Cancer incidence in urban, rural, and densely populated districts close to core cities in Bavaria, Germany.

OBJECTIVE: An ecologic study on the level of districts was performed to evaluate the possible association between district type and risk of cancer in Bavaria, Southern Germany. METHODS: Cancer incidence data for the years 2003-2012 were obtained from the population-based cancer registry Bavaria according to sex and cancer site. Data on district type, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption were obtained from publicly available sources. The possible association between district type and cancer risk adjusted for age, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption was evaluated using multivariable multi-level negative binomial regression. RESULTS: We found a significantly reduced cancer risk in densely populated districts close to core cities and/or rural districts compared to core cities with respect to the cancer sites mouth and pharynx (women only), liver (both sexes), larynx (both sexes), lung (both sexes), melanoma of the skin (both sexes), mesothelioma (men only), connective and soft tissue (both sexes), corpus uteri, other urinary tract (men only), urinary bladder (both sexes), and non-Hodgkin lymphoma (both sexes). CONCLUSION: Our findings require further monitoring. Since the apparently increased cancer risk in core cities may be related to lifestyle factors, preventive measures against lifestyle-related cancer could be specifically targeted at populations in deprived core cities.

[Small-scale analysis of suspected cancer clusters based on cancer registry data]. / Kleinräumige Analyse vermuteter Krebscluster anhand von Krebsregisterdaten.

Cancer registries collect data about the occurrence and temporal changes of the occurrence of all types of cancer. This information is an important basis for health administration as well as for the evaluation of possible cancer causes. Cancer clusters can be detected by analysis of registry data according to place or district of residence of diseased persons. Cancer registries frequently receive enquiries from concerned citizens asking for investigation of the causes of suspected cancer clusters. The management of suspected cancer clusters can be described as crisis management due to the mixing of medical, biological, political, and psychological factors. In this article, we present an overview of current guidelines and methods for handling suspected cancer clusters by cancer registries. Moreover, the numerical analysis of small-scale cancer registry data is illustrated using two examples from the Bavarian Cancer Registry.

[Rising incidence of papillary thyroid carcinoma in Germany]. / Inzidenzzunahme des papillären Schilddrüsenkarzinoms in Deutschland.

BACKGROUND: The incidence of thyroid cancer (TC), a rare malignancy, has strongly risen in recent decades. Possible causes of this rise include increasing diagnostic activity, nuclear tests after World War II, and the Chernobyl disaster. AIM: This article presents the time trends of TC incidence between 2003 and 2008 in Germany according to histological tumor type and sex, and provides a description of TC incidence according to districts (Kreise) and sex in Germany. METHODS: Data on persons newly diagnosed with thyroid cancer (ICD-10 code, C73) between 2003 and 2008 were obtained from the Center of Cancer Registry Data at the Robert Koch Institute. Official population and mortality data were used. Age-specific and age-standardized incidence rates (ASIR) were calculated according to sex and tumor histology. RESULTS: Between 2003 and 2008, the ASIR of TC rose from 2.7 to 3.4 (men) and from 6.5 to 8.9 (women) per 100,000 per year. This rise can be almost completely attributed to the rising incidence of papillary TC. The steepest rise in frequency was observed in TNM-T1 tumors. A positive north-south gradient of TC incidence was found. DISCUSSION: The cause of the marked rise of TC incidence in recent decades is unknown. The positive north-south gradient of the TC incidence may possibly be attributed in part to long-standing differences of iodine intake between different German regions. CONCLUSION: An epidemiological study of the possible causes of the rising TC incidence and of the regional differences of TC incidence in Germany is recommended.

Association between drinking water uranium content and cancer risk in Bavaria, Germany.

OBJECTIVE: To evaluate the possible association between uranium (U) content in public drinking water on the one hand and the risk of cancer of the colorectum, lung, female breast, prostate, kidney, and urinary bladder, total cancer, and leukemia on the other hand in Bavaria, an ecologic study on the level of municipalities was performed. METHODS: Cancer incidence data for the years 2002-2008 were obtained from the population-based cancer registry Bavaria according to sex. Current U content data of public drinking water on the level of municipalities were obtained from a publicly available source. The possible association between drinking water U content and cancer risk adjusted for average socio-economic status was evaluated using Poisson regression. RESULTS: Drinking water U content was below 20 µg/L in 458 out of 461 included municipalities. We found a significantly increased risk of leukemia in men in the intermediate (U level, 1.00-4.99 µg/L; relative risk [RR], 1.14) and in the highest U exposure category (U level, ≥5 µg/L; RR, 1.28). Moreover, in women, a significantly elevated risk was identified with respect to kidney cancer in the highest exposure category (RR, 1.16) and with respect to lung cancer in the intermediate exposure category (RR, 1.12). CONCLUSION: The slightly increased risk of leukemia in men, kidney cancer in women, and lung cancer in women may require further investigation. If an increased cancer risk is confirmed, preventive measures (e.g., introduction of U filters in public water systems) may be considered.

Outdoor work and skin cancer incidence: a registry-based study in Bavaria.

OBJECTIVE: To analyse the association between occupational ultraviolet (UV) light exposure and skin cancer (basal cell carcinoma, BCC; squamous cell carcinoma, SCC; cutaneous malignant melanoma, CMM) based on data from the Bavarian population-based cancer registry. METHODS: The population-based cancer registry of Bavaria (Germany) provided data on incident cases of BCC, SCC, and CMM, respectively, during the period 2001 until 2005. Eleven Bavarian districts with complete skin cancer registration were included in this analysis based on 2,156,336 person years. Cases were assigned to "indoor", "mixed indoor/outdoor", and "outdoor" exposure categories according to their job title. We computed age-specific and age-adjusted incidence rates of BCC (n = 1,641), SCC (n = 499), and CMM (n = 454) by work type, and the relative risk (RR) of skin cancer occurrence for "outdoor" and "mixed indoor/outdoor" workers, respectively, compared to "indoor" workers. RESULTS: The risk of BCC was substantially elevated in male (RR, 2.9; 95% CI, 2.2-3.9) and female (RR, 2.7; 95% CI, 1.8-4.1) outdoor workers compared to male and female indoor workers, respectively. We also found an elevated risk of similar magnitude for SCC in male (RR, 2.5; 95% CI, 1.4-4.7) and female (RR, 3.6; 95% CI, 1.6-8.1) outdoor workers compared to male and female indoor workers, respectively. CMM risk was not significantly associated with outdoor work. CONCLUSION: Our study confirms previous reports on the increased risk of BCC and SCC in outdoor workers compared to indoor workers.

Pre-emptive intra-articular administration of local anaesthetics/opiates versus postoperative local anaesthetics/opiates or local anaesthetics in arthroscopic surgery of the knee joint: a prospective randomized trial.

AIM: Arthroscopic surgery on the knee joint is increasingly being performed as day-case surgery. This necessitates adequate postoperative pain therapy. We performed a study to compare three different intra-articular regimens of pain treatment. The hypothesis was that preoperative intra-articular pain management is superior to postoperative procedures. METHOD: In this study we compared the preoperative administration of 0.1 mg fentanyl + 5 ml bupivacaine 0.5% with the postoperative administration of either 0.1 mg fentanyl + 5 ml bupivacaine 0.5% or 5 ml bupivacaine 0.5% alone in a total of 564 patients. Participants were randomly assigned to three groups. Each group was subdivided into patients with and without synovitis. RESULTS: The preoperative administration of fentanyl and bupivacaine significantly decreased the perceived pain. The efficiency increased with major arthroscopic procedures. Postoperative administration of bupivacaine alone had the least effect. There was variation within each group depending on whether synovitis was present or not. CONCLUSION: This study demonstrated the superiority of the preoperative intra-articular administration of a combination of fentanyl and local anaesthetic over postoperative fentanyl and local anaesthetic or postoperative local anaesthetic alone.

Association between split selection instability and predictive error in survival trees.

OBJECTIVES: To evaluate split selection instability in six survival tree algorithms and its relationship with predictive error by means of a bootstrap study. METHODS: We study the following algorithms: logrank statistic with multivariate p-value adjustment without pruning (LR), Kaplan-Meier distance of survival curves (KM), martingale residuals (MR), Poisson regression for censored data (PR), within-node impurity (WI), and exponential log-likelihood loss (XL). With the exception of LR, initial trees are pruned by using split-complexity, and final trees are selected by means of cross-validation. We employ a real dataset from a clinical study of patients with gallbladder stones. The predictive error is evaluated using the integrated Brier score for censored data. The relationship between split selection instability and predictive error is evaluated by means of box-percentile plots, covariate and cutpoint selection entropy, and cutpoint selection coefficients of variation, respectively, in the root node. RESULTS: We found a positive association between covariate selection instability and predictive error in the root node. LR yields the lowest predictive error, while KM and MR yield the highest predictive error. CONCLUSIONS: The predictive error of survival trees is related to split selection instability. Based on the low predictive error of LR, we recommend the use of this algorithm for the construction of survival trees. Unpruned survival trees with multivariate p-value adjustment can perform equally well compared to pruned trees. The analysis of split selection instability can be used to communicate the results of tree-based analyses to clinicians and to support the application of survival trees.

Anterograde tracing and immunohistochemical characterization of potentially mechanosensitive vagal afferents in the esophagus.

Vagal mechanosensitive afferents with an important functional role in esophageal peristalsis are well known from physiological studies. It is not known whether these fibers represent a separate subpopulation among all vagal afferents projecting to the esophageal wall. A morphological and immunohistochemical description of vagal afferents was undertaken to define their possible homo- or heterogeneity. The peripheral projections of vagal afferents were anterogradely labeled by injection of wheatgerm agglutinin conjugated to horseradish peroxidase into the nodose ganglion of rats. The anterogradely transported tracer was detected by tyramide amplification in conjunction with immunohistochemistry for Ca(2+)-binding proteins recently identified in different types of mechanosensory endings. It was found that vagal afferents represented a morphologically and structurally homogeneous population projecting to the myenteric ganglia of the esophagus, where they terminated as highly branched endings. Vagal afferent terminals, however, were different in their staining intensity for calretinin and calbindin, which ranged from intense to no detectable immunofluorescence. The fluorescence intensity of Ca(2+)-binding proteins within the vagal terminating branches was graded and the average staining intensity determined of all terminating branches in the upper, middle, and lower thirds of the esophagus. The average staining intensity was highest in the upper third of the esophagus and then declined in a statistically significant manner in the middle and lower thirds. This result suggests different requirements for intracellular Ca(2+)-buffering capacities in vagal afferents depending on their position along the esophageal axis and corroborates studies reporting a segmental organization of esophageal motility. Immunohistochemical evidence of substance P (SP) in a subset of vagal terminals was demonstrated. Hence, an effector role of vagal afferents on esophageal peristalsis by the release of SP, as has been proposed by physiological studies, is also supported by immunohistochemical data.

Botulinum toxin treatment of cocontractions after birth-related brachial plexus lesions.

The authors studied botulinum toxin type A therapy of severe biceps-triceps cocontractions after nerve regeneration following birth-related brachial plexus lesions. Six children (age, 2 to 4 years) were treated two to three times over a period of 8 to 12 months with 40 mouse units of botulinum toxin at two sites of the triceps muscle. Elbow range of motion improved from 0 to 25 to 50 deg to 0 to 25 to 100 deg (p < 0.05), and muscle force of elbow flexion increased from a mean of Medical Research Council classification 1.7 to 3.7 (p < 0.05). After a 1-year follow-up, there was no clinical recurrence.

Adverse drug reactions in patients with gastroenterological diseases: does age increase the risk?

BACKGROUND: It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease-group specific risks and none for patients with liver and gastrointestinal diseases. AIMS: To determine the incidence and characteristics of adverse drug reactions and the physicians' awareness of adverse drug reactions. METHODS: During a 7-month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary-care university hospital, using intensive bedside and computer-assisted drug surveillance methods. RESULTS: No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P < 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction-associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians. CONCLUSION: In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.

Critical illness polyneuropathy: clinical findings and cell culture assay of neurotoxicity assessed by a prospective study.

OBJECTIVE: First, to evaluate the role of typical intensive care-related conditions like sepsis, prolonged ventilation, drug effects and metabolic disorders in the pathogenesis of critical illness polyneuropathy (CIP); second, to investigate the possible significance of patient serum neurotoxicity assessed by an in vitro cytotoxicity assay with respect to CIP development. DESIGN: Prospective study. SETTING: Neurological intensive care unit. PATIENTS AND PARTICIPANTS: Twenty-eight patients who were on mechanical respiratory support for at least 4 days during a 21-month study period. RESULTS: Diagnosis of CIP was established by clinical and electrophysiological examination in 16 (57%) of 28 patients. Patients were investigated on days 4, 8 and 14 of mechanical ventilation. Two of 16 CIP patients had clinical signs of polyneuropathy at initial examination. Factors that correlated significantly with the development of CIP were: the multiple organ failure score on day 8 of ventilation, the total duration of respiratory support, the presence of weaning problems and the manifestation of complicating sepsis and/or lung failure. The in vitro toxicity assay showed serum neurotoxicity in 12 of 16 CIP patients. Electrophysiological investigations yielded false positive results of the toxicity assay in six patients (not developing CIP) and false negative results in four patients (developing clinical and electrophysiological signs of CIP). Statistical analysis did not reveal a significant correlation between the diagnosis of CIP and the finding serum neurotoxicity. CONCLUSION: The results support the hypothesis of a multi-factorial aetiopathogenesis of CIP. We observed serum neurotoxicity in the majority of CIP patients, indicating the possible involvement of a so far unknown, low-molecular-weight neurotoxic agent in CIP pathogenesis.

Experimental hypertrophy of myenteric neurones in the pig: a morphometric study.

Muscular hypertrophy in the ileum of two pigs aged 6 weeks was induced using two different surgical techniques, narrowing of the gut circumference (mechanical stenosis) and segmental reversal of an ileal loop which results in a persistent antiperistalsis of that segment (functional stenosis). These pigs were sacrificed 5-6 weeks postoperatively. Cross sections through the gut wall at various distances from the operation sites revealed marked muscular hypertrophy in the pre-stenotic regions and in the reversed segment. Whole mounts from pre- and post-stenotic, as well as reversed ileal regions, were silver- impregnated. The corresponding ileal region of a third, nonoperated pig served as control. Using a computer-aided morphometric device, somal areas of five morphological neurone types were measured at various distances orally and anally from the operation sites and along the control ileum. Values between hypertrophic and nonhypertrophic zones as well as between two corresponding zones of nonoperated ileum were compared statistically. Along the control ileum, values revealed no differences in soma sizes. Within the experimentally altered material, somal areas of type VI neurones showed marked hypertrophy related to the sites of muscular hypertrophy whereas the other types remained constant throughout (II, IV in segmental reversal) or showed slightly larger somal areas within the post-stenotic, nonhypertrophied zones (I, V, IV in stenosis). Additionally, within the reversed segment, neuronal perikarya of type I, II, IV and V neurones were larger as compared to the neighbouring regions. However, this enlargement of perikarya within the reversed segment may not be correlated with muscular hypertrophy but rather with the transections of intramural axons before reversing this segment. The results suggest that morphologically distinct neurone types may play different roles within the mechanically stressed small intestine and possibly also in the coordination of normal muscular function.

Impact of riluzole on the relationship between patient and physician.

To date, there has been little systematic research on the patient-physician relationship in amyotrophic lateral sclerosis (ALS). Important factors in this relationship are the emotional state, or mood, of the patients and their expectations of successful therapeutic intervention. In many patients there is a gradual deterioration of mood with disease progression-a view supported by studies comparing the initial and late phases of the disease. The few studies examining patients' expectations of therapy revealed a strong desire to be informed about the disease and its course without destroying every hope. In the later stages of the disease patients expected compassion and help with immediate problems. To our knowledge there has been no systematic study on the attitude of physicians towards ALS patients. The lack of effective treatment and the wish to avoid full information about the poor prognosis are almost unique problems involved in dealing with ALS patients. The new option to treat with a drug that slows disease progression provides some alleviation for the physician. Riluzole, at least, partially meets this expectation. Although its efficacy is too limited to satisfy fully the wishes of patients and physicians, it is the first available drug that has been shown to slow disease progression. Thus, it may bring to an end the feeling that there is nothing that can be done for these patients. In our experience this provides relevant alleviation in the management of ALS patients.

Alteration of early components of the visual evoked potential in amyotrophic lateral sclerosis.

Evoked potentials were recorded in three different visual experiments in 14 patients with amyotrophic lateral sclerosis (ALS) and 14 matched control subjects. Control subjects' evoked potentials (EPs) were characterized by an initial positivity in the 90-140 ms range (P1) at the temporo-occipital site. This component was absent from the group average of the ALS patients as well as the individual patients' EPs. As the P1 is known to emanate from inferior occipito-temporal areas, this finding provides electrophysiological evidence for a cortical involvement in ALS including visual areas.

Differentiation of Parkinson's disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT.

BACKGROUND: Differential diagnosis between idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA) is often difficult in early disease stages. Since MSA is misdiagnosed as PD in more than 20% of the early stages, there is need for methods refining the differentiation of the two disease entities. In PD postganglionic involvement of the autonomic nervous system (ANS) predominates whereas in MSA the ANS is mainly affected in its preganglionic structures. The functional integrity of postganglionic cardiac sympathetic neurons can be investigated using I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT). OBJECTIVES: We investigated whether I-123-MIBG-SPECT allows to differentiate between early stages of PD and MSA in patients not yet requiring L-dopa therapy. METHODS: Thirty patients (10 PD and 20 MSA patients) underwent MIBG-SPECT and evaluation of heart rate variability (HRV). Patients on any medication interfering with MIBG-accumulation were excluded from the study. Cardiac perfusion was evaluated by myocardial scintigraphy. RESULTS: The median cardiac MIBG uptake was significantly decreased in PD as well as MSA patients compared to controls (P<0.001). However, in the PD group MIBG uptake was significantly lower than in MSA (P=0.03). Even in PD patients without clinical signs of autonomic failure, MIBG uptake was significantly lower than in MSA patients (P=0.03). Analysis of heart rate parameters did not differentiate between PD and MSA patients. The median coefficient of variation was significantly smaller in PD and MSA patients compared to control subjects. CONCLUSIONS: Our study shows that MIBG-SPECT identifies autonomic cardiac dysfunction in very early stages of both, PD and MSA. More importantly, the technique facilitates differentiation of MSA and PD in the early stages. The different pathology with prominent peripheral, postganglionic sympathetic dysfunction in PD and primarily central and preganglionic lesions in MSA accounts for a lower MIBG uptake in PD compared to MSA patients.

Dendritic hypertrophy of Stach type VI neurons within experimentally altered ileum of pigs.

Myenteric neurons were investigated morphometrically to answer the question if type-specific somal hypertrophy of type VI neurons in mechanically stressed ileum of pigs, which was known from an earlier study, is correlated with an increased dendritic arborization, that is, with dendritic hypertrophy. Muscular hypertrophy was induced in the ileum of two juvenile pigs by narrowing the gut circumference (mechanical stenosis) and by reversing a loop of ileum which results in an antiperistaltic segment (functional stenosis), respectively. After a survival time of 6 weeks, wholemounts from the pre- and poststenotic ileal regions, from the antiperistaltic segment as well as from an age matched control animal, were silver impregnated. Dendritic parameters of Stach types IV and VI neurons were recorded using a computer-aided morphometric program and analysed statistically. Type IV neurons showed no change of dendritic parameters, neither within control nor within stenosed ileal segments. In contrast, the type VI neurons displayed increased dendritic parameters within zones of muscular hypertrophy such as total dendritic length, numbers of dendrites, of dendritic branching points and of dendritic endings. We suggest that type VI neurons may participate as descending nitrergic interneurons or motorneurons in the control of muscular function, thus, undergoing plastic changes in case of experimental muscular hypertrophy. Type IV neurons which are involved in the regulation of mucosal processes were not affected by muscular hypertrophy.

Comparison of tree-based methods for prognostic stratification of survival data.

Tree-based methods can be used to generate rules for prognostic classification of patients that are expressed as logical combinations of covariate values. Several splitting algorithms have been proposed for generating trees from survival data. However, the choice of an appropriate algorithm is difficult and may also depend on clinical considerations. By means of a prognostic study of patients with gallbladder stones and of a simulation study, we compare the following splitting algorithms: log-rank statistic adjusted for measurement scale with (AP) and without (AU) pruning, exponential log-likelihood loss (EP), Kaplan-Meier (KP) distance of survival curves, unadjusted log-rank statistic (LP), martingale residuals (MP), and node impurity (ZP). With the exception of the AU algorithm (based on a Bonferroni-adjusted p-value driven stopping rule), trees are pruned using the measure of split-complexity, and optimally-sized trees are selected using cross-validation. The integrated Brier score is used for the evaluation of predictive models. According to the results of our simulation study and of the clinical example, we conclude that the AU, AP, EP, and LP algorithm may yield superior predictive accuracy. The choice among these four algorithms may be based on the required parsimonity and on medical considerations.

A simulation model for small-area cancer incidence rates.

OBJECTIVES: Cancer epidemiologists are often asked by members of the interested public about possible associations between suspected carcinogens and apparently increased small-area cancer incidence rates. Frequently, no systematic incidence differences can be demonstrated. Nevertheless, it is necessary to address public concerns about suspected cancer clusters. To facilitate explanations about the large random variation of small-area tumor incidence, we implemented a software simulation tool in R. METHODS: Under the assumption of no cancer causes other than chance, the tool simulates a small village population with an average number of five inhabitants per house and allows graphical visualisation of ten streets with 100 houses. Published age-specific incidence and mortality data are used for event sampling based on the binomial distribution. Program parameters include sample size, age distribution, cancer incidence, and mortality rates. RESULTS: On average, 22 percent (2.2/10) of all houses per street have been inhabited by at least one cancer patient during the last five years in our simulated small village. A situation where all (10) houses in a street have been inhabited by at least one cancer patient during the last five years appears to be very rare (less than one in a million streets). CONCLUSIONS: Our software tool can be used effectively for numerical and graphical visualisation of small-area tumour incidence and prevalence rates due to chance alone. The explanation of basic epidemiological concepts to members of the public can help to increase public motivation and support for population-based cancer registration. Our simulation tool can be used to support this goal.

Revascularized muscle transfer for facial reanimation after long-standing facial paralysis.

The aim of the present study was to evaluate the results of a group of patients who had received free vascularized muscle transfer to the face for the treatment of long-standing facial paralysis. In 15 patients, neurovascular transfer of 16 segments of the gracilis muscle to the cheek was performed for reanimation of oral commissure movement. Voluntary muscle activation was evaluated by electromyography (EMG) and clinical function was assessed both metrically from frontal photographs and by a rating system with 6 categories. Patient satisfaction was explored through a self-administered questionnaire of general health (SF-36 health survey). The average follow-up period was 49.3 months. All patients showed voluntary activation of the grafted muscles in the EMG. Symmetry of the static and dynamic position of the oral commissure at rest and under function was considerably improved. In general, however, there was a tendency for undercorrection particularly in a vertical direction. Under function, the excursion of the oral commissure on the grafted side reached 63.7% and 65.5% of the nonparetic side in vertical and horizontal directions, respectively. Subjective rating of patient well-being showed that the scores were higher than or comparable to those of healthy adults in six of eight areas of evaluation.

Histomorphometric analysis of irradiated recipient vessels and transplant vessels of free flaps in patients undergoing reconstruction after ablative surgery.

The aim of the study was to investigate, histomorphometrically, quantitative and qualitative changes in irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses in free flaps in patients undergoing preoperative radiotherapy and chemotherapy. In 55 patients receiving 42 radial forearm flaps, 6 latissimus dorsi flaps, 6 osteomyocutaneous fibula grafts and 1 lateral arm flap, a total of 220 vessels were obtained from neck recipient vessels and transplant vessels during anastomosis. Three groups were formed: Group 1 (16 patients) treated with no radiotherapy or chemotherapy; Group 2 (20 patients) treated with preoperative irradiation (40-50 Gy) and chemotherapy (800 mg/m2 5-FU and 20 mg/m2 cisplatin) 1.5 months prior to surgery; Group 3 (19 patients) treated with radiotherapy (60-70 Gy) (median interval 78.7 months; IQR 31.3 months) prior to surgery. From each of the 220 vessel specimens, 3 sections each were histomorphometrically investigated, both qualitatively and quantitatively. To evaluate these changes as a function of age, radiation dose and chemotherapy, a statistical analysis was performed using analysis of covariance and chi-square tests. In Group 3, qualitative changes (intima dehiscence, hyalinosis) were found in recipient arteries significantly more frequently (25%, P=0.009) than in Groups 1 and 2. For Group 3 recipient arteries, histomorphometry revealed a significant decrease in the ratio of media area/total vessel area (median 0.53, IQR 0.10) in comparison with Group 1 (P= 0.02) (median 0.60, IQR 0.29) and Group 2 (P=0.046) (median 0.59, IQR 0.10). No significant differences were found between the vessels of Groups 1 and 2 (P= 0.48). Age and chemotherapy did not appear to have a significant influence on vessel changes in this study.