Prognostic markers for the clinical course in the blood of patients with SARS-CoV-2 infection.

BACKGROUND: The presentation of peptides and the subsequent immune response depend on the MHC characteristics and influence the specificity of the immune response. Several studies have found an association between HLA variants and differential COVID-19 outcomes and have shown that HLA genotypes are associated with differential immune responses against SARS-CoV-2, particularly in severely ill patients. Information, whether HLA haplotypes are associated with the severity or length of the disease in moderately diseased individuals is absent. METHODS: Next-generation sequencing-based HLA typing was performed in 303 female and 231 male non-hospitalized North Rhine Westphalian patients infected with SARS-CoV2 during the first and second wave. For HLA-Class I, we obtained results from 528 patients, and for HLA-Class II from 531. In those patients, who became ill between March 2020 and January 2021, the 22 most common HLA-Class I (HLA-A, -B, -C) or HLA-Class II (HLA -DRB1/3/4, -DQA1, -DQB1) haplotypes were determined. The identified HLA haplotypes as well as the presence of a CCR5Δ32 mutation and number of O and A blood group alleles were associated to disease severity and duration of the disease. RESULTS: The influence of the HLA haplotypes on disease severity and duration was more pronounced than the influence of age, sex, or ABO blood group. These associations were sex dependent. The presence of mutated CCR5 resulted in a longer recovery period in males. CONCLUSION: The existence of certain HLA haplotypes is associated with more severe disease.

Acute cardiac side effects after COVID-19 mRNA vaccination: a case series.

BACKGROUND: Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). PATIENTS AND METHODS: Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. RESULTS: Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. CONCLUSIONS: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Low-dose radiation treatment for painful plantar enthesophyte: a highly effective therapy with little side effects.

AIM: Plantar enthesophyte is a common degenerative disorder. Surgical and medical treatment options are associated with either poor outcome or high percentage of relapse. Observations have indicated a beneficial effect of radiation therapy. We therefore wanted to evaluate pain reduction using orthovolt or cobalt-based radiation treatment for painful plantar enthesophyte and determine long-term response as well as prognostic parameters in this condition. METHODS: We identified a total of 102 consecutive patients treated for a total of 117 symptomatic heel spurs. 59 patients were treated with cobalt radiation, 31 patients with orthovolt therapy and 12 patients with both radiation systems. Primary outcome measure was pain reduction being scored using the modified Rowe Score prior therapy, at the end of each treatment series as well as after 6 weeks. Secondary outcome measure was long-term outcome, evaluated in patients with a follow-up period of longer than 3 years. RESULTS: Before radiation therapy, 61 patients (60.4%) had a score of 0, significant strong pain. At the time of completion of radiation treatment, 3 patients (2.7%) were pain-free (score of 30), whereas 8 patients (7.9%) had still severe pain (score 0). 6 weeks after radiation therapy, 33 patients (32.7%) were pain-free and 8 patients (7.9%) had severe pain (score 0), while at the time data of collection, 74 patients (73%) were free of pain and 1 patient (1%) had strong pain (score 0). Duration of pain before the start of radiation treatment was a significant prognostic factor (p = 0.012) for response to treatment. CONCLUSION: Radiotherapy of painful plantar enthesophyte is a highly effective therapy with little side effects providing long-term therapeutic response. The only significant prognostic parameter for response to treatment is the duration of pre-radiation therapy pain. Early integration of radiation therapy in the treatment seems to result in superior pain reduction.

Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma-Results of a Network Meta-Analysis.

BACKGROUND: The standard treatment of high-risk soft-tissue sarcoma consists of surgical resection followed by risk-adapted radiation therapy. Further treatment options that may improve local and systemic tumor control, including chemotherapy, are not well established. Due to the heterogeneity of the disease, different systemic approaches as well as their application at different time points have been attempted. METHODS: We conducted a systematic literature search for randomized clinical trials in the treatment of localized, resectable high-risk adult soft-tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model. RESULTS: The literature search identified 25 trials including 3453 patients. Five different treatment modalities were compared in the network meta-analysis. The addition of adjuvant chemotherapy significantly improved OS compared to surgery ± radiotherapy alone (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017). Likewise, neoadjuvant chemotherapy combined with regional hyperthermia (naCTx + HTx) also led to superior OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195 and HR = 0.66; CI-95%: 0.30-1.48; p = 0.317, respectively). Histology-tailored chemotherapy (htCTx) also did not improve survival compared to surgery ± radiotherapy (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The network analysis of DFS, LRFI, and DRFI revealed a similar pattern between the different treatment regimens. Adjuvant chemotherapy significantly improved DFS, LRFI, and DRFI compared to surgery ± radiotherapy. In direct comparison, this advantage of adjuvant chemotherapy was restricted to male patients (HR = 0.78; CI-95%: 0.65-0.92; p = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90-1.29; p = 0.410). CONCLUSIONS: Standardized chemotherapy in high-risk soft-tissue sarcoma appears to be of added value irrespective of timing. The benefit of adjuvant chemotherapy seems to be restricted to male patients. The addition of regional hyperthermia to neodjuvant chemotherapy achieved the best effect sizes and might warrant further investigation.

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19.

BACKGROUND: COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients' adaptive immune responses without progression to severe disease with patients' Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C-C chemokine receptor type 5 (CCR5). PATIENT AND METHODS: An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients' humoral antiviral immune response patterns by longitudinal observation. RESULTS: Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. CONCLUSION: The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

BACKGROUND: COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2. METHODS: We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects. RESULTS: The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled. CONCLUSION: Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

Correction to: The role of passive immunization in the age of SARS-CoV-2: an update.

An amendment to this paper has been published and can be accessed via the original article.

Face masks: benefits and risks during the COVID-19 crisis.

BACKGROUND: The German government has made it mandatory to wear respiratory masks covering mouth and nose (MNC) as an effective strategy to fight SARS-CoV-2 infections. In many countries, this directive has been extended on shopping malls or public transportation. The aim of this paper is to critically analyze the statutory regulation to wear protective masks during the COVID-19 crisis from a medical standpoint. METHODS: We performed an extensive query of the most recent publications addressing the prevention of viral infections including the use of face masks in the community as a method to prevent the spread of the infection. We addressed the issues of practicability, professional use, and acceptability based on the community and the environment where the user resided. RESULTS: Upon our critical review of the available literature, we found only weak evidence for wearing a face mask as an efficient hygienic tool to prevent the spread of a viral infection. However, the use of MNC seems to be linked to relevant protection during close contact scenarios by limiting pathogen-containing aerosol and liquid droplet dissemination. Importantly, we found evidence for significant respiratory compromise in patients with severe obstructive pulmonary disease, secondary to the development of hypercapnia. This could also happen in patients with lung infections, with or without SARS-CoV-2. CONCLUSION: Epidemiologists currently emphasize that wearing MNC will effectively interrupt airborne infections in the community. The government and the politicians have followed these recommendations and used them to both advise and, in some cases, mandate the general population to wear MNC in public locations. Overall, the results seem to suggest that there are some clinically relevant scenarios where the use of MNC necessitates more defined recommendations. Our critical evaluation of the literature both highlights the protective effects of certain types of face masks in defined risk groups, and emphasizes their potential risks.

The history and value of face masks.

In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.

The role of passive immunization in the age of SARS-CoV-2: an update.

The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.

Adjuvant radiochemotherapy vs. chemotherapy alone in gastric cancer: a meta-analysis.

BACKGROUND: As an adjuvant therapeutic strategy in advanced gastric cancer, both adjuvant chemotherapy (CTx) and postoperative radiochemotherapy (RCTx) can be considered. Both approaches have been shown to improve overall survival compared to resection alone. Several prospective randomized trials have compared the two postoperative concepts. METHODS: We performed a literature search to identify prospective randomized trials which compared adjuvant chemotherapy to adjuvant radiochemotherapy in patients with advanced gastric cancer. As effect sizes, we extracted hazard ratios (HR) as well as event rates from the included trials for the endpoints overall survival, disease-free survival and locoregional control. RESULTS: We identified seven studies that enrolled 1807 patients overall. Combined radiochemotherapy showed no significant improvement of overall survival in comparison to chemotherapy alone (HR = 0.93; 95%CI: 0.82-1.06; p = 0.28). For disease-free survival (HR = 0.86; 95%CI: 0.76-0.98; p = 0.023) and locoregional control (odds ratio [OR] = 0.56; 95%CI: 0.42-0.75; p = <0.001) we detected significant advantages from the addition of radiation to chemotherapy. A subgroup analysis demonstrated an improvement in survival when the radiochemotherapy protocol was not de-intensified. CONCLUSIONS: Adjuvant chemotherapy or radiochemotherapy demonstrate similar oncologic efficacy and therapy-associated toxicity. Individual patient characteristics should therefore determine the therapeutic approach in a multidisciplinary discussion. Irradiation added to standard-dose chemotherapy possibly results in a survival benefit.

Increased CD44s and decreased CD44v6 RNA expression are associated with better survival in myxofibrosarcoma patients: a pilot study.

BACKGROUND: New prognostic markers may be of value in determining survival and informing decisions of adjuvant treatment in the heterogeneous group of soft tissue sarcomas known as malignant fibrous sarcomas (MFS). Increased CD44 expression has been associated with a better outcome in cancers such as bladder tumors and could potentially relate to cell-cell interaction as a marker for potential invasion/metastasis. The aim of this pilot study was to determine if there is a correlation between the expression rate of CD44 in adult patients with MFS and clinical outcomes. METHODS: The clinical outcome of 34 adult MFS patients (19 males and 15 females, average age 62 years, median 63 years, range: 38-88 years) who underwent surgical treatment were evaluated. Twenty-five of these patients had additional adjuvant radiotherapy. Extracted RNA from sarcoma tissues was used to measure the transcripts of CD44s (standard form) and isoform expression.The pooled data for each variant of CD44 was divided in half at the median expression value into two equally sized groups (low and high). Survival modeling and multivariate analysis were used with these two groups to determine if there were differences in survival times and whether this was independent of known factors such as tumor stage/grade, patient age and resection margin status. RESULTS: High CD44s and low of CD44v6 expression significantly correlated with an improved outcome (P <0.05 and P <0.02, respectively) whereas CD44v8 and hCD44 (isoforms) did not. Differences in survival were apparent within 6-12 months of operation with >30% difference in survival between low/high expressions at 5 years. These finding were independent of the other measured MFS survival predictors, though the group was homogenous. CONCLUSIONS: High CD44s and low CD44v6 expression may be an independent predictor of improved survival in MFS patients in this pilot data. This is contrary to other MFS data, which did not account for the CD44 isoforms but is confirmed by data from other cancer types. Further investigation is needed to confirm CD44 isoform expression data as a relevant survival biomarker and whether it could be used to inform clinical decisions such as adjuvant therapy.

Preventively enteral application of immunoglobulin enriched colostrums milk can modulate postoperative inflammatory response.

Several studies demonstrated acute inflammatory response following traumatic injury. Inflammatory response during surgical interventions was verified by a significant increase of endotoxin plasma levels and a decrease of the endotoxin neutralizing capacity (ENC). However, the incidence of elevated endotoxin levels was significantly higher (89%) than detected bacterial translocation (35%). Thus parts or products of Gram-negative bacteria seem to translocate more easily into the blood circulation than whole bacteria. Along with the bacterial translocation, the inflammatory response correlated directly with the severity of the surgical intervention. In comparison after major and minor surgery Interleukin-6 (IL-6) and C-reactive protein (CRP) was also significantly different. Similar effects in mediator release were shown during endovascular stent graft placement and open surgery in infrarenal aortic aneurysm. Open surgery demonstrated a significant stronger endotoxin translocation and a decrease of ENC. Strategies to prevent translocation seem to be sensible. Colostrum is the first milk produced by the mammary glands within the first days after birth. It contains a complex system of immune factors and has a long history of use in traditional medicine. Placebo-controlled studies verified that prophylactic oral application of immunoglobulin-enriched colostrum milk preparation diminishes perioperative endotoxemia, prevents reduction of ENC and reduces postoperative CRP-levels, suggesting a stabilization of the gut barrier. This effect may be caused by immunoglobulin transportation by the neonatal receptor FcRn of the mucosal epithelium.In conclusion, there is an association of perioperative endotoxemia and the subsequent increase in mediators of the acute phase reaction in surgical patients. A prophylactic oral application of colostrum milk is likely to stabilize the gut barrier i.e. reduces the influx of lipopolysaccharides arising from Gram-negative bacterial pathogens and inhibits enterogenic endotoxemia. This appears to be a major mechanism underlying the therapeutic effect in patients at risk for Gram-negative septic shock.

[Hemangiosarcoma after breast-conserving therapy of breast cancer: report of four cases with molecular genetic diagnosis and literature review]. / Hämangiosarkom nach brusterhaltender Therapie beim Mammakarzinom: vier Fallbeispiele mit molekulargenetischer Diagnostik und Literaturübersicht.

BACKGROUND: Hemangiosarcomas of the breast represent a rare disease of the breast mainly occurring as secondary neoplasias with a latency of 5-10 years after primary treatment of breast cancer and are associated with an unfavourable prognosis. Radiation therapy, which is integrated within the concept of breast conserving therapy ranks as the main risk factor. PATIENTS AND METHODS: In this report we describe the clinical course of 4 patients including their molecular genetic pattern and give a summary of the actual literature. RESULTS: Hemangiosarcomas occur as a secondary neoplasm with a latency of 5-10 years after primary treatment of breast cancer and have an unfavorable prognosis. A genetic predisposition is assumed, but we could not find a significant role of tumor suppressor genes BRCA1, BRCA2 or p53 in our patients. CONCLUSION: Due to limited data available for these tumors, recommendations for therapy include radical tumor resection achieving wide free margins and inconsistent regimens of chemo- and/or immunetherapy modalities. In the majority these are based on systemic therapy regimens for other cutaneous sarcomas, such as Kaposi's sarcoma. Efforts should be taken for a nation-wide systematic registration of all cases of post-irradiation hemangiosarcomas.

Compartmental resection for subfascial extremity soft tissue sarcoma and quality of life in long-term survivors.

The surgical management of soft tissue sarcoma has changed over the past years, resulting in an interdisciplinary multimodal approach and limb-preserving treatment modalities. From 464 consecutive patients with a soft tissue sarcoma (STS) of an extremity, a compartmental resection was performed in 82 patients, usually for primary subfascial large tumors. Postoperative quality of life was evaluated using the EORTC Score C30. In our study population, 52% of STS was poorly differentiated, 32% moderately, and 16% well differentiated. Survival proved to be dependent on tumor grade and tumor biology, but not on tumor size. The overall survival rate was 81.5%, 71.9%, and 58.3% after 2, 3, and 5 years, respectively. Leiomyosarcoma (39%) and malignant fibrous histiocytoma (42%) are associated with poor 5-year survival rate compared to liposarcoma (82%). Metastases were observed in 33% of T1 and 43% of T2 tumors corresponding to 51% with G3 tumors, 52% with G2 and 23% with G1 tumors. We found a decreased quality of life score in our patients in all dimensions compared to a normal population. Despite the elevated risk of a functional deficit, compartmental resection reduces the risk of local recurrence comparable to the recurrence rates after the most radical surgery limb amputation.

Cystatin C - a fast and reliable biomarker for glomerular filtration rate in head and neck cancer patients.

PURPOSE: Determination of renal function is a prerequisite for planning therapy in cancer patients. Limitations of creatinine as marker for the glomerular filtration rate (GFR) led to the proposal of cystatin C as a more accurate biomarker especially in mild renal insufficiency or in patients with low muscle mass. We compared the accuracy of cystatin C- and creatinine-based equations to estimate GFR in head and neck cancer (HNC) patients receiving platinum-based radiochemotherapy. PATIENTS AND METHODS: The study population consisted of 52 HNC patients (GFR range, 37-105 mL/min/1.73 m(2) complemented by 17 patients with known renal insufficiency (GFR range, 10-60 mL/min/1.73 m(2)). Intraclass correlation coefficients were calculated between the reference method (51)Cr-EDTA clearance and estimated GFR by creatinine clearance and equations based on creatinine (Cockroft-Gault, modification of diet in renal disease (MDRD), Wright) or cystatin C (Larsson, Dade-Behring, Hoek). In addition, sensitivity and specificity to discriminate GFR > 60 mL/min/1.73 m(2) were evaluated by receiver operating characteristic curve (ROC). RESULTS: The highest correlation coefficients were found for the cystatin C-based estimates in comparison with creatinine-based estimates or creatinine clearance, even though Bland-Altman plots revealed GFR overestimation for all equations tested. The cystatin C-based Hoek formula exhibited the highest overall precision and accuracy. GFR of < 60 mL/min/1.73 m(2) was assumed as a cut-off for chemotherapy. ROC analyses revealed the highest AUC to predict a GFR > 60 mL/min/1.73 m(2) for the creatinine-based Wright formula, closely followed by the MDRD formula and cystatin C-based equations of Larsson, Dade-Behring, and Hoek. CONCLUSION: Cystatin C-based GFR estimates showed the overall strongest correlation to the reference method. Thus, we recommend cystatin C for GFR estimation in HNC patients as an alternative method to the estimated creatinine clearance in clinical practice.

Pancreatic incidentalomas: a growing clinical challenge exemplified by an intrapancreatic accessory spleen.

In part owing to an increasing use of high resolution imaging technologies a growing number of incidental pancreatic lesions are detected. A 40-year-old patient was admitted to our hospital to undergo resection for an unclear solid pancreatic tumor in the pancreatic tail. Preoperative imaging studies suspected an inactive neuroendocrine neoplasm. After distal pancreatectomy, the histopathological analysis revealed an intrapancreatic accessory spleen. Since reliable biomarkers are not established the clinical management of pancreatic incidentalomas is still challenging.

Bevacizumab as a treatment option for radiation-induced cerebral necrosis.

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiationinduced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy.

Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma.

INTRODUCTION: Chemotherapy-associated mucositis often prevents completion of an entire chemotherapy cycle. The underlying pathophysiology of chemotherapy-associated mucositis has not been well established. The individual immunologic predisposition of patients seems to play an important role. METHODS: One hundred fifty-six patients with locally advanced or metastatic esophageal adenocarcinoma received neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin followed by resection. Before the neoadjuvant therapy, monocytes were isolated from blood samples and were stimulated with lipopolysaccharide and interferon. An enzyme-linked immunosorbent assay was used to measure interleukin (IL)-10 and -12 levels and correlated with patients' clinical course. RESULTS: Twenty-two patients (14,1%) developed grade III to IV mucositis (according to the NCI-Common toxicity criteria scales) within the neoadjuvant chemotherapy. Pretherapeutic low IL-10 (<24.1 pg/ml) and high IL-12 (>5500 pg/ml) levels were significantly associated with mucositis causing a therapy interruption or even cessation. Patients with high IL-10 (>43.6 pg/ml) and low IL-12 (<4408.5 pg/ml) levels had an uneventful neoadjuvant chemotherapy. CONCLUSIONS: Pretherapeutic individual monocyte function is correlated with the development and the grade of chemotherapy induced mucositis. This knowledge might help us in predicting the grade of mucositis and in understanding the genesis regarding the association to pro- and anti-inflammatory effects of monocyte cytokines.