Study on pyoverdine and biofilm production with detection of LasR gene in MDR Pseudomonas aeruginosa.

In cystic fibrosis individuals, chronic lung infections and hospital-acquired pneumonia are caused by Pseudomonas aeruginosa. P. aeruginosa generates siderophores such as pyoverdine (PVD) as iron uptake systems to cover its needs of iron ions for growth and infection. lasR quorum sensing (QS) gene has a crucial function in PVD production and biofilm generation in P. aeruginosa. Fifty isolates of P. aeruginosa were obtained from clinical specimens of sputum (collected from individuals suffering from pulmonary infections). Antibiotic sensitivity test was performed for 50P. aeruginosa isolates by using 10 different types of antibiotics. All isolates of P. aeruginosa showed resistance for all 10 using antibiotics in this study. Ten multidrug resistant isoloates of P. aeruginosa were selected for next tests. Virulence factors of ten multidrug resistant isolates of P. aeruginosa, such as biofilm generation, PVD production, and lasR gene were detected. From results, all 10P. aeruginosa isolates can produce biofilm, PVD, and contain lasR gene. The produced amplicon for the lasR gene was 725 bp. After mice injection by fresh and heated PVD produced by P. aeruginosa PS10 LC619328.2, the fresh PVD caused 100 % mortality within five days using 0.3 ml of its concentration (37.4 µM), while (15.3 µM) of heated PVD (toxoid) caused 50 % mortality.

Characterization of Volatile Flavor Compounds in Supercritical Fluid Separated and Identified in Gurum (Citrulluslanatus Var. colocynthoide) Seed Oil Using HSME and GC-MS.

In this study, the volatile compound profiles of gurum seed oil were determined using two methods: supercritical CO2 extraction (SFE) and the screw press process (SPP). For volatile compounds extraction and identification, headspace solid-phase micro-extraction (HS-SPME) and GC-MS were used, respectively. A total number of 56 volatile compounds were revealed and identified in oil extracted by SFE, while only 40 compounds were detected in extracted oil by SPP. Acids, aldehydes, esters, ketones, furans, and other components were present in the highest ratio in oil extracted by SFE. In contrast, alcohols and alkenes were found in the highest proportion in oil extracted by SPP. In this study, it was observed that SFE showed an increase in the amounts of volatile compounds and favorably impacted the aroma of gurum seed oil. The results reveal that different extraction methods significantly impact the volatile components of gurum seed oil, and this study can help evaluate the quality of the oil extracted from gurum seeds.

Accuracy of contrast swallow study in assessment of caustic esophageal stricture length in children: Agreement study.

BACKGROUND: Caustic esophageal stricture length assessment is essential for planning endoscopic management and predicting its prognosis. We aimed to assess the accuracy of contrast swallow study (CSS) in measuring stricture length in comparison to endoscopy (definitive investigation for actual length measurement). METHOD: Medical records of caustic esophageal strictures between 2010 and 2020 were retrospectively reviewed. Reliability study was done to compare between radiological and endoscopic measurement of stricture length. RESULT: 124 CSSs for 91 patients were analyzed. Six studies showed no stricture, single stricture was reported in 101 studies, double strictures were reported in 16 studies, triple strictures were reported in one study (136 radiological stricture). Endoscopy revealed 133 true strictures. Number of the strictures was consistent between CSS and endoscopy in 112 studies (90.3%) and different in 12 studies (9.7%). Eight endoscopies revealed strictures not reported in CSS (5.5% false negative strictures), while 10 CSSs reported 11 strictures that were not detected during the endoscopy (7.6% false positive strictures). Reliability analysis revealed interclass correlation coefficient = 0.6 (95% CI 0.5 to 0.7) indicating moderate reliability. CONCLUSION: CSS is not accurate in assessing caustic esophageal stricture length. Combination of CSS and endoscopic investigation is better for proper evaluation of these patients. Level III of evidence.

Predictors of successful endoscopic management of caustic esophageal strictures in children: When to stop the dilatations?

BACKGROUND: Caustic esophageal strictures are mainly managed by endoscopic dilatations. Cases that do not respond to the dilatations eventually require an esophageal replacement. The aim of our study was to identify factors that could allow us to predict if the dilatations will be successful or not. METHODS: We retrospectively reviewed the chart of 100 patients with caustic esophageal injuries treated at our center between 2012 and 2019. Collected data included age, gender, type of caustic substance, duration of the dilatations, length and extent of the strictures, number and time interval between dilatations, presence of gastroesophageal reflux, occurrence of esophageal perforation, and outcome of the dilatation program. RESULTS: The patient ages ranged from 1 to 8 years old. The overall success rate was 98.2% for patients with short strictures and 81.8% for patients with long strictures (>3 cm). A long stricture, a pharyngeal extension of the stricture, the occurrence of an esophageal perforation, and the presence of gastroesophageal reflux were strong predictors of the failure of the dilatation program. The median treatment time for the patients to achieve a cure was 5 months in cases of short strictures and 17 months in cases of long strictures. Within the subgroup of patients with long strictures, a dysphagia-free period within the first year of management of 8 weeks was associated with the success of the dilatation program. CONCLUSION: A length of more than 3 cm, pharyngeal involvement, the occurrence of esophageal perforation, and the presence of gastroesophageal reflux are predictors of failure of dilatations for the management of caustic esophageal strictures. A dysphagia-free period of 8 weeks or more within the first year of dilatations is considered a predictor of success of dilatations in patients with long strictures. LEVEL OF EVIDENCE: Level II.

Iatrogenic esophageal perforation caused by endoscopic dilatation of caustic stricture: Current management and possibility of esophageal salvage.

BACKGROUND: Iatrogenic esophageal perforation (EP) is an undesirable complication of endoscopic dilatation of caustic esophageal stricture. We reported our current management protocol with possibility of continuing the dilatation program. PATIENTS AND METHODS: From January 2009 to January 2020 medical records were reviewed for patients presented with iatrogenic EP. Management according to each case condition was reported. RESULTS: 24 patients were enrolled, aged from 1.5 to 6 years old. Perforation was cervical in one case, abdominal in two cases, and thoracic in 21 cases. Immediate surgical repair was performed in the abdominal cases. Conservative management was chosen in 22 cases; two cases didn't respond and underwent esophageal diversion, and one of them died owing to severe sepsis. Three patients refused another trial of dilatation. Two cases failed to be redilated. 17 patients continued a dilatation program. Time passed between perforation and redilatation ranged from 35 days to 7 months. 15 patients were cured completely from dysphagia, one patient had marked improvement of his dysphagia, and one case with a resistant stricture was referred for esophageal replacement. CONCLUSION: Preserving the native esophagus is possible after iatrogenic EP of caustic esophageal stricture. A conservative approach should be attempted with caution not to endanger patient's life. Level IV of evidence.

Addressing Cancer Treatment Shortages in Saudi Arabia: Results of a National Survey and Expert Panel Recommendations.

PURPOSE: Cancer treatment shortages are complex and a persistent problem worldwide. Patients with cancer are most vulnerable to drug shortages, which provides opportunities to examine the extent of the challenge(s) facing Saudi Arabia and to provide recommendations toward mitigating the impact of cancer treatment shortages on patient outcomes. MATERIALS AND METHODS: A qualitative methodologic approach was conducted in April 2019 using a validated questionnaire and structured panel discussion for data generation. RESULTS: Overall, 55 responses were received from practicing oncology health care professionals (26 pharmacists and 29 physicians). The annual average number of treated patients with cancer per institution was 640 (adults [n = 400] and pediatric [n = 240]). All respondents (100%) reported that cancer treatment shortages constitute a current problem in their center, with an average of 5 (range, 1-9) per month. The panelists recognized 2 fundamental points. First, the definition of cancer drug shortages should be standardized and recognized at the national level. Second, the current system must be improved to ensure proper and efficient use of the current resources. On that basis, the panelists developed 9 recommendations for action. CONCLUSION: Cancer drug shortage is a significant problem in all health centers in Saudi Arabia. This study presents challenges that should be addressed at the national level and essential consensus recommendations for a coordinated action developed by a panel of experts to tackle the current national problem of cancer treatment shortages. Implementing these recommendations will provide a blueprint for management of national drug shortages in general and cancer treatment shortages in particular.

Assessment of The Role of Serum Neutrophil Gelatinase-Associated Lipocalin in Egyptian Childhood Bronchial Asthma: One Centre Study.

Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a potential biomarker in many medical conditions including asthma. The aim of this study was to assess the role of serum NGAL in Egyptian childhood bronchial asthma. The study included 156 patients and 39 apparently healthy control children. Full clinical examination, pulmonary function tests; CBC, CRP, IgE, liver function tests, and renal function tests, and serum NGAL level were performed. The difference between the studied groups was statistically significant regarding IgE, eosinophils and NGAL (P= 0.001 for each). In addition, the difference between the subgroup with severe persistent asthma and the subgroup with mild intermittent asthma was significant (P=0.001). ROC curve analysis showed that at a cut-off value of 0.884 the sensitivity and specificity of differentiating severe bronchial asthma patients from controls was 82 % and 76 %, respectively. In conclusion, NGAL may represent a potential marker of bronchial asthma in children with severe disease.

Colonic replacement of the esophagus: towards standardization of the technique.

Since we have started colonic replacement of the esophagus in children, several successive modifications have led to evolution of the surgical technique aiming to decrease complications and achieve the best functional outcome. Currently, our surgical group has reached a single standardized technique that has been applied to all cases included in this report. A colonic flap (including the transverse colon) is prepared based on the left colic vessels. The proximal end of the colonic flap is transferred upwards passing at first behind the stomach and then anteriorly through the lesser omentum to traverse the thoracic cavity via a previously prepared retrosternal tunnel. The proximal end of the colonic flap is anastomosed to the proximal esophagus in the neck (end to end anastomosis). Most specifically, the distal end of the colonic flap is anastomosed to the posterior wall of the body of the stomach in order to prevent regurgitation of gastric contents into the colonic flap. The retro-sternal colon bypass is among the successful options to replace the esophagus in children. Adding a posterior cologastric anastomosis to the procedure greatly prevents gastric regurgitation that can be responsible for short- and long-term complications. LEVEL OF EVIDENCE: This is a case series with no comparison group (level IV evidence).

Surgical management of corrosive-induced gastric injury in children: 10years' experience.

AIM: The purpose of this study was to report surgical management and outcome of corrosive-induced gastric injuries in children at our institute over the last decade. PATIENTS & METHOD: Medical records of patients admitted for corrosive-induced gastric injury at the Pediatric Surgery Department of Ain Shams University between January 2007 and January 2017 were retrospectively reviewed. RESULTS: Twenty six cases (17 boys and 9 girls) were enrolled. Mean age was 3.61±1.29. Ingested agent was acid in all the patients. Main presenting symptom was gastric output obstruction in 22 cases. The interval between corrosive ingestion and presentation ranged from one to 135days (mean=43.9±34). Surgical procedure included total gastrectomy (n=2), partial gastrectomy (n=2), augmentation gastroplasty (n=1), Billroth I (n=2), antrectomy (n=2), antroplasty (n=3), gastrojejunostomy (n=2), Heineke-Mikulicz pyloroplasty (n=9), Finney pyloroplasty (n=5), and feeding jejunostomy (n=4). Anastomotic stricture requiring a second operation developed in one patient. There were three mortalities related to the associated esophageal strictures. The mean follow-up period is 3.5years. All patients are free of symptoms and gained adequate weight. CONCLUSION: Surgery is the mainstay of management for corrosive-induced gastric injuries with good long-term results. Surgical procedure should be tailored according to the patient's general condition and extent of gastric injury. LEVEL OF EVIDENCE: This is a case series with no comparison group (level IV).

Trends in the Aggressiveness of End-of-Life Cancer Care in the State of Qatar.

PURPOSE: Quality of end-of-life (EOL) care is a key component of excellence in cancer care, and monitoring indicators for quality of EOL cancer care is crucial to providing excellent care. The aim of the current study is to describe the relative aggressiveness of EOL cancer care in the state of Qatar and to compare it with international figures. METHODS: We analyzed all deaths from cancer in Qatar between January 1, 2009 and December 31, 2013. A total of 784 eligible patients were studied to assess aggressiveness of cancer care at EOL. RESULTS: The average number of intensive care unit admissions per person decreased from 0.44 to 0.22 (P < .001) over the period of study. In addition, patients spent fewer days in the intensive care unit (2.79 to 1.82 days; P = .006) and made fewer visits to the emergency department (1.00 to 0.52 visits; P < .001) in the last 30 days of life. Fewer patients had at least one aggressive treatment measure at EOL during the 5-year period (82.3% to 71.0%; P = .038). The mean composite score for aggressiveness of EOL care decreased from 2.24 to 1.92 (P < .01). CONCLUSION: The aggressiveness of EOL cancer care has significantly decreased over time in Qatar; however, despite this decrease, the rate is still higher than that reported internationally. The integration of community palliative care services in Qatar may further decrease the aggressiveness of cancer care at EOL.

Patterns in place of cancer death in the State of Qatar: a population-based study.

BACKGROUND: International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD). This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement. METHOD: This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224). The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR) were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward) versus least preferred (ICU and general medicine ward) PoDs in Qatar, stratified by nationality. RESULTS: The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7-35.3%) followed by ICU (31.4%; 95% CI 28.7-34.3%), APCU (26.9%; 95% CI 24.3-29.6%), and general medicine ward (9.2%; 95% CI 7.6-11.1%). APCU trended upward (+0.057/year; p<0.001), while the hematology/oncology ward trended downward (-0.055/year; p<0.001). No statistically significant changes occurred in the other PoDs; home deaths remained low (0.4%; 95% Cl 0.38-0.42). Qataris who died from liver cancer (OR 0.23) and aged 65 or older (OR 0.64) were less likely to die in the APCU or hematology/oncology ward (p<0.05). Non-Qataris who died from pancreatic cancer (OR 3.12) and female (OR 2.05) were more likely to die in the APCU or hematology/oncology ward (p<0.05). Both Qataris and non-Qataris who died from hematologic malignancy (OR 0.18 and 0.41, respectively) were more likely to die in the ICU or general medicine ward (p<0.05). CONCLUSION: A high percentage of cancer deaths in Qatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice programs are needed to improve end-of-life cancer care.

Immune profiling of BALB/C and C57BL/6 mice reveals a correlation between Ureaplasma parvum-Induced fetal inflammatory response syndrome-like pathology and increased placental expression of TLR2 and CD14.

PROBLEM: Both BALB/c and C57BL/6 mice are susceptible to intrauterine infection with Ureaplasma parvum, but only protypical TH2/M2 BALB/c mice develop severe chorioamnionitis, fetal infection, and fetal inflammatory response syndrome-like (FIRS) pathology. METHOD OF STUDY: Microscopy, gene expression analysis, and ELISA were used to identify placental innate immune responses relevant to macrophage polarity, severe chorioamnionitis, and fetal infection. RESULTS: Both mouse strains exhibited a pro-M2 cytokine profile at the maternal/fetal interface. In BALB/c mice, expression of CD14 and TLRs 1, 2, 6 was increased in infected placentas; TLR2 and CD14 were localized to neutrophils. Increased TLR2/CD14 was also observed in BALB/c syncytiotrophoblasts in tissues with pathological evidence of FIRS. In contrast, expression in C57BL/6 placentas was either unchanged or down-regulated. CONCLUSION: Our findings show a link between increased syncytiotrophoblast expression of CD14/TLR2 and FIRS-like pathology in BALB/c mice. Functional studies are required to determine if CD14 is contributing to fetal morbidity during chorioamnionitis.

Intracranial germ cell tumors: a single-institution experience.

BACKGROUND AND OBJECTIVES: Intracranial germ cell tumors (GCTs) are not a common disease. We reviewed the experience of a single institution to determine the variables that affect treatment outcome. DESIGN AND SETTING: A retrospective review of patients with the diagnosis of intracranial germ cell tumors treated in a single institution (KFSHRC) during the period from March 1985 to December 2007. PATIENTS AND METHODS: Fifty-seven patients with the diagnosis of intracranial GCT were recorded in the KFSHRC Tumor Registry during the period from 1985 to 2007. Seven patients with a pineal region tumor treated as germinomas in the earlier years without a tissue diagnosis were excluded. This retrospective study was restricted to the remaining 50 patients with a tissue or marker diagnosis: 31 germinomas and 19 non-germinomatous germ cell tumors (NGGCTs). RESULTS: The 10-year overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were 87%, 88% and 96% for patients with germinoma, with a median follow-up of 4.5 (range 2-17) years, compared with 26%, 29% and 46% for patients with NGGCT with a median follow-up of 3 (range 1.5-13) years. For NGGCT, variables favorably influencing OS were younger age (< 16 y vs ≥16 y, P=.01), higher radiation dose (>50 Gy vs ≤50 Gy; P=.03) and later year of diagnosis (>1990 vs <1990 P=.002). CONCLUSIONS: Tissue diagnosis of GCTs is mandatory prior to treatment except for patients with elevated markers. In germinoma, localized radiotherapy (RT) for M0 patients may be adequate. Long-term follow-up is needed to define the benefit of adding chemotherapy. For NGGCT, the use of combined modality treatment and RT dose ;gt;50 Gy are important factors that influence the outcome. Second-look surgery and resection of residual/ refractory tumors is always recommended.

Enhancement of targeted homologous recombination in Mycoplasma mycoides subsp. capri by inclusion of heterologous recA.

A suicide plasmid, pExp1-ctpA::tetM-recAec, employing recA from Escherichia coli and tetM as a selection marker, was used to generate ctpA knockout mutants in Mycoplasma mycoides subsp. capri through targeted gene disruption. Inclusion of E. coli recA greatly enhanced both the consistency and the recovery of mutants generated by homologous recombination.

Complicated urinary tract infection is associated with uroepithelial expression of proinflammatory protein S100A8.

F344 rats chronically infected with Ureaplasma parvum develop two distinct profiles: asymptomatic urinary tract infection (UTI) and UTI complicated by struvite urolithiasis. To identify factors that affect disease outcome, we characterized the temporal host immune response during infection by histopathologic analysis and in situ localization of U. parvum. We also used differential quantitative proteomics to identify distinguishing host cellular responses associated with complicated UTI. In animals in which microbial colonization was limited to the mucosal surface, inflammation was indistinguishable from that which occurred in sham-inoculated controls, and the inflammation resolved by 72 h postinoculation (p.i.) in both groups. However, inflammation persisted in animals with microbial colonization that extended into the deeper layers of the submucosa. Proteome profiling showed that bladder tissues from animals with complicated UTIs had significant increases (P < 0.01) in proteins involved in apoptosis, oxidative stress, and inflammation. Animals with complicated UTIs (2 weeks p.i.) had the highest concentrations of the proinflammatory protein S100A8 (P

Expression of survivin and p16(INK4a)/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells.

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined, and therapeutic approaches based on the genetics of these tumors are currently lacking. In the present study we have used the immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are differentially expressed in primary meningioma cells with 20-, 30- and 36-fold difference between the lowest and the highest levels of each protein, respectively. In addition, we present evidence that the level of the anti-apoptosis survivin protein is high in these benign tumors. Moreover, the annexin V-associated flow cytometry technique was used to show that 60% of meningioma cell cultures underwent apoptosis in response to both gamma-rays and cisplatin, and 50% of these cells exhibited significant sensitivity to hydroxyurea. These agents triggered apoptosis through the mitochondrial pathway, by increasing the Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation and cisplatin was significant in all cells that expressed low levels of p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular biology of meningioma cells and suggest that survivin and proteins of the RB pathway could play a determinant role in the development and the treatment of meningiomas.

The p53/p21 DNA damage-signaling pathway is defective in most meningioma cells.

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined. In the present study we have used the immuno-blotting technique to study the expression level of the tumor suppressor proteins p53, p21 and PTEN in primary meningioma cells. We have also studied the induction of p21 and p53 in response to both UV light and gamma-rays. We present evidence that the p53/p21-dependent gamma-ray signaling pathway is defective in 5 out of 8 (62%) of these cells. Furthermore, we have shown that the tumor suppressor p21, p53 and PTEN proteins are differently expressed in these cells, with up to 40-folds difference between the lowest and the highest levels of each protein. These results suggest that the tumor suppressors p53/p21 signaling pathway and PTEN play important roles in the development of benign meningiomas.

Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosis.

Survivin, an inhibitor of apoptosis, is over-expressed in foetal tissues and human cancers, but it is almost undetectable in normal tissues. Here we have assessed the level of the survivin protein in some benign tumors of the nervous system: meningioma, schwannoma, low-grade ependymoma, pilocytic astrocytoma and pituitary adenoma. Using immuno-blot analysis we present evidence that these low-grade tumors are positive for survivin expression. In agreement, flow cytometrical analysis showed that both spontaneous and radiation-induced apoptosis levels are very low in these neoplasms. Using host cell reactivation assay we have also shown that these tumor cells are proficient in the repair of gamma-ray-induced DNA damage. However, they are deficient in the removal of ultraviolet (UV) light-induced DNA photolesions, especially the shwannoma- and the pituitary adenoma-derived cells. These results suggest that survivin overexpression may be an early event in the stepwise tumoregenesis and hence could be responsible for the onset as well as the growth advantage during tumoregenic progression of malignant as well as benign neoplasms.

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84. RESULTS: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.

VIP (etoposide, ifosfamide, cisplatin) in adult patients with recurrent or refractory Ewing sarcoma family of tumors.

Despite the fact that Ewing sarcoma family of tumors (ET) is chemosensitive, long-term survival is extremely rare for patients with primary refractory or recurrent disease. There is no standard salvage chemotherapy regimen available in this context. In this study the authors reviewed their experience with the combination of etoposide, ifosfamide, and cisplatin in adult patients with recurrent or refractory disease. From February 1997 through December 2001, they evaluated the efficacy of etoposide (75 mg/m2/day for 5 days), ifosfamide (1,200 mg/m2/day for 5 days), and cisplatin (20 mg/m2/day for 5 days) combination chemotherapy (VIP regimen), as second-line salvage therapy in 27 patients with recurrent or refractory ET. All patients were evaluated for response, time to progression, and overall survival. Twenty-one male and 6 female patients with recurrent (n = 14) and refractory (n = 13) disease were treated with the VIP regimen. Median age was 18 years (range, 16-34 years). Twenty-two patients were previously treated with vincristine, Adriamycin, ifosfamide, and actinomycin-D; and 5 patients were treated with cyclophosphamide, Adriamycin, and vincristine. Sites of recurrent or progressive disease included local (n = 3), distant (n = 11), and both local and distant (n = 13). A total of 129 cycles of VIP were given (median, 5 cycles/patient; range, 1-14 cycles/patient). One patient (4%) had a complete response (CR) and 8 patients (30%) had a partial response (PR), for an overall response rate of 34%. The median number of cycles given to patients with CR + PR was 6 (range, 3-14 cycles). Nine patients (33%) had stable disease and 9 (33%) had disease progression. Median time to progression and median overall survival were 6.6 months and 8.1 months respectively for all patients, and 12.8 months and 14.2 months respectively for responders. There were no toxic deaths. Major toxicities included grade IV granulocytopenia in 19 patients and grades III/IV thrombocytopenia in 15 patients. At a median follow-up of 8 months (range, 2-56 months), 24 patients died of disease progression, 2 patients are alive with disease, and 1 patient is alive with no evidence of disease. The authors conclude that the VIP combination is active in patients with recurrent/refractory ET, with acceptable toxicity, and offers good palliation. Cisplatin-based combination chemotherapy merits further investigation, possibly as first-line treatment in this disease.