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Biomedical subjects

M Rusca

Publications and source records attributed to M Rusca.

At least 19 recordsLinked to original sources

Effect of inducible FHIT and p53 expression in the Calu-1 lung cancer cell line.

Loss of FHIT expression and p53 mutations are critical events in the early stages of lung carcinogenesis. The restoration of Fhit function in FHIT-negative cancer cells has been reported to cause tumour suppression by inhibition of cell proliferation and/or activation of apoptotic pathways. However, the studies designed to elucidate the biological role of Fhit and its potential interaction with p53 have produced conflicting results. We investigated here the effects of the simultaneous restoration of FHIT and p53 in Calu-1 cells by using a hormone-inducible gene expression system. We demonstrate that the restoration of FHIT expression reinforces the anti-proliferative effect associated with the simultaneous replacement of p53. Indeed, a more pronounced inhibition of cell proliferation associated with an earlier and higher induction of p21(waf1) mRNA and protein expression was observed in Fhit/p53-expressing cells compared with cells expressing p53 alone. This effect was not due to Fhit-mediated up-regulation of p53 expression; in fact p53 protein was expressed at the same level in both FHIT-positive and FHIT-negative cell clones. Consistent with this result, Fhit did not affect the expression of MDM2, a protein known to interact directly with p53 and target p53 for proteolytic degradation, thus down-regulating its activity.

Acid Anhydride Hydrolases↗

Endotracheal migration of a central venous catheter.

Subcutaneous infusion ports for prolonged central venous access are commonly used for drug administration and parenteral nutrition in a wide range of chronic diseases. The extensive use of these devices has to be balanced against its complications, some of which potentially life-threatening. We describe the case of a patient admitted to our unit with haemoptysis and cough. At bronchoscopy the tip of the central venous catheter was discovered protruding into the tracheal lumen. The catheter was pulled out from the subcutaneous pouch under simultaneous surgical control of the tracheal fistula orifice.

Adult↗

Disposition of voriconazole during continuous veno-venous haemodiafiltration (CVVHDF) in a single patient.

OBJECTIVES: To determine whether voriconazole dosage adjustment is required during continuous veno-venous haemodiafiltration (CVVHDF). METHODS: Voriconazole pharmacokinetics were studied in a critically ill patient under CVVHDF. The analysis was carried out for 12 h following a 6 mg/kg dose. Voriconazole concentrations were measured by HPLC in blood inlet and outlet lines and in dialysate. RESULTS: The total body clearance of voriconazole was 20.3 L/h, with a terminal half-life of 13.7 h and a distribution volume of 399 L. The estimated sieving coefficient was 0.53 and the filtration-dialysis clearance 1.2 L/h. CONCLUSIONS: CVVHDF does not significantly affect voriconazole disposition and requires no dosage adjustment.

Aged↗

Surgical outcome of combined pulmonary and atrial resection for lung cancer.

OBJECTIVES: The study was carried out to assess the short and long-term outcome of patients with non-small cell lung cancer infiltrating the left atrium treated by surgery. METHODS: We retrospectively collected the hospital files of twenty-three consecutive patients operated on between 1982 and 2001 in two units of Thoracic Surgery. Four patients received an induction regimen. Fourteen right pneumonectomies, 8 left pneumonectomies and 1 right inferior lobectomy were performed. No cardiopulmonary bypass was employed. RESULTS: In all patients the diagnosis of T4 atrial invasion was confirmed by pathological examination. A complete resection was achieved in nineteen patients (83%). With respect to nodal staging, there were 13 N0, 5 N1 and 4 N2 cases, respectively. Two deaths occurred during the one month postoperative period (9%). Three patients had postoperative atrial fibrillation. Two other patients had postpneumonectomy empyema without bronchopleural fistula and recovered, one after thoracoscopic debridement and the second after open window thoracostomy. Follow-up was completed on September 2002; only one patient was lost to follow-up. Median survival, excluding the perioperative mortality, was 20 months (range 4 - 62 months). The survival rate, calculated with the Kaplan-Meier method, was estimated as 63% at 1 year, 2 % at 3 years and 10% at 5 years. Using a Cox model analysis, lymph node stage and completeness of resection were not independent prognostic factors. CONCLUSIONS: In cases of NSCLC with left atrial invasion complete resection is technically feasible in most instances without cardiopulmonary bypass. The acceptable operative risk and the encouraging long-term survival observed in this series suggest that NSCLC invading the left atrium should not be systematically considered as a definitive contraindication to surgery.

Adult↗

Biological markers in non-small cell lung cancer. Retrospective study of 10 year follow-up after surgery.

BACKGROUND: The biological markers in non-small cell lung cancer (NSCLC) have been widely studied and encouraging results have shown that products of some oncogenes and other molecular markers can predict the aggressiveness of the disease and the outcome of the patients. METHODS: To verify the reliability of these prognostic markers we have studied retrospectively the expression of c-erbB-2 and 67Ki (growth regulation), p53 (cell cycle regulation and apoptosis), bcl-2 (apoptosis) and CD31 and CD34 (angiogenesis) in 78 patients operated on for NSCLC with curative intent between January 1987 and December 1988 and followed up for 10 years. For the determination of the biological markers we have used the ABC (Avidin-Biotin-Peroxidase complex) immunohistochemical method. The Cox regression model was used for the univariate and multivariate analysis. RESULTS: Nineteen patients (24%) were alive after 10 years and 59 (76%) died. The univariate analysis of the relationship between the 10-year survival and the expression of the markers was significant only for p53 (p=0.0097). Stratifying the patients according to the 3 histological subtypes (squamous cell carcinoma, adenocarcinoma and large cell undifferentiated carcinoma) the correlation between markers and survival pointed out that the only significant one was p53 (p=0.0459) in adenocarcinoma. In the same way considering the stages p53 was significant in stage IIIa (p=0.0357). The multivariate analysis emphasized that p53 was the only significant marker with respect to the 10-year survival (p=0.0091). Examining the histological groups significant was only p53 in adenocarcinoma (p=0.0192) and in large cell undifferentiated carcinomas (p=0.0290). This marker is also significant in pathological stage II (p=0.0271) and IIIa (p=0.0402). Apart from histology and staging the 10-year survival was 33% for p53 negative versus 10% for p53 positive. In patients with adenocarcinoma the 10-year survival was 40% for p53 negative and 6% for p53 positive. CONCLUSIONS: In conclusion our results emphasize the importance of p53 as a prognostic factor in 10-year survival in patients with adenocarcinoma and in stage II and IIIa.

Adult↗

Unusually located hydatid cysts miming a pulmonary tumor invaliding the spine.

Hydatid disease is a worldwide encountered zoonosis but at present very rare in Europe, liver and lungs being the most frequently involved sites. Bone involvement is very uncommon and the vertebral spine is the most common site of skeletal involvement (less than 1% overall). We report a case of vertebral hydatid disease with secondary pleuro-pulmonary involvement successfully treated by emergency spinal decompression followed by lung resection en bloc with chest wall and partial vertebrectomy.

Adult↗

Surgical treatment of primary and metastatic sternal tumours.

BACKGROUND: Primary and metastatic malignancies of the sternum are uncommon. Surgery that is the best treatment for the majority of primary sternal tumors, and arguably for metastatic lesions, has improved permitting us to perform wide resection and simultaneous reconstruction safely. METHODS: From January 1988 to December 1998 we treated 13 patients, 4 with primary chondrosarcoma and 9 with sternal metastasis, 5 breast cancer, 3 kidney cancer and 1 thyroid cancer. In 3 patients total sternectomy was performed and in 10 a partial sternectomy associated with resection of the anterior segment of the ribs in 7 cases and resection of the clavicle in 5 patients. Bone reconstruction was done in the majority of cases (5) with Marlex mesh with methylmethacrylate and in 3 cases rib grafts were used to strengthen a Vicryl mesh. The major pectoralis muscle was the most frequently used soft tissue, 9 of 12. RESULTS: Our postoperative mortality was 15%, 2 cases. The median overall survival was 48 months. All the primary tumours were alive after a mean follow-up of 34 months (range 4-84 months). While survival of the sternal metastasis was 24 months. CONCLUSIONS: Surgical resection and reconstruction of sternal lesions represent a basic step in the treatment of the primary tumors with encouraging survival results while in the metastatic lesions surgery can be a part of a multimodality approach with unsatisfactory results.

Aged↗

The bilobectomies for lung cancer.

BACKGROUND: The purpose of our retrospective study is to confirm that bilobectomy is a feasible operation with an oncological value. METHODS: From 1981 to 1998, 46 patients underwent bilobectomy for lung cancer. Eight upper and middle lobectomies (UML) and 38 middle and lower lobectomies (MLL) were performed. Intraoperative pneumoperitoneum was done in 11 MLL. We have considered operative mortality, postoperative complications, the persistence of drainage tubes and the length of hospital stay and the data were statistically compared with those relative to right lobectomies. Survival was estimated with the Kaplan-Meier method and the curves were compared with those of the right lobectomies and right pneumonectomies using the log-rank test. RESULTS: Overall morbidity was 43.4%. Mortality was 6.5%. Mean chest tube persistence was 7.8 days and mean hospital stay was 14 days. No statistical significance was found about these data comparing the UML and MLL separately and the bilobectomies with the right lobectomies. The pneumoperitoneum done in the MLL enabled a shorter hospital stay, statistically significant, in comparison with MLL without pneumoperitoneum. The overall 5-year survival rate was 38%. Considering the I and the II stages no statistical differences in survival were found considering the right lobectomies and right pneumonectomies. CONCLUSIONS: The bilobectomies can have a role in treatment of lung cancer that is equal to the other standard major resections.

Adult↗

The modified "hemi-clamshell" approach for tumors of the cervicothoracic junction.

The anterior approaches proposed for treatment of the apical chest tumors (anterior transcervical, transmanubrial, and hemi-clamshell) have precise advantages and limits. To avoid these limits we have modified the hemi-clamshell with the resection of the first costal cartilage and the costoclavicular ligament. This allows a wider opening of the sternocostal flap, with safe control of the entire subclavian vessels as well as easier access to the T1 to T3 vertebral bodies and the posterior chest wall.

Adenocarcinoma↗

Biological variables in non-small cell lung cancer: comparison between immunocytochemical determination on fine needle aspirates from surgical specimens and immunohistochemical determination on tissue sections.

A number of biological and predictive markers of non-small cell lung cancer (NSCLC) have been sought, but these have so far been mainly evaluated on surgically resected specimens. Given that fine needle aspiration biopsy (FNAB) is being increasingly used in the diagnosis of NSCLC, its application could be extended to the immunocytochemical detection of biological parameters at the time of diagnosis before surgery. In order to assess the reliability of estimating biological markers on fine needle aspirates (FNAs) from NSCLC, the aim of this study was to compare Ki67 growth fraction, p53 and bcl-2 protein expression as revealed by the immuncytochemical assessment of FNAs obtained from surgical samples with the immunohistochemical results obtained from the corresponding histological sections. FNAs were performed on surgical specimens obtained from 29 NSCLC patients. Ki67, p53 and bcl-2 were cytologically and histologically evaluable in respectively 25, 27 and 19 cases. Concordance between FNAs and corresponding paraffin sections was 84% for Ki67, 93% for p53 and 95% for bcl-2. All of the specimens whose biological parameters were studied by immunocytohistochemistry also underwent flow cytometric DNA analysis of FNAs taken from fresh surgical specimens. Of the 29 cases, 22 were aneuploid and seven diploid. The S-phase fraction (SPF) was evaluable in 62% of cases. Comparison of SPF results on FNAs with Ki67 values evaluated on the corresponding histologic and cytologic specimens, revealed a significant correlation only with histology. Good reproducibility was also found in relation to the immunocytochemical results obtained on FNAs from different areas of the same tumour, showing that tumour heterogeneity does not affect the method. The concordance between the immunocytochemical and immunohistochemical results suggests that FNAB may be a reliable procedure for the biological characterization of NSCLC. Given its limited invasiveness, FNAB could be used in vivo for the preoperative assessment of biological parameters in patients with operable or metastatic NSCLC.

Biomarkers, Tumor↗

Spontaneous intercostal pulmonary hernia.

A case of spontaneous intercostal pulmonary hernia as a result of vigorous coughing is reported in a 67-year-old man. The great majority of acquired pulmonary hernias are post-traumatic; rare cases are spontaneous, resulting from prolonged and/or repeated increased intrathoracic pressure. This hernia was successfully repaired with a polyglactin absorbable mesh and approximation of the ribs with heavy stitches. When required, surgical repair is the treatment of choice.

Aged↗

Experimental tracheal transplantation using a cryopreserved aortic allograft.

BACKGROUND: The tracheal reconstruction after wide resections remains a critical surgical problem. Our aim was to replace trachea with a tissue easy to vascularize, which allows a simple reconstruction and does not require an immunosuppressive regimen. MATERIALS AND METHODS: A segment of cryopreserved aorta was used in order to verify its adequacy as tracheal substitute. In phase 1, the thoracic aorta of 10 rabbits was excised, obtaining 20 segments that were cryopreserved. Ten segments were implanted in the omentum of 10 rabbits that were sacrificed on postoperative days 7, 14 and 21, and the grafts were examined histologically. In phase 2, a segment of cryopreserved aorta arranged with a silicone prosthesis was transplanted in 10 rabbits and wrapped with omentum. The animals were sacrificed on postoperative days 7, 14 and 21. RESULTS: In phase 1, the neovascularization of the grafts was present after 7 days, and after 14 days the fibroblasts invaded the lumen of the aorta. In phase 2, 8 rabbits survived and the histologic examination after 7, 14 and 21 days showed neovascularization, the absence of rejection and the proliferation of fibroblasts inside the lumen of the aorta; this growth has been restrained by an endoluminal prosthesis. CONCLUSIONS: Our study demonstrated that replacing the trachea with cryopreserved aorta is technically feasible and does not evoke immunologic reactions. It requires, however, a silicone tube inside the allograft to limit the colonization of fibroblasts.

Animals↗

A standard muscle-sparing utility thoracotomy for VATS procedures.

BACKGROUND: Improvements in surgical equipment have rendered video-assisted thoracic surgery (VATS) an effective device for thoracic surgeons and nowadays several intrathoracic diseases can benefit from this approach. This development has expanded potential use and recently the technical feasibility of major lung resections by VATS has been demonstrated. The authors present their experience with a standard muscle-sparing utility thoracotomy (UT) utilized for all VATS procedures, including major lung resections. METHODS: From November 1996 to October 1997, 30 patients were operated on. There were 22 males and 8 females (medium age 58 years; range 24-78). There were 13 anatomical lung resections (i.e.: 11 lobectomies, 1 left pneumonectomy, 1 segmental resection), 8 wedge resections, 3 lung biopsies, 2 debridements of pleural empyema, 2 mediastinal nodes biopsies, 1 esophageal resection for leiomyoma, 1 excision of benign mediastinal cyst. RESULTS: No mortality or major morbidity were recorded, as well as no rib fractures due to the rib spreader. Two patients suffered from prolonged air-leaks after respectively left upper lobectomy and lung biopsy and required prolonged chest drainage. Concerning anatomic major lung resections the medium hospital stay was 7.9 days and medium chest tube time was 5.6 days. The utility thoracotomy through the auscultatory triangle proved to be a safe approach and confirmed the technical feasibility of various type of surgical procedures with results comparable to standard open thoracotomy. Our data shows that VATS approach did not seriously affect the duration of hospital stay, chest tube time, the overall morbidity or lung function. CONCLUSIONS: As the real benefit of this approach remains controversial, the majority of the studies comparing the VATS approach to conventional muscle-sparing thoracotomy neither nor prospective nor randomized, and several parameters are difficult to evaluate in the literature further study are mandatory.

Adult↗

Pulmonary abnormalities in Cowden's disease.

Cowden's disease is an inheritable multiple neoplastic syndrome represented by benign and malignant lesions of skin, digestive tract, mucosae, breast and thyroid. The syndrome, first described by Lloyd and Dennis in 1963, includes benign lung lesions, described in the literature only as hamartomas. The unusual condition of our case consists of multiple and bilateral lipomatous lesions of the lung and of adipose colonic polyps, diagnosed respectively by video assisted mini-thoracotomy and by endoscopic biopsies.

Biopsy↗

Postoperative pneumoperitoneum for prolonged air leaks and residual spaces after pulmonary resections.

BACKGROUND: Postoperative air leaks and pleural residual spaces are often encountered during partial lung resections and may adversely affect the immediate outcome prolonging the hospital stay. At present the only treatment consists of maintenance of the chest drainage under suction until resolution of the leaks. METHODS: From January 1995 to December 1997 the authors have operated on and subsequently treated 12 patients presenting prolonged air leaks with residual pleural spaces after lobectomies for lung cancer. The patients underwent respectively: left or right lower lobectomies (n=7), left upper lobectomies (n=3), right upper lobectomies (n=2). In this study the air leak was considered prolonged if it continued and delayed the discharge after surgery beyond the postoperative day 8. The pneumoperitoneum was carried out under local anesthesia. The air was insufflated through a needle inserted just above the umbilical scar as for laparoscopic surgery access up to an amount of about 1200 cc-1300 cc. RESULTS: We have obtained in all cases and without complications an immediate reduction in the air leaks and a complete resolution of the residual pleural spaces. Chest drainages were removed from 3 to 4 days after the procedure. CONCLUSIONS: The good results achieved suggest that this procedure might be considered for selected cases, being a minor procedure, performed under local anesthesia and with minimum discomfort for the patient.

Chest Tubes↗