Renzo Lodi

Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer

OBJECTIVES The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications. METHODS The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models. RESULTS The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up. CONCLUSIONS The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.

Hydrogen sulfide slows down progression of experimental Alzheimer’s disease by targeting multiple pathophysiological mechanisms

It has been previously reported that brain hydrogen sulfide (H2S) synthesis is severely decreased in Alzheimers disease (AD) patients, and plasma H2S levels are negatively correlated with the severity of AD. Here we extensively investigated whether treatment with a H2S donor and spa-waters rich in H2S induces neuroprotection and slows down progression of AD. Studies with sodium hydrosulfide (a H2S donor) and Tabianos spa-water were carried out in three experimental models of AD. Short-term and long-term treatments with sodium hydrosulfide and/or Tabianos spa-water significantly protected against impairment in learning and memory in rat models of AD induced by brain injection of β-amyloid1-40 (Aβ) or streptozotocin, and in an AD mouse model harboring human transgenes APPSwe, PS1M146V and tauP301L (3xTg-AD mice). The improvement in behavioral performance was associated with hippocampus was size of Aβ plaques and preservation of the morphological picture, as found in AD rats. Further, lowered concentration/phosphorylation levels of proteins thought to be the central events in AD pathophysiology, namely amyloid precursor protein, presenilin-1, Aβ1-42 and tau phosphorylated at Thr181, Ser396 and Ser202, were detected in 3xTg-AD mice treated with spa-water. The excitotoxicity-triggered oxidative and nitrosative stress was counteracted in 3xTg-AD mice, as indicated by the decreased levels of malondialdehyde and nitrites in the cerebral cortex. Hippocampus reduced activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in phosphorylation of tau protein but also in inflammation and apoptosis, was also found. Consistently, decrease in tumor necrosis factor-α level, up-regulation of Bcl-2, and down-regulation of BAX and the downstream executioner caspase-3, also occurred in the hippocampus of 3xTg-AD mice after treatment with Tabianos spa-water, thus suggesting that it is also able to modulate inflammation and apoptosis. Our findings indicate that appropriate treatments with H2S donors and Tabianos spa-waters, and may be other spa-waters rich in H2S content, might represent an innovative approach to slow down AD progression in humans by targeting multiple pathophysiological mechanisms.

Results of surgical resection in patients over the age of 70 years with non small-cell lung cancer.

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.

A new portable chest drainage device

BACKGROUND Persistent air leak is a frequent complication in lung operation. The Heimlich valve is the standard system for venting the pleural cavity. The device achieves good results and is well tolerated, but the main problem is when air leak is associated with fluid leakage. METHODS In order to improve the outpatient management of persistent air and fluid drainage after resectional procedures, we developed an original device. It is a portable system provided with a one-way valve connected to the chest tube for drainage of air and fluid, a reservoir for collecting fluid, and a one-way exhaust valve to evacuate air from the bag. RESULTS We analyze the advantages of our device versus the Heimlich valve in the first series of 18 selected patients. Our system is drier and cleaner, easier to manage, and ambulatory visits are seldom needed. There is also a cost savings. CONCLUSIONS Our device enhances ambulation, independence, and the quality of life of the patients, and decreases the need for hospital and outpatient care.

TRICUSPID VALVE INCOMPETENCE CAUSED BY NONPENETRATING THORACIC TRAUMA

Tricuspid valve incompetence from ruptured papillary muscle or chordae as a result of nonpenetrating trauma is uncommon. Blunt trauma causing partial detachment of a leaflet from the annulus is very rare. We report the case of a young adult involved in a car accident who had these findings. Operative repair with resuture of the leaflet to the annulus and annuloplasty using a Carpentier ring resulted in complete recovery.

Extrapleural takedown of the internal mammary artery as a pedicle

Four hundred thirty-three patients underwent coronary bypass grafting using both internal mammary artery (IMA) and saphenous vein graft. In 233 patients the IMA was exposed with a conventional technique (group 1), whereas in the remaining patients the IMA was harvested leaving the pleura intact and performing an associated lysis of the endothoracic fascia (group 2). Postoperative course and complications of these groups were studied and compared in a period of time ranging from 8 to 28 months. Postoperatively, the blood transfused was significantly less in group 2 patients than in group 1; group 2 also had a reduction of surgical reexploration. Pleural effusion and hemidiaphragm impairment were infrequent or absent in group 2 patients, whereas pericarditis, severe postoperative chest pain, and respiratory insufficiency were noted only in group 1 patients. Our data suggest that extrapleural access without pleurotomy may be preferred owing to its low rate of chest wall complications.

Preoperative embolization in surgical treatment of mediastinal hemangiopericytoma

The case of a 47-year-old man with a tumor of the posterosuperior mediastinum is reported. Surgical biopsy sample revealed a hemangiopericytoma, but radical excision was impossible because of massive bleeding. Percutaneous embolization of mediastinal tumor was performed to reduce peroperative blood loss. It allowed uneventful complete removal of the lesion. We recommend preoperative embolization in cases of hypervascular mediastinal tumors.

Migration of pectus excavatum correction metal support into the abdomen

The authors describe a case of migration of a metal support, used to fix a corrected pectus excavatum deformity, into the peritoneal cavity. The migrated wire caused abdominal pain. A video laparoscopic removal of the wire was undertaken and the patient made a full recovery. A review of the literature shows that this has not been reported before and that serious complications related to metal struts are very uncommon. We do not believe that a revision of this surgical technique is needed; anyway, foreign body migration should always be considered as a cause for unusual symptoms in patients undergoing this operation.

Melanocortins protect against multiple organ dysfunction syndrome in mice.

BACKGROUND AND PURPOSE Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve‐mediated cholinergic anti‐inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple organ damage following systemic inflammatory response, here we investigated the effects of the melanocortin analogue [Nle4, D‐Phe7]α‐MSH (NDP‐α‐MSH) in a widely used murine model of multiple organ dysfunction syndrome (MODS).

Yellow nail syndrome associated with chronic recurrent pericardial and pleural effusions.

The authors describe a case of yellow nail syndrome in a 44-year-old male patient, with a clinical picture characterized by hand and foot onychodystrophy, lymphedema in the legs and recurrent pleural and pericardial effusions. They indicate subxiphoid pericardiostomy and pleural drainage as the rational surgical procedure for the treatment of this particular associated pathology.