Chemotherapeutic Courses Research Articles

Two cases of gastric cancer with elevated serum levels of KL-6

BackgroundThe serum level of Krebs von den Lungen-6 (sKL-6) is a biomarker of interstitial pneumonia and has been reported to be elevated in patients with cancers. However, there have been few cases of gastric cancer (GC) with elevated sKL-6 that were treated by chemotherapy. We herein report two cases of GC with elevated sKL-6 that were treated with oxaliplatin plus S-1 (SOX) chemotherapy and discussed the resulting changes in sKL-6.Case presentationThe first patient was a 79-year-old woman complaining of loss of appetite. Esophagogastroduodenoscopy (EGD) showed a type-3 tumor in the gastric antrum and biopsy specimens showed adenocarcinoma. Computed tomography (CT) showed multiple liver metastases. sKL-6 was elevated to 1,292 U/ml, but a CT revealed no obvious lesions of the lungs, including interstitial pneumonia. The tumor was diagnosed as GC with liver metastases and elevated sKL-6. Respiratory function data were normal. SOX therapy using oxaliplatin and S-1 was performed. After 3 courses of SOX therapy, CT showed reductions of the liver metastases as well as the primary tumor, and sKL-6 was decreased to 201 U/ml. After the 44 courses, sKL-6 was slightly elevated. Chest CT showed interstitial pneumonia and chemotherapy was stopped. The patient is still alive without any metastasis 72 months later. The second patient was a 69-year-old woman complaining of upper abdominal pain. EGD revealed a type-3 tumor in the gastric antrum showing adenocarcinoma with HER2-positive pathology. CT showed multiple node metastases around the abdominal aorta. sKL-6 was elevated to 2,239 U/ml, but a respiratory function test showed no abnormalities, and CT of the lungs showed no obvious lesions. The tumor was diagnosed as GC with distant node metastases and elevated sKL-6. The patient received SOX therapy combined with trastuzumab. After 6 courses, the size of the primary tumor and multiple node metastases were reduced, and sKL-6 was decreased to 284 U/ml.ConclusionsThese two cases suggest that sKL-6 may be important not only as an indicator of interstitial pneumonia in chemotherapeutic courses, but also as a tumor marker in GC patients with multiple metastases.

SENSITIVITY OF S+ERUM PROTEINS OF GI CANCER PATIENTS TO CHEMOTHERAPY COURSES

Gastrointestinal cancers (GI) are one of the most abundant types of cancers among the world population, though statistical data indicate that in eastern Asia these types of cancer occur 4 times more often than in Western Europe. Absence of treatment of bacterial infections, obesity, and lack of vegetable food in a diet can be the case of GI cancer. All pathologies are inevitably connected to the changes in cell cycle, abnormal protein amount and their dysfunction. Serum proteins are widely used as an additional source of information about body condition, also changes in protein composition can point out the mechanism of disease development and effectiveness of treatment. In the presented work we studied protein composition of GI cancer patients in different stages of cancer development, after and before chemotherapy and compared these data to protein composition of healthy control group of voluntaries. Treatment of patients was performed according the guidelines appropriate for the GI cancer. Association of the effectiveness of treatment at the different stages of chemotherapeutic courses and changes of protein composition of blood serum has been assessed. Proteins composition was studies by SDS-PAGE electrophoresis and densitometry analysis. Experimentally gained molecular and statistical information exposed the most vulnerable groups of proteins affected by chemotherapeutic agents indicating targets for searching new biomarkers for treatment effectiveness. Research involving human patients performed in accordance with the requirements of the Council of Europe Convention on Human Rights and Biomedicine, Biomedical Research, as well as the UNESCO Declaration of Bioethics and Human Rights.

SENSITIVITY OF SERUM PROTEINS OF GI CANCER PATIENTS TO CHEMOTHERAPY COURSES

Gastrointestinal cancers (GI) are one of the most abundant types of cancers among the world population, though statistical data indicate that in eastern Asia these types of cancer occur 4 times more often than in Western Europe. Absence of treatment of bacterial infections, obesity, and lack of vegetable food in a diet can be the case of GI cancer. All pathologies are inevitably connected to the changes in cell cycle, abnormal protein amount and their dysfunction. Serum proteins are widely used as an additional source of information about body condition, also changes in protein composition can point out the mechanism of disease development and effectiveness of treatment. In the presented work we studied protein composition of GI cancer patients in different stages of cancer development, after and before chemotherapy and compared these data to protein composition of healthy control group of voluntaries. Treatment of patients was performed according the guidelines appropriate for the GI cancer. Association of the effectiveness of treatment at the different stages of chemotherapeutic courses and changes of protein composition of blood serum has been assessed. Proteins composition was studies by SDS-PAGE electrophoresis and densitometry analysis. Experimentally gained molecular and statistical information exposed the most vulnerable groups of proteins affected by chemotherapeutic agents indicating targets for searching new biomarkers for treatment effectiveness. Research involving human patients performed in accordance with the requirements of the Council of Europe Convention on Human Rights and Biomedicine, Biomedical Research, as well as the UNESCO Declaration of Bioethics and Human Rights. Keywards: Gastrointestinal cancer, chemotherapy, proteins, biomarkers.

Clinical Significance of TF and VEGF Expressions on Peripheral CD14 Positive Monocytes in Patients with Diffuse Large B Cell Lymphoma

To investigate the clinical significance of tissue factor (TF) and vascular endothelial growth factor (VEGF) expression on peripheral blood CD14 positive monocytes in patients with diffuse large B cell lymphoma (DLBCL). The expressions of TF and VEGF on peripheral CD14+ monocytes in 41 patients with DLBCL (DLBCL group) before chemotherapy and after 4 chemotherapeutic courses, and in 20 healthy subjects (control group) were detected by flow cytometry respectively, meanwhile, the relationship of the expression of TF and VEGF with international prognostic indexes (IPI) and short-term effects were analysed. The expression levels of TF and VEGF on peripheral CD14+ monocytes in DLBCL group were significantly higher than those in control group (P<0.01), and a positive correlation was found between the two groups (r=0.755, P<0.01). The expression of TF and VEGF on CD14+ monocytes in patients with prognostic risk factors significantly increased as compared with those in patients without prognostic risk factors (P<0.05), but there were no significant differences of TF and VEGF expressions on CD14+ monocytes in DLBCL group with different sex, age, subtypes (P＞0.05). As compared with patients without prognostic risk factors, the expression levels of TF and VEGF on CD14+ monocytes of patients with prognostic risk factors significantly increased (P<0.05). The expression of TF and VEGF on CD14+ monocytes in DLBCL group showed an increasing tendency along with the increase of IPI index (P<0.01). The expression levels of TF and VEGF on CD14+ monocytes in remission group before chemotherapy were lower than those in non-remission group (P<0.01); after chemotherapy, the expression levels of TF and VEGF on CD14+ monocytes in remission group were lower than those before chemotherapy (P<0.05), while the TF and VEGF expression levels in non-remission group were no singnificauly different from TF and VEGF levels before chemtherapy (P>0.05), the survival of patients in group with low expression of TF and VEGF was superior to that in group with high expression of TF and VEGF (P<0.05). The paripheral blood CD14+ monocytes in DLBCL patients highly express the TF and VEGF, which relate with IPI, therapeutic efficacy and survival, thus the TF and VEGF expression levels are of reference significance for evaluating the therapeutic efficacy and prognosis of patients.

Intensity and duration of neutropenia relates to the development of oral mucositis but not odontogenic infection during chemotherapy for hematological malignancy.

BackgroundD-index which combines the intensity and duration of neutropenia is reported as a tool for evaluating the dynamics of neutropenia. This study aimed to analyze the relationship between D-index and oral complications (i.e., oral mucositis [OM] and odontogenic infection [OI]) during chemotherapies for hematological malignancies.MethodsA total of 421 chemotherapeutic courses in 104 patients were analyzed. Chemotherapeutic courses in patients who finished all of the prophylactic dental treatments were defined as “treatment Finish”. Chemotherapeutic courses in patients who did not finish prophylactic dental treatments were defined as “treatment not-Finish”. OM was evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. D-index was compared between chemotherapeutic courses with versus without oral complications.ResultsD-index was significantly higher in chemotherapeutic courses with grade 1 or 2 OM (p < 0.001) than courses without OM. In contrast, higher D-index did not relate to the development of OI (p = 0.18). The occurrence of OI (p < 0.001) but not OM (p = 0.56) during chemotherapy was significantly higher in chemotherapeutic courses without the completion of dental intervention.ConclusionsHigher D-index relates to the development of OM. In contrast, OI occurs due to untreated odontogenic foci, and its occurrence does not relate to higher D-index.

Role and timing of second-line therapies for patients with recurrent platinum-resistant ovarian epithelial cancer.

To explore the regimens and prognoses of second-line therapies for recurrent platinum-resistant ovarian epithelial cancer (OEC). The clinical profiles and second-line regimens were retrospectively analyzed for 65 recurrent platinum-resistant OEC patients treated at Zhejiang Provincial Tumor Hospital during January 2003 to January 2013. In conjunction with literature reviews, the second-line therapies for platinum-resistant recurrent OEC were discussed. Their average age was 55.2 years. The stages were I (n=4), II (n=3), III (n=45), and IV (n=13). The predominant type was serous adenocarcinoma (n=47, 72.3%). Chemotherapy was refused (n=14) and resistant (n=5 1). One case was lost to follow-up and another three withdrew early. An average of four chemotherapeutic courses were offered in 61 cases. Among them, five cases selected chemotherapy after a second operation. The average therapy-free interval (TFI) was 3.5 months. The efficacies were evaluated for 61 cases. CR (n=5) and partial remission (PR, n=22). The overall survival (OS) rate was 43.6% and average progression-free survival (PFS) was 15.44 months. The efficacy of second-line therapy for recurrent platinum-resistant OEC is rather poor and the feasibility and efficacy of second operation are to be further explored.

English

Application of hemofiltercytological analysis shows its ample opportunities in assessment of polychemotherapy completeness and quality through the study of drug pathomorphosis. The objective of the study was development and studying of the clinical relevance of hemofiltercytological venous blood test as completeness and quality control of patients with colorectal cancer adjuvant chemotherapy. 35 of 39 tested cancer patients who underwent radical surgery for colorectal cancer of different localization, including cases of locally advanced stage had cancer cells in peripheral blood. Thus, the percentage of patients who had atypical cells in venous blood in postoperative period was 89.7. Adjuvant chemotherapy was offered to all 35 patients with diagnosed carcinemia and after their consent it was held in modes FOLFOX-4 and XELOX. Evaluation of anticancer drugs therapeutic action is traditionally carried out using the criteria of objective and subjective effects. The criterion of objective effect during chemotherapy of solid tumors is reduction of tumor and metastases and the criterion of subjective one is well-being of a patient. In addition, it is important to notice the highest drug resistance observed at rectum cancer, because there is a predominance of smaller stages I to II of drug pathomorphosis (9 to 7) over greater stages III-IV (7 to 1) among these cancer patients. Consequently, hemofiltercytological blood test provides a real opportunity to assess the effect of polychemotherapy and to solve the problem of chemotherapeutic treatment courses number necessary to stabilize the cancer process. Key words: Calibrated filter, hemofiltercytological blood test, carcinemia, microscreening.

Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model

Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients.

Reduced relative dose intensity of primary chemotherapy does not influence prognosis of patients with Hodgkin lymphoma

A retrospective analysis of patients with Hodgkin lymphoma (HL) was performed to assess their outcome regarding relative dose intensity (RDI) of chemotherapy administered in primary treatment. A total of 194 patients were divided into three groups with different RDI of primary chemotherapy (100%, 90-99% and <90%). Reduced RDI in two groups (90-99% and <90%) was caused by the delay of the interval between the administration of some chemotherapeutic courses. The probability of complete remission (CR), disease relapse, event-free survival (EFS) and overall survival (OS) as the basic parameters of patient outcome were statistically compared. Multivariate analysis showed here were no significant differences in probability of CR (HR 0.9, 95% CI [0.75-1.08], P=0.5), risk of relapse (HR 1.34, 95% CI [0.92-1.94], P=0.11) or death (HR 1.52, 95% CI [0.94-2.5], P=0.13). There were also no significant differences in probability of EFS (mean 13 vs. 10 vs. 12 years, P=0.17; HR 1.54, 95% CI [0.91-2.6], P=0.22) or OS (mean 15 vs. 13 vs. 14 years, P=0.13; HR 1.52, 95% CI [0.93-2.5], P=0.13). We found no significant impact of primary chemotherapy delay resulting in reduced RDI on outcome in HL patients.

Model Pharmacoeconomic Study on Iressa® (Gefitinib) as a First Line Treatment of Non-Small Cell Lung Cancer at Stage IIIB/IV in EGFR Mutation Positive Bulgarian Patients

ABSTRACTThis investigation fully looks into a pharmacoeconomic issue and analyzes several therapeutic strategies for management of non-small cell lung cancer (NSCLC) advanced to stage IIIB/IV as a first line of treatment in patients with a mutation in the gene for the Epidermal Growth Factor Receptor (EGFR). The most relevant conclusions that have been published in the scientific expert literature and the national specific data for the Bulgarian healthcare system are included in this research.The pharmacoeconomic analysis employed several methods such as “Costs-of-therapy” and “Budget Impact Analysis, BIA” in order to evaluate the therapy with the novel biotechnological medication gefitinib (IRESSA®) when it was applied as a first line treatment for non-small cell lung cancer in EGFR positive patients. IRESSA® therapy was compared to the most commonly used alternative therapeutic strategies. The performed analysis is based on the clinical experience and practice of the Bulgarian oncologists from the Department of Chemotherapy in the University Hospital “Tsaritsa Yoanna—ISUL”. The study evaluated the efficiency of the gefitinib treatment compared to other current alternative therapeutic strategies.Patients diagnosed with advanced NSCLC in stage IIIB/IV, naive in terms of previous chemotherapeutic courses and with a mutation in the gene for EGFR (EGFR M+) were analyzed. As selection criteria the methodology for the IPASS study was referenced. This pharmacoeconomic study was performed from the perspective of the healthcare insurance fund to serve the drug reimbursement system. As a basis for evaluation of the effectiveness the calculated expenses for the use of the different medications were analyzed. A standard period of six months was considered in the study for the application of the different therapeutic strategies for first line therapy of non-small cell lung cancer in EGFR M+ patients.The implementation of cost-benefit analysis showed that gefitinib should be the medication of choice for the treatment of EGFR M+ non-small cell lung cancer warranted by the significant difference in both the survival period and costs for therapy when compared to alternative therapeutic strategies.

Risk factors for recurrence of optimally staged/debulked ovarian or tubal cancer patients with adjuvant paclitaxel/carboplatin combination chemotherapy

16571 Background: This was an exploratory study to find the risk factors for ovarian or tubal cancer recurrence. Methods: Consecutive patients with stage II-IV optimally staged/debulked ovarian or tubal cancer patients with adjuvant paclitaxel/carboplatin combination chemotherapy treated in our department from August 2000 to July 2005 were retrospectively evaluated. The endpoint of this study was disease free survival. Those analyzed as risk factors for recurrence were; age, stage, histological type, residual tumor, interval between operation and first dose of chemotherapy, total course of chemotherapy before recurrence, dose and dose intensity (DI), basal and nadir levels of blood count (white cells, neutrophils, platelets, hemoglobin) and that of albumin. Colony stimulating factor (CSF) usage was also analyzed. Results: There were 25 cases with total of 139 courses of the chemotherapy that met the eligible criteria. There were 16 cases of recurrence. Median follow up for disease free patients was 24 months. Median age was 54 years. There were 4, 19, and 2 cases with stage II, III, and IV. Histological type consists of 11 serous, 4 endometrioid, 2 mucinous, 4 clear cell, 1 undifferentiated, and 3 carcinosarcoma. Median of relative DI of paclitaxel and carboplatin were both 0.85. There were 71 and 45 courses of grade 3 and 4 neutropenia, respectively. There were median of 6.5 days of CSF usage in all but one course. Multivariate analysis with cox proportional hazard model revealed that the prognostic factors for recurrence [hazard ratio; 95% confidence interval] were; neither serous nor endometrioid type histology; mucinous and clear [10.6; 1.98–56.8], undifferentiated and carcinosarcoma [43.0; 5.73–322], nadir neutrophil count fell below 210/mm3 [0.22; 0.06–0.83], and the case more than two-thirds of courses were with further neutropenia despite of CSF usage [0.10; 0.02–0.51]. Conclusion: Within these highly selected cases, the histological type is a prognostic factor. Furthermore, the severity of neutropenia during chemotherapeutic courses is also a prognostic factor that may be controlled by “optimize” dosage of chemotherapeutic agent. No significant financial relationships to disclose.

HMGA2 expression and response to anthracycline-based preoperative chemotherapy in patients with operable breast cancer

22035 Background: Preclinical data suggest that increased expression of high mobility group A2 (HMGA2) protein could enhance chemosensitivity towards doxorubicin in breast cancer cells. The present study investigated the predictive value of HMGA2 immunoreactivity in patients (pts) with operable breast cancer (BC) treated preoperatively with regimens including anthracyclines. Methods: We reviewed the pretreatment biopsies of 94 pts with large (> 2 cm) operable BC treated with preoperative anthracycline-based chemotherapy, performing immunohistochemistry for HMGA2 and other biological markers (ER, PgR, HER2, MIB1, topoisomerase II α). Characteristics of preoperative chemotherapy (i.e. number of courses, type of anthracycline or taxane) were also analyzed. Association between clinico-biological factors and pathological, clinical (by caliper) and radiological (by mammography, ultrasound and MRI) response was assessed. Results: In univariate analysis, high expression of HMGA2 was significantly associated with clinical complete response [odds ratio (OR) = 4.9, 95% CI 1.3–18.9] and with tumor shrinkage assessed by MRI (OR = 2.9, 95% CI 1.1–7.7). No statistically significant association was observed between HMGA2 and clinical or pathological response in multivariate analysis. Among the other variables, the following were associated with complete pathological response (pCR): ER (p = 0.005), MIB-1 (p = 0.01) and topoisomerase II alfa (p = 0.05). In multivariate analysis, ER was the only independent predictor of pCR (OR = 0.2, 95% CI 0.03–0.9). The number of chemotherapeutic courses was independently associated with tumor shrinkage assessed by caliper (OR = 9.9, 95% CI 2.4–40.5) and by mammography (OR = 4.02, 95% CI 1.4–11.3). MIB-1 expression was independently associated with tumor shrinkage assessed by ultrasound (OR = 3.8, 95% CI 1.1–13.4) and by MRI (OR = 3.6, 95% CI 1.2–11.3). Conclusions: Immunohistochemical evaluation ofHMGA2 significantly predicted clinical complete response and tumor shrinkage assessed by MRI in patients treated with preoperative anthracycline-based chemotherapy. Although no independent association with response was observed, the potential predictive role of this protein deserves further evaluation. No significant financial relationships to disclose.

Radiothérapie postopératoire après chirurgie laser avec ou sans chimiothérapie dans les cancers évolués de la tête et du cou

Thirty-five previously untreated patients with stage Ib, IIa, and IIb squamous cell carcinoma of uterine cervix with bulky mass (more than 4 cm) were treated with initial chemotherapy of vinblastine, bleomycin, and cis-platinum combined regimen (VBP, one to five courses) and subsequent radical surgery. The effectiveness of the preoperative chemotheapy was evaluated in the surgical specimen. The overall clinical response rate was 89% and included a complete response in 16 (46%) and a partial response in 15 patients (43%). There were no differences in the response rate by age, stage, or the geographic contour of the tumor. The number of chemotherapeutic courses correlated well with the response of the primary tumor (P = 0.0004) up to three courses. Histologic examination of the resected primary tumor revealed no evidence of disease (Grade IV) in 44% of complete responders, microscopic foci (Grade III) in 38% (6), and macroscopic disease (Grade II) in 18% (3). Of 15 patients with stage IIb, 11 (73%) had a stage-down. Lymphnode metastases after chemotherapy were found in 26% (935) of the patients. All nodal metastases were found among the patients who had a partial response or a stable disease, and none was found in those with a complete response (P = 0.0029). This preliminary study suggests that initial chemotherapy before surgery is effective in reducing tumor volume or stage of the disease providing better circumstances for surgery, offers selection of high-risk groups of patients requiring additional chemotherapy, and might be able to eliminate effectively diseases in lymphnodes and possibly micrometastases. This regimen is now being evaluated to test its impact on survival.

Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis

To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis. One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18), chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival. The mean survival periods of the patients in four groups were 3.6, 7.3, 10.1, and 15.1 mo respectively. There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (P<0.001). Multivariate analysis revealed that the strategy of treatment (P<0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT. Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation. Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.

Influence of the administration of amifostine on the pharmacokinetics of 5-fluorouracil in patients with metastatic colorectal carcinoma.

A high dose antineoplastic therapy with 5-fluorouracil (5-FU) is associated with severe side effects. It is thought that the cytoprotective drug amifostine can reduce these side effects when it is given prior to a chemotherapeutic course. In this study, the pharmacokinetic parameters of 5-FU are monitored in six patients, who received two chemotherapeutic courses of 2,600 mg/m2 BSA 5FU over 24 h, one course with 700 mg/m2 BSA amifostine prior to the 5-FU infusion and the other without. 20 serum samples were drawn during each infusion time and the 5-FU concentrations were determined by a sensitive and selective GC-MS assay. The statistical analysis of the serum concentrations revealed no significant differences in the pharmacokinetic parameters of 5-FU, whether amifostine is administered or not. The conclusion can be drawn that a reduction of side effects is due to the cytoprotective effect of amifostine and not to a change in the serum concentrations of 5-FU.

Facial paralysis: a presenting feature of rhabdomyosarcoma

The purpose of this paper is to present a child with embryonal rhabdomyosarcoma involving the left middle ear, who initially presented with unilateral facial paralysis. A 5-year-old boy presented with a 4-week history of left-sided facial weakness, associated with persistent otitis media on that side. Examination revealed complete left lower motor neuron facial weakness and hearing loss. A myringotomy revealed a soft tissue mass behind the tympanic membrane. Biopsy and oncologic assessment confirmed a stage II, group III left middle ear embryonal rhabdomyosarcoma. Despite debulking surgery, local irradiation and multiple chemotherapeutic courses the child deteriorated quickly. He developed carcinomatous meningitis and died 9 months after his initial presentation. In conclusion, middle ear tumors should be considered in the differential diagnosis of unresolving otitis media, particularly when associated with persistent ipsilateral facial paralysis. An ear mass, discharge, facial swelling, or systemic symptoms may be initially absent despite the presence of this aggressive malignancy. Careful examination of the middle ear is recommended in children with facial weakness. A myringotomy incision may be necessary including a complete assessment of the middle ear cavity, particularly when there is no fluid return.

Pharmacokinetic studies on Elobromol in children with brain tumors

Systemic pharmacokinetics of high dose (500 mg/m2), orally administered Elobromol (dibromodulcitol, DBD) were studied in 16 chemotherapeutic courses administered to five patients. Cerebrospinal fluid (CSF) DBD levels were also analyzed in two patients. Bromoepoxydulcitol (BED), dianhydrodulcitol (DAD) are cytotoxic, whereas bromoanhydrodulcitol (BAD) and anhydroepoxydulcitol (AED) are inactive metabolites detectable during the biotransformation of DBD. The HPLC method, developed by our team, is suitable for the determination of both DBD and its main metabolites (DAD and BAD). Our publication is the first in the literature to describe the pharmacokinetic properties of these three hexitol derivatives in pediatric patients. With the exception of one patient, concentration time curves were analyzed by the one-compartment model. From 30 min following administration, DBD was detectable in all plasma samples for at least 12 h; its concentration, however, was usually undetectable by 24 h. Though highly variable in value, DAD concentrations were detectable during all but one of the therapeutic courses. The following peak concentrations were observed: DBD = 3.46-30.63 microM, DAD = 1.70-6.17 microM and BAD = 0-5.63 microM. The correlation of AUCBAD and AUCDBD values were exponential up to 200 microM h with no additional increase detectable above this limit: the distribution of AUCBAD and AUCDBD was described by a maximum curve. The possibility of enterohepatic recirculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives was detectable in CSF even if the concentration of the individual metabolite remained undetectable in plasma. DBD CSF concentrations were almost constant in the period from 2.5 to 8 h following administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent advances in the treatment of meningitis, including steroids

Despite advances in antimicrobial chemotherapy, central nervous system infections continue to be an important cause of morbidity and mortality in infants. It is expected that as a result of bacterial vaccine improvements, the incidence of bacterial meningitis will decline in the near future. In the meantime, however, adjunctive therapeutic approaches, oriented to diminish brain inflammation, are proving valuable. An improved prognosis for survivors indicates a normal neurologic outcome for more than 80% of survivors. Other advances include rapid diagnostic techniques for viral and tuberculous central nervous system infections as well as short, intensive chemotherapeutic courses for the latter. Finally, imidazole antifungal agents are of potential value in pediatric infections.

Preoperative adjuvant chemotherapy in the treatment of cervical cancer stage Ib, IIa, and IIb with bulky tumor

Thirty-five previously untreated patients with stage Ib, IIa, and IIb squamous cell carcinoma of uterine cervix with bulky mass (more than 4 cm) were treated with initial chemotherapy of vinblastine, bleomycin, and cis-platinum combined regimen (VBP, one to five courses) and subsequent radical surgery. The effectiveness of the preoperative chemotheapy was evaluated in the surgical specimen. The overall clinical response rate was 89% and included a complete response in 16 (46%) and a partial response in 15 patients (43%). There were no differences in the response rate by age, stage, or the geographic contour of the tumor. The number of chemotherapeutic courses correlated well with the response of the primary tumor ( P = 0.0004) up to three courses. Histologic examination of the resected primary tumor revealed no evidence of disease (Grade IV) in 44% of complete responders, microscopic foci (Grade III) in 38% (6), and macroscopic disease (Grade II) in 18% (3). Of 15 patients with stage IIb, 11 (73%) had a stage-down. Lymphnode metastases after chemotherapy were found in 26% ( 9 35 ) of the patients. All nodal metastases were found among the patients who had a partial response or a stable disease, and none was found in those with a complete response ( P = 0.0029). This preliminary study suggests that initial chemotherapy before surgery is effective in reducing tumor volume or stage of the disease providing better circumstances for surgery, offers selection of high-risk groups of patients requiring additional chemotherapy, and might be able to eliminate effectively diseases in lymphnodes and possibly micrometastases. This regimen is now being evaluated to test its impact on survival.

Local control and survival related to radiation dose and volume and to chemotherapy in non-metastatic Ewing's sarcoma of pelvic bones

This manuscript reviews 25 patients with non-metastatic Ewing's sarcoma of the pelvis. In 4/25 (16%) the disease recurred locally and then metastasized. In addition, 15/25 patients have shown widespread metastases without local recurrence. Thus, only 10/25 (40%) remain with no evidence of disease at this writing. Patients who received VAC$ and Adriamycin (Regimen I) seemed to have a lower incidence of local recurrence than those who received VAC alone, even when radiation dose and/or volume were not optimum. Further study including isotope bone scanning and lymphangiograms are recommended for future clinical study to evaluate the natural history of disease for this site. More intensive chemotherapy has been instituted by reducing the “rest” period to 3 weeks instead of 6 weeks chemotherapeutic courses.