Contrast and Luminance Gain Control in the Macaque's Lateral Geniculate Nucleus.

There is substantial variation in the mean and variance of light levels (luminance and contrast) in natural visual scenes. Retinal ganglion cells maintain their sensitivity despite this variation using two adaptive mechanisms, which control how responses depend on luminance and on contrast. However, the nature of each mechanism and their interactions downstream of the retina are unknown. We recorded neurons in the magnocellular and parvocellular layers of the lateral geniculate nucleus (LGN) in anesthetized adult male macaques and characterized how their responses adapt to changes in contrast and luminance. As contrast increases, neurons in the magnocellular layers maintain sensitivity to high temporal frequency stimuli but attenuate sensitivity to low-temporal frequency stimuli. Neurons in the parvocellular layers do not adapt to changes in contrast. As luminance increases, both magnocellular and parvocellular cells increase their sensitivity to high-temporal frequency stimuli. Adaptation to luminance is independent of adaptation to contrast, as previously reported for LGN neurons in the cat. Our results are similar to those previously reported for macaque retinal ganglion cells, suggesting that adaptation to luminance and contrast result from two independent mechanisms that are retinal in origin.

Morphological evidence for multiple distinct channels of corticogeniculate feedback originating in mid-level extrastriate visual areas of the ferret.

Complementary reciprocal feedforward and feedback circuits connecting the visual thalamus with the visual cortex are essential for visual perception. These circuits predominantly connect primary and secondary visual cortex with the dorsal lateral geniculate nucleus (LGN). Although there are direct geniculocortical inputs to extrastriate visual cortex, whether reciprocal corticogeniculate neurons exist in extrastriate cortex is not known. Here we utilized virus-mediated retrograde tracing to reveal the presence of corticogeniculate neurons in three mid-level extrastriate visual cortical areas in ferrets: PMLS, PLLS, and 21a. We observed corticogeniculate neurons in all three extrastriate areas, although the density of virus-labeled corticogeniculate neurons in extrastriate cortex was an order of magnitude less than that in areas 17 and 18. A cluster analysis of morphological metrics quantified following reconstructions of the full dendritic arborizations of virus-labeled corticogeniculate neurons revealed six distinct cell types. Similar corticogeniculate cell types to those observed in areas 17 and 18 were also observed in PMLS, PLLS, and 21a. However, these unique cell types were not equally distributed across the three extrastriate areas. The majority of corticogeniculate neurons per cluster originated in a single area, suggesting unique parallel organizations for corticogeniculate feedback from each extrastriate area to the LGN. Together, our findings demonstrate direct feedback connections from mid-level extrastriate visual cortex to the LGN, supporting complementary reciprocal circuits at multiple processing stages along the visual hierarchy. Importantly, direct reciprocal connections between the LGN and extrastriate cortex, that bypass V1, could provide a substrate for residual vision following V1 damage.

Optogenetic activation of corticogeniculate feedback stabilizes response gain and increases information coding in LGN neurons.

In spite of their anatomical robustness, it has been difficult to establish the functional role of corticogeniculate circuits connecting primary visual cortex with the lateral geniculate nucleus of the thalamus (LGN) in the feedback direction. Growing evidence suggests that corticogeniculate feedback does not directly shape the spatial receptive field properties of LGN neurons, but rather regulates the timing and precision of LGN responses and the information coding capacity of LGN neurons. We propose that corticogeniculate feedback specifically stabilizes the response gain of LGN neurons, thereby increasing their information coding capacity. Inspired by early work by McClurkin et al. (1994), we manipulated the activity of corticogeniculate neurons to test this hypothesis. We used optogenetic methods to selectively and reversibly enhance the activity of corticogeniculate neurons in anesthetized ferrets while recording responses of LGN neurons to drifting gratings and white noise stimuli. We found that optogenetic activation of corticogeniculate feedback systematically reduced LGN gain variability and increased information coding capacity among LGN neurons. Optogenetic activation of corticogeniculate neurons generated similar increases in information encoded in LGN responses to drifting gratings and white noise stimuli. Together, these findings suggest that the influence of corticogeniculate feedback on LGN response precision and information coding capacity could be mediated through reductions in gain variability.

Physiological characterization of a rare subpopulation of doublet-spiking neurons in the ferret lateral geniculate nucleus.

Interest in exploring homologies in the early visual pathways of rodents, carnivores, and primates has recently grown. Retinas of these species contain morphologically and physiologically heterogeneous retinal ganglion cells that form the basis for parallel visual information processing streams. Whether rare retinal ganglion cells with unusual visual response properties in carnivores and primates project to the visual thalamus and drive unusual visual responses among thalamic relay neurons is poorly understood. We surveyed neurophysiological responses among hundreds of lateral geniculate nucleus (LGN) neurons in ferrets and observed a novel subpopulation of LGN neurons displaying doublet-spiking waveforms. Some visual response properties of doublet-spiking LGN neurons, like contrast and temporal frequency tuning, were intermediate to those of X and Y LGN neurons. Interestingly, most doublet-spiking LGN neurons were tuned for orientation and displayed direction selectivity for horizontal motion. Spatiotemporal receptive fields of doublet-spiking neurons were diverse and included center/surround organization, On/Off responses, and elongated separate On and Off subregions. Optogenetic activation of corticogeniculate feedback did not alter the tuning or spatiotemporal receptive fields of doublet-spiking neurons, suggesting that their unusual tuning properties were inherited from retinal inputs. The doublet-spiking LGN neurons were found throughout the depth of LGN recording penetrations. Together these findings suggest that while extremely rare (<2% of recorded LGN neurons), unique subpopulations of LGN neurons in carnivores receive retinal inputs that confer them with nonstandard visual response properties like direction selectivity. These results suggest that neuronal circuits for nonstandard visual computations are common across a variety of species, even though their proportions vary.NEW & NOTEWORTHY Interest in visual system homologies across species has recently increased. Across species, retinas contain diverse retinal ganglion cells including cells with unusual visual response properties. It is unclear whether rare retinal ganglion cells in carnivores project to and drive similarly unique visual responses in the visual thalamus. We discovered a rare subpopulation of thalamic neurons defined by unique spike shape and visual response properties, suggesting that nonstandard visual computations are common to many species.

Morphological heterogeneity among corticogeniculate neurons in ferrets: quantification and comparison with a previous report in macaque monkeys.

The corticogeniculate (CG) pathway links the visual cortex with the lateral geniculate nucleus (LGN) of the thalamus and is the first feedback connection in the mammalian visual system. Whether functional connections between CG neurons and LGN relay neurons obey or ignore the separation of feedforward visual signals into parallel processing streams is not known. Accordingly, there is some debate about whether CG neurons are morphologically heterogeneous or homogenous. Here we characterized the morphology of CG neurons in the ferret, a visual carnivore with distinct feedforward parallel processing streams, and compared the morphology of ferret CG neurons with CG neuronal morphology previously described in macaque monkeys [Briggs et al. (2016) Neuron, 90, 388]. We used a G-deleted rabies virus as a retrograde tracer to label CG neurons in adult ferrets. We then reconstructed complete dendritic morphologies for a large sample of virus-labeled CG neurons. Quantification of CG morphology revealed three distinct CG neuronal subtypes with striking similarities to the CG neuronal subtypes observed in macaques. These findings suggest that CG neurons may be morphologically diverse in a variety of highly visual mammals in which feedforward visual pathways are organized into parallel processing streams. Accordingly, these results provide support for the notion that CG feedback is functionally parallel stream-specific in ferrets and macaques.

Corticogeniculate feedback sharpens the temporal precision and spatial resolution of visual signals in the ferret.

The corticogeniculate (CG) pathway connects the visual cortex with the visual thalamus (LGN) in the feedback direction and enables the cortex to directly influence its own input. Despite numerous investigations, the role of this feedback circuit in visual perception remained elusive. To probe the function of CG feedback in a causal manner, we selectively and reversibly manipulated the activity of CG neurons in anesthetized ferrets in vivo using a combined viral-infection and optogenetics approach to drive expression of channelrhodopsin2 (ChR2) in CG neurons. We observed significant increases in temporal precision and spatial resolution of LGN neuronal responses to drifting grating and white noise stimuli when CG neurons expressing ChR2 were light activated. Enhancing CG feedback reduced visually evoked response latencies, increased spike-timing precision, and reduced classical receptive field size. Increased precision among LGN neurons led to increased spike-timing precision among granular layer V1 neurons as well. Together, our findings suggest that the function of CG feedback is to control the timing and precision of thalamic responses to incoming visual signals.

A cross-species comparison of corticogeniculate structure and function.

The corticogeniculate circuit is an evolutionarily conserved pathway linking the primary visual cortex with the visual thalamus in the feedback direction. While the corticogeniculate circuit is anatomically robust, the impact of corticogeniculate feedback on the visual response properties of visual thalamic neurons is subtle. Accordingly, discovering the function of corticogeniculate feedback in vision has been a particularly challenging task. In this review, the morphology, organization, physiology, and function of corticogeniculate feedback is compared across mammals commonly studied in visual neuroscience: primates, carnivores, rabbits, and rodents. Common structural and organizational motifs are present across species, including the organization of corticogeniculate feedback into parallel processing streams in highly visual mammals.

From vision to action: roadmapping as a strategic method and tool to implement climate change adaptation - the example of the roadmap 'water sensitive urban design 2020'.

As the central product of the BMBF-KLIMZUG-funded Joint Network and Research Project (JNRP) 'dynaklim - Dynamic adaptation of regional planning and development processes to the effects of climate change in the Emscher-Lippe region (North Rhine Westphalia, Germany)', the Roadmap 2020 'Regional Climate Adaptation' has been developed by the various regional stakeholders and institutions containing specific regional scenarios, strategies and adaptation measures applicable throughout the region. This paper presents the method, elements and main results of this regional roadmap process by using the example of the thematic sub-roadmap 'Water Sensitive Urban Design 2020'. With a focus on the process support tool 'KlimaFLEX', one of the main adaptation measures of the WSUD 2020 roadmap, typical challenges for integrated climate change adaptation like scattered knowledge, knowledge gaps and divided responsibilities but also potential solutions and promising chances for urban development and urban water management are discussed. With the roadmap and the related tool, the relevant stakeholders of the Emscher-Lippe region have jointly developed important prerequisites to integrate their knowledge, to clarify vulnerabilities, adaptation goals, responsibilities and interests, and to foresightedly coordinate measures, resources, priorities and schedules for an efficient joint urban planning, well-grounded decision-making in times of continued uncertainties and step-by-step implementation of adaptation measures from now on.

A sodium-pump-mediated afterhyperpolarization in pyramidal neurons.

The sodium-potassium ATPase (i.e., the "sodium pump") plays a central role in maintaining ionic homeostasis in all cells. Although the sodium pump is intrinsically electrogenic and responsive to dynamic changes in intracellular sodium concentration, its role in regulating neuronal excitability remains unclear. Here we describe a physiological role for the sodium pump in regulating the excitability of mouse neocortical layer 5 and hippocampal CA1 pyramidal neurons. Trains of action potentials produced long-lasting (∼20 s) afterhyperpolarizations (AHPs) that were insensitive to blockade of voltage-gated calcium channels or chelation of intracellular calcium, but were blocked by tetrodotoxin, ouabain, or the removal of extracellular potassium. Correspondingly, the AHP time course was similar to the decay of activity-induced increases in intracellular sodium, whereas intracellular calcium decayed at much faster rates. To determine whether physiological patterns of activity engage the sodium pump, we replayed in vitro a place-specific burst of 15 action potentials recorded originally in vivo in a CA1 "place cell" as the animal traversed the associated place field. In both layer 5 and CA1 pyramidal neurons, this "place cell train" generated small, long-lasting AHPs capable of reducing neuronal excitability for many seconds. Place-cell-train-induced AHPs were blocked by ouabain or removal of extracellular potassium, but not by intracellular calcium chelation. Finally, we found calcium contributions to the AHP to be temperature dependent: prominent at room temperature, but largely absent at 35°C. Our results demonstrate a previously unappreciated role for the sodium-potassium ATPase in regulating the excitability of neocortical and hippocampal pyramidal neurons.

[Extrathoracal pulmonary sequestration in the differential diagnosis of paravertebral tumors in the neonate]. / Extrathorakale Lungensequestration als Differenzialdiagnose paravertebraler Raumforderungen beim Neugeborenen.

BACKGROUND: Paravertebral masses of the fetus are often detected during routine prenatal ultrasonography. The most common differential diagnoses of these tumors are neuroblastoma, adrenal hemorrhage, schwannoma and germ cell tumors. CASE REPORT: We report on a mature male newborn, who was diagnosed antenatally at 23 + 3 weeks of gestation with a tumor in the left paravertebral region. After birth the child was transferred to a neonatal unit. Tumor markers like urinary catecholamines were within normal limits, neuron-specific enolase was slightly elevated. MRI as well as ultrasonography confirmed a 3.2 x 2.2 x 1.6 cm large smoothed edged tumor in the left paravertebral region at the level of T10-T12. An open biopsy was performed, and the tumor which was located below the diaphragma was subtotally resected. Histopathology showed an extralobar pulmonary sequestration. Surgery as well as postoperative course was uneventful. CONCLUSIONS: Extralobar pulmonary sequestrations represent rare congenital anomalies, which are usually asymptomatic. Clear differentiation between tumor and pulmonary sequestration is seldom possible despite high resolution imaging studies. Hence, a biopsy procedure should be done for diagnosis of paravertebral masses.

[Resection of combined or sequential lung and liver metastases of colorectal cancer: indication for everyone?]. / Resektion kombinierter oder sequenziell auftretender Leber- und Lungenmetastasen kolorektaler Karzinome: Welche Patienten profitieren?

UNLABELLED: Successful sequential resection of isolated hepatic and pulmonary metastases of colorectal cancer (crc) has been reported, however long-term results of large series are lacking. Therefore, we retrospectively analysed data of patients in whom sequential hepatic and pulmonary resection for metastases was performed. PATIENTS AND METHOD: From the records of our hospital we identified 25 patients (19.5 % of all patients operated for hepatic or 33 % for lung metastases due to crc) with colorectal cancer who had pulmonary and hepatic resection for metastatic disease between 1991 and 2002. 11 of these had primary colonic cancer and 14 rectal cancer. None of the patients died perioperatively. Long-term results were correlated with the staging of the primary tumour, the number of metastases, disease free interval between primary tumour operation and occurrence of metastatic disease. RESULTS: Five-year survival rate was 33.5 % following the resection of the first metastasis. Three year survival after resection of the second metastasis was 39 %. The disease free interval was 20 months (mean). Long-term results were clearly influenced by the disease free interval: < 1 year (n = 6) median 50 months after resection of the crc; > 1 year median 90 months (n = 19). Further on R0 resection was important for long-term survival: Median survival was 32.5 (+/- 4.1) months following resection of the second metastasis but only 9.9 months after R > 0 resection. CONCLUSION: These results confirm that sequential resection of hepatic and pulmonary metastases can be performed with curative intention provided a systemic spread of the disease is excluded. The surgeon's opinion of resectability should be obtained in patients with such metastases before the patient is scheduled for palliative conservative treatment.

[Radiofrequency ablation of malignant lung tumours. Judicious approach?]. / Radiofrequenzablation maligner Lungentumore. Eine sinnvolle Methode?

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive technique and well established in the treatment of malignant hepatic tumours. This method could also find application in patients with malignant lung tumours who, for functional reasons, have to be excluded from standard surgery. Until now, however, very little data have been available on the application of RFA in malignant pulmonary tumours. PATIENTS AND METHODS: From November 2001 to January 2004, eleven malignant lesions of the lung were treated with RFA. The indication for RFA resulted from an inadequate pulmonary reserve and additional severe risk factors. RESULTS: Eleven lesions were treated in ten patients with RFA. The malignancies were primary non-small cell bronchial carcinomas (n=9) as well as metastases of non-small cell carcinomas (n=2). Early complications of RFA were pneumothorax, hemorrhagic intrapleural effusion, bronchopleural fistula and pericarditis. Two weeks after RFA, pneumonia appeared as a late complication. No patient's death was related to the RFA procedure. After a mean follow-up of 8.5 months five patients died. Five patients are still alive, two of whom exhibit no tumour recurrence. CONCLUSION: RFA in patients with lung tumours is possible from a technical viewpoint. It is possibly a therapeutic alternative for patients with localized tumours that are inoperable. However, in this series, the morbidity of the procedure -- taking the degree of invasiveness into account -- is high, and the oncological results are unsatisfactory, possibly due to a small cohort of patients.

[Completion pneumonectomy. Indications and results]. / Sekundäre Pneumonektomien. Indikationen und Langzeitergebnisse.

Completion pneumonectomy (CP) is widely known to be associated with high morbidity and lethality. However, in certain instances, it offers the only chance for cure. The results of the following CPs (N=86) were investigated: progressive or recurrent benign disease (N=6, group I), recurrence of a malignant tumor (N=41, group II), and complication after lung resection (N=39, group III). Right completion pneumonectomy was carried out in 48 cases and left completion pneumonectomy in 38. The overall 30-day lethality of CP was 20.2%, 0% in group I, 10% n group II, and 33.3% n group III. This lethality was significantly higher on the right side (29.8%) than on the left (7.7%; P=0.014). Differentiation between emergency and urgent indications resulted in 30-day lethalities of 54% and 23%, respectively. This difference is significant (P=0.002). The 30-day lethality for patients with anastomotic or stump insufficiency was 41% (P=0.002). Five-year survival was 26% in the group of patients with malignant disease and 32% in those with complications after lung resection. The results show: the lethality of CP remains high, especially after complications from operating in emergency conditions. However, considering the long-term survival, CP is certainly justified.

Completion pneumonectomy for lung metastases.

OBJECTIVE: Completion pneumonectomy (CP) for malignant disease is generally accepted but controversial for lung metastases. The data available show a high perioperative morbidity and mortality with a poor long-term prognosis. We analysed the postoperative outcome and long-term results of our patients undergoing CP. PATIENTS AND METHODS: Between January 1986 and May 2003, nine patients underwent completion pneumonectomy for lung metastases. This represents 10% (9/86) of all CPs performed and 1.7% (9/525) of all pneumonectomies. RESULTS: One to three metastasectomies in the form of wedge resection (16), segment resection (5) and lobectomies (3) were performed prior to CP. The mean time interval between the operation of the primary tumour and the first metastasectomy was 38 months, the first and second metastasectomy 12 months, the second and third metastasectomy 14 months, and the third metastasectomy and CP 25 months. Six patients had an extended completion pneumonectomy. Operative morbidity and mortality was 0%. One patient is still alive and recurrence-free 9 months after CP. Two patients have recurrent pulmonary contralateral metastases under chemotherapy and six patients died of metastatic disease. Actual survival is 33%, recurrence-free survival (RFS) is 11%. The 3-year survival is 34%. CONCLUSION: Since there was no morbidity and mortality in our series, CP for lung metastases seems to be justified but the long-term survival is limited by the occurrence of contralateral or extrapulmonary metastatic disease. Multiple resections of metastases have a positive influence on survival, but the last step of resection in the form of CP does not seem to improve long-term survival.

Disease-free survival after resection of lung metastases in patients with breast cancer.

AIMS: Metastatic breast cancer is a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. METHODS: Retrospective analysis of 25 patients with suspected pulmonary metastases operated between March 1989 and September 1998. Survival probabilities and disease-free survival was analysed using the Kaplan-Meier method and the log-rank test. RESULTS: The median survival rate after resection of lung metastases for the 21 patients was 96.9 months. The disease-free survival (DFS) after resection of lung metastases was 27.6 months. Survival was not influenced by the receptor status, lymph node involvement, number of lung metastases (p=0.8) or the disease-free interval (DFI) (0.59). DFS was, however, influenced by the DFI. With a DFI of <2 years survival was 8.5 months, whereas with a DFI >2 years it was 36.1 months (p=0.012). The DFS was influenced, but not statistically significant, by the number of lung metastases (n=1/n>1). The median DFS was 28.8 months with one metastasis and 13.1 months with multiple metastases (p=0.29). CONCLUSIONS: The indication to remove solitary lung metastases in patients with previous breast cancer is supported by these findings. Especially when the disease-free interval is greater than two years.

Experimental use of an albumin-glutaraldehyde tissue adhesive for sealing tracheal anastomoses.

AIM: The purpose of this study was to test the performance of an albumin-glutaraldehyde tissue adhesive (BioGlue, manufactured by CryoLife Inc., Kennesaw, GA, USA) when used on tracheal resections in rabbits, which is a sensitive model to investigate the biocompatibility of the glue. METHODS: The 24 animals were anesthetized and underwent cervicotomy with resection of a 10 mm long tracheal segment. The experimental group (18 animals with 2, 4 and 12 week endpoints) had a tracheal anastomosis performed with a maximum of 4 sutures for the approximation of the tissue margins. The anastomotic line was then circumferentially covered with the adhesive. Control animals (6 animals, 4 week endpoint) had a tracheal anastomosis performed with the use of twice interrupted, airtight running suture. The experiments were conducted after approval by the Institutional Ethics Committee and in accordance with the European Convention on Animal Care. RESULTS: Macroscopic evaluation revealed a tight closure of the anastomosis in 23 animals. One rabbit developed tracheo-cutaneous fistula, 2 rabbits experienced intraluminal granulations due to infection, and 1 rabbit developed tracheal stenosis due to insufficient sutures with axis-displacement of the anastomosed tracheal lumina. On microscopic examination, after 2 weeks an inflammatory tissue response consisting of neutrophils, macrophages and foreign body giant cells was found surrounding the glued area. After 4 weeks the tissue was granulomatous in character with an increasing number of multinucleated giant cells. In general, persistent granulomatous inflammation and fibrous scar tissue was seen after 12 weeks. Both, macroscopically and microscopically, fibroangioblastic tissue responses were found in the control group after 4 weeks. CONCLUSIONS: Despite secondary healing disruptions such as granuloma formation, our investigations suggest that the results of albumin-glutaraldehyde tissue adhesive sealed tracheal anastomoses with a few approximating sutures are comparable with those using suture technique. Short term results demonstrated good biocompatibility of the glue.

[Bronchoscopy and rhythmic disorders. Premedication with atropine-sulfate, as a rule?]. / Bronchoskopie und Herzrhythmusveränderungen. Ist eine Prämedikation mit Atropin stets erforderlich?

Ikeda has introduced flexible bronchoscopy in the seventies of the last century. Since then the over one hundred year old procedure of direct airways inspection has widely spread and enhanced the diagnostic and therapeutic means. Thus the flexible bronchoscopy has become an important part of modern medicine. The close combination of atropine as premedication with bronchoscopy is justified with the terms "cardioprotection" and reduction of mucus secretion. As there is to this date no controlled study to prove this assumption, with the start of bronchoscopy we controlled every patient with a holter-ecg for 24-hours and estimated semiquantitatively the mucus secretion during procedure by a four point scale. Consecutively 55 patients could be randomised, 25 (7 females, 18 males) in the group with and 30 (7 females, 18 males) without atropine. In the records there were no detectable significant differences between the groups with atropine (A) and without atropine (P), as well as for registered bradycardias (A: 0 vs. P: 0, minimum of heart beats A: 63.8 vs. P: 74.1 min -1) as well as for alterations of heart rhythms, e. g. SVES (A: 7.3 % vs. P: 5.5 %), VES (A: 9.0 % vs. P: 9.0 %) or a combination of SVES with VES (A: 12.7 % vs. P: 10.9 %). The same results could be seen for each single of the first twenty minutes, additionally the first and the second recorded hour and the whole registered 24 hours. Moreover the times needed to complete the bronchoscopy showed no significant difference (mean of t A: 16.8 vs. P: 15.6 min, t-minimum 10 vs. 10 min, t-maximum A: 30 vs. P: 35 min). The same absence of differences was seen in estimated endobronchial mucus secretion (mean A: 1.88 vs. P: 2.0). According to these results of our studied group, there are no reasons, why a premedication with atropine in flexible bronchoscopy in local anaesthesia should be used. Even without the administration of atropine, flexible bronchoscopy could be performed as a safe and sophisticated method in direction of not inducing relevant arrhythmia, with low impact on patients.

[Removing lung metastases. With surgical success 36% of patients survive 5 years]. / Lungenmetastasen entfernen. Bei OP-Erfolg überleben 36% der Patienten fünf Jahre.

Resection of lung metastases can improve the long-term survival of many oncological patients. This can be achieved only by complete resection, which necessitates careful prior staging. With few exceptions (renal cell carcinoma, carcinoma of the colon metastasizing to the lungs and liver, chest wall and lung metastases) no extrapulmonary metastases should be present. Solitary round lesions should always be resected, since the prognosis for single lesions is favorable, and the primary may be a bronchial carcinoma, which is often curable. Although overall morbidity and mortality rates are low, the indication for surgical treatment of lung metastases should nevertheless be considered with care.

[Epidemiology and costs of lung cancer in Germany]. / Epidemiologie und Kosten des Bronchialkarzinoms in Deutschland.

OBJECTIVE: Lung cancer shows the leading incidence of all cancers among men in the developed world and an increasing incidence among women. We performed a cost of illness study that aimed to assess the economic burden of lung cancer in Germany and to identify the main cost drivers. METHODS: Costs were estimated for the year 1996. In a retrospective analysis we calculated direct and indirect costs based on secondary data from governmental institutions as well as from the pharmaceutical industry. We chose the cost perspective of sickness funds to estimate direct costs. The human capital approach was applied for the calculation of indirect costs. RESULTS: Total estimated costs were DM 8.31 billion per year. The indirect costs of DM 7.40 billion accounted for 89 % of total estimated costs. The most important cost driver of the indirect costs, early death, represented on its own DM 4.85 billion, according to 58 % of total estimated costs. Of the direct costs, 93 % were due to hospitalization, amounting to DM 0.85 billion. CONCLUSIONS: This cost of illness study concerning lung cancer illustrates the outstanding importance of the indirect costs, mostly due to early death, for total costs. Based on these findings and on the leading role of smoking in the etiology of lung cancer, we suggest that studies dealing with the net costs of smoking to society should include indirect costs.