheduled for mediastinal lymph node VATS biopsy at the Oncologic Thoracic Surgery Department of the National Cancer Institute in Milan. Fifty patients underwent lymph nodal thoracoscopic biopsy (96%), whereas for the other 2 patients, histologic diagnosis was done by pleural metastatic nodule thoracoscopic biopsy (4%). We performed 17 lymph nodal biopsies in level 5 (33%), 14 in level 6 (27%), 12 in level 7 (23%), and 7 in level 8 (13%). No postoperative complications were observed, and 19 subjects (36%) underwent open lung resection. The histologic diagnosis was adenocarcinoma in 25 cases (48%), epidermoid carcinoma in 14 (27%), microcytoma in 9 (17%), and giant-cell lung carcinoma in 4 (8%); 10 patients were at stage I (19%), 9 at stage II (17%), 31 at stage III (60%), and 2 at stage IV (4%). The use of VATS allowed diagnosis of the suspected involved mediastinal lymph nodes in lung cancer patients and obviated the need for painful thoracotomy, enabling accurate staging and thus selection of the optimal treatment.

Clinical and pathologic predictors of survival in patients with thymic tumors.

BACKGROUND: The aim of this study is to evaluate the impact of thymectomy in patients with thymic neoplasms and to identify clinical and histopathological factors associated with improved long-term outcome of surgery. METHODS: We treated 74 patients between February 1987 and July 1993. There were 29 total and 36 simple thymectomies. These last cases, all non-myasthenic, had benign thymomas (n=30) but 6 had thymic carcinomas. Nine tumors were no-resected (5 thymomas and 4 thymic carcinomas). Minimum follow-up by Department of Thoracic Surgery Istituto Nazionale Tumori was 60 months after thymectomy. We divided the specimens according to Marino and Muller-Hermelink's classification: 54 thymomas, 18 thymic carcinomas and 2 no-diagnosis specify thymomas. There were 53 stage I, 1 stage II, 13 stage III, 5 stage IVa and 2 stage IVb according to Masaoka. RESULTS: Forty-six patients with treated thymoma were alive without disease at the end of follow-up, the remaining 8 died from recurrence in 6, a new tumor in 1 and a heart attack in the last. Of 18 thymic carcinomas 9 were alive at the end of follow-up (1 with recurrence), only 4 dead from recurrence. The actuarial survival of patients with thymomas was 88.5% at 5 years, (73.6% in cortical type, 85.7% in medullary type, 93.9% in mixed type, 100% in predominantly cortical type). Myasthenia gravis didn't influence the survival: 87.3 (no MG) vs 90%. Advanced stage thymomas significantly increased the risk of death from early stage I: 32.4 vs 100% at 5 years. In thymic carcinoma patients with well-differentiated thymic carcinoma (WDTC) died less than others: the actuarial probability of survival at 5 years was 90 vs 68%. CONCLUSIONS: Thymectomy was the best treatment to long term outcome. In our experience, survival was related to histotype and to local extension of tumor.

Linkage disequilibrium pattern in the L-myc gene in Italian and Japanese non-small-cell lung-cancer patients.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3-3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism.

[Significance of video-assisted thoracoscopic surgery in the diagnosis and staging of primary pulmonary neoplasms]. / L'importanza della chirurgia toracoscopica video-assistita nella diagnostica e nella stadiazione delle neoplasie polmonari primitive.

The authors describe the usefulness of video-assisted thoracoscopic surgery (VATS) in the staging and diagnosis of primary lung cancer. In the Oncological Thoracic Surgery Department of Milan's National Cancer Institute, over the period from January 1995 to January 2000, 46 patients, suspected of having mediastinal lymphadenopathies in the presence of lung cancer, were proposed for a VATS biopsy. Forty-four patients underwent a thoracoscopic lymph node biopsy (95%), while in 2 subjects, in whom pleural metastases were found, the histological diagnosis was established by pleural metastatic nodule thoracoscopic biopsy (5%). A VATS lymph node biopsy was performed in 16 cases at level 5 (35%), in 13 at level 6 (28%), in 9 at level 7 (19%) and in 6 at level 8 (13%). Lymph node biopsies were ipsilateral in 37 patients (80%) and contralateral in 7 (15%). No postoperative complications were observed. Histological examination revealed adenocarcinoma in 23 cases (50%), epidermoid carcinoma in 12 (26%), microcytoma in 8 (17%) and giant-cell lung carcinoma in 3 (7%). Two patients were classified as stage IV (5%), 7 as stage III B (15%) and 21 as stage III A (45%). The subsequent treatment was neoadjuvant chemotherapy for stage III A patients and chemotherapy in association with radiotherapy for stage III B subjects. The patients with microcytoma underwent integrated radiotherapy and chemotherapy and pan-encephalic radiotherapy. Sixteen patients, with negative frozen-section histological findings for mediastinal lymph node neoplastic disease, underwent pulmonary resection after thoracotomy in the same operating session (35%) and were subsequently classified as stages I and II. In conclusion, VATS proved extremely useful in the diagnosis and staging of patients affected by lung cancer with synchronous lymph node enlargement. This procedure allowed the diagnosis of suspect involved mediastinal lymph nodes in all cases thus affected and the exclusion of lymph node disease in patients subsequently treated by lung resection in a single session. The precise staging obtained then made it possible to direct the patients towards the most appropriate form of treatment.

[Pulmonary metastasis of basal cell carcinoma of the skin. 3 case reports]. / Le metastasi polmonari da carcinoma basocellulare della cute. Presentazione di tre casi.

The Authors describe three cases of lung metastasis from a basal cell carcinoma of the skin observed in the Department of Thoracic Surgery of the National Cancer Institute in Milan. The incidence of this rare occurrence reported in the literature is approximately 0.1%, The aim of the study was to evaluate the therapeutic treatment adopted in these unusual situations. In all cases the primary basal cell carcinoma of the skin was located in the head. All three patients had several local and regional recurrences and underwent multiple surgical excisions and subsequent plastic procedures. In each case complementary radiotherapy was implemented. The metastases appeared in the lung 9, 17 and 21 years, respectively, after onset of the primary tumour as bilateral nodules in two cases and as a single nodule in one. Curative surgery was possible only in one subject, consisting in a bilateral metastasectomy via a midline sternotomy, with 5-year survival. Surgery was withheld in the other two subjects owing to advanced age and the presence of bilateral nodules with concomitant bone metastasis, respectively. Both were treated by chemotherapy and the patient with synchronous bone metastasis also received radiotherapy. The elderly subject died after six months, and the other patient after 19 months despite partial remission of disease. In our experience, curative therapy proves difficult due to multiple metastases. In the literature there are few reports regarding this rare type of metastatic lung disease, but surgical intervention would appear to be the therapy offering the best chance of long-term survival while chemotherapy constitutes the second-choice treatment.

A rare complication of surgical management for esophageal tumor: a non neoplastic belated fistula between stomach and main right bronchus.

The fistula between stomach and bronchus after surgery for cancer of the esophagus is a rare occurrence. We describe a gastric non neoplastic ulceration that arose late after six years from an esophagectomy, with an end-side cervical esophagogastrostomy, for a spino-cellular carcinoma. After the partial failure of surgical technique, of the endoscopic treatment and for the bad general conditions of patient we decided to treat the fistula by transluminal drainage. This technique involved a progressive resolution of the fistula, becoming, nowadays, in our division, the preferred treatment for these kinds of postoperative complications.

[Surgery in the treatment of metachronous homolateral non-small cell lung cancer]. / La chirurgia nel trattamento del tumore del polmone non a piccole cellule metacrono omolaterale.

The authors describe their experience with the surgical treatment of metachronous homolateral lung cancer by completion pneumonectomy. In the Department of Thoracic Surgery of the National Cancer Institute of Milan, over a period ranging from 1982 to 1996, 30 completion pneumonectomies were performed for local relapses or second primary tumors. The patients submitted to this intervention had a lobectomy as their first operation in 23 cases (77%), a bilobectomy in 4 (13%) and a typical segmentectomy in 3 (10%). Associated with these interventions we performed 2 en bloc chest wall resections and a contralateral wedge resection. Two subjects received neoadjuvant chemo-therapy. Histology revealed squamous carcinoma in 14 cases (47%) and adenocarcinoma in 16 (53%). Seventeen patients (57%) were classified as stage I, 8 as stage II (26%), 4 as stage III (13%) and 1 as stage IV (4%). Four patients received adjuvant chemotherapy and/or radiotherapy. Lung cancer relapse occurred as a single lesion in 27 cases (90%) and as multiple lesions in 3 (10%). We performed 18 right (60%) and 12 left (40%) completion pneumonectomies. In 1 case (4%) a sleeve pneumonectomy was necessary. Associated with these interventions we performed 5 en bloc chest wall resections. The perioperative mortality was 10% and the postoperative morbidity 40%. Histological tests showed 12 squamous carcinomas (40%) and 18 adenocarcinomas (60%). Two patients (7%) had a different histology. Disease was classified as stage I in 13 cases (44%), as stage II in 9 (30%) and as stage III in 8 (26%). Four patients received adjuvant chemotherapy and/or radiotherapy. Two subjects developed a metachronous contralateral tumor (7%). The disease-free interval was 22.70 +/- 14.69 months, with a median value of 17 months (range: 7-53 months). Mean survival after completion pneumonectomy was 49.77 +/- 49.29 months, with a median value of 26.5 months (range: 4-190 months). The 5-year actuarial survival rate, calculated using the Kaplan-Meier method, was 30%. Completion pneumonectomy is a technically very demanding intervention carrying a high risk of morbidity. On the basis of the analysis of our data, we can affirm that mean postoperative survival seems to be satisfactory and to justify this aggressive attitude towards recurrent tumor. We should stress the importance of careful evaluation of indications and precise selection of patients.

IgG, IgG1 and IgM response in Trichinella spiralis-infected mice treated with 4-deoxypirydoxine or fed a Vitamin B6-deficient diet.

The aim of this study was to investigate the effect of pyridoxine (Vitamin B6) deficiency on the immunological response of BALB/c mice infected with the parasite T. spiralis. Specific anti-parasite IgM and IgG immunoglobulins were detected by ELISA method in the serum of treated animals at different periods for 60 days post infection. Vitamin B6-deficiency was induced in two separate groups of mice by either (1) maintaining the mice on a Vitamin B6-deficient synthetic pellet diet for 40 days before infection, or (2) by daily intraperitoneal injection of 8 x 10(5) M/100 microl of 4-Deoxypyridoxine (4-DPD), a potent antagonist of Vitamin B6 for 20 days prior to infection. These two groups of mice were then injected with 100 larvae (L1-T. spiralis) per os. Parasite burdens in the mice were observed by light microscopy. Cysts were present in the diaphragms of the mice after 60 days post-infection. Parasite specific IgG, as well as IgG1 levels were determined in the sera of infected mice fed a normal diet. These levels were found to be lower in the 4-DPD-treated mice compared to the untreated mice. The inhibition started from the 10th day and continued to the 60th day, and in the 4-DPD-treated group the inhibition initiated after 24 h to 60 days. IgM level also was depressed by 4-DPD, starting from 24 h after injection of the compound. In mice fed Vitamin B6-deficient diets the levels of IgG were lower than in mice fed normal diets. These results show that BALB/c mice infected with T. spiralis and fed either a Vitamin B6-deficient diet or a diet which included the Vitamin B6-antagonist, 4-DPD, both influence the course of IgG, IgG1 and IgM production.

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.

Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo.

Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. However, the exact role, function, and implication in inflammatory diseases remain to be determined. Here we report that subcutaneous injections (0.2 ml) of a saturated water solution (1:40) of potassium permanganate crystals induces the generation of granuloma tissue at the site of injection in the rat, and reaches its peak of formation after 1 week. The size and weight of the granulomas were increased by i.p. lipopolysaccharide (LPS) (6 microgram/200 microliter) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 300 microgram/200 microliter) treatments in rats, injected 18 hours before sacrifice. Moreover, steady-state levels of MCP-1 mRNA in the granuloma tissue (control), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-treated) whereas in animals treated with Dxs, there was a decrease in (P < 0.05) in formation of mRNA protein. When the granuloma tissues were homogenized the generation of MCP-1 was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in the Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples were further incubated in vitro with LPS (100 ng/ml) overnight. A Strong increase (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calcified tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dxs.