Interferon-alpha (IFN-alpha) is a cytokine exerting pleiotropic activities, including antimicrobial effects, especially directed against intracellular infectious bacteria. It may be administered by aerosol to reach the lower respiratory tract without systemic side effects. The aim of the study reported here was the evaluation of aerosolized IFN-alpha treatment (3 MU/dose, given three times a week; total study dose: 72 MU/2 mo) in combination with conventional antimycobacterial therapy in patients with pulmonary tuberculosis. Two groups of 10 patients each were compared before and after 2 mo of conventional antituberculous chemotherapy with or without inhaled IFN-alpha. Several biologic (bronchoalveolar lavage fluid [BALF] cellularity, Mycobacterium tuberculosis [MT] number in sputum), biochemical (BALF concentrations of 10 cytokines, BALF IFN-alpha receptor levels), and clinical (fever, vital signs, high-resolution computed tomography [HRCT] images) measures were made in these patients at the time of their enrollment and at the end of the observation period of the study. Fever, MT number in sputum, and abnormalities in HRCT images showed significantly earlier resolution in the IFN-alpha-treated group, together with a more significant decrease in BALF interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) concentrations and significantly greater pre- versus posttreatment variations in IL-2 and IFN-gamma. These data, taken together, suggest that IFN-alpha administration may favorably affect the evolution of pulmonary tuberculosis when combined with antimycobacterial therapy.

Background: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. Objectives: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. Methods: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. Results: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 ± 6 vs. 19.5 ± 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO₂/FiO₂ as compared with spontaneous breathing (group A: 148.5 ± 52 vs. 99 ± 39, p = 0.0004; group B: 134 ± 36 vs. 89 ± 26, p = 0.0004). NIV reduced the respiratory rate (26 ± 7 vs. 36 ± 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2–6 months). Conclusions: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches.

Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.

Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. This microorganism is capable of inducing a delayed hypersensitivity reaction in the lung, with subsequent expression of the disease. This reaction depends on the presence of different cytokines that exert specific functions. The aim of this study was to evaluate the presence and the concentrations of nine different modulators in bronchoalveolar lavage fluid (BALF). For this purpose, 15 patients with active pulmonary tuberculosis were enrolled at the time of diagnosis, prior to institution of antituberculous therapy. All the patients demonstrated M. tuberculosis in the sputum, and their disease extention was defined by high-resolution computed tomography (HRCT) using a score which included the presence of six findings: miliary nodules, nodules < 10 mm, consolidation, ground glass, cavity and bronchial wall thickening. This score was more sensitive than an equivalent score calculated on the basis of chest radiology. HRCT score was calculated for each area of the two lungs in order to define the more and the less affected lung for each patient. The bronchoalveolar lavage (BAL) was performed in the more affected area for each lung. The HRCT total score for each washed area ranged between 1 and 15, and showed more significant differences between the more and less affected lungs (p = 0.0004) than those obtained with the individual radiologic findings (p ranged between 0.60 and 0. 004). The BAL concentrations of the nine cytokines evaluated for the more and less affected lungs were compared: interleukin-6 (IL-6), IL-8, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) showed significant differences (p ranged between 0. 016 and 0.0007). In addition, each cytokine concentration was correlated with the HRCT score. Significant correlations were found with IL-12, IL-6, IL-8, IL-2, and TNF-alpha. The correlations between cytokines and HRCT total score were better than those observed with the individual radiologic findings. A correlation matrix for the different cytokines evaluated one against each other, has also been added to show common behavior of these modulators. A similar analysis was also performed for the radiologic abnormalities.

Idiopathic pulmonary fibrosis has been associated with emphysema in cigarette smokers as a new clinical entity: combined pulmonary fibrosis and emphysema (CPFE). In order to compare histomorphometrical, roentgenological and immunohistochemical aspects of usual interstitial pneumonia (UIP) with and without associated pulmonary emphysema, 17 patients with biopsy-proven UIP were evaluated. Morphometrical evaluation of lung parenchyma destruction was used to divide patients in two subgroups: emphysema/UIP (n=9) and UIP alone (n=8); four patients with biopsy-proven emphysema without fibrosis were also evaluated. At HRTC scan, emphysematous lesions were prevalent in the upper fields of both emphysema/UIP and emphysema groups and the distribution of fibrotic lesions was similar in emphysema/UIP compared to UIP alone. The semiquantitative histopathological fibrotic score was also similar in emphysema/UIP and UIP alone. In addition, the expression of tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-2, MMP-9, MMP-7 and membrane type 1-metalloproteinase (MT1-MMP) by fibroblasts of myofibroblastic foci was similar in emphysema/UIP and UIP alone patients. In contrast, fibroblasts in areas of parenchymal destruction of emphysema/UIP expressed MMP-2, MMP-9, MMP-7 and MT1-MMP at variable but significantly higher levels when compared to emphysema subjects, in the presence of similar levels of TIMP-1, TIMP-2 and TNF-alpha. Fibrotic and emphysematous lesions in emphysema/UIP patients appear to follow the roentgenological and histopathological patterns expected for either UIP or emphysema. Interstitial fibroblast activation is more pronounced in the areas of lung destruction in emphysema/UIP compared to those with emphysema alone, as for exaggerated tissue remodeling.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by widespread localization of calcispherites in the alveolar spaces. The patients are symptomless for a long time. Nevertheless, this disease slowly develops into pulmonary fibrosis and cardiac failure. The chest X-rays and high-resolution computed tomography strongly point towards a diagnosis of PAM. As for therapeutic approaches, repeated broncho-alveolar lavages (BAL) have been performed with improvement of symptoms but without recovery, and a new oral drug treatment is still under way. We report 2 familial cases of PAM. Both patients underwent chest X-ray examination showing diffuse bilateral micronodular opacities of calcific density. After 5 years, in May 1993, one of them developed exertional dyspnoea, cyanosis, dry cough and was admitted to our Division. Cardiokinetic and diuretic drugs as well as oxygen were administered with satisfactory results. Then repeated BAL were performed. The chest X-ray after 6 months of sodium etidronate (300 mg t.i.d.) administration was unchanged.

Since Kocher and Billroth refined an acceptable technique, the thyroidectomy has become one of the most frequent procedures in endocrine surgery and bilateral total thyroidectomy is performed in the majority of thyroid diseases. This work evaluated the use of the Harmonic(®) FOCUS and traditional suture ligation (knot and tie) technique in a prospective, randomized study of open thyroidectomy. Eighty two patients were randomized and divided into two similarly sized groups: the Harmonic(®) FOCUS group (F group) and traditional group (T group). The use of the harmonic FOCUS shows some statistically significant advantages limited to a few intraoperative parameters: surgical time and volume of blood loss. The surgical time was significantly shorter in F group than in the T group (105 ± 27 min vs 143 ± 32 respectively; p < 0.05). Intraoperative volume blood loss was significantly more in the T group than in the F group (36 ± 23 ml vs. 24 ± 18; p < 0.05). The postoperative parameters (volume of drainage fluid, serum calcium at 12 and 48 h, hypocalcemia, wound complication, RLN palsy, postoperative pain and length of hospital stay) showed no statistical difference. The Harmonic Focus may provide a cost-effective option only in high volume centers where reducing operative time may balance the number of daily procedures.

Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs’ in vitro and in vivo sensitivity values correspond to patients’ responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.