Search

Constrictive pericarditis is the final common result of a number of processes that affect the pericardium. Establishing the diagnosis and determining the underlying etiology of constrictive pericarditis are often a diagnostic rendezvous. Here, we describe a patient who presented to the general practitioner with edema, ascites, and weight gain and was found to have constrictive pericarditis secondary to an inflammatory myofibroblastic tumor of the mediastinum. Interestingly, she had a relative lack of cardiorespiratory complaints, and, aside from the edema and mildly elevated jugular venous pressure, she had an unremarkable cardiac and pulmonary examination. During the diagnostic evaluation for constrictive pericarditis, she was found to have hypogammaglobulinemia and profound lymphocytopenia. A stool α-1-antitrypsin level was sent and was elevated, which confirmed the diagnosis of protein-losing enteropathy, a rare but important complication of constrictive pericarditis. This case highlights important diagnostic considerations and management of these complications for the general practitioner.

The serotonin transporter (5-HTT) is a key molecule of serotoninergic neurotransmission and target of many anxiolytics and antidepressants. In humans, 5-HTT gene variants resulting in lower expression levels are associated with behavioral traits of anxiety. Furthermore, functional magnetic resonance imaging (fMRI) studies reported increased cerebral blood flow (CBF) during resting state (RS) and amygdala hyperreactivity. 5-HTT deficient mice as an established animal model for anxiety disorders seem to be well suited for investigating amygdala (re-)activity in an fMRI study. We investigated wildtype (5-HTT+/+), heterozygous (5-HTT+/-), and homozygous 5-HTT-knockout mice (5-HTT-/-) of both sexes in an ultra-high-field 17.6 Tesla magnetic resonance scanner. CBF was measured with continuous arterial spin labeling during RS, stimulation state (SS; with odor of rats as aversive stimulus), and post-stimulation state (PS). Subsequently, post mortem c-Fos immunohistochemistry elucidated neural activation on cellular level. The results showed that in reaction to the aversive odor CBF in total brain and amygdala of all mice significantly increased. In male 5-HTT+/+ mice amygdala RS CBF levels were found to be significantly lower than in 5-HTT+/- mice. From RS to SS 5-HTT+/+ amygdala perfusion significantly increased compared to both 5-HTT+/- and 5-HTT-/- mice. Perfusion level changes of male mice correlated with the density of c-Fos-immunoreactive cells in the amygdaloid nuclei. In female mice the perfusion was not modulated by the 5-Htt-genotype, but by estrous cycle stages. We conclude that amygdala reactivity is modulated by the 5-Htt genotype in males. In females, gonadal hormones have an impact which might have obscured genotype effects. Furthermore, our results demonstrate experimental support for the tonic model of 5-HTTLPR function.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

Despite sizeable short-term effects of neurofeedback (NF) therapy on attention-deficit and hyperactivity disorder (ADHD), longer-term clinical, comorbidity and self-regulation outcomes are less systematically studied. The aim of this largest NF follow-up to date was to evaluate these outcomes 6 months after NF compared to a semi-active control to disentangle specific from unspecific sustained effects. We performed a multicenter, randomized, parallel, controlled, clinical, superiority trial in five German university outpatient departments. Participants were eligible if they fulfilled DSM-IV-TR criteria for ADHD and were aged from 7 to 9 years. Participants were randomly assigned (1:1-ratio) to 25 sessions of slow cortical potential (SCP)-NF or electromyogram biofeedback (EMG-BF). Participants were not blinded, since they received instructions according to each treatment setting. Primary outcomes were parent ratings of ADHD. The trial was registered, number ISRCTN761871859. Both groups showed improvement of ADHD symptoms compared to baseline at 6-months follow-up with large effect sizes for SCP-NF (d = 1.04) and EMG-BF (d = 0.85), but without group differences. When analyzing all assessments (pre-test, post-test-1, post-test-2 and follow-up), a group-by-time interaction emerged (p = 0.0062), with SCP-NF showing stable improvement following treatment but EMG-BF showing a relapse from post-test-1 to post-test-2, and subsequent remission at follow-up. Six months after the end of treatment, improvement after SCP-NF remained large and stable. However, the lack of group differences at follow-up suggests shared specific and unspecific effects contributing to this clinical outcome. Our correlational results indicate specificity of SCP-NF for selected subscales after training, but not at follow-up.

Anxiety disorders represent one of the most prevalent mental disorders in today's society and early adversity has been identified as major contributor to anxiety-related pathologies. Serotonin (5-hydroxytryptamine, 5-HT) is implicated in mediating the effects of early-life events on anxiety-like behaviours. In order to further elucidate the interaction of genetic predisposition and adversity in early, developmental stages on anxiety-related behaviours, the current study employed tryptophan hydroxylase 2 (Tph2)-deficient female mice, as a model for lifelong brain 5-HT synthesis deficiency. Offspring of this line were exposed to maternal separation (MS) and tested, in the open-field (OF) or the dark-light box (DLB). Subsequently, neural activity was assessed, using c-Fos immunohistochemistry. In the DLB, MS rescued the observed decrease in activity in the light compartment of homozygous Tph2-deficient mice and furthermore in-creased the incidence of escape-related jumps in animals of the same genotype. In the OF, MS increased escape-related behaviours in homo-and heterozygous Tph2-deficient offspring. On the neural level, both behavioural tests evoked a distinct activation pattern, as shown by c-Fos immunohistochemistry. Exposure to the DLB resulted in Tph2-dependent activation of paraventricular nucleus and basolateral amygdala, while OF exposure led to a specific activation in lateral amygdala of maternally separated animals and a Tph2 genotype-and MS-dependent activation of the ventrolateral and dorsolateral periaqueductal grey. Taken together, our findings suggest that MS promotes active responses to aversive stimuli, dependent on the availability of brain 5-HT. These effects might be mediated by the distinct activation of anxiety-relevant brain regions, due to the behavioural testing. (c) 2018 Elsevier B.V. and ECNP. All rights reserved.

Article-at-a-Glance Background A study was conducted to test whether patient reports of medical errors via surveys could produce sufficiently accurate information to be used as a measure of patient safety. Methods A survey mailed regularly by a large multispecialty medical group to recent patients to assess their satisfaction and error experiences was expanded to collect more details about the patient-perceived errors. Following an initial mailing to 3,109 patients and parents of child patients soon after they had office visits in June 2005, usable mailed or phone follow-up responses were obtained from 1,998 respondents (65.1% adjusted). Responses were reviewed through a two-stage process that included chart audits and implicit physician reviewer judgments. The analysis categorized the review results and compared patient-reported errors with satisfaction. Results Of the 1,998 respondents, 219 (11.0%) reported 247 separate incidents, for a rate of 12.4 errors per 100 patients. After complete review, only 5 (2.0%) of these incidents were judged to be real clinician errors. Most appeared to represent misunderstandings or behavior/communication problems, but 15.4% lacked sufficient information to categorize. Women, Hispanics, and those aged 41–60 years were most likely to report errors. Those respondents making error reports were much more likely to report visit dissatisfaction than those not reporting them (odds ratio [OR] = 13.8, p Discussion Although patient reports of perceived errors might be useful to improve the patient experience of care, they cannot be used to measure technical medical errors and patient safety reliably without added evaluation. This study's findings need to be replicated elsewhere before generalizing from one metropolitan region and a patient population that is about two-thirds members of one health plan.

Purpose To study how survival of palliative cancer patients relates to subjective prediction of survival, objective prognostic factors (PFs), and individual psychological coping. Patients and Methods Survival was estimated according to three categories (< 1 month, 1 to 6 months, and > 6 months) by two physicians (A and B) and the institutional tumor board (C) for 216 patients recently referred for palliative radiotherapy. After 6 months, the accuracy of these estimates was assessed. The prognostic relevance of clinical symptoms, performance status, laboratory tests, and self-reported emotional distress (Hospital Anxiety and Depression Scale) was investigated. Results In 61%, 55%, and 63% of the patients, prognoses were correctly estimated by A, B, and C, respectively. κ statistic showed fair agreement of the estimates, which proved to be overly optimistic. Accuracy of the three estimates did not improve with increasing professional experience. In particular, the survival of 96%, 71%, and 87% of patients who died in less than 1 month was overestimated by A, B, and C, respectively. On univariate analysis, 11 of 27 parameters significantly affected survival, namely performance status, primary cancer, fatigue, dyspnea, use of strong analgesics, brain metastases, leukocytosis, lactate dehydrogenase (LDH), depression, and anxiety. On multivariate analysis, colorectal and breast cancer had a favorable prognosis, whereas brain metastases, Karnofsky performance status less than 50%, strong analgesics, dyspnea, LDH, and leukocytosis were associated with a poor prognosis. Conclusion This study revealed that physicians' survival estimates were unreliable, especially in the case of patients near death. Self-reported emotional distress and objective PFs may improve the accuracy of survival estimates.

Purpose Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown. Patients and Methods Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time. Results The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001). Conclusion Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.

Background and purpose By virtue of their high linear energy transfer (LET) characteristics the biologic effectiveness of neutrons is less dependent on tissue oxygenation tension and cell cycle phase as compared to that with photons. Hence, an improved clinical benefit is to be expected predominantly in large, hypoxic and slowly growing tumors. Since a short course of radiotherapy is required for clinical reasons, it prompted the authors to initiate a randomly controlled trial on locally advanced breast cancer. Patients and methods Between 1996 and 1999, 27 patients with locally advanced breast cancer were irradiated with photons (60 Gy, 30 fractions; 8 MV, (60)Co) or neutrons (18 Gy, twelve fractions; 66 MeV(p-->Be)). The mean tumor diameters were 699 +/- 399 ml for the photon group and 1,097 +/- 831 ml in the neutron group. Results After a mean follow-up period of 21.5 months tumor involution was evaluated in 22 patients. Partial and complete remissions were registered in 6/10 patients of the photon group and 5/12 patients of the neutron group. Late grade 3-4 morbidity according to RTOG definition was scored in 5/10 patients in the photon group and in 6/12 patients in the neutron group. With regard to tumor control and late radiation morbidity no differences between the two treatment arms were observed. Conclusion The underlying data indicate that no benefit is to be expected from neutron therapy in breast cancer.

Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (

BACKGROUND. The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS. Seventy patients treated at the University Hospital Dusseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage 1, 26% Stage 11, 43% Stage 111, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS. In univariate analysis, KPS (P < 0.001), histologic type (P = 0.0093), and stage (P = 0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%, The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P = 0.36) and median survival (P = 0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS. Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.

This retrospective analysis was undertaken to determine the incidence of interstitial pneumopathy and the clinical course after mantle field irradiation for Hodgkin's disease focusing on the role of radio- and chemotherapy. 136 patients were evaluable, 40 having received radiotherapy only and 96 patients having received combined radio-chemotherapy. The median follow-up time was 21.5 months. The overall incidence was 19%; 4 patients died of severe interstitial pneumopathy and 3 died of simultaneous severe complications. The radiation dose was correlated with the incidence of interstitial pneumopathy (P = 0.0021).

Persisting symptomatology after breast-conserving surgery and radiation is frequently reported. In most cases, symptoms in the breast resolve without further treatment. In some instances, however, pain, erythema, and edema can persist for years and can impact the patient's quality of life. Hyperbaric oxygen therapy was shown to be effective as treatment for late radiation sequelae. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment.Forty-four patients with persisting symptomatology after breast-conservation therapy were prospectively observed. Thirty-two women received hyperbaric oxygen therapy in a multiplace chamber for a median of 25 sessions (range, 7-60). One hundred percent oxygen was delivered at 240 kPa for 90-min sessions, 5 times per week. Twelve control patients received no further treatment. Changes throughout the irradiated breast tissue were scored prior to and after hyperbaric oxygen therapy using modified LENT-SOMA criteria.Hyperbaric oxygen therapy patients showed a significant reduction of pain, edema, and erythema scores as compared to untreated controls (p0.001). Fibrosis and telangiectasia, however, were not significantly affected by hyperbaric oxygen therapy. Seven of 32 women were free of symptoms after hyperbaric oxygen therapy, whereas all 12 patients in the control group had persisting complaints.Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy.

Side effects of chemo- and radiotherapy are granulo- and thrombocytopenia. However, the long-term effects of in vivo granulocyte-colony-stimulating factor (G-CSF) stimulation of the hematopoietic system during radiotherapy are not yet completely understood. In the present study, we sought to determine the bone marrow effect of G-CSF during radiotherapy.In a prospective, randomized clinical trial 10 patients (6 m, 4 f, 30-64 yrs, mean 50.6 yrs) were assigned to large field radiotherapy (RT). 7 patients (pat.) with non-Hodgkin lymphoma, one patient with Hodgkin's disease and 2 patients with small-cell carcinoma of the lung were included. The patients were randomized to either radiotherapy alone (group A) or radiotherapy with simultaneous G-CSF (group B) treatment and assessed for acute and late toxicity. Blood samples were drawn and analyzed before and after G-CSF stimulation. The mobilization effectivity of G-CSF on CD34 superset+ progenitor cells was measured using flow cytometry and colony forming units (CFU) testing on admission and during the complete follow-up period (1, 3 and 18 months post RTx).Overall, 50 pat. were intended to be included to the protocol. However, the preliminary analysis revealed a significant decrease of thrombocytes and CD34 superset+ progenitor cells in the G-CSF treatment group. According to the study protocol further treatment was stopped. Peripheral leukocyte counts ranged between 2800 - 4375 /mul in 9/10 pat. In group B mean thrombocyte levels dropped below 30.000 mg/l and CD34 superset+ progenitor cells to 50% (interruption criteria, p0.02, Student's t-test). Hemoglobin values did not vary. Differential blood smears showed differences in granulocyte counts and a higher proportion of neutrophils in group B. Lymphocyte counts of patients randomized to group A were significantly decreased when compared to group B. In group A, 3/5 pat. developed an overshooting reaction (4,7 x increase) after G-CSF-stimulation. In arm B circulating CD34 superset+ progenitor cells dropped. In arm A, 3/5 pat. had an initial overshoot reaction when compared to none in group B. CFU (40 cells) and cluster (4 -39 cells) showed considerable variations.Our results demonstrate that simultaneous treatment with G-CSF during radiotherapy reduces the mobilization of CD34+ progenitor cells and exhaust the bone marrow capacity while peripheral leukocyte counts remain at baseline levels.

OBJECTIVE In this report, we describe our experience with the use of dexmedetomidine in spontaneously breathing as well as in mechanically ventilated patients, after congenital cardiac and thoracic surgery. DESIGN Retrospective case series. SETTING University hospital, pediatric cardiac intensive care unit. PATIENTS Thirty-three spontaneously breathing and five mechanically ventilated patients who received dexmedetomidine after cardiothoracic surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thirty-eight patients, age 8 +/- 1.1 yrs old and weight 29 +/- 3.8 kg, were included. Seven patients (18%) were

Malignant fibrous histiocytoma (MFH) is a soft-tissue sarcoma created from fibroblast cells and characterized by a high rate of metastasis or recurrence with poor prognosis. We report a case of initially well differentiated (G1) MFH of the trunk in a 33-year-old woman. Two years after primary diagnosis, metastases were found in the lung, trunk, gluteus region, upper extremities and brain. Histopathological findings indicated a stromal tumor consisting of spindle cells, and immunohistochemical examination of resected specimens established the definite diagnosis of poorly differentiated MFH (G3). Initial surgery of several solid tumors on the trunk, lung and extremities was performed. There was a high local recurrence and metastasis rate, and the patient was treated with radiotherapy and conventional chemotherapy followed by tandem high-dose chemotherapy and peripheral blood stem-cell transplantation. She is currently well seven years after the transplant, with no signs of metastasis and recurrence. We review the clinical picture of the tumor in this patient and discuss its diagnosis, pathogenesis and treatment.

The purpose of the paper was to generate up-to-date, representative osteoarthritis prevalence data for individual population subgroups and to identify potential risk factors.A cross-sectional study, the "First National Health Survey", investigated the prevalence of osteoarthritis, comorbidity and health-relevant behaviours of the post-unification German population on the basis of interviews with physicians and medical evaluations conducted in the period from October 1997 to March 1990. The study was based on a net sample comprising 6205 subjects aged 18-79 years.The three main correlates for osteoarthritis are age, obesity and occupational stress factors. Osteoarthritis patients are more likely to have osteoporosis, thyroid disease, chronic bronchial disease, hypertension and elevated blood lipids, but do not tend to have a higher incidence of diabetes.Our data show the importance of preventive behavioural approaches such as weight management and workplaces designed to limit joint overuse.

Evaluation of remission rates after neoadjuvant chemotherapy alone or followed by preoperative radiotherapy.194 women with 198 biopsy-proven breast tumors were evaluated in this retrospective study. Of the 198 cases evaluated, 64 received neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (CT group). In 134 cases, sequential preoperative chemo-/radiotherapy (CT-RT group) was given. In both groups, endocrine treatment was initiated in case of positive hormone receptor status after chemotherapy. The whole breast was homogeneously irradiated using 2-Gy fractions up to a total dose of 50 Gy, followed by a boost of 6-11 Gy to the tumor.A histologically proven complete remission (pCR) was achieved in 3% (2/64) in the CT and in 42% (56/134) in the CTRT group. The logistic regression analysis, including clinical tumor category (cT), lymph node (cN) and metastasis status (cM), grading (G), hormone receptor status (HRS), number of preoperative chemotherapy cycles, preoperative tumor volume, and preoperative radiotherapy, revealed that HRS (p = 0.0232) and radiotherapy (p0.0001) were significant factors for achieving pCR.Combination of neoadjuvant chemo-/radiotherapy results in significantly higher rates of complete remission than neoadjuvant chemotherapy alone. The significance for tumor-free and overall survival has to be evaluated.

The report describes a case of post-mortem scavenging by a songbird. A married couple had opened the cage of an astrild (finch) prior to their joint death. The body of the wife showed unusual patchy epidermal lesions on parts of the body not covered by the clothing, which were obviously caused by the songbird. According to the observations made by Roll and Rous they are attributable to "pecking and pulling". The behaviour of the bird was most probably due to lack of fluid.

Despite sophisticated surgical methods only a few pediatric CNS tumors can be controlled by operation alone. Therefore multimodality treatment regimens are needed to improve quality of life and survival, which is most important in malignant neoplasms. Since 1998 we have treated 16 children with malignant CNS tumors. All 16 patients have been treated on an interdisciplinary basis and are therefore accompanied by a pediatric neuro-oncology group consisting of a neurosurgeon, pediatric oncologist, and radiotherapist. Depending on tumor histology, child"s age, and extent of surgery, further adjuvant therapy is planned by this group. Newly diagnosed tumors are typically treated by a specific chemotherapy protocol according to a multi-institutional study. In recurrent tumors more individual treatment regimens are considered. Data concerning surgery, adjunctive treatment, complications, and outcome of all patients and four case reports are presented.

Purpose: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. Patients and methods: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6–164) months. Results: Masaoka's stage was predictive of aneuploidy (P < 0.01) and disease-free survival (P < 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P < 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. Conclusion: DNA image cytometry may provide additional information about the prognosis of resected thymoma.

The value of palliative surgery for adenocarcinoma of the cardia (AC) is controversial, and specific studies are lacking. The aim of this study was to report the results of a palliative resection for AC in 69 patients.From 1980 to 1993, 69 patients (mean age 59 +/- 10 years) underwent a palliative resection for AC. Palliative resection was defined by macroscopically incomplete resection, tumoral involvement of resection margins, visceral or serosal metastasis, or N3 metastatic nodes. Patients were classified according to the diagnosis of palliation established preoperatively (group A, n = 26), peroperatively (group B, n = 35), or postoperatively (group C, n = 8) respectively.Six patients (8.7%) died postoperatively. Mortality rates were 3.8%, 8.6% and 25% in groups A, B and C, respectively. Twenty one patients (30%) had postoperative non-fatal complications. Median global survival was 9 months (mean 11 +/- 7 months) without significant difference between groups A, B and C. Forty-four out of 51 patients (86%) followed until death did not have dysphagia. The other patients were free of dysphagia during an average of 70% of the follow-up duration. Among the 14 patients surviving postoperatively with a tumoral esophageal margin, none experienced dysphagia from anastomotic recurrence during follow-up.In selected patients with AC, a palliative resection can be achieved with an acceptable mortality and a very good functional result. This result can justify a prospective comparison between palliative surgery and alternative treatments.

Our objective was to investigate the effectiveness of hyperbaric oxygenation (HBO) in the treatment of radiation proctitis. The current literature was reviewed with regard to the necessary number of HBO treatments.Two patients with proctitis after pelvic irradiation were treated with 40 and 38 HBO treatments, respectively. Hyperbaric oxygenation was delivered at 240 kPa over 90 min.In one patient, proctosigmoidoscopy showed a significant improvement after 40 HBO sessions. The other patient interrupted therapy after 38 HBO treatments without subjective change. The reported number of HBO sessions for a successful treatment of radiation proctitis ranges from 12 to 90.HBO should be considered before more invasive treatment modalities are performed for radiation proctitis.

Medulloblastoma is the most frequent malignant brain tumor in pediatric patients. Early treatment strategies, combining surgery and radiotherapy alone, resulted in survival rates of about 40 % only. In the last 15 years, chemotherapy was used more frequently in combination with surgery and radiotherapy. The rationale was to increase the survival rate and to decrease radiation toxicity in young children. Forty-six patients younger than 16 years were treated between July 1977 and September 1995 in our institution (32 boys and 14 girls). Thirty-nine patients could be evaluated according to their postoperative treatment with regard to different protocols such as SIOP 1, SIOP 2, HDMTX/VCR, HIT protocol 89/91 and Carbo-PEI (one patient). In total, 21/39 patients are alive without evidence of disease (EFS 55 ± 7 %) with a follow-up of 26 to 210 months. Four children are lost to follow-up. Twelve patients died after relapse, 1 child died of MTX-induced brain atrophy, 1 patient developed a secondary malignancy (acute lymphoblastic leukemia) and died. The best results were seen in patients treated according to the HIT 89/91 protocol as first-line treatment (CR 9/10). The improvement in outcome of our patients with medulloblastoma in recent years suggests the benefit of intensified chemotherapy on survival. In addition, refinement in surgical and radiological treatment have certainly also contributed to the better results.

The aim of the presented protocol was to investigate tumour remission and breast conservation rates with and without flap supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. 101 patients with stage IIA-IIIA breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. 96 patients underwent salvage surgery. Complete pathologic response was not related to tumour diameter at diagnosis, the applied chemotherapy regime, number of chemotherapy cycles, overall radiation treatment time and time interval between radiotherapy and surgery. A breast conserving approach was possible in 55 patients (54%). After a median follow-up of 18 months no patient developed an isolated local recurrence.

The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia.One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy 192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 x 2 Gy/week. Local hyperthermia with 43.5-44.5 degrees C over 60 minutes was delivered immediately before interstitial radiotherapy.One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases.In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.

The kinetic profile of ethanol and ethyl glucuronide (EtG) in serum was investigated in three subject groups: 1) Healthy, moderately drinking volunteers (daily intake less than 30 g ethanol) who ingested a single dose of ethanol. In this group the maximum of serum ethyl glucuronide concentration (SEtGC) and of serum ethanol concentration (SEC) did not exceed 3.7 mg/L and 1.5 g/L respectively. EtG peaked 2 to 3.5 h later than ethanol. EtG was eliminated with a terminal half-life of 2 to 3 h. EtG decreased slower than ethanol--the metabolite could still be determined in serum up to 8 h after complete ethanol elimination. 2) In serum samples of teetotalers neither ethanol nor EtG could be found. 3) In 37 of 50 serum samples of drivers suspected of driving under the influence of ethanol, SEtGC was found between the limit of detection (0.1 mg/L) and 20 mg/L. If the SEC is less than 1 g/L and the SEtGC is significantly higher than 5 mg/L, we assume alcohol misuse.

To assess the teratogenic potential of Airol cream (0.05% tretinoin, CAS 302-79-4), plasma concentrations were compared after repeated dermal applications of the maximum dose which could be applied reliably and after oral administration of the highest non-teratogenic dose. The test preparation was applied dermally in two equal portions to rats and rabbits at 2 g/animal/d (equivalent to a tretinoin dose of 3.7 mg/kg/d) and at 6 g/kg/d (equivalent to 3 mg tretinoin/kg/d), respectively. After a single oral administration of 2 mg/kg, Cmax and AUC for tretinoin in rat plasma were 285 +/- 14.6 ng/ml and 595 +/- 123 ng h/ml, respectively. Corresponding values for the rabbit were 78.4 +/- 16.9 ng/ml and 126 +/- 25.4 ng h/ml. In both species, plasma concentrations of tretinoin after dermal application were consistently below the assay quantification limit (5 ng/ml and2 ng/ml for rat and rabbit, respectively), despite marked irritation of the skin. Thus repeated topical application of the test preparation produced plasma concentration of tretinoin which were well below the plasma concentrations produced by a non-teratogenic oral dose of 2 mg/kg in the rat and rabbit.

Neutron therapy should be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work the potential therapeutic gain of a clinical neutron beam is evaluated by quantifying the variations in radiosensitivity of different cell lines to neutrons and photons.Different cell lines were exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays. Micronuclei frequencies in binucleated cells and surviving fractions were determined for each cell type.Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed for 2 Gy photons. A weak but significant correlation between the variation in neutron RBE values, determined from survival curve inactivation parameters and the mean inactivation doses for photon exposures, was also established.It is concluded that although neutron and photon sensitivities are related, the use of this high energy neutron source may constitute a potential therapeutic gain for tumor types that can be identified as very resistant to photons. Considering that a definitive oxygen gain factor has been established for this neutron beam the observed therapeutic gain is expected to be further enhanced in tumors where hypoxia protects cells from conventional radiation damage.

Purpose : To test the feasibility of recombinant human granulocyte colony stimulating factor application during large-field radiotherapy. Methods and Materials : Fifteen patients with clinically and histologically proven malignancy who received large-field radiotherapy entered this study. Administration of recombinant granulocyte colony stimulating factor (G-CSF) at a dose of 300 μg subcutaneously was started on Friday and was continued on Saturday and Sunday after the first radiotherapy treatment, which began on the Monday before. In this way four courses of G-CSF were applied every Friday, Saturday, and Sunday during the radiotherapy period. Absolute neutrophil cell (ANC) and blood counts were monitored twice a week and compared to a second group of 15 patients who received large-field radiotherapy without G-CSF. Before and at the end of every cycle of G-CSF, ANC, blood counts, and biochemistry were measured. We compared the myelotoxicity of the patients treated with G-CSF with 15 patients without G-CSF treated at the same period with large-field radiotherapy, in match pair technique. Results : G-CSF increased the ANC throughout the period of irradiation, and the treatment time needed for completing radiotherapy was shorter in the group who received G-CSF. Fourteen of 15 patients who received G-CSF treatment completed large-field radiotherapy without pause. Only 1 of 15 patients not receiving G-CSF was able to receive radiation treatment on schedule. Patients receiving G-CSF completed treatment with the mantle-field technique in 24 days and those with the abdominal bath technique in 26.5 days. Conversely, patients treated without G-CSF completed treatment with the mantle-field technique in 30.5 days and those with the abdominal bath technique in 36 days. The most frequent side effect was musculoskeletal pain. Conclusion : The prophylactic application of G-CSF during large-field radiotherapy before the onset of neutropenia was feasible in this schedule. Whether or not this shortening of treatment duration will translate into an improvement in efficacy is not clear.

A total of 721 patients were treated in the neutron therapy programme at NAC from February 1989-March 1995 with a p(66)/Be isocentric unit. The preliminary results showed: 3-year local control and survival probabilities of 57 and 79% respectively for advanced salivary gland tumours; increased local control for twice-daily neutron therapy for advanced head and neck cancer compared with photon therapy; local control rates of 68 and 83% for locally advanced breast cancer treated with 17 and 19 Gy respectively; complete response rates of 67% for macroscopic residual soft tissue sarcomas and those with irresectable disease of less than 10 cm; complete response rate of 56% for macroscopic residual uterine sarcoma with a median follow up of 38 months; 2-year local control rate and survival of 44 and 38% respectively for advanced squamous carcinoma of the maxillary antrum; complete response rate of 38% for advanced osteosarcomas and chondrosarcomas.

Interphase-FISH (fluorescence in situ hybridization) studies have been devoted to the determination of clonality of aberrant karyotypes in human leukemia. Various levels of its extent have been examined, including the meaning of a single aberrant karyotype as representing a microclone, the use of FISH to confirm clonality in bi- or multiclonal leukemia, the estimation of the residual (aberrant) clone after contrasexual bone marrow transplantation, and the redetectability in interphase of the abl/bcr rearrangement. The quantitative findings of all these lines of interphase FISH analyses were based on the comparison with data from a large-scale "control" study on normal cells using the same DNA probes which have been chosen for the determination of clonality, i.e. centromeric DNA probes for chromosomes #1, #3, from #6 to #12, from #15 to #18, #20, X and Y, and a specific probe for the abl/bcr rearrangement. In addition, the validity of interphase-FISH analysis on classical bone marrow smears was examined. As a common outcome it was concluded that interphase-FISH technique is a valuable tool for defining clonality of karyotypic changes and, as a consequence, yields additional prognostic information in many human leukemias. It is recommended to perform interphase FISH in routine cytogenetics of leukemia, whenever reasonable.

For that reason absorption of bile acids was investigated using the 75Se-homotaurocholate (SeHCAT) in 239 patients with diarrhoea. SeHCAT retention time was measured as 7 day retention time in a whole body counter. An intact bile acid absorption (negative SeHCAT test) was confirmed in 23 healthy volunteers within the range of 11 to 50% (mean +/- double standard deviation).In 135 patients with a possible type I bile salt malabsorption the SeHCAT test was positive in 78%, thus indicating bile salt malabsorption. The test is very sensitive detecting bile salt malabsorption in Crohn's disease, identifying ileal disease more precisely than radiology. The SeHCAT test ascertained type II primary bile salt malabsorption in 7 patients, as well as type III bile salt malabsorption in patients (9 out of 28) with cholecystectomy, vagotomy, partial gastrectomy and chronic pancreatitis. In addition, a positive SeHCAT test indicating bile acid malabsorption was found in 5 out of 11 patients with irritable syndrome, diarrhoeic form, and in 4 out of 12 patients with lactose intolerance.SeHCAT retention should be measured routinely in patients with chronic diarrhoea for which the cause is not obvious.

In-depth advice about contraception is important for type I diabetic women since special medical aspects have to be considered and because pregnancy should be planned. The actual contraceptive practice in diabetic women living in Germany had not been investigated before.In December 1992 type I diabetic women of 16 to 46 yrs of age who had consecutively participated in a diabetic treatment and teaching programme (n = 1028) were mailed a multiple-choice questionnaire about reproductive and contraceptive issues. 409 non-diabetic women were also questioned and served as a control group.808 diabetic women (age 32[7] yrs, duration of diabetes 14[8] yrs) returned the questionnaire. The percentage of women using a method of contraception was comparable between diabetic and control women (76 vs. 72%). Of these, fewer diabetic women used oral contraceptives (OC) (33 vs. 57%). The OC-using diabetic women were younger than those using other methods (27[5] vs. 33[7] yrs), however 63% had at least one of the contraindications for OC-use (smoking, hypertension, proteinuria, retinopathy, poor metabolic control) and 18% were using high-dose preparations. More diabetic than control women used IUDs (19 vs. 12%) and more diabetic women were sterilised (19 vs. 9%). Compared to controls diabetic women had had sterilisation at a younger age (31[5] vs. 36[4] yrs) and more sterilised women were childless (29 vs. 14%). Methods of lower efficacy (condom, diaphragma, spermatocides) were used by 26% of diabetic women (controls 20%), p0.05. Nearly half of the diabetic women had received contraceptive advice exclusively by gynaecologists. 22% of all pregnancies were unplanned (controls 17%); 00.05).More diabetic women should use methods of contraception with high efficacy. However, when prescribing OCs more attention must be payed to special contraindications. Sterilisation should be recommended more cautiously to diabetic women without advanced diabetic complications. Contraceptive advice to diabetic women must be given by gynaecologists and diabetologists.

Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1- and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed.

Divergent opinions exist on the value of adjuvant treatment in endometrial cancer. This paper aims at clarifying the indications for adjuvant radiotherapy by reviewing the literature and presenting own data.For endometrial cancer 5-year survival data are analysed with respect to the value of adjuvant radiotherapy and/or chemo-/hormone therapy.Adjuvant radiotherapy in FIGO stage I and II tumors reduces pelvic recurrence rates from 15 to 20% to 1 to 5%. In high risk stage I patients the 5-year survival rate is increased by 30 to 40% using pre-operative high dose endocavitary brachytherapy or postoperative external beam therapy. In stage II disease the 5-year survival rate is increased to 60 to 80% when applying 50 to 60 Gy post surgery. In stage III and IV tumors primary radiotherapy results in 5-year survival rates of 16 to 40%.In stage I and II endometrial cancer primary treatment consists of surgery followed by radiotherapy in eligible cases. In stage III and IV tumors primary radiotherapy is generally advocated. No properly randomized trials are available to date on the value of adjuvant treatment. There is a great demand for such trials in order to confirm the available data. According to the extent of the disease and the discrimination of certain risk groups these trials should include external beam pelvic irradiation, brachytherapy, para-aortic irradiation as well as systemic chemo-or hormone therapy.

We carried out a trial to evaluate the complication rate of intravesical (LP) versus extravesical (Lich) ureteroneocystostomy in recipients of renal transplantation. Ureteric stenosis was the predominant complication in the LP technique, which was more difficult to correct. Complications by the Lich technique were urinary leaks, which were managed successfully by prolonged bladder drainage. We conclude that the Lich technique is simpler to perform and avoids the complication of ureteric stenosis, and should therefore be the procedure of choice for ureteric implantation in recipients of renal transplants.

The distribution of prothipendyl (Dominal) in two cases of fatal poisoning are reported. The highest concentration of prothipendyl were found in liver (1.2 g/kg to 1.8 g/kg) and kidney (0.6 g/kg). Prothipendyl concentrations in these organs far exceeded those in blood. In the first case we found a blood concentration 200 times over the therapeutic range. Prothipendyl was detected in all specimens tested including: lung, muscle and stomach. These results are in agreement with limited, previously reported data and indicate that more then 4 g of prothipendyl is fatal overdose. In this report the survival time and dose are discussed.

From 1987 to 1991, 100 evaluable patients with advanced head and neck carcinomas (T2-4, N0-3) were treated with radiotherapy and simultaneous carboplatin. Tumors were located in the oral cavity in 33 patients, oropharynx in 8 patients, and hypopharynx in 7 patients. Four patients had a tumor of the epipharynx, 3 of the larynx, and 45 had involvement of two or more compartments. Radiotherapy was performed in a fractionation of 5 x 2 Gy/week up to a dose of 50 Gy. Carboplatin was administered in a dose of 60 or 70 mg/m2 from days 1-5 and 29-33. After a 2-week interval, tumor involution was evaluated and a decision was made on the patients' operability. In cases of inoperability, radiotherapy was continued up to a dose of 70-74 Gy. Thirty patients underwent surgery after 50 Gy. Eight patients showed a histologically complete remission (CR), 7 showed microscopic residual tumor, and 15 showed macroscopic tumor. Seventy patients were treated with radiotherapy and concomitant carboplatin only. Thirty-nine of them achieved a CR and 30 a partial remission (PR). The residual tumor was operable in 8 of the latter patients. Only a minor response was achieved in the remaining patient. At the end of the treatment 77 patients achieved a CR with this combined modality. From 1990 to 1992, 20 patients with locally advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, 5 days per week: total dose, 64-67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1-5 and 29-33) in a pilot study. Fifteen patients had T4 and 5 had T3 tumors. Six weeks after the end of treatment, 16 patients (80%) had CR, and PR was seen in the other 4 patients (20%). Overall and disease-free survival at 1 year was 82 and 81%, respectively. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial CR rate of 80% is encouraging. Because of the results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy with carboplatin or hyerfractionated accelerated irradiation with carboplatin. Results will be forthcoming.

Between 1980 and 1988, 116 patients with invasive breast cancer were treated by limited surgery with axillary node dissection followed by radiation therapy. Radiotherapy was performed by individually computerized treatment planning. The target volume dose was 50 Gy to the whole breast followed by an electron boost of 10 Gy to the tumor bed. The median follow-up period was 59 months. The actuarial overall survival rate is 93%, and the disease-free survival 75.2%. Ten (8.6%) breast recurrences occurred. Analysis of clinical and pathological prognostic factors revealed that local control was impaired by young age, negative hormone receptors, G3-4 tumors and intraductal growth. The recurrence rate for T3- and T4-tumors was 12.5%.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.

Report on suicide with chloroquine in combination with maprotiline and trimipramine. Chloroquine and his metabolite monodesethylchloroquine could be determined in organs and body fluids. The highest organ-concentrations of chloroquine were found in liver and kidney. The survival time and dose are discussed.

From 1990 to 1991 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, five days/week, total dose 64.0 to 67.2 Gy) and simultaneous intravenous application of Carboplatin (60 mg/m2, days 1 to 5 and 29 to 33) in a pilot study. Eleven patients had T4 and four had T3 tumours. At the end of treatment twelve patients had a complete tumour remission and in the others a partial tumour involution was seen. Although acute side-effects were more pronounced compared to conventional irradiation this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging.

Nuclear DNA content in soft tissue sarcoma was determined by image cytometry using archival, paraffin embedded material. In a retrospective study 138 specimens of 81 patients have been analysed. The ploidy level was correlated to clinical outcome regarding tumor volume and histological grading, the most important prognostic parameters. Ploidy has a significant prognostic value and correlates well with histological grading (p = 0.01). Tumour volume was found to be an independent prognostic factor (p = greater than 0.1) [chi 2 test]. The DNA content of the primary tumour and of multiple local recurrences remained similar.

The long term results of 24 patients treated with postoperative irradiation for aggressive fibromatosis are presented. Tumour sites were the pelvis (8), chest wall (5), shoulder (5), extremities (4) and head and neck (2). Macroscopic complete resection (R1) was performed in 3 cases. 17 patients presented postoperatively with gross disease (R2), 8 of which were recurrent tumours. 4 patients with inoperable disease had biopsies only. Radiation doses ranged from 28 to 64 Gy at a fractionation of 5 × 2 or 4 × 2,5 Gy/week. 4 patients had external irradiation in combination with 192Ir implants, 2 were irradiated with implants alone. In the combined treatment group, external doses ranged from 28 to 52 Gy and additional interstitial doses from 35 to 50 Gy. 192Ir treatment alone was given with 45 and 57 Gy to the contour of the target volume. The 10 year recurrence free survival rate is 75%. A dose response relationship has been established in the dose range of 30–60 Gy revealing an expected 80% persistent tumour control rate at 60 Gy. A dose volume relationship however, could not be derived from our data. Moderate fibrosis without functional impairment developed in 5 patients (21%). These data support a policy of postoperative radiotherapy with 60 Gy in patients with incompletely excised or gross residual tumour following surgery.

Fifty-six untreated patients with inoperable squamous cell carcinoma of the head and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33 in combination with simultaneous conventional radiation up to a target volume dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons, 21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two courses of carboplatin. Patients who showed pCR after surgery received no further radiotherapy. In all other patients radiotherapy was continued using a shrinking field technique up to a target absorbed dose of 70-74 Gy. Combined modality induced 66% complete remission (CR) and an overall response rate of 98%. After completion of the whole treatment program (combined modality +/- surgery) 53 (94%) of the 56 patients were disease free. The median survival for all patients is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression was the most frequent toxicity, but rarely was severe; leukopenia and thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and ototoxicity were not seen. The addition of carboplatin did not increase the rate of surgical complication over that expected for preoperative radiotherapy. Two patients died of pulmonary embolism after surgery. Combined modality with carboplatin and simultaneous radiation is a highly active and well-tolerated regimen for untreated patients with inoperable squamous cell carcinoma of the head and neck.

Questionnaires and psychological tests were used to assess the psychosocial impact of mandibular prognathism. Patients with mandibular prognathism were asked to assess the impediments caused by their dentofacial deformity. In addition, they were asked to rate their appearance and to report the effect that it had on their social contacts. The self-assessment revealed that patients felt esthetically impaired, but that they had a fairly positive autostereotype, as revealed by their self-descriptive choices on a personality scale. These results were compared with the assessments made by two different control groups composed of persons with no esthetic impairment. The attitudes of the control groups toward the patients were more negative than perceived by the patients, indicating that mandibular prognathism does result in a social handicap.