Outcome for sinonasal malignancies: a population-based survey.

PURPOSE: Sinonasal malignancies (SNM) represent a rare and complex group of cancers that includes a wide range of histopathological subtypes. Data from population-based cohorts are scarce but warranted as a basis for randomized controlled treatment trials (RCTs). Our aim was to assess overall and histology subset-specific outcomes for SNM patients treated at a tertiary referral centre. METHODS: A retrospective, population-based, consecutive cohort of patients with SNMs diagnosed from 2001 through 2019 was examined. Outcome was analysed in relation to age, gender, site, stage, histopathology, and treatment. RESULTS: Two-hundred and twenty-six patients were identified, whereof 61% presented with stage IV disease. 80% completed treatment with curative intent, which comprised surgery with neoadjuvant (29%) or adjuvant (37%) radiotherapy, monotherapy with surgery (22%), definitive chemoradiotherapy (7%), or radiotherapy (5%). Median follow-up was 106 months. The 5- and 10-year overall survival rates were 57% and 35%, respectively. Median overall survival was 76 months (esthesioneuroblastoma: 147 months; adenocarcinoma: 117; salivary carcinoma: 88; mucosal melanoma: 69; squamous cell carcinoma: 51, undifferentiated carcinoma: 42; neuroendocrine carcinoma: 9; and NUT-carcinoma 5). The 5- and 10-year disease-free survival rates were 63% and 54%, respectively, and disease-specific survival 83% and 66%. Increasing age, stage IVB, melanoma histopathology, and treatment with definitive chemoradiotherapy emerged as significant independent prognostic risk factors for disease-specific mortality (p ≤ 0.001). CONCLUSION: The results indicate a seemingly good outcome in comparison to previous reports, particularly for mucosal melanoma, adenocarcinoma, and undifferentiated carcinoma. The study provides additional background for future RCTs focusing on histology subset-specific treatment for SNM.

The macromolecular crystallography beamline I911-3 at the MAX IV laboratory.

The macromolecular crystallography beamline I911-3, part of the Cassiopeia/I911 suite of beamlines, is based on a superconducting wiggler at the MAX II ring of the MAX IV Laboratory in Lund, Sweden. The beamline is energy-tunable within a range between 6 and 18 keV. I911-3 opened for users in 2005. In 2010-2011 the experimental station was completely rebuilt and refurbished such that it has become a state-of-the-art experimental station with better possibilities for rapid throughput, crystal screening and work with smaller samples. This paper describes the complete I911-3 beamline and how it is embedded in the Cassiopeia suite of beamlines.

Outcomes of external and endonasal dacryocystorhinostomy according to a modified Lacrimal Symptom Questionnaire (Lac-Q).

Background: Nasolacrimal duct obstruction is usually treated using endoscopic or external dacryocystorhinostomy (DCR). The anatomic outcomes of both the endoscopic and external approaches are considered excellent. However, anatomic success does not translate into patient satisfaction. The current study assessed pre- and postoperative lacrimal problems using the symptom-based Lacrimal Symptom Questionnaire (Lac-Q) and investigated patient satisfaction depending on the choice of surgical technique. Methods: A total of 112 eligible patients with lacrimal problems treated using external or endonasal DCR at the ophthalmology and ear, nose, and throat clinics at Skane University Hospital, Scania, Sweden, over a four-year period, were enrolled in this retrospective study. Patients were considered eligible if they experienced preoperative epiphora and had lacrimal duct stenosis. They were offered treatment using either external or endonasal DCR and were allowed to freely choose the technique. Exclusion criteria consisted of previous ipsilateral DCR, congenital NLDO, age < 18 years, presence of cancer, previous orbital trauma, or noncompliance with postoperative follow-up. After surgery, the patients were sent the Lac-Q to evaluate their lacrimal symptoms pre- and postoperatively. Complementary questions were added pertaining to the operative scar and the patients' overall satisfaction with the operation. Results: In total, 67 (60%) patients with ages ranging from 18 to 88 years completed the questionnaire, 33 (49%) of whom underwent external DCR and 34 (51%) endonasal DCR. Of the 67 respondents, 51 (76%) were women and 16 (24%) were men. Patients scored preoperative lacrimal problems highly on the Lac-Q, reporting both symptomatic and social problems due to epiphora. Following surgery, the group that underwent external DCR remained home from work for 2 - 14 days (median, 3.5 days). However, 17 (52%) were retired. After the endonasal DCR, the patients remained home for 0 - 7 days (median, 2 days). Most patients were satisfied after DCR surgery, with both techniques significantly improving total, lacrimal symptom, and social impact scores (all P < 0.001). No differences in postoperative satisfaction were observed between the external DCR and endonasal DCR groups (P > 0.05). A small number of patients expressed scar-related concerns after external DCR. Conclusions: The patients perceived lacrimal problems as a significant symptomatic and social burden. Postoperative satisfaction and symptom relief were good regardless of the surgical approach. Further prospective studies assessing patient satisfaction and its correlation with anatomical and functional success rates after external and endonasal DCR could provide robust, practical, real-world implications.

Human papillomavirus (HPV), DNA aberrations and cell cycle progression in anal squamous cell carcinoma patients.

UNLABELLED: Human papillomavirus (HPV) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated. PATIENTS AND METHODS: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients' biopsies. The HPV typing was conducted by pyrosequencing. Cell cycle and DNA content were analysed by cytometry. RESULTS: Ninety percent of the carcinoma biopsies carried high-risk oncogenic HPV in their malignant cells. Eighty-one percent of these demonstrated a single infection with HPV16, 18 or 33 and 19% were double infected with HPV16 and HPV18. Accumulations of viral genes were seen at the necrotic area of the tumours. The HPV genome in the tumour cell influenced significantly the host cell cycle progression, but not DNA aberrations. Within these patients, HPVstatus in the malignant cells was not found to be associated with patient survival time. CONCLUSION: High-risk oncogenic HPV may play an important role in the initiation of host cell proliferation in anal squamous cell carcinoma. However, infection with HPV may not have any direct influence itself on the clinical outcome of these patients considering the treatments currently available.

Quality of Life and Work Capacity Are Unrelated to Approach or Complications After Pituitary Surgery.

OBJECTIVE: Endoscopic pituitary surgery has shown favorable clinical outcomes. Less is known about the impact of surgical approaches on health-related quality of life (HRQoL) and work capacity. The present study was undertaken to compare transsphenoidal microscope-assisted surgery with endoscopic transsphenoidal surgery regarding preoperative and surgical factors for the final outcome of HRQoL and work capacity. METHODS: In a retrospective study of patients operated on for pituitary adenoma, outcome was compared between those operated on before and after transition with endoscopic surgery at our department. Data were gathered via patient questionnaires and patients' files. RESULTS: After exclusions, 235 patients were included (99 microsurgical and 136 endoscopic). Frequency of complications was similar but tumor size was significantly larger in the endoscopic group. Complications did not affect HRQoL or work capacity. HRQoL was not affected by surgical technique but showed an overall trend toward lower values compared with the general population. Sick leave, return to work frequency, and permanent sick leave were not affected by surgical technique. Female gender was a factor for lower ratings in all outcome variables. CONCLUSIONS: Surgical technique does not influence HRQoL or work capacity in this long-term follow-up although both are decreased compared with the general population. We conclude that fully endoscopic pituitary surgery, despite including larger tumors, bears the same risk for complications as microsurgery. In addition, females have a greater risk for decrease in HRQoL and work ability. This factor should be taken into account when informing patients and appreciating expectations of treatment.

Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols.

PURPOSE: The primary therapy in epidermoid anal cancer is radiotherapy, generally with chemotherapy. The use of neoadjuvant chemotherapy has been infrequently reported in the literature. This study presents results from a large population-based series and provides comparisons between different treatments. METHODS AND MATERIALS: Between 1985 and 2000, 308 patients with invasive epidermoid anal cancer were diagnosed in the Stockholm Health Care Region. Treatment was given according to defined protocols. External beam radiotherapy alone or with concomitant bleomycin and neoadjuvant chemotherapy followed by radiotherapy alone were the primary treatments. Radical surgery was reserved for poor responders or recurrences. Data were reviewed with regard to treatment, outcome, and prognostic factors. RESULTS: Among the 276 patients (90%) treated with curative intent, 264 (96%) received treatment in accordance with the protocols. The overall 5-year survival rate was 68%. Among the 142 patients with locally advanced tumors (T > or =4 cm or N+), patients treated with neoadjuvant platinum-based chemotherapy (n = 91) had significantly better complete response rates compared with patients treated with radiotherapy with or without bleomycin (n = 51) (92% vs. 76%, p < 0.01). A significantly increased overall 5-year survival rate was also found among patients receiving neoadjuvant therapy (63% vs. 44%, p < 0.05). CONCLUSION: Structured treatment protocols result in favorable outcome on a population level. The results further suggest a significant therapeutic gain from including neoadjuvant chemotherapy in the treatment of locally advanced anal cancer.

Loss of size-selectivity at histamine-induced exudation of plasma proteins in atopic nasal airways.

Plasma proteins occur in the airway lumen in inflammatory airway diseases. This study tests the hypothesis that airway microvascular-epithelial exudation of plasma proteins, as induced by a non-injurious inflammatory mediator, is characterized by loss of size-selectivity. Using a nasal pool-device, the nasal mucosa of 10 allergic individuals, without current disease, was sequentially exposed to saline and histamine (40 and 400 microg ml(-1)). Nasal lavage fluid and blood-levels of albumin (69 kD) and alpha2-macroglobulin (720 kD) were determined. Histamine produced concentration-dependent exudation of albumin and alpha2-macroglobulin. The albumin/alpha2-macroglobulin concentration ratio of the saline lavage fluid (baseline) was 40+/-19. However, at the histamine challenges the ratios were 25+/-3 and 22+/-2, respectively, which did not differ from that of circulating plasma (22+/-2). We conclude that there is minor and size-selective luminal entry of plasma proteins at baseline. However, at concentration-dependent exudative responses to histamine, plasma proteins enter the airway lumen without being sieved. These data indicate that inflammatory stimulus-induced extravasation, lamina propria distribution and paracellular epithelial passage of plasma occur with minimal size-selectivity. Inferentially, the full immunological capacity of plasma proteins may readily be made available at the surface of human intact airway mucosa.

Effects of loratadine on red wine-induced symptoms and signs of rhinitis.

OBJECTIVE: Intake of red wine may produce nasal symptoms. Little is known about the pathophysiology and pharmacology of this condition. The aim of this study was to examine whether nasal symptoms produced by red wine are reproducible, associated with mucinous secretion or plasma exudation and affected by antihistamine treatment. MATERIAL AND METHODS: Twenty-eight subjects with a history of nasal symptoms associated with red wine intake received oral challenges with red wine and raspberry juice in a crossover design. Nasal symptoms and peak inspiratory flow (PIF) were assessed. Nasal lavages were performed and levels of fucose and alpha2-macroglobulin were determined as indices of mucinous secretion and plasma exudation, respectively. Twelve responders (according to preset criteria) were re-challenged 1 h after loratadine (10 mg) treatment, in a double-blind, placebo-controlled crossover design. Nasal symptoms and PIF were reassessed. Nasal lavages were performed and levels of fucose were redetermined. RESULTS: Red wine intake produced nasal symptoms (p < 0.05) and decreased nasal PIF (p < 0.01-0.05). A total of 54% of subjects were categorized as responders, and in this group red wine produced a slight increase in lavage fluid levels of fucose (p < 0.05). In contrast, levels of alpha2-macroglobulin were unaffected. A total of 83% of responders developed symptoms at re-challenge. Loratadine reduced post-challenge nasal secretion (p < 0.05). Also, red wine failed to reduce nasal PIF in patients receiving loratadine. CONCLUSION: Nasal symptoms associated with red wine intake can be reproduced by oral red wine challenges. This symptomatology may be associated with mucinous secretion, but not with plasma exudation. Loratadine may partially reduce nasal symptoms associated with intake of red wine.

The Hume-Rothery Compound Mn8 Ga27.4 Zn13.6 : Separated Zn13 -Clusters Interspersed in a Primitive Cubic Host Lattice.

Separated Zn13 cluster entities unexpectedly occur in the solid-state structure of Mn8 Ga27.4 Zn13.6 (the central building block is shown). They correspond to centered cuboctahedra, that is, small volumes of face-centered cubic metal. The intriguing segregation of Ga and Zn atoms in Mn8 Ga27.4 Zn13.6 was verfied by Rietveld refinement of neutron powder diffraction data.

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines.

OBJECTIVE: To evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines. MATERIAL: Clinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 54-64Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin) according to different protocols, stratified by tumor stage. RESULTS: High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation. CONCLUSIONS: Good treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors.

Efficacy of pegylated liposomal doxorubicin in patients with advanced hepatocellular carcinoma.

Presently, no effective systemic therapy is available for patients with advanced hepatocellular carcinoma (aHCC). We sought to determine whether systemic treatment with pegylated liposomal doxorubicin (PLD) would yield a response rate of 20% in chemotherapy naïve patients with aHCC. The study was designed according to the phase II Gehan two-step procedure with a precision of 10%. Enrollment criteria included histological diagnosis and radiological documentation of unresectable/metastatic HCC, WHO PS 0-2, relatively normal organ function, life expectancy greater than three months, lack of cardiomyopathy and active cardiac disease NYHA > or = II. PLD (40 mg/m(2) IV 1h-infusion) was administered on d1 q 4 wk and response to treatment was evaluated radiologically every 3rd cycle (WHO-criteria). Secondary endpoints included overall (OS) and progression free survival (PFS) and registration of toxicity. The median number of administered PLD cycles was 3. The best radiological response among the first 14 patients was 1 PR, 5 SD, 3 PD, and 6 NE due to progressive disease clinically (Step 1). The 15th patient did not respond to the PLD-therapy and the study was closed for accrual as the pre-planned analysis could be executed (Step 2). A response rate > or = 20% could be ruled out. The median PFS and OS survival was 82 days and 130 days, respectively. Adverse events were generally mild in the subgroup of patients without signs of moderate hepatic failure at base line. Patients with WHO PS 2, liver tumour involvement >50%, bilirubin > or = 34 micromol/L, albumin <33 g/L, and/or Child Pugh B were unlikely to survive >90 days. PLD can be delivered safely in patients with aHCC and no signs of moderate hepatic failure. The therapy resulted, however, in few responses or cases of disease stabilization and has thus very limited activity in aHCC. Future studies on systemic chemotherapy should focus on patients without moderate hepatic failure, with WHO PS <2, and with liver tumour involvement <50%.

XAFS experiments at beamline I811, MAX-lab synchrotron source, Sweden.

A description of a new facility for X-ray absorption spectroscopy at the materials science beamline, I811, at MAX-lab synchrotron source, Lund, Sweden, is given. The beamline is based on a superconducting multipole wiggler source inserted in a straight section of the 1.5 GeV MAX-II ring. X-rays in the energy range 2.4-12 keV are extracted by a standard optical scheme consisting of a vertical collimating first mirror, double-crystal monochromator, and a second vertically focusing mirror. The second monochromator crystal provides sagittal focusing. The total flux impinging on the sample at 9 keV is 5 x 10(11) photons s(-1), for a minimum beam spot of 0.5 mm x 0.5 mm. The beamline has facilities for experiments in transmission, fluorescence and total-electron-yield mode and experiments have been performed by international research groups on a wide range of materials, such as dilute systems with metal concentrations below 10 p.p.m.

Azinyl sulfides. LXXXI.(1)14-Phenyl-7-thiapyrano[2,3-c;6,5-c']diquinoline-14-carbonitrile.

The molecules of the title compound, C26H15N3S, have a pentacyclic ring system which is almost planar, with the central ring in a flattened boat conformation. The folding angle between the two quinoline rings is 6.75 (7) degrees. The 14-phenyl substituent is in a quasi-axial conformation, while the 14-cyano substituent is in a quasi-equatorial conformation with respect to the thiopyran ring. The S...C-C(phenyl) and S...C-C(CN) angles are 116.8 (2) and 129.3 (2) degrees, respectively. The plane of the phenyl group is nearly coplanar with the plane bisecting the dihedral angle of the pentacyclic ring system.

Long-term symptoms after external beam radiation therapy for prostate cancer with three or four fields.

The aim of this study was to investigate whether external beam radiation treatment with three or four fields affects the risk of long-term distressful symptoms. The study included 145 patients who had been treated in Stockholm from 1993 to 1996 for localized prostate cancer. Bowel, urinary and sexual function as well as symptom-induced distress were assessed by means of a postal questionnaire 29-59 months after therapy. Among patients treated with a multileaf collimator, defecation urgency, diarrhoea and loose stools were more common after four fields than after three fields, but faecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common (although not statistically significantly so). Among bowel symptoms, the strongest association with gastrointestinal distress was found for faecal leakage. Three fields without a multileaf collimator entailed a higher risk of defecation urgency than three fields with a multileaf collimator. We conclude that the choice of three or four fields may imply a contrasting risk scenario for defecation urgency or diarrhoea in comparison with faecal leakage.

Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid.

BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 microg produced greater improvement than mometasone furoate 200 microg for nasal PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.