Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Variability in colonization of arbuscular mycorrhizal fungi and its effect on mycorrhizal dependency of improved and unimproved soybean cultivars.

Breeding selection of germplasm under fertilized conditions may reduce the frequency of genes that promote mycorrhizal associations. This study was developed to compare variability in mycorrhizal colonization and its effect on mycorrhizal dependency (MD) in improved soybean genotypes (I-1 and I-2) with differential tolerance to drought stress, and in unimproved soybean genotypes (UI-3 and UI-4). As inoculum, a mixed native arbuscular mycorrhizal fungi (AMF) was isolated from soybean roots, showing spores mostly of the species Funneliformis mosseae. At 20 days, unimproved genotypes followed by I-2, showed an increase in arbuscule formation, but not in I-1. At 40 days, mycorrhizal plants showed an increase in nodulation, this effect being more evident in unimproved genotypes. Mycorrhizal dependency, evaluated as growth and biochemical parameters from oxidative stress was increased in unimproved and I-2 since 20 days, whereas in I-1, MD increased at 40 days. We cannot distinguish significant differences in AMF colonization and MD between unimproved and I-2. However, variability among improved genotypes was observed. Our results suggest that selection for improved soybean genotypes with good and rapid AMF colonization, particularly high arbuscule/hyphae ratio could be a useful strategy for the development of genotypes that optimize AMF contribution to cropping systems.

Preoperative chemotherapy in advanced resectable OCSCC: long-term results of a randomized phase III trial.

BACKGROUND: Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer. PATIENTS AND METHODS: A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (120-h infusion administered every 21 days) in stage T2-T4, N0-N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death. RESULTS: Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P=0.6337), nor in distant metastasis development (P=0.1527). There was also no difference between groups in overall survival (P=0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P=0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%). CONCLUSIONS: Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.

Treatment-related outcome of oropharyngeal cancer patients differentiated by HPV dictated risk profile: a tertiary cancer centre series analysis.

BACKGROUND: To date, no treatment modality has been identified as more effective for oropharyngeal cancer (OPC), and no predictive factors are known to guide treatment decision for this disease. This retrospective study evaluates the differential effects of diverse treatment options for OPC according to patient risk profiles. PATIENTS AND METHODS: We considered two series of locally advanced squamous cell OPC patients treated with either surgery followed by radiotherapy (surgical series) or chemoradiation (CRT) with/without induction docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CRT series). Smoking habits, tumor p16 expression/human papillomavirus (HPV) status and T and N stage were analyzed to stratify the patients according to Ang's risk profile (low, intermediate and high risk). Overall survival (OS) and disease-free survival were calculated with the Kaplan-Meier method. RESULTS: Globally, 171 patients were considered, 56 in surgical and 115 in CRT series. Patients were stratified in low- (20% of surgical and CRT groups), intermediate- (23% and 41%) and high-risk (57% and 39%) groups. In the surgical series, 5-year OS was 54.5%, 46.9% and 40.0% in low, intermediate and high Ang's risk profiles, respectively, whereas in the CRT series those were 100%, 78.9% and 46.7%, respectively. In the multivariable analyses, adjusting for inhomogeneity between the treatment group, the CRT effect was significantly higher in the low- and intermediate-risk groups (P-value for the interaction treatment risk group = 0.034 in the OS analysis). CONCLUSIONS: In this retrospective analysis, low- and intermediate-risk OPC patients had a better survival when treated with CRT compared with open surgery followed by radiation therapy. These data suggest that different treatment approaches might be essential in determining outcome results.

Apoptosis: its role in pituitary development and neoplastic pituitary tissue.

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke's pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.

Pain and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

Self-contamination following removal of two personal protective equipment suits: a randomized, controlled, crossover simulation trial.

BACKGROUND: Healthcare personnel are often at high risk of contamination when participating in airway management and other aerosol-generating procedures. AIM: To explore the differences in self-contamination after removal of gown and coverall personal protective equipment (PPE) using an ultraviolet-fluorescent solution. METHODS: This prospective, randomized, controlled crossover trial was set in a third-level university health centre in Buenos Aires, Argentina between August and October 2020. The study included 60 anaesthesia personnel volunteers, and no participants were excluded from the study. A two-period/two-intervention design was chosen; each intervention comprised audio-guided placement of PPE, full-body spraying of fluorescent solution, audio-guided removal of PPE, and self-contamination assessment through ultraviolet light scanning. The primary outcome was the mean within-participant difference (any traces) between PPE suits. Statistical significance was tested using t-tests for paired data. The allocation ratio was 25/35 (gown followed by coverall/coverall followed by gown). FINDINGS: Self-contamination after removal of coveralls was greater than that after removal of gowns, with a mean within-participant difference of 11.45 traces (95% confidence interval 8.26-14.635; P<0.001). Significant differences were found for the number of self-contaminated body zones, small fluorescent traces and large fluorescent traces. Removal of a gown was associated with a markedly lower risk of self-contamination. CONCLUSIONS: Quick one-step removal of a gown and gloves may reduce self-contamination in the arm/hand area. Fluorescent solutions can help to identify self-contamination and compare outcomes between available PPE suits. Repeated training sessions and enhanced knowledge on self-contamination following removal of PPE are paramount. CLINICAL TRIAL REGISTRATION NUMBER: NCT04763304 (on ClinicalTrials.gov).

Time-resolved photoelectron spectroscopy using synchrotron radiation time structure.

Synchrotron radiation time structure is becoming a common tool for studying dynamic properties of materials. The main limitation is often the wide time domain the user would like to access with pump-probe experiments. In order to perform photoelectron spectroscopy experiments over time scales from milliseconds to picoseconds it is mandatory to measure the time at which each measured photoelectron was created. For this reason the usual CCD camera-based two-dimensional detection of electron energy analyzers has been replaced by a new delay-line detector adapted to the time structure of the SOLEIL synchrotron radiation source. The new two-dimensional delay-line detector has a time resolution of 5 ns and was installed on a Scienta SES 2002 electron energy analyzer. The first application has been to characterize the time of flight of the photoemitted electrons as a function of their kinetic energy and the selected pass energy. By repeating the experiment as a function of the available pass energy and of the kinetic energy, a complete characterization of the analyzer behaviour in the time domain has been obtained. Even for kinetic energies as low as 10 eV at 2 eV pass energy, the time spread of the detected electrons is lower than 140 ns. These results and the time structure of the SOLEIL filling modes assure the possibility of performing pump-probe photoelectron spectroscopy experiments with the time resolution given by the SOLEIL pulse width, the best performance of the beamline and of the experimental station.

Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia.

Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the database of a web-based survey registry developed by the Italian Fibromyalgia Network (IFINET). Tests of convergent validity showed that the FAS index and FIQ significantly correlated with each other (rho=0.608, p<0.0001), but there were also significant correlations between the FAS index and other clinical measures of disability, including the HAQ (rho=0.423, p<0.0001), anxiety (rho=0.138, p=0.0009), depression (rho=0.174, p<0.0001) and, especially, the number of comorbidities (rho=0.147, p=0.0004). The FAS index revealed a statistically significant difference between males and females (p=0.048), analysed using the Mann-Whitney U-test for all pair wise comparisons. The FAS index is a valid three-item instrument (pain, fatigue and sleep disturbances) that performs at least as well as the FIQ in FM patients, and is simpler to administer and score. Both questionnaires may be useful when screening FM patients, with the choice of the most appropriate instrument depending on the setting.

Ketoconazole Treatment Decreases the Viability of Immortalized Pituitary Cell Lines Associated with an Increased Expression of Apoptosis-Related Genes and Cell Cycle Inhibitors.

Ketoconazole, which was initially developed as an antifungal agent, is a potent inhibitor of adrenal steroidogenesis and has therefore been used in the management of Cushing's disease. Surprisingly, the reduction of cortisol levels during ketoconazole treatment is not accompanied by the expected elevation in plasma adrenocorticotrophic hormone (ACTH) at the loss of negative cortisol feedback from corticotrophic cells, suggesting a direct effect of ketoconazole on these cells. To characterize the direct effects of ketoconazole, we evaluated its in vitro effect on cell viability using the pituitary tumoural cell lines AtT-20 (which secretes ACTH), GH3 (which secretes growth hormone and prolactin) and αT3.1 (which secretes α-subunit) and we also determined the expression levels of genes involved in apoptosis and DNA replication by the quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also evaluated ACTH levels in AtT-20 cells during ketoconazole treatment. We observed a ketoconazole concentration-dependent decrease in pituitary cell viability and reduced ACTH levels in AtT-20 cells after removal of the drug. We also observed increased expression of cell death receptors (e.g. Fas, tumour necrosis factor receptor) and caspases (e.g., caspase-6, caspase-7, caspase-9), suggesting activation of the apoptosis pathway. In addition, we observed increased gene expression of the cell cycle inhibitors p21 and p27 in GH3 cells and increased expression of p21 in αT3.1 cells. In conclusion, our findings suggest that ketoconazole significantly reduces cell viability in a concentration-dependent manner in pituitary tumour cell lines and is associated with an increase in apoptosis- and cell cycle regulation-related gene expression.

Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome.

PURPOSE: To determine (1) the appropriate omeprazole (Prilosec) dose required for adequate acid suppression in asthmatics with gastroesophageal reflux, (2) whether aggressive acid suppressive therapy of gastroesophageal reflux improves asthma outcome in asthmatics with gastroesophageal reflux, (3) the time course of asthma improvement, and (4) demographic, esophageal, or pulmonary predictors of a positive asthma response to antireflux therapy. PATIENTS AND METHODS: Thirty nonsmoking adult asthmatics with gastroesophageal reflux (asthma defined by American Thoracic Society criteria and reflux defined by symptoms and abnormal 24-hour esophageal pH testing) were recruited from the outpatient clinics of a 900-bed university hospital. Patients underwent baseline studies including a demographic questionnaire, esophageal manometry, dual-probe 24-hour esophageal pH test, barium esophogram, and pulmonary spirometry. During the 4-week pretherapy phase, patients recorded reflux and asthma symptom scores and peak expiratory flow rates (PEFs) upon awakening, 1 hour after dinner, and at bedtime. Patients began 20 mg/d omeprazole, and the dose was titrated until acid suppression was documented by 24-hour pH test. Patients remained on this acid suppressive dose for 3 months. Responders were identified by a priori definitions: asthma symptom reduction by >20% and/or PEF increase by >20%. Asthma symptom scores, PEF's baseline and posttherapy pulmonary spirometry were analyzed. RESULTS: Twenty-two (73%) patients were asthma symptom and /or PEF responders: 20 (67%) were asthma symptom responders, and 6 (20%) were PEF responders. Responders reduced their asthma symptoms by 57% (P<0.001), improved their morning and night PEFs by 8% and 9% (both P <0.005), and had improvement in forced expiratory volume at 1 second (P <0.02), mean forced expiratory flow during the middle half (25% to 75%) of the forced vital capacity (P <0.04), and peak expiratory flow (P <0.01) with acid suppressive therapy. Mean acid suppressive dose of omeprazole was 27 mg/d (+/-2.2) with 27% (8) patients requiring more than 20 mg/d. The presence of regurgitation or excessive proximal esophageal reflux predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%. CONCLUSIONS: Acid suppressive therapy with omeprazole improves asthma symptoms and/or PEFs by >20% and improves pulmonary function in 73% of asthmatics with gastroesophageal reflux after 3 months of acid suppressive therapy. Many asthmatics (27%) required >20 mg/d of omeprazole to suppress acid. The presence of regurgitation and/or excessive proximal esophageal reflux predicts a positive asthma outcome.

24-h esophageal pH testing in asthmatics: respiratory symptom correlation with esophageal acid events.

BACKGROUND: Gastroesophageal reflux (GER) may be a trigger for asthma and may be clinically silent. Twenty-four-hour esophageal pH testing accurately diagnoses GER in asthmatics. There are no reports correlating respiratory symptoms with esophageal acid events. This study examines the prevalence and severity of GER in asthmatics with and without reflux symptoms and examines respiratory symptom correlation with esophageal acid. METHODS: All esophageal manometry and 24-h esophageal pH tests performed were reviewed in asthmatics who met entrance criteria from July 1, 1989, through November 1, 1994. GER was present if esophageal pH tests were abnormal. Results of esophageal tests were compared for asthmatics with reflux symptoms and GER and asthmatics without reflux symptoms and GER. Respiratory symptoms correlated with esophageal acid events if the esophageal pH was < 4 simultaneously with the respiratory event or within 5 min before its onset. RESULTS: Of 199 asthmatics who qualified for analysis, 164 (82%) had reflux symptoms. The results of 24-h esophageal pH tests were abnormal in 118 of 164 asthmatics with reflux symptoms (72%), compared with 10 of 35 asthmatics without reflux symptoms (29%). Among asthmatics with GER, 119 of 151 respiratory symptoms (78.8%) were associated with esophageal acid. Seventy-six of 84 reported coughs (90.5%) were associated with esophageal acid. Theophylline did not alter esophageal parameters. CONCLUSIONS: There is a strong correlation between esophageal acid events and respiratory symptoms in asthmatics with GER. Respiratory symptom correlation with esophageal acid events further supports that GER may be a trigger for asthma.

Autonomic regulation in asthmatics with gastroesophageal reflux.

STUDY OBJECTIVE: To study the role of autonomic regulation in asthmatics with gastroesophageal reflux (GER). DESIGN: Prospective study. SETTING: Autonomic function laboratory of a 908-bed university hospital. PARTICIPANTS: Fifteen nonsmoking asthmatics with GER (six men, nine women; average age, 36 years). INTERVENTIONS: Subjects were connected to an ECG monitor. BP was measured by sphygmomanometer at set intervals. After a resting period, each subject had heart rate and BP monitored during an 80 degrees passive tilt, Valsalva maneuver, quiet and deep breathing, handgrip, and an echo stress test of cortical arousal. Each autonomic function test was analyzed and defined as normal, hypervagal, hyperadrenergic, or mixed (a combination of hypervagal and hyperadrenergic responses) as compared with 23 age-matched normal control subjects from our laboratory (14 men, 9 women; average age, 35 years) and published normal control values. Each subject had an overall response score that was determined by the results of the tilt, Valsalva maneuver, and deep breathing maneuvers. RESULTS: All asthmatics with reflux had at least one autonomic function test display a hypervagal response. Overall response scores show that eight of 15 asthmatics with GER had an overall hypervagal response, and seven had a mixed response. Of the seven asthmatics with GER who had a mixed response score, two had a hypervagal predominant response. CONCLUSIONS: Asthmatics with GER have evidence of autonomic dysfunction. Heightened vagal tone may be partially responsible for the heightened airway responsiveness to esophageal acidification in asthmatics with reflux.

Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor?

STUDY OBJECTIVE: To evaluate the role of microaspiration in gastroesophageal reflux-induced bronchoconstriction. DESIGN: Prospective study blinded to the subject. SETTING: Outpatient laboratory of a 908-bed university hospital. PARTICIPANTS: Thirty nonsmoking adults divided into two groups: asthmatics with reflux (AR), 20; and subjects with gastroesophageal reflux (R), 10. INTERVENTIONS: Dual esophageal pH probe placed. Esophageal infusions of normal saline solution, 0.1N hydrochloric acid, then normal saline solution, each lasting 18 min, were followed by two 20-min recovery periods. Subjects remained in the supine position throughout. Spirometry and specific airway resistance (SRaw) performed at baseline, after each esophageal infusion and recovery period. Proximal esophageal acid exposure, a requirement for microaspiration, was assessed by the proximal esophageal pH probe. RESULTS: Peak expiratory flow rate (PEF) decreased with esophageal acid in the AR group and did not recover immediately despite esophageal acid clearance with a significant main effect of subject groups (p < 0.021) by repeated measures analysis of covariance. This decrease in PEF was not associated with the presence of proximal esophageal acid exposure (p = 0.618). Specific airway resistance increased in the AR group with esophageal acid and worsened despite acid clearance, especially during the second recovery phase, with a significant phase (p < 0.009) and group by treatment effect (p < 0.009). The presence of proximal esophageal acid exposure was not associated with this deterioration in SRaw (p = 1.0). CONCLUSIONS: Esophageal acid infusions given in the supine position caused a decrease in PEF and an increase in SRaw in the asthma with reflux group, which did not improve despite acid clearance. These responses were not dependent on proximal esophageal acid exposure. Also, SRaw continued to worsen during the recovery phase in the AR group, which may represent a delayed bronchoconstrictor effect. These data suggest that microaspiration does not play a significant role in esophageal acid-induced bronchoconstriction.

Role of kinins and nitric oxide on the rabbit arthritis induced by Bothrops jararaca venom.

The effects of the nitric oxide synthase inhibitor N(omega)Nitro-L-arginine-methyl ester (L-NAME) and of the bradykinin B(2) receptor antagonist HOE 140 were evaluated in the inflammatory reaction induced by Bothrops jararaca venom (BjV) in New Zealand White rabbits. Arthritis was induced by injecting 0.5 ml of a sterile solution of BjV (1-64 microg/ml) into the knee intraarticular cavity. The contralateral joint was injected with bovine serum albumin (BSA) diluted in sterile saline. At selected times thereafter (4, 24 and 48 h), the vascular permeability and the leukocyte influx in both the synovial fluid and synovium were evaluated. BjV caused a dose-dependent increase in both leukocyte influx and protein extravasation which reached a maximal response at 16 microg. Bothrops jararaca venom also induced the increase in the leukocyte accumulation in the synovium and in the concentration of both NO(2)/NO(3) in the synovial fluid. Chronic administration of L-NAME (20 mg/kg/day in the drinking water for 2 weeks) markedly reduced the leukocyte accumulation (90%), protein leakage (44%), and NO(2)/NO(3) (50%) levels in the synovial fluid, measured at the 4th h. Hoe 140, given i.v. (0.3 mg/kg, 30 min before) also reduced leukocyte accumulation (75%), protein leakage (48%), and NO(2)/NO(3) (79%) levels in the synovial fluid, measured at the 4th h. Similar results were obtained with acute administration of L-NAME (30 mg/kg, i.v., 30 min before). These results indicate that arthritis induced by BjV is triggered by kinin formation and that the increase in both vascular permeability and leukocyte accumulation is modulated by NO release.

Mucosal malignant melanoma of head and neck: forty-eight cases treated at Istituto Nazionale Tumori of Milan.

A series of 48 cases of malignant mucosal melanomas treated at the Milan Cancer Institute from 1975 to 1990 is retrospectively reviewed. There were 34 males and 14 females, and their ages ranged from 21 to 79 years (mean, 58). The site of origin of the tumor was the nasal cavity in 26 cases, the oral cavity in 15, larynx in two, lip mucosa in two, pharynx in two and upper esophagus in one. At presentation, the neoplasm was limited to the primary site in 60.4% of the patients. Most patients (34) were treated with surgery alone. Nine were treated with surgery combined with chemo- and/or radiotherapy and five with radiotherapy combined with chemotherapy and/or immunotherapy. Only when surgery was part of the treatment (42 of 48 cases) the patients were rendered disease free, but no further relapse of disease was documented in only five of these patients. The observed 2- and 5-year survival rate of the entire group was 45% and 21%, respectively. The 4-year disease-free survival rate was 7%. The median interval between therapy and the first relapse was 8.5 months (range, 1-66). In 44% of the patients the first recurrence of the tumor was at the primary site.

Multiloculated peritoneal inclusion cysts with splenic involvement: a case report.

Multilocular peritoneal inclusion cysts (MPICs) are most commonly found in women of reproductive years and involve the abdomen, pelvis, and retroperitoneum. It is commonly thought that these cysts are due to an inflammatory reaction. Patients usually present with chronic abdominal or pelvic pain and are diagnosed by ultrasound or CT scan. Although there are experimental medical treatment options surgical excision remains the current recommended primary therapy for symptomatic disease. The following case describes a pregnant female with rare MPIC involving the spleen and peritoneum. Biological behavior of MPIC and current therapy options are also discussed.

Primary mucosal malignant melanoma of the larynx: case report and review of the literature.

We report a case of primary melanoma of the larynx in a patient who died of disseminated disease 13 months later. It is a rare malignant tumor in the head and neck, accounting for 0.4-10% of all melanomas of this site. Histologically, the presence of in situ changes within the laryngeal mucosa strongly supports our diagnosis of primary melanoma of the larynx.

Malignant fibrous histiocytoma of the maxillary sinus. A case report.

We report a case of malignant fibrous histiocytoma of the left maxillary sinus in a 30 year-old man. The major problem encountered was the histological diagnosis of the first biopsy, which showed a non specific fasciculated, myxoid, alveolar pattern suggestive of a mesenchymal malignancy, thus preventing the correct diagnosis that became possible only when the surgical specimen was available.