Cost of a population-based programme of chest x-ray screening for lung cancer.

BACKGROUND: After the implementation of a population-based programme of chest x-ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was significantly reduced. Analysis of the incremental costs due to this type of screening programme is needed to evaluate its economic impact on the healthcare system. METHODS: In July 1997 a population-based cohort, consisting of all high-risk smokers (n=5,815) identified among 60,000 adult residents from the Varese province, was invited to a LC screening programme (an annual CXR for five years) in a general practice setting, and was observed through 2006. Invitees received National Health Service (NHS) usual care, with the addition of CXRs in screening participants. At the end of observation, among the 245 LCs diagnosed in the entire screening-invited cohort the observed LC deaths were 38 fewer than expected. To estimate the incremental direct cost due to screening in the invited cohort for the period July 1997-2006, we compared the direct cost of screening administration, CXR screens and LC management in the invited cohort and in the uninvited and unscreened controls in NHS usual care setting. RESULTS: Over the 9.5 years, the total incremental direct healthcare costs (including screening organization/administration, CXR screens, additional procedures prompted by false-positive tests, overdiagnosed LCs) were estimated to range from euro 607,440 to euro 618,370 (in euros as of 2012), equating to between euro 15,985- euro 16,273 per patient out of the 38 LC deaths averted. CONCLUSIONS: In a general practice setting, the incremental cost for a CXR screening programme targeted at all high-risk smokers in a population of 60,000 adults was estimated to be about euro 65,000 per annum, approx. euro 16,000 for each LC death averted.

Pulmonary resections of single metastases from colorectal cancer.

BACKGROUND: Surgical resection is the treatment of choice of pulmonary metastases from colorectal cancer. We retrospectively reviewed our experience of pulmonary resections of single metastases from colorectal cancer, in order to document postoperative clinical outcome and survival. MATERIALS AND METHODS: In the years 1997-2007, in 23 patients we performed 26 curative resections of pulmonary metastases from colorectal cancer (19 rectal and 7 colon; 12 males and 11 females; mean age 64.5 years). All patients had single lung metastasis. Three of the 23 patients underwent re-resection of the lung for treatment of a subsequent lung metastasis. Interval between resection of primary tumor and diagnosis of lung metastasis (disease-free interval (DFI)) was >36 months in 19 patients (73%) and was <36 months in 7 patients (27%). In 21 patients the metastases were metachronous; in 2 patients metastases were synchronous with primary colorectal cancer. The type of lung resection was wedge resection in 18 cases (70%); lobectomy in 6 cases (23%); pneumonectomy in 2 cases (7%). Of the 18 wedge resections, 12 (66%) were done thoracoscopically. After lung metastasectomy patients were followed up for 5-121 months (median: 61 months). RESULTS: We had 1 early postoperative mortality (after re-resection) from cardiac complication (3.8%). Postoperative morbidity (within 30 days) was observed in 7 cases (27%): 1 pneumonia, 1 empyema, 1 arrhythmia and 4 prolonged air leaks requiring chest drainage >7 days. Median survival was 74 months (Kaplan-Meier). CONCLUSIONS: Resection of single metachronous lung metastases from colorectal cancer has low mortality and morbidity and in our experience it correlated with prolonged postoperative survival. Re-resection of the lung for treatment of subsequent metachronous metastases carries higher risk.

Use of heat and moisture exchanging (HME) filters in mechanically ventilated ICU patients: influence on airway flow-resistance.

OBJECTIVE: To investigate the flow-resistance of a new generation of Heat Moisture Exchanging Filters (HME filters) during 24 h of clinical use. DESIGN: Before-after trial. SETTING: A general Intensive Care Unit of a university hospital. PATIENTS: A consecutive series of 96 patients undergoing mechanical ventilation for respiratory insufficiency of various etiology and severity. METHODS: The characteristics of the secretions collected by tracheal suctioning and the pressure/flow relationship of the HMEs before and after 24 h of clinical use were analyzed. RESULTS: The resistance of the HMEs when dry was 2 hPa/l.s, and it increased to a maximum of 1 hPa/l.s in 83% of the patients after 24 hours; in four patients with particularly heavy secretions HME resistance was 4-5 hPa/l.s. There were no significant modifications of the secretions within the investigation period, excluding, in particular, an increase in density with consequent tracheal tube obstruction. CONCLUSION: The gas conditioning efficiency and design performance of the tested HMEs did not create a significant obstacle to airflow medium term mechanical ventilation; however, these devices should be cautiously used in patients with heavy bronchial secretions.

The clinical use of 99m-Tc-labeled WBC scintigraphy in critically ill surgical and trauma patients with occult sepsis.

OBJECTIVE: To evaluate the clinical use of radionuclide-labeled white blood cell scintigraphy in the detection of focal sepsis. DESIGN: Prospective clinical study. SETTING: A medical/surgical 12-bed intensive care unit (ICU) in a university hospital. PATIENTS: 26 trauma and surgical patients affected by sepsis of unknown origin were studied. MEASUREMENTS AND RESULTS: After the usual diagnostic approach, patients were submitted to a total body scan by using the patient's leukocytes labeled with technetium-99m (99m-Tc) HMPAO; three scintigraphy were performed within 20 h of tracer injection; the result of scan was completed with all clinical and instrumental data, including ultrasound (US) arnd computed tomography (CT), and the diagnostic efficacy was demonstrated for each patient on discharge from the ICU. The scan was able to detect 20 sites of infection; it was possible to rule out 11 suspected sites; only in two cases was the result considered to be false positive or false negative; in two cases the result was considered to be uncertain. These results show the high sensitivity (95%), specificity (91%) and accuracy (94%) of the method. CONCLUSIONS: In ICU patients with sepsis, nuclear medicine can provide additional data, as the injection of radionuclide-labeled white blood cells (WBCs) allows the imaging of sites of infection. Analysis of our results suggests that scintigraphy with 99m-Tc-labeled WBCs can be considered a useful tool in the detection of the source of infection.

Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater.

Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study. The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score. A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls. The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.

Sepsis score and acute-phase protein response as predictors of outcome in septic surgical patients.

In a series of 135 patients with severe surgical infections, we determined the sepsis score and the plasma level of the acute-phase proteins alpha-1-acid glycoprotein, alpha 1-antitrypsin, complement factor B, and C3. The initial sepsis score was a strong determinant of survival: in survivors it was significantly lower than in nonsurvivors. Only 8% of patients with a sepsis score above 20 survived. At the onset of severe sepsis, the plasma levels of all four acute-phase proteins were significantly lower in nonsurvivors. A significant elevation of C3a levels in the plasma of both surviving and nonsurviving patients indicated marked consumption of complement components in all patients with severe sepsis. A linear equation was developed to predict survival: sepsis index of survival (SIS) % = 121 + 0.26 (complement factor B) + 0.36 (alpha-1-acid glycoprotein)-6 (sepsis score). Based on our analysis, at the onset of severe sepsis, an SIS of 50% or more can correctly predict 88% of survivors and an SIS less than 50% can correctly predict 86% of nonsurvivors several days in advance of clinical outcome.

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy.

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).

Immunological function and nutritional assessment.

Theoretically, a large number of tests of immunologic functions could be used for nutritional assessment. However, many of these immunologic tests require specialized laboratory skills and take a long time to perform. These tests provide little additional information to the clinician concerning the nutritional status of the patient, compared to the data that can be obtained from a few simple, selected immunologic measurements. Only a few immunologic tests are sufficiently simple, reproducible, and reliable indicators of nutritional status to be of practical value for routine nutritional assessment. These are the total lymphocyte count and skin tests. At present, all of the other immunologic measurements that have been reviewed should be considered as research tools for nutritional assessment. Immunological tests can be affected by many clinical variables unrelated to nutrition, such as specific pathologic conditions, immunodepressive therapies, accidental or surgical trauma, and infection, and this fact should be considered when using immunological tests to assess nutritional status. Malnutrition suppresses the acute-phase response of plasma proteins. The measurement of the acute-phase response of selected acute-phase proteins can be a functional measurement of nutritional status.

Intact protein versus free amino acids in the nutritional support of thermally injured animals.

This study compared the nutritional effects of intact protein with that of constituent amino acids as the sole source of nitrogen in a burn guinea pig model. Forty-five guinea pigs bearing a gastrostomy feeding tube were given 30% total body surface area, full thickness flame burn and were randomized into four groups. Group I (n = 12) and group III (n = 15) received a diet containing whey protein, while group II (n = 9) and group IV (n = 9) received an otherwise identical diet containing free amino acids in a whey protein pattern. Full strength continuous intragastric feeding was initiated immediately postburn in groups I and II, but a 72-hr adaptive period was provided in groups III and IV. Resting metabolic expenditure was measured by indirect calorimetry on postburn days 2, 6,9, and 13. After 14 days of enteral feeding, the animals were killed. Immediate enteral feeding of intact protein or free amino acids reduced postburn hypermetabolic response (p less than 0.01). However, the intact protein was found to maintain body weight and provide nitrogen retention better than the amino acid mixture (p less than 0.05). The animals on the intact protein diet also showed statistically significant benefits in carcass, liver, and gastrocnemius muscle weights and in serum albumin, transferrin and C3 levels. It is concluded that intact protein is superior to free amino acids for nutritional support following burn injury.

Optimal lipid content for enteral diets following thermal injury.

This study was performed to determine the effects of different amounts of lipid in enteral diets during the postburn period. Forty-five guinea pigs with catheter gastrostomy received a 30% total body surface area full thickness flame burn. After burn they were given intragastric tube feedings using five diets at different dietary lipid composition: 0, 5, 15, 30, and 50% of nonprotein calories. Total calories administered (175 kcal/kg/day), protein content and composition (20% of total calories), total volume, and vitamin and mineral content were constant in all animals. At postburn day 14, body weight, carcass weight, and muscle weight were the greatest in 0 and 5% lipid groups, and the least in 30 and 50% lipid groups. Serum transferrin was highest in the 5 and 15% lipid groups, and lowest in the 30 and 50% lipid groups. Total nitrogen content in muscle and cumulative nitrogen balance were best in the 15% lipid group. Liver fatty infiltration, caused from a larger proportion of carbohydrate administration, was greater in the 0 and 5% lipid groups and less in 15 and 30% groups. It is concluded that dietary lipid levels between 5 and 15% of nonprotein calories are optimal for nutritional support after burn injury. The nutritional management of postburn patients with higher levels of dietary lipid should be reconsidered.

Evaluation of possible causes of delayed hypersensitivity impairment in cancer patients.

The separate roles of malnutrition, advanced age, and stage of tumor growth as causes of impairment of delayed hypersensitivity response (DHR) was studied in 111 patients with solid tumors and in 56 nonneoplastic control patients matched for age, anatomical site of disease, degree of illness, and nutritional status. Pretreatment DHR to recall antigens (tuberculin, Candida, streptokinase-streptodornase, trichophyton) and to dinitrochlorobenzene in cancer patients with 9% anergic, 43% hypoergic, and 48% normoergic; the distribution of DHR in controls was not significantly different. In cancer patients, the serum albumin level showed an inverse correlation with the stage of tumor (p less than 0.01) and a positive correlation with the DHR (p less than 0.001); the serum albumin level was also in the controls positively correlated with the DHR (p less than 0.01), indicating that malnutrition in neoplastic or benign disease may cause depression of DHR. In well-nourished controls, age was inversely correlated with DHR (p less than 0.05), showing that aging itself may be another relevant cause of depression of DHR. The results of this study indicate that DHR in patients with solid tumors is similar to the DHR of nonneoplastic patients if matched for age, sex, and nutritional status. DHR impairment in cancer patients appears to be caused mainly by aging and by malnutrition due to the advanced progression of cancer.

Enteral feeding in burn hypermetabolism: nutritional and metabolic effects of different levels of calorie and protein intake.

Enteral nutrition was provided by continuous pump-controlled gastrostomy tube feeding for 14 days in 97 guinea pigs bearing a 30% full thickness burn. Seven defined combinations of caloric and protein intake were studied. With a caloric intake of 175 kcal/kg/day, equaling the measured energy expenditure, the animals receiving 10% of calories as protein had a significantly greater postburn weight loss (p less than 0.05) and muscle mass depletion (p less than 0.05), and a significantly lower muscle nitrogen concentration (p less than 0.05), serum albumin level (p less than 0.01) and liver nitrogen content (p less than 0.01). With the same caloric intake but with more than 20% of calories as protein, the weight loss and the muscle wasting were reduced, but not abolished, and the serum albumin level and liver nitrogen content were normalized. Also with the diets containing 200 kcal/kg/day the muscle tissue depletion could not be abolished. However, with this caloric intake, the animals given 20% of calories as protein had a lower weight loss and a higher serum albumin level (p less than 0.01), but also a greater fat infiltration of the liver (p less than 0.01). At both levels of caloric intake, the nitrogen balance correlated significantly with the level of nitrogen intake but did not correlate with the changes of body weight. The incidence of diarrhea was lowest in animals fed 20% protein calories at a caloric intake of 175 kcal/kg/day. All things considered, the best metabolic and nutritional results were obtained with diets containing 20 to 30% of calories as protein and providing a caloric intake that paralleled the measured energy expenditure.

Lung cancer screening and the surgical oncologist: the controversy.

Although screening for lung cancer is not currently recommended, randomized trials consistently demonstrate that chest x-ray screening is associated with significant advantages in stage distribution, resectability, and long-term survival. Because these advantages have not been accompanied by a reduction in lung cancer mortalities a because an excess number of lung cancers were detected in experimental populations in two studies, it has been suggested that screening leads to the detection of clinically unimportant lung cancers. This hypothesis, known as overdiagnosis, is the only obstacle to the conclusion that chest x-ray screening saves lives. However, abundant evidence convincingly demonstrates that the overdiagnosis hypothesis is myth with regard to chest x-ray screening for lung cancer. With more than one million deaths from lung cancer on a worldwide basis every year, public policy regarding screening for lung cancer is in urgent need of reconsideration.

Risk factors in surgery.

Improved surgical and anesthetic techniques and postoperative care have not significantly changed wound infection rates over the last 30 years. Many risk factors, related both to the host and to the surgical practice, have been identified in different studies. Control of nosocomial infections has become more challenging recently, due to a widespread bacterial resistance to antibiotics and to more frequent surgical indications in elderly patients at increased risk. A change in the microbiology of postoperative infections has also been noticed, characterized by a greater incidence of infections caused by methicillin-resistant Staphylococcus aureus, by polymicrobic flora and by fungi. This paper reviews the most important risk factors encountered in general surgery, that we observed during a 6-year prospective study of wound infection carried out in our Department of Surgery at the University of Insubria in Varese. Furthermore, the epidemiologic data on wound infections recorded in 4,002 patients undergoing general surgical procedures (mostly gastrointestinal operations), are presented and discussed.

Effects of surgical trauma of laparoscopic vs. open cholecystectomy.

The effects of surgical trauma resulting from laparoscopic cholecystectomy and open cholecystectomy, were compared by assessing the postoperative acute phase alterations of selected plasma proteins, hormones and lymphocyte subpopulations in fifty-seven patients prior to elective cholecystectomy. Patients were prospectively randomized to undergo either laparoscopic cholecystectomy (n = 30) or open cholecystectomy (n = 27). Duration of operation and general anesthesia was similar in the two patient groups. The laparoscopic cholecystectomy patients had a shorter postoperative stay in hospital (3.1 (0.5) days vs. 7.1 (1.6) days; p < 0.001). In open cholecystectomy patients a significantly greater postoperative acute phase increase in plasma C-reactive protein (p < 0.001), cortisol (p < 0.05), and prolactin blood level (p < 0.001) was recorded. The postoperative acute phase decrease in the blood total-T-lymphocyte count (CD3 cells) and in the activated-lymphocyte count (OKDR cells) was significantly greater after open cholecystectomy (p < 0.05). These results, showing that acute phase responses are less marked after laparoscopic cholecystectomy than after open cholecystectomy, support the concept that the laparoscopic procedure is less traumatic.

Infected pancreatic necrosis complicated by multiple organ failure.

BACKGROUND/AIMS: Sixteen patients with bacteriologically proven severe infected pancreatic necrosis (IPN) undergoing sequential surgical treatment were studied prospectively. METHODOLOGY: The severity of IPN was documented pre-operatively using the following scores: 1) degree of necrosis by CT scan [< 30% in three patients (19%); 30-50% in nine patients (56%); > 50% in four patients (25%)]; 2) Elebute and Stoner's sepsis score (16 +/- 4 points); 3) Goris' score of multiple organ failure (MOF) (5 +/- 2 points). Sequential surgical treatment was carried out by the same surgical team, as follows: 1) abdominal re-explorations through a zipper for the first 7-10 days; 2) open abdomen and repeated peritoneal debridements for the following 7-10 days; 3) continuous closed peritoneal lavage with multiple drainage, until resolution of infection (range: 15-85 days). No patient required further re-exploration. RESULTS: Mortality occurred in 3/16 patients (19%), due to MOF in all 3 cases. The 13 survivors (81%) were discharged convalescent with closed abdominal wound, feeding orally, after 73 +/- 33 days, without fistulae. These results indicate that by treating severe IPN with the technique of sequential abdominal re-explorations, open drainage and continuous closed lavage, a low 19% mortality can be achieved. CONCLUSION: This study provides an assessment of the pre-operative severity of sepsis and of MOF in each patient with IPN: these data could facilitate future comparison of results obtained with other treatment modalities.

Postoperative infections and variations of complement components in cancer patients.

Sequential determinations of C4 and factor B serum levels were performed pre- and postoperatively in 56 cancer patients. Patients who underwent radical mastectomy and excision of melanoma had an incidence of surgical infections of 7% and 15%, respectively, and showed a significant postoperative acute-phase increase of C4 and factor B serum levels. A higher incidence of postoperative infections, mostly Gram negative, was recorded in patients who underwent gastric resection (35%) and colorectal resection (73%); these failed to show an early acute-phase response of complement postoperatively. The results of this study confirm the high susceptibility of cancer patients to postoperative infections. Moreover, the lack of postoperative acute-phase increase of C4 and factor B observed in cancer patients who developed postoperative infections suggests an active role of complement in host defense mechanisms against surgical infections.

Sequential evaluation of immunoreactivity in patients with melanoma undergoing surgery and adjuvant therapy.

The immunologic profile of 15 patients undergoing surgery and adjuvant chemoimmunotherapy for cutaneous melanoma was studied for a mean period of 18 months. In vivo cellular immunity was assayed by evaluation of delayed hypersensitivity response (DHR) to primary antigen and a panel of recall antigens. In vitro cellular immunity was evaluated to means of total and T-lymphocyte counts in peripheral blood and by the lymphocyte blastogenic response to phytohemagglutinin stimulation. Humoral immunity was assayed by determining the serum levels of IgG, IgA and IgM and of complement components C3c, C4 and Factor B. Phagocytic activity was studied by testing leukocyte chemotaxis, neutrophil phagocytosis and leukocyte random migration. The in vitro parameters were determined preoperatively at diagnosis, 6 times during the first 2 postoperative weeks, and then every month during adjuvant therapy. No correlation was found between DHR and clinico-pathologic stage of tumor, or with subsequent clinical course. Significant depression of total lymphocyte and T-lymphocyte count and blastogenic response of lymphocytes was found at diagnosis. The lymphocyte response to PHA decreased significantly in the early postoperative period but returned to preoperative levels one week after surgery. Periodic fluctuations of lymphocyte blastogenic response and progressive decrease of total lymphocyte counts and T-lymphocyte counts were observed during the 18-month follow-up. No significant alterations of immunoglobulin levels were recorded at diagnosis or during the postoperative period. Complement levels were within normal values preoperatively; in the early postoperative period a transient increase of C3c, C4 and Factor B was recorded, then complement levels progressively decreased. Parameters of phagocytic activity were normal at diagnosis and fluctuated within the normal range throughout the whole period of study.

[Controlled study of unspecific cellular immunity in cancer patients]. / Studio controllato dell'immunità cellulare aspecifica in pazienti neoplastici.

Cellular immunity has been studied in 92 patients with solid tumors undergoing surgery, in order to evaluate immunocompetence at the time of diagnosis and to assess the prognostic value of parameters of cellular immunity. The results show that total lymphocyte counts, T-lymphocyte counts and lymphocyte blastogenic responses are moderately depressed at diagnosis in the cancer patients as compared to age matched controls. These parameters of cell mediated immunity "in vitro" seem to be of limited prognostic value, since no correlation was found with the clinical course during the first 6 postoperative months. Depression of delayed hypersensitivity response to cutaneous antigens appeared to be an index of poor prognosis.

[Postoperative pneumonia caused by Candida in 500 lung surgery patients]. / Le polmoniti da Candida in 500 interventi di resezione polmonare.

BACKGROUND: Postoperative infections continue to be one of the most frequent complications in hospitalized patients. The incidence of fungal infection has been steadily rising. While Candida albicans remains the most common yeast species isolated in hospitalized patients, other Candida species have been increasingly isolated. METHODS: From 1996 to 2001, a prospective study of 500 consecutive lung surgery patients treated by the same surgical team was conducted to monitor the number of postoperative infections and to evaluate the epidemiology of bacterial and fungal infections. RESULTS: At least one postoperative infection developed in 18% of patients. Of the 51 patients who developed postoperative pneumonia, 24 underwent microbiological examination of sputum. In 19 of them, the culture yielded isolates of one or more Candida species. Slightly under half of patients (47%) with cultures positive for mycetes received treatment with fluconazole until the clinical infection resolved. The drug was well tolerated by all treated patients. CONCLUSIONS: The incidence of fungal infection has increased also at our center. In 19 of 24 patients with postoperative pneumonia, sputum cultures yielded Candida species isolates. Many factors may be contributing to the rise in fungal infections after surgery. As pneumonia caused by Candida led to a significantly longer length of hospital stay in our case series, we draw attention to the importance of early diagnosis of postoperative mycotic lung disease in order to institute timely and targeted therapy.