Therapy-induced Complications Research Articles

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

Levodopa therapy remains the most effective drug for the treatment of Parkinson's disease, and it is associated with the greatest improvement in motor function as assessed by the Unified Parkinson's Disease Rating Scale. Dopamine agonists have also proven their efficacy as monotherapy in early Parkinson's disease but also as adjunct therapy. However, the chronic use of dopaminergic therapy is associated with disabling motor and nonmotor side effects and complications, among which levodopa-induced dyskinesias and impulse control behaviors are the most common. The underlying mechanisms of these disorders are not fully understood. In the last decade, classic neuroimaging methods and more sophisticated techniques, such as analysis of gray-matter structural imaging and functional magnetic resonance imaging, have given access to anatomical and functional abnormalities, respectively, in the brain. This review presents an overview of structural and functional brain changes associated with motor and nonmotor therapy-induced complications in Parkinson's disease. Magnetic resonance imaging may offer structural and/or functional neuroimaging biomarkers that could be used as predictive signs of development, maintenance, and progression of these complications. Neurophysiological tools, such as theta burst stimulation and transcranial magnetic stimulation, might help us to integrate neuroimaging findings and clinical features and could be used as therapeutic options, translating neuroimaging data into clinical practice. © 2020 International Parkinson and Movement Disorder Society.

Chemotherapy Effect on Fertility in Male Patients with Hodgkin and Non-Hodgkin Lymphoma

Introduction: The chemotherapeutic agents are effective in destroying cancerous cells for patient with hematological malignancies, but can damage the germinal cells. Hence, the infertility is the therapy-induced complication, which can be transient or permanent, depending on type of treatment protocol used and other factors. The aim of the study was to assess the fertility status among patients treated for Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). Methods: A chart review was done for patients followed up in hematology clinic. All male patients treated for hematological malignancies during the period from 2004-2014 were assessed. The infertility status was assessed using WHO infertility criteria. The fertility status was defined based on semen analysis or having a child post chemotherapy. The data was captured for type of protocol, number of cycles, fertility status, having a child pre and post chemotherapy, and sperm bank utilization. Results were summarized as frequency and percentages. Data was analyzed using SAS. Results: 400 medical charts were reviewed. 208/400 were included based on age inclusion criteria (18-60 years). 59/208 included based on available fertility data, of which 31 were diagnosed with HL, 21 NHL, 4 acute lymphocytic leukemia, and 3 acute myeloid leukemia. Only HL and NHL were considered for further analysis. 9/31 (29%) with HL and 1/21 (4.7%) with NHL had infertility prior to starting chemotherapy based on semen analysis with no follow-up fertility assessment done post-treatment. The final sample consisted of 42 patients who had data available on their fertility status post-treatment (22 HL and 20 NHL) (Figure 1). The mean age was 38 ± 8 years. 25(68%) had advanced disease. Among HL, 8/22 (36.36%) were fertile (7 conceived a child and 1 with normal semen analysis) (Figure 2). This includes 6 out of 9 (66.7%) patients who received ABVD protocol alone, 0 out of 6 who received ABVD + BEACOPP protocol, and 2 (28.6%) out of 7 who received salvage chemotherapy. Among the NHL, 11/20 (55%) were fertile (8 conceived a child and 3 with normal semen analysis) (Figure 2). This includes 7 out of 11 (63.6%) who received CHOP +/-Rituximab protocol, 3 out of 5 (60%) who received CHOP + other chemotherapy (MTX/CVP), 1 out of 3 (33.3%) who received only other chemotherapies (Hyper CVAD/MTX) (Figure 2). 9 out of 22( 41%) HL and 6 out of 20 NHL patients had sperm banking done, and only two utilized their sperms with one successful conception in a patient with NHL (Figure 3). Conclusion: Although the sample size is very small, we found a trend that may suggest HL to affect fertility and that ABVD protocol may not be as safe as it thought to be on fertility. The advanced stage of the disease being the majority may have influenced this finding. We found the documentation of fertility status among patients receiving chemotherapy to be scarce. Hence, it is important to educate physicians and dedicate a protocol for assessment of fertility pre- and post-treatment with encouragement to utilize sperm banking. Disclosures No relevant conflicts of interest to declare.

The impact of levodopa therapy-induced complications on quality of life in Parkinson\u2019s disease patients in Singapore

The objective of this study was to investigate the impact of levodopa therapy-induced complications on the quality of life (QoL) of Parkinson’s disease (PD) patients in Singapore over a 1-year follow-up period. 274 PD patients were prospectively recruited, of which 78 patients completed the follow-up. Patients were evaluated on: (1) motor symptoms, (2) non-motor symptoms, (3) levodopa therapy-induced complications and (4) QoL. Levodopa-induced complications including dyskinesia and OFF symptoms occurred in 13.5% and 55.9% of the study population, respectively. In patients who completed the 1-year follow-up, there was a trend suggestive of increasing dyskinesia duration, more disabling dyskinesia as well as longer, more sudden and unpredictable OFF periods. There was a significant decline in the overall QoL at follow-up, in particular, activities of daily living, emotional well-being, cognition and communication domains were the most affected. The multivariable analysis demonstrated that worsening of UPDRS IV total score over 1-year interval was associated with worsening in PDQ-Summary Index score (d = 0.671, p = 0.014). In conclusion, levodopa-induced complications had significant adverse impacts on QoL. This study substantiates the importance for clinicians to closely monitor and promptly manage levodopa therapy-induced complications that may arise in patients.

2017 update on pain management in patients with chronic kidney disease.

The prevalence of pain has been reported to be >60–70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease. We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications.

Cancer therapy-related complications in the bowel and mesentery: an imaging perspective.

Cancer therapy-induced complications in the bowel and mesentery are fairly common. It is important for clinicians to be aware of these complications and the agents most frequently implicated. Cancer therapy is rapidly evolving and often encompasses both classic cytotoxic drugs and newer molecular targeted agents. Drugs from both broad classes can have numerous adverse effects on the bowel and mesentery that can be detected on imaging. These adverse effects include ileus, various forms of enterocolitis, gastrointestinal perforation, pneumatosis intestinalis, secretory diarrhea, and sclerosing mesenteritis. These complications are diverse and range from relatively benign to life threatening. The management is also variable, but many of these conditions are easily controlled and reversed with supportive care and cessation of the particular cancer therapy. The objective of this pictorial essay is to demonstrate some of the more common cancer therapy-induced complications of the bowel and mesentery, with a focus on the radiographic findings.

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations.

There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. This study is a narrative non-systematic review. We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.

Abstract A50: Mutational analysis of a mouse model of second malignant neoplasms

Abstract Purpose: Second malignant neoplasms (SMNs) are therapy-induced malignancies and severe late complications that develop in pediatric cancer survivors. Ionizing radiation (IR) is a known mutagen and can cause SMNs. The mutational landscape of fractionated IR-induced tumorigenesis is not well-characterized on a genome level and but may reveal biological mechanisms that specifically contribute the development of SMNs. To study the influence of clinically relevant radiation delivery and germline mutations in a tumor suppressor gene, we previously developed mouse models of SMNs by delivering focal, fractionated irradiation to wildtype and Nf1 mutant mice. Irradiated mice developed diverse malignancies replicating the sarcomas and carcinomas observed as SMNs in pediatric cancer survivors. The goal of this study is to characterize the mutational profile of tumors induced by ionizing radiation that models clinical radiotherapy and to determine whether germline Nf1 mutations independently influence the mutational landscape. Materials/Methods: Whole exome sequencing was performed on 25 IR-induced malignancies arising in wildtype and Nf1 mutant mice. Indexed paired-end libraries were prepared using the Agilent SureSelectXT Mouse All Exon kit and sequencing was performed using Illumina HiSeq2000 technology (Illumina, San Diego, CA, USA). Alignments and somatic variants were identified using established procedures. Each exome was sequenced to a minimum of 5 Gb. Results: 6,623 somatic mutations were identified, of which 4,633 were non-synonymous. Tumors had an average mutation rate of 265 total SNVs/sample. Most nucleotide substitutions were C -> T or G-> A transitions. We analyzed the immediately flanking sequence context for each somatic variant using non-negative matrix factorization, and extracted 3 stable and distinctive mutational signatures. These signatures are present in multiple types of radiation-induced histologies, are uniquely distinguishable from mutational signatures of other well-recognized mutagens such as UV, and are similarly present in tumors arising in wildtype mice as well as Nf1 mutant mice, suggesting that the IR mutational signature persists in genetic backgrounds either resistant or susceptible to IR-induced tumorigenesis. We compared copy number alterations between tumors from wildtype and Nf1 mutant mice, and found significant differences between genetic backgrounds. Conclusions: IR-induced malignancies possess distinguishable and unique mutational signatures characterized by base substitutions occurring in very specific and unique sequence contexts. This analysis suggests that IR and genetic background influence the mutational landscape of tumors in very specific and discrete ways that are distinguishable from other cancer-promoting processes. SMNs from pediatric cancer survivors may harbor distinctive mutational motifs, and continued studies are needed to examine this. This data also suggest that the mutational landscape may differ between malignancies from different germline mutations or genetic backgrounds in pediatric cancer survivors. From a clinical standpoint, defining distinct mutational mechanisms in SMNs may improve the ability to predict which pediatric cancer survivors are at greatest risk for SMN formation as well as enable the development of strategies to mitigate and manage this risk. Citation Format: Amy Sherborne, Philip Davidson, Katharine Yu, Alice Nakamura, Mamunur Rashid, Jean Nakamura. Mutational analysis of a mouse model of second malignant neoplasms. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A50.

Identifying dehydration risk in head and neck cancer patients undergoing radiation therapy using remote, sensor-based monitoring: A randomized controlled trial.

152 Background: Early identification and mitigation of cancer therapy-induced complications can improve quality of life and reduce complications and health care costs. We are evaluating the efficacy of a system, called CYCORE (CYberinfrastructure for Comparative effectiveness Research), to systematically and accurately collect daily weight, blood pressure, pulse and symptom data from head and neck cancer (HNC) survivors during their 6 to 7-week radiation treatment (RT) regimen using home-based biometric and other sensors integrated with a cyber-physical system. Aims include: 1) evaluate CYCORE’s efficacy in reducing hospitalization and emergency room visits related to dehydration; and, 2) evaluate related impact on costs related to treating dehydration. Methods: Remote, sensor-based monitoring via CYCORE identifies HNC survivors at increased risk for dehydration (i.e., reduced blood pressure and weight, increased pulse, and patient-reported outcomes (PROs) including decreased food and fluid intake). Upon initation of RT, HNC survivors are randomized to either: 1) standard care plus use of the CYCORE system, wherein biometric sensor data and PROs (e.g., pain, nausea, medications, food/fluid intake) are collected ; or, 2) standard care. Outcomes include hospital and emergency room admissions, and related costs. Results: To date, 113 survivors are enrolled (88.9% recruitment and 90.3% retention rates). Those randomized to CYCORE take daily home readings of weight, blood pressure and pulse via Bluetooth-enabled devices, and complete daily PRO assessments on a mobile application. Survivors’ data are available for viewing and clinical decision-making via a Web-based interface by their physicians and other providers. Previously, 59% of HNC survivors on RT showed physiologic signs of dehydration while using the CYCORE system. Worse ratings of nausea and vomiting predicted dehydration risk. Conclusions: CYCORE may serve as one model for integrating mobile and sensor technologies during critical periods of cancer care that occur outside of the clinic setting, and may improve management of treatment side effects, quality of life, and greater satisfaction with care. Clinical trial information: NCT02253238.

Abstract A1-03: Mutational analysis of ionizing radiation-induced neoplasms

Abstract Introduction: Ionizing radiation is a known mutagen and can cause cancers in different contexts, for example second malignant neoplasms (SMNs). SMNs are therapy-induced malignancies and severe late complications that develop in cancer survivors, particularly survivors of pediatric cancers who have received radiotherapy. The mutational landscape of ionizing radiation-induced tumorigenesis is not well-characterized on a genome level. Because ionizing radiation produces DNA damage that differs from damage produced by other genotoxins (UV for example), the mutational landscape of ionizing-radiation induced neoplasms may differ from the mutational landscape induced by other mutagens. Defining the mutational landscape of malignancies induced by ionizing radiation may reveal biological mechanisms that specifically contribute to this process. This insight has clinical implications, particularly with regard to understanding the pathogenesis of SMNs. We previously developed mouse models of SMNs by delivering focal, fractionated irradiation to wildtype and Nf1 mutant mice, and established that the Nf1+/- genetic background is sensitized to radiation-induced tumorigenesis. Diverse malignancies recapitulating clinical SMNs arose in irradiated wildtype and Nf1 mutant mice. The goal of this study is to characterize the mutational profile of tumors induced by ionizing radiation that models radiotherapy delivered to patients and is typically responsible for SMNs. Experimental Procedures: Whole exome sequencing was performed on 25 ionizing radiation-induced malignancies generated from our mouse models (sarcomas, carcinomas and hematopoietic malignancies) and a germline control. Malignancies from Nf1 mutant and wildtype mice were sequenced. Indexed paired-end libraries were prepared using the Agilent SureSelectXT Mouse All Exon kit covering all Ensembl genes and miRNAs (50Mb), Sequencing was performed using Illumina HiSeq2000 technology. Alignments were processed and variants were called according to standard practices. Exome sequencing of a 129/Sv-C57BL/6 heterozygote was used as a normal control and only somatic variants were considered for analysis. Each exome was sequenced to a minimum of 5 Gb. Results: In the entire cohort, 7566 somatic mutations were identified, of which 5187 were non-synonymous. Tumors had an average of 200 mutations (range, 31-594). Most nucleotide substitutions were C -> T transitions. In addition to examining somatic variants comprised of nucleotide substitutions, we analyzed immediately flanking sequence context for each somatic variant using an approach developed at the Wellcome Trust Sanger Institute. We applied non-negative matrix factorization methods to exome data and extracted 3 stable and distinctive mutational signatures. These signatures are characterized by unique, context-dependent, patterns of base substitutions, and were present in neoplasms arising from wildtype or Nf1+/- genetic backgrounds. Pathway analysis and functional validation of recurrently mutated genes are underway. Conclusions: Ionizing radiation-induced malignancies display a unique mutational landscape that is shared among different tumor histologies. Three distinct signatures were identified and these are not genotype-dependent (wildtype vs. Nf1 mutant). The enrichment of specific substitutions in each of the signatures implicates discrete mechanisms of DNA repair and operational enzymes. These mechanisms and recurrently mutated genes are being functionally tested in tumor cell lines we established from our mouse models. Ionizing radiation-induced malignancies possess a mutational landscape that is distinguishable from those associated with other common mutagens. Citation Format: Amy L. Sherborne, Philip R. Davidson, Katharine Yu, Alice O. Nakamura, Jean L. Nakamura. Mutational analysis of ionizing radiation-induced neoplasms. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-03.

Preservation of organ function in head and neck cancer.

Preservation of function is a crucial aspect for the evaluation of therapies applied in the field of head and neck cancer. However, preservation of anatomic structures cannot automatically be equated with preservation of function. Functional outcome becomes increasingly important particularly for the evaluation of alternative treatment options with equivalent oncological outcomes.As a result, present studies take into account three topic areas with varying emphasis: (1) the effects of cancer therapy on essential physiological functions, (2) additional therapy-induced side-effects and complications, and (3) health-related quality of life. The present article summarizes vital aspects of clinical research from recent years. Functional outcomes after surgical and non-surgical treatment approaches are presented according to tumor localization and staging criteria. Additional methodological aspects relating to data gathering and documentation as well as challenges in implementing the results in clinical practice are also discussed.

Optimization of Postoperative Analgesia during Traumatic Interventions in Angiologic Care

Objective: to search for a procedure for drug injection into the pulmonary artery to enhance the efficiency of thrombolytic therapy. Subjects and methods. Twenty patients with submassive unilateral pulmonary thromboembolism were examined. Selective thrombolysis was performed in 10 patients of Group 1. Local thrombolytic therapy (RF patent No. 2376042) was used in 10 patients of Group 2. The authors simulated thrombolysis with a contrast agent and studied pressure in the pulmonary artery in the sites of its bifurcation and a thrombus and the concentration of a fibrinolytic agent at the site of a thrombus and in the cubital vein. Thrombolytic therapy-induced complications were analyzed. Results. Pressure at the site of the pulmonary artery bifurcation was recorded to be, on the average, 6.2±0.9 mm Hg higher than that at the site of the thrombus. Simulation of selective thrombolysis by the contrast agent showed its movement to the area contralateral to the thrombus. Local thrombolysis simulation indicated the spread of the contrast agent along the thrombus and its failure to enter the systemic bloodstream. In local thrombolysis, the concentration of a fibrinolytic agent at the site of the thrombus after administration of a test dose was 930 times greater than that during selective thrombolysis. With local thrombolysis, the peripheral venous concentration of Actilyse was significantly lower than that with selective thrombolysis. During the latter, there were no differences in the Actilyse concentration at the site of the thrombus and in the peripheral vein. Hemorrhagic events were recorded in Group 1 patients. These were absent in Group 2. Conclusion. The findings demonstrate that selective thrombolytic therapy is ineffective. The administered fibrinolytic agent is washed out into the systemic bloodstream, as confirmed by the absence of differences in the concentrations of Actilyse at the site of the thrombus and in the peripheral vein. As compared with selective thrombolysis, local one elevates the concentration of the agent at the site of the thrombus; by spreading along the thrombus, the agent fails to enter the systemic bloodstream, which reduces the number of complications. The efficiency of the method is evidenced by normalization of pulmonary pressure. Key words: local thrombolysis, selective thrombolysis, pulmonary thromboembolism, Actilyse concentration, thrombolysis simulation.

Clinical Outcome of Aortic Valve Replacement With 16-mm ATS-Advanced Performance Valve for Small Aortic Annulus

Various surgical techniques have been proposed to treat small aortic annulus. We have used small-diameter mechanical valves for small aortic annulus. The present study examined aortic valve replacement with small diameter mechanical valves to determine their effectiveness. The study included 67 patients who underwent elective, isolated aortic valve replacement with ATS-Advanced Performance (AP) valves (ATS Medical, Inc, Minneapolis, MN) within our department. The patients were divided into two groups; patients receiving the 16-mm AP valve (16-mm group) and those receiving valves 18-mm AP or larger (>16-mm group). The mean age of the 16-mm group was significantly higher than that of the >16-mm group. Body surface area was significantly smaller in the 16-mm group than the >16-mm group. We found no significant differences in preoperative conditions between the groups. The effective orifice area index of the mechanical valve was lower in the 16-mm group (0.87+/-0.06 vs 1.12+/-0.13 cm2/m2, p<0.0001). Six patients (40%) in the 16-mm group fell into the category of prosthesis-patient mismatch cases. Although the postoperative pressure gradient was higher in the 16-mm group (33.7+/-12.5 vs 23.16+/-8.78, p<0.01), left ventricular mass index and left ventricular ejection fraction at early and at late follow-up improved from the preoperative period in both groups. We found no significant differences in incidence of postoperative complications, including death. We believe aortic valve replacement with small-diameter mechanical valves (the ATS-AP valves) in patients with a small annulus provides satisfactory remote prognosis. The use of mechanical valves in elderly patients is considered acceptable with strict clinical monitoring to prevent thromboembolism and anticoagulation therapy-induced complications.

Current treatment strategies of the German Hodgkin Study Group (GHSG)

Hodgkin's Lymphoma (HL) has developed to one of the best curable human cancers and overall about 80% of patients experience long-term disease free survival. Therefore, current treatment strategies aim at further improving treatment outcome, thereby trying to by minimize therapy-induced complications, such as infertility, cardiopulmonary toxicity, and secondary malignancies. Ongoing trials investigate a reduction of chemotherapy in terms of dose or cycles given, and the application of lower radiation doses and smaller radiation fields. For patients with a specific high-risk profile, new approaches with more intense drug combinations are currently being investigated. Moreover, the advent of effective salvage high-dose therapy for relapsed disease and a better understanding of prognostic factors have further improved the management of HL. Here, we summarize current strategies of the German Hodgkin Study Group (GHSG) in diagnostics and treatment of primary and relapsed HL, together with recent approaches for specific subgroups of HL patients.

Hepatocellular carcinoma treated with interventional procedures: CT and MRI follow-up

In the past decade, a variety of interventional procedures have been employed for local control of hepatocellular carcinoma (HCC). These include transcather arterial chemoembolization (TACE) and several tumour ablation techniques, such as percutaneous ethanol injection (PEI), radio-frequency ablation (RFA), or percutaneous microwave coagulation therapy (PMC), laser-induced interstitial thermotherapy (LITT), etc. For a definite assessment of the therapeutic efficacy of interventional procedures, histological examination using percutaneous needle biopsy may be the most definite assessment of the therapeutic efficacy of interventional therapy, however, it is invasive and the specimen retrieved does not always represent the entire lesion owing to sampling errors. Therefore, computed tomography (CT) and magnetic resonance imaging (MRI) play a crucial role in follow-up of HCC treated by interventional procedures, by which the local treatment efficacy, recurrent disease and some of therapy-induced complications are evaluated. Contrast enhanced axial imaging (CT or MR imaging) may be the most sensitive test for assessing the therapeutic efficacy. The goal of the review was to describe the value of CT and MRI in the evaluation of interventional treatments.

Endoscopic drainage of symptomatic pancreatic pseudocysts. An efficient and safe therapy in the clinical routine?

Clinical studies have demonstrated excellent success and low complication rates of endoscopic therapy of pancreatic pseudocysts. But it is not known, if these results can be reached in gastroenterological centers outside clinical studies. We investigated the outcome of endoscopic therapy in 21 patients (15 male, 6 female, age 40 - 81) with pancreatic pseudocysts treated in our clinic between 1997 and 2002. A follow-up examination was included. Similar to the results of reported clinical studies the initial clinical success rate was 18/21 with symptomatic recurrences in two patients. All therapy-induced complications were successfully treated conservatively. Excellent results of endoscopic therapy of pancreatic pseudocysts can be reached in a gastroenterological center. Surgical treatment can be reserved for cases, when endoscopic therapy fails.

Which Factors Render Cost-Covering Lump-Sum Charging Difficult for the Treatment of Patients with Acute Leukemias?

Background: Growing budget limitations and the planned charging subject to Diagnosis-Related Groups (DRG) points raise the question as to what costs are incurred by the induction therapy and early consolidation treatment of patients with acute myeloid leukemias (AML) and whether these can be compensated in a cost-covering manner by a system based on DRG points. Patients and Methods: For 100 patients recruited within the framework of the ‘Kooperative AML-Studie 96’ of the Süddeutsche Hämoblastosegruppe a process cost analysis was made between 1996 and 1999. All manpower and material costs incurred in the department itself and in the secondary services departments as well as the basic cost shares were recorded taking into due account the length of stay. The cost breakdown was effected based on a double induction therapy and one early consolidation treatment. Results: It turns out that substantial differences exist between lower und upper limits of the length of stay and costs. For all three therapy blocks for patients up to 60 years the cost spread varies between 63 and 204 kDM with a median of 105 kDM, and for older patients between 55.6 and 146.6 kDM with a median of 87.6 kDM. On average, the costs subject to length of stay were roughly 70%. Conclusions: As the costs per case are subject to a spread and, for this relatively small group of patients, are extremely high, the fixing of a case-related lump sum is problematic, the more so as age of patient, comorbidity, type of therapy, ist outcome, and therapy-induced complications represent decisive influencing factors.

Complications of cancer therapy in children: a radiologist's guide.

As advances in cancer therapy improve the prognosis of patients with childhood malignancies, awareness of the consequences of treatment methods assumes increasing importance. All cancer treatment modalities are associated with toxic effects, and the spectrum of therapy-induced complications involves all organ systems. Radiologists have a pivotal role in detecting these sequelae, which can be categorized by the affected organ system and by whether they occur (a) at diagnosis or during initial therapy or (b) after the completion of treatment. The first group consists of oncologic emergencies, infectious complications, and irritant effects. Oncologic emergencies can be further categorized as space-occupying lesions (e.g., superior vena cava syndrome or spinal cord compression), vascular abnormalities (e.g., hyperleukocytosis, anemia, coagulopathy), and metabolic emergencies (e.g., tumor lysis syndrome). Common complications developing after completion of treatment include leukoencephalopathy and neurocognitive defects; cataract formation; cardiomyopathy and congestive heart failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal dysfunction; graft-versus-host disease; and development of secondary malignancies. Physician awareness of these complications will permit more effective patient surveillance, which may afford patients the opportunity for earlier intervention in these situations and improved quality of life.

Pleuropulmonary manifestations of systemic vasculitis

Pleuropulmonary manifestations of systemic vasculitis are common, polymorphic and of ambiguous significance: the same pulmonary lesion may reveal a specific manifestation of vasculitis as well as a therapy-induced complication, especially infection which may favor per se a flare-up. Two questions will be successively studied: what are the pleuropulmonary characteristics of Wegener's granulomatosis, Churg-Strauss syndrome, periarteritis nodosa, Behçet's disease, Takayasu's disease and temporal arteritis? What are the major adverse effects that may occur in the course of a treated systemic vasculitis?

Late Therapy-Induced Cardiac and Pulmonary Complications in Cured Patients with Hodgkin's Disease Treated with Conventional Combination Chemo-Radiotherapy

In recent years, with the advent of modern therapeutic approaches, patients with advanced Hodgkin's disease achieve high cure rates. Accordingly, more attention is now focused upon the late complications of chemotherapy and irradiation, occurring in cured patients many years after successful therapy for HD. In this report, we review the incidence and presentation of some of the cardiovascular and pulmonary complications which may appear in cured patients up to 20 years after therapy.

Chronic myelogenous leukemia after treatment with 131I for thyroid carcinoma : Report of a case and review of the literature

A patient who developed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) 5 years after successful treatment for thyroid carcinoma, is reported. The Philadelphia chromosome was the typical 9;22 translocation. Southern blot analysis showed breakpoint cluster region rearrangement as observed in classical CML. Up to now, only two cases of CML have been reported following treatment for thyroid carcinoma. This rare complication has also been described after therapy for other malignancies. At present, it is not clear whether the development of CML after thyroid carcinoma represents a therapy-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself.