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.

Five-year survival of stage IIIA-IIIB (non-N3) non-small cell lung cancer patients after platinum/gemcitabine induction chemotherapy and surgery.

The 5-year survival rate of marginally resectable nonsmall cell lung cancer (NSCLC) patients treated by platinum/gemcitabine induction chemotherapy and surgery is not well documented. We studied 47 consecutive patients with NSCLC stage IIIA-IIIb (non-N3) treated with platinum/gemcitabine induction chemotherapy (median: 3 cycles) and evaluated the objective response, resectability, surgical morbidity/mortality and long-term survival rate. The induction chemotherapy was completed by 45/47 patients. Objective response was: 36% partial, 32% stable disease, 28% progression, 0% complete; two patients (4%) died during induction chemotherapy. Tumor resectability was 74%, postoperative morbidity 34%, mortality nil. 26% of patients were unresectable. in the whole cohort the 5-year survival was 25% (95%CI, 17%-32%) and the median survival was 22 months (28 months in resected patients; 7 months in unresectable).In conclusion, in the intention-to-treat population undergoing platinum/gemcitabine induction chemotherapy, resectability was high (74%) and the 5-year survival rate was 25%. Median survival in resected cases was three-fold greater than in the unresected.

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.

Lung cancer in Teesside (UK) and Varese (Italy): a comparison of management and survival.

BACKGROUND: The survival of lung cancer patients in the UK is lower than in other similar European countries. The reasons for this are unclear. METHODS: Two areas were selected with a similar incidence of lung cancer: Teesside in Northern England and Varese in Northern Italy. Data were collected prospectively on all new cases of lung cancer diagnosed in the year 2000. Comparisons were made of basic demographic characteristics, management, and survival. RESULTS: There were 268 cases of lung cancer in Teesside and 243 in Varese. Patients in Teesside were older (p<0.05), were more likely to have smoked (p<0.001), had a higher occupational risk (p<0.001), higher co-morbidity (p<0.05), and poorer performance status (p<0.001). Fewer patients in Teesside presented as an incidental finding (p<0.001) and the histological confirmation rate was lower than in Varese (p<0.01). In Teesside there were more large cell carcinomas (p<0.001), more small cell carcinomas (p<0.05), and fewer early stage non-small cell lung cancers (p<0.05). The resection rate was lower in Teesside (7% v 24%; p<0.01) and more patients received no specific anti-cancer treatment (50% v 25%; p<0.001). Overall 3 year survival was lower in Teesside (7% v 14%; p<0.001). Surgical resection was the strongest multivariate survival predictor in Varese (HR = 0.46) and Teesside (HR = 0.31). Co-morbidity in Teesside resulted in a significantly lower resection rate (p<0.001). CONCLUSIONS: Patients with lung cancer in Teesside presented at a later stage, with more aggressive types of tumour, and had higher co-morbidity than patients in Varese. As a result, the resection rate was significantly lower and survival was worse.

[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.

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.

Screening for lung cancer.

The large clinical studies of lung cancer screening carried out more than 20 years ago were interpreted as evidence against screening. Those studies have been recently reassessed in the light of methodologic flaws in the randomization of subjects at risk for lung cancer. There is no evidence to support the former conclusion that screening is ineffective and the consequent official recommendation not to screen for lung cancer. The hypothesis of overdiagnosis of lung cancers diagnosed by screening is false. Clinical evidence supports the concept that the current dogma against screening for lung cancer is untrue. Indeed, the 5-year survival rate of patients with NSCLC detected in stage I and radically resected ranges from 60% to 80%. This rate is in sharp contrast to the 10% survival rate of stage I NSCLC not resected. About 90% of lung cancer cases are detected among smokers and former smokers; these well-known at-risk subjects should be offered a screening test with the goal of detecting the disease when it is in stage I. It is expected that the techniques for early detection of lung cancer will be refined and become more sensitive in the near future, so that it will be possible to detect an increasingly large proportion of lung cancers when they are truly in stage I (i.e., nonmetastatic) and curable by radical surgical resection. Low-dose helical CT scan is currently believed to represent a very useful technique for screening for lung cancer, with a higher sensitivity than chest radiograph screening. Chest radiography for lung cancer screening, however, is cheaper and ubiquitously available, and it should still be recommended if CT scan is locally unavailable. As underscored in a recent commentary in The Lancet, the existing public health policy discouraging the screening for lung cancer is in urgent need of reconsideration.

Stage I nonsmall cell lung carcinoma: analysis of survival and implications for screening.

BACKGROUND: Skepticism about the radical curability of lung carcinoma, even when diagnosed in Stage I, has been long fostered by the epidemiologists' dogma against lung cancer screening, and by official recommendations not to screen for lung carcinoma. Follow-up of patients with asymptomatic screen-detected Stage I nonsmall cell lung carcinoma (NSCLC), however, shows that patients who underwent radical resection have long term survival rates, whereas patients nonsurgically treated or undergoing suboptimal operations have much poorer prognosis. The latter clinical outcome data strongly suggest the importance of detecting lung carcinoma when it is in Stage I and cast serious doubts on the recommendation not to screen for lung carcinoma. DATA: The scrutiny of the biology, epidemiology, and clinical features of Stage I NSCLC clarifies important aspects of the ongoing controversy concerning the value of screening for early diagnosis (Stage I) of lung carcinoma. The biologic characteristics of Stage I NSCLC (histologic types, doubling time, metastases) indicate its malignant potential. The asymptomatic screen-diagnosed Stage I carcinomas have longer doubling time than the more advanced cancers; nevertheless, they are not overdiagnosed tumors because they cause fatal outcome if they are not resected. Chest X-ray screening identifies approximately 50% of cancers in Stage I. Screening by helical low dose computed tomography scan detects greater than 80% of lung carcinomas in Stage I. The resectability, the surgical techniques (lobectomy vs. limited resections), and the influence of the extent of surgical resection of Stage I NSCLC on prognosis are reviewed. These data show that radical surgical treatment offers 5-year survival rate to 60-80% of patients with Stage I NSCLC. SYNTHESIS: Asymptomatic Stage I lung carcinomas, detected by screening or by incidental findings, are truly malignant, because they metastasize and cause fatal outcome if they are not radically resected. The possibility to cure lung carcinomas relies on radical resection (lobectomy or, less frequently, pneumonectomy) of early diagnosed (Stage I) disease, which is usually asymptomatic. The limited parenchymal resections (segment or wedge resections) do not fulfill the requirements of radicality because they are accompanied by higher incidence of local recurrences and shorter survival rates. CONCLUSIONS: The documented improvement of long term survival of NSCLC, which can be achieved by early diagnosis and radical resection, strongly indicates that the current dogma against lung cancer screening is untrue. Every effort should be made to detect the disease when it is in Stage I and radically operable, by implementing screening in at risk smokers and former smokers, with the most effective screening method that is locally available.

Lung cancer screening in cigarette smokers in the province of Varese, Italy.

BACKGROUND: For heavy cigarette smokers and recent former smokers who have accumulated a high risk of lung carcinoma, a primary objective is the early detection of that disease; this goal can be achieved by annual screening with one of the radiologic imaging methods available. While awaiting for the implementation of computed tomography or of other, more sensitive methods, it is quite reasonable to screen those who are at risk with annual chest X-ray (CXR), an examination that is readily available at low cost. Indeed, with the annual CXR screening of heavy smokers, it is possible to detect about 50% of lung carcinomas in TNM Stage I. The 5-year survival rate of patients with asymptomatic, screen-detected Stage I disease after radical surgery is significantly greater than the survival rate of patients with symptomatic disease. METHODS: At the Center for Thoracic Surgery of the University of Insubria Medical School in Varese we developed a project, called "PRE.DI.CA" (an acronym for "early diagnosis of cancer"), of annual CXR screening for the early diagnosis of asymptomatic lung carcinoma in the high risk population of heavy cigarette smokers and recent former smokers in the province of Varese, Italy. From June 1997 to August 1999, 2444 heavy smokers were enrolled in the PRE.DI.CA project. RESULTS: About 75% of participants complied with the annual screening protocol. Overall, 23 patients (all males) with asymptomatic lung carcinoma were detected by CXR screening; moreover, 1 patient developed symptoms of lung carcinoma 6 months after his initially negative CXR and was diagnosed with interval carcinoma (Stage IIIA). In the initial (prevalence) screening, the authors detected 16 patients with lung carcinoma in 2444 screened participants (0.65%). In the subsequent incidence screening, the authors detected 7 patients with lung carcinoma in 1361 screened participants (0.51%); it is noteworthy that 5 of 7 patients (71%) with lung carcinoma that was detected by incidence CXR screening had Stage I disease. CONCLUSIONS: In the province of Varese, Italy, it is possible to make an early diagnosis of lung carcinoma with CXR annual screening in asymptomatic, high risk smokers. Incidence screening in 1361 participants detected 7 patients with asymptomatic lung carcinoma; 5 of 7 patients (71%) with such screen-detected lung carcinoma had Stage I disease.

Perception, paradox, paradigm: Alice in the wonderland of lung cancer prevention and early detection.

BACKGROUND: In less than a century, lung cancer has progressed from a medical curiosity to the most deadly of all malignant diseases on our planet. Because cigarette smoking is responsible for the existing global lung cancer epidemic, policy initiatives have focused almost exclusively on primary prevention. There is no question that smoking prevention is the most effective method of reducing future lung cancer mortality rates among children, adolescents, and young adults. However, smoking cessation has limited effectiveness as a lung cancer prevention strategy among long term smokers, particularly in the short term. PERCEPTION: Conventional wisdom maintains that screening for lung cancer is ineffective. This is because no randomized trial has demonstrated a significant reduction in lung cancer mortality. Indeed, mortality was higher in two of four randomized trials focusing on chest X-ray (CXR) screening for lung cancer. Accordingly, the recommendation against CXR screening is believed to be based upon powerful and direct evidence from randomized trials that CXR screening is ineffective. PARADOX: Because lung cancer is almost uniformly fatal, a plausible explanation for the ineffectiveness of lung cancer screening, at least with CXR, is readily apparent. Coventional widsom maintains that in lung cancer, the asymptomatic preclinical interval is so short that apparently localized cancers are already metastatic when they are detected at an apparently localized stage. Accordingly, "early" lesions are not truly amenable to cure through surgical resection. The problem with this interpretation, however, is that it pays no heed to what the data actually show. While mortality reductions have not been observed, significant stage and long term survival advantages have consistently been demonstrated in populations randomized to screening. Interpretation of existing trials within the strict constraints of our accepted paradigm lends support to the hypothesis that CXR screening detects and labels as cancer a substantial number of early stage lesions that are clinically unimportant in that they would never have become clinically evident during the life of the patient. The paradox is that this hypothesis, known as overdiagnosis, is biologically implausible and is not supported by any epidemiologic or clinical evidence. PARADIGM: Based upon our accepted paradigm, a reduction in cause specific mortality in a population-based randomized trial is accepted without question as an unbiased and definitive measure of screening effectiveness. The mortality paradigm is dependent upon two assumptions, which relate first, to the randomization process, and second, to the confounding influence of screening biases on other endpoints. The fundamental problem, however, is that these assumptions, which should always have been the focus of investigation rather than supposition, are invalid. Reconsideration of our assumptions is imperative to a proper understanding of the effect of interventions in population-based research. Indeed, reexamination of our paradigm is key to reducing the global burden of lung cancer mortality.

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.

Intraoperative localization of gut endocrine tumors with radiolabeled somatostatin analogs and a gamma-detecting probe.

Gut endocrine tumors are sometimes difficult to localize by radiological techniques. Carcinoids and gastrinomas, however, possess high density of somatostatin receptors, thus, scintigraphy with radiolabeled somatostatin analogs may prove useful for detection of occult gastro-enteropancreatic endocrine tumors when conventional diagnostic methods fail. A novel method of radioguided surgery with a hand-held gamma-detecting probe (GDP) has been used to localize gut endocrine tumors by binding radiolabeled somatostatin analogs. We also applied the method in a patient with occult carcinoid: after injecting 125-Iodine (125I)-octreotide intraoperatively, we obtained accurate localization of the jejunal carcinoid and of a liver metastasis previously undetected. Seventeen cases of gut endocrine tumors detected by this technique that have been reported in the literature are reviewed and discussed. Intraoperative localization of gastrointestinal endocrine tumors with radiolabeled somatostatin analogs and a GDP expands the possibility of accurate tumor detection one step beyond that obtained by conventional imaging and by intraoperative inspection and palpation.

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.

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.

Sonographic features of liver metastases from pancreatic glucagonoma and acinar cell carcinoma. Case reports.

The previously unreported ultrasonographic (US) features of liver metastases of pancreatic glucagonoma and of pancreatic acinar cell carcinoma are described. They present as complex masses with hyperechoic solid component, containing echo-free cystic areas; these sonographic features markedly differ from the echo-poor US pattern of the much more common metastases of pancreatic ductal carcinoma. Survival from diagnosis of liver metastases was 45 months in the patient with pancreatic glucagonoma and 23 months in the patient with acinar cell carcinoma. These survivals were much longer than the expected survival of patients with pancreatic ductal carcinoma metastatic to the liver. The US finding of highly reflective lesions in the liver, containing echo-free cystic areas, should alert one that the primary pancreatic tumor has a histotype different from ductal carcinoma. Such US findings could affect the decision to resect the pancreatic tumor and its liver metastases, if histology confirms a malignancy less aggressive than ductal carcinoma.

Alterations in lymphocyte subsets as prognosticators of postoperative infections.

OBJECTIVE: To evaluate changes in lymphocyte subsets after major abdominal and thoracic operations, and to correlate changes with the development of clinically relevant infections postoperatively. DESIGN: Open study. SETTING: University hospital, Italy. SUBJECTS: 33 patients who were to undergo major abdominal or thoracic operations. INTERVENTIONS: Lymphocyte subsets were measured by cytofluorimetry before operation and 1, 3, 5, and 7 days postoperatively. MAIN OUTCOME MEASURES: Correlation between changes in the number of lymphocyte subsets and development of infection. RESULTS: Lymphocyte subsets were within the reference range in all patients before operation. 10/33 Patients developed infections (pneumonia, bacteraemia, or wound or urinary tract infections) between the second and the ninth days postoperatively (30%). On day 1 the numbers of all lymphocyte subsets had decreased significantly compared with the preoperative measurements in all patients (CD3 p < 0.01, CD4 p < 0.001, and CD8 p < 0.05). The reduction in CD3 was significantly greater in the group that developed infections (p < 0.001). Among patients who did not develop infections the numbers of lymphocyte subsets had returned to the reference range within a week of operation whereas among patients who developed infections they remained depressed (p < 0.05). CONCLUSION: The synchronous reduction in numbers of all lymphocyte subsets on the first day postoperatively to below 50% of the reference range (CD3 to < 600/microliters, CD4 to < 400/microliters, and CD8 to < 250/microliters) predicted the development of infection postoperatively with an accuracy of 89%, a sensitivity of 80%, and a specificity of 96%.