An exploration of testicular cancer survivors' experience of ejaculatory dysfunction following retroperitoneal lymph node dissection-a sub-study of the PREPARE clinical trial.

PURPOSE: Ejaculatory dysfunction secondary to retrograde ejaculation or anejaculation is a complication of retroperitoneal lymph node dissection (RPLND) for survivors of testicular cancer. We explored survivors' experiences of ejaculatory dysfunction following RPLND. METHODS: In a sub-study of a single-arm phase 2 clinical trial (ACTRN12622000537752/12622000542796), participants reporting ejaculatory dysfunction ≥ 6 months following RPLND were invited to complete semi-structured interviews. Purposive sampling was used. Interviews continued until thematic saturation occurred, and codebook thematic analysis of interviews was performed. RESULTS: Of 58 individuals recruited to the trial, 33 (57%) reported ejaculatory dysfunction. Of these, 32 (97%) agreed to interview and 15 participated. Participants interviewed had median age 34 years (range 24-66), 12 (80%) in a long-term relationship with median time from surgery 36 months (range 11-112). Three overarching themes were identified. The first reflected the value of RPLND despite ejaculatory dysfunction. The second illuminated the impact(s) of ejaculatory dysfunction closely mapped to life stage, with flow-on impacts to fertility, sex, psychological wellbeing and communication. The third reflected information needs. Fertility was a substantial source of concern for some participants. Ejaculatory dysfunction had no effect on sex for some, whilst for others, sex was less pleasurable. Some reported benefits. Few reported ejaculatory dysfunction challenged masculinity, confidence, or self-esteem. CONCLUSIONS: Future research should examine interventions to reduce distress related to fertility, challenged masculinity and body image. IMPLICATIONS FOR CANCER SURVIVORS: Whilst most participants considered ejaculatory dysfunction to have little impact on their sexual function and relationships, some reported significant difficulties varying by life stage and relationship status.

Excisional endometriosis surgery with hysterectomy and bilateral salpingo-oophorectomy versus excisional endometriosis surgery alone for pelvic pain associated with deep endometriosis.

Background: There is no agreed consensus on the optimal surgical treatment for pain associated with endometriosis. Objectives: To compare improvement in symptoms and quality-of-life in patients undergoing excisional endometriosis surgery (EES) versus EES with hysterectomy and bilateral salpingo-oophorectomy (EES-HBSO). Methods: This study evaluated patients undergoing EES and EES-HBSO at a single endometriosis centre between 2009 and 2019. Data was obtained from the British Society for Gynaecological Endoscopy database. Adenomyosis was assessed by blinded re-analysis of imaging and/or histology data. Main outcome measures: Pain scores (numeric rating scale 0-10) and quality-of-life scores (EQ-VAS) before and after EES and EES-HBSO. Results: We included 120 patients undergoing EES and 100 patients undergoing EES-HBSO. After controlling for baseline characteristics and the presence of adenomyosis, there was greater post-op improvement in non-cyclical pelvic pain amongst patients undergoing EES-HBSO compared to EES alone.The baseline pain scores had improved in the EES-HBSO cohort by 2.106/10 at 6 months (95%CI 0.469-3.742, p=0.012), 2.642/10 at 12 months (95%CI 0.871-4.413, p=0.004), and 2.548/10 at 24 months (95%CI 0.681-4.414, p=0.008), when compared to the EES group. Greater improvement amongst EES-HBSO patients was also seen for dyspareunia, non-cyclical dyschaezia and bladder pain. Patients undergoing EES-HBSO had greater improvement in EQ-VAS, although this was no longer statistically significant after controlling for adenomyosis. Conclusion: EES-HBSO appears to provide greater benefit than EES alone for symptoms including non-cyclical pelvic pain as well as for quality-of-life. Further research is required to determine which patients benefit the most from EES-HBSO, and whether removal of the ovaries, uterus or both is the key to this additional benefit in symptom control.

Impact of the COVID-19 pandemic on surgery for severe endometriosis in the UK: a national database study.

Background: The COVID-19 pandemic has had a significant effect on healthcare services, particularly affecting patients who suffer from chronic conditions. However, the pandemic's effect on endometriosis surgery is not yet known. Objectives: To determine the impact of the COVID-19 pandemic on surgery for severe endometriosis in the UK at a national, regional and centre-level. Materials and Methods: The British Society for Gynaecological Endoscopy (BSGE) collects data nationally on all operations for severe endometriosis which involve dissection of the pararectal space. Annual audits of this database were obtained from the BSGE. Publicly available data on COVID-19 cases and population were obtained from the UK Office for National Statistics. Main outcome measures: Numbers of annual BSGE-registered endometriosis operations. Results: A total of 8204 operations were performed. The number of operations decreased by 49.4% between 2019 and 2020 and then increased in 2021, but remained 10.5% below average pre-pandemic levels, indicating at least 980 missed operations between 2019-2020. Median operations per centre decreased by 51.0% in 2020 (IQR 29.4% - 75.0%) and increased in 2021 but remained 33% below pre-pandemic levels. There was no change in the type of surgery performed. All 11 administrative regions of Great Britain had reduced numbers of operations in 2020 compared with the average for 2017-2019, with a median 44.2% decrease (range 13.3% - 67.5%). Regional reduction in operations was correlated with COVID-19 infection rates (r=0.54, 95% CI of r 0.022 - 1.00, p=0.043). Conclusion: The number of operations performed annually in the UK for severe endometriosis fell dramatically during the COVID-19 pandemic and is yet to normalise. What's new?: This study shows the dramatic effect that the COVID-19 pandemic has had on UK services for endometriosis surgery, which may continue to affect patients and clinicians for a considerable time to come.

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma.

BACKGROUND: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. METHODS: We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan-Meier method and compared by the Log Rank test. RESULTS: Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). CONCLUSION: Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma.

Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods: From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

Towards a global cancer knowledge network: dissecting the current international cancer genomic sequencing landscape.

BACKGROUND: While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community. METHODS: A multi-item survey was conducted assessing demographics, clinical data collection, genomic platforms, privacy/ethics concerns, funding sources and data sharing barriers for sequencing initiatives globally. Additionally, respondents were asked as to provide the primary intent of their initiative (clinical diagnostic, research or combination). RESULTS: Of 107 initiatives invited to participate, 59 responded (response rate = 55%). Whole exome sequencing (P = 0.03) and whole genome sequencing (P = 0.01) were utilized less frequently in clinical diagnostic than in research initiatives. Procedures to identify cancer-specific variants were heterogeneous, with bioinformatics pipelines employing different mutation calling/variant annotation algorithms. Measurement of treatment efficacy varied amongst initiatives, with time on treatment (57%) and RECIST (53%) being the most common; however, other parameters were also employed. Whilst 72% of initiatives indicated data sharing, its scope varied, with a number of restrictions in place (e.g. transfer of raw data). The largest perceived barriers to data harmonization were the lack of financial support (P < 0.01) and bioinformatics concerns (e.g. lack of interoperability) (P = 0.02). Capturing clinical data was more likely to be perceived as a barrier to data sharing by larger initiatives than by smaller initiatives (P = 0.01). CONCLUSIONS: These results identify the main barriers, as perceived by the cancer sequencing community, to effective sharing of cancer genomic and clinical data. They highlight the need for greater harmonization of technical, ethical and data capture processes in cancer sample sequencing worldwide, in order to support effective and responsible data sharing for the benefit of patients.

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma.

BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.

High-dose chemotherapy with autologous stem cell transplantation in relapsed or refractory germ cell tumours: outcomes and prognostic variables in a case series of 17 patients.

BACKGROUND: Optimal therapy for men relapsing after initial chemotherapy for germ cell tumours (GCT) is poorly defined. Both conventional dose salvage regimens and high-dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) have been utilised. AIMS: To examine patients who received HDCT-ASCT for relapsed GCT within a single Australian centre. METHODS: Records between 2000 and 2012 were analysed for baseline characteristics, treatment-related toxicity and survival. Prognosis at the time of HDCT-ASCT was classified according to the International Prognostic Factors Study Group (IPFSG). RESULTS: Seventeen patients received HDCT-ASCT, median age 34 (21-46), with 41% having primary refractory disease and 53% with high/very high risk disease by IPFSG. The most common regimen utilised was paclitaxel/ifosfamide followed by high-dose carboplatin/etoposide (TI-CE; n = 12). The median duration of grade 4 (G4) neutropenia was 11 days (range 9-17) with febrile neutropenia in 90% resulting in four intensive care unit admissions (8%). Median duration of G4 thrombocytopenia was 10 days (range 8-19) requiring a median of two pooled platelets bags (range 0-33) per episode. Transplant-related mortality occurred in one patient (veno-occlusive disease). Twenty-seven per cent of HDCT-ASCT cycles were associated with grade 3 mucositis (median total parenteral nutrition days = 5 (0-23)). Two-year progression-free survival (PFS) and overall survival (OS) rates were 59% and 71%. Patients who received HDCT-ASCT as second or subsequent relapse fared worse than those treated with HDCT-ASCT at first relapse (hazard ratio 0.23 (95% confidence interval: 0.04, 1.37; P-value 0.09). Three-year OS for those who received TI-CE at first relapse was 90%. CONCLUSIONS: HDCT-ASCT for relapsed GCT is effective with acceptable toxicity. There was encouraging PFS/OS, particularly in a poor-prognosis cohort.

Denosumab: a new treatment option for giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is an osteolytic, usually benign neoplasm characterized by infiltration with osteoclast-like giant cells, and the osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL) is heavily involved in its pathogenesis. Denosumab belongs to a new class of drugs that inhibit RANKL. Prior to denosumab, multimodality treatment in refractory, recurrent and metastatic GCTB has shown variable results. Recent phase II data have demonstrated denosumab's activity with regard to disease and symptom control, without significant adverse effects. On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity. Ongoing questions remain, including the optimal scheduling, patient selection, use in the adjuvant setting and long-term toxicity concerns.

Including the effect of motion artifacts in noise and performance analysis of dual-energy contrast-enhanced mammography.

In contrast-enhanced mammography (CEM), the dual-energy dual-exposure technique, which can leverage existing conventional mammography infrastructure, relies on acquiring the low- and high-energy images using two separate exposures. The finite time between image acquisition leads to motion artifacts in the combined image. Motion artifacts can lead to greater anatomical noise in the combined image due to increased mismatch of the background tissue in the images to be combined, however the impact has not yet been quantified. In this study we investigate a method to include motion artifacts in the dual-energy noise and performance analysis. The motion artifacts are included via an extended cascaded systems model. To validate the model, noise power spectra of a previous dual-energy clinical study are compared to that of the model. The ideal observer detectability is used to quantify the effect of motion artifacts on tumor detectability. It was found that the detectability can be significantly degraded when motion is present (e.g., detectability of 2.5 mm radius tumor decreased by approximately a factor of 2 for translation motion on the order of 1000 µm). The method presented may be used for a more comprehensive theoretical noise and performance analysis and fairer theoretical performance comparison between dual-exposure techniques, where motion artifacts are present, and single-exposure techniques, where low- and high-energy images are acquired simultaneously and motion artifacts are absent.

Quality control in neuroradiology: impact of trainees on discrepancy rates.

BACKGROUND AND PURPOSE: Prior studies have found a 2%-8% clinically significant error rate in radiology practice. We compared discrepancy rates of studies interpreted by subspecialty-trained neuroradiologists working with and without trainees. MATERIALS AND METHODS: Subspecialty-trained neuroradiologists reviewed 2162 studies during 41 months. Discrepancies between the original and "second opinion" reports were scored: 1, no change; 2, clinically insignificant detection discrepancy; 3, clinically insignificant interpretation discrepancy; 4, clinically significant detection discrepancy; and 5, clinically significant interpretation discrepancy. Faculty alone versus faculty and trainee discrepancy rates were calculated. RESULTS: In 87.6% (1894/2162), there were no discrepancies with the original report. The neuroradiology division had a 1.8% (39/2162; 95% CI, 1.3%-2.5%) rate of clinically significant discrepancies. In cases reviewed solely by faculty neuroradiologists (16.2% = 350/2162 of the total), the rate of discrepancy was 1.7% (6/350). With fellows (1232/2162, 57.0% of total) and residents (580/2162, 26.8% of total), the rates of discrepancy were 1.6% (20/1232) and 2.2% (13/580), respectively. The odds of a discrepant result were 26% greater (OR = 1.26; 95% CI, 0.38-4.20) when reading with a resident and 8% less (OR = 0.92; 95% CI, 0.35-2.44) when reading with a fellow than when reading alone. CONCLUSIONS: There was a 1.8% rate of clinically significant detection or interpretation discrepancy among academic neuroradiologists. The difference in the discrepancy rates between faculty only (1.7%), fellows and faculty (1.6%), and residents and faculty (2.2%) was not statistically significant but showed a trend indicating that reading with a resident increased the odds of a discrepant result.

Addressing an unmet need in oncology patients: rehabilitation of upper aerodigestive tract function.

BACKGROUND: Laryngeal dysfunction in the oncology population is common and may detract from quality of life (QoL) due to vocal restriction and aspiration. Therapies to address this complex issue have not been explored to date. We examined the outcomes among oncology patients treated with a minimally invasive office-based surgical approach for the rehabilitation of laryngeal dysfunction. PATIENTS AND METHODS: A retrospective analysis was carried out of oncology patients referred for laryngeal dysfunction. Patients who underwent minimally invasive injection laryngoplasty (IL) were selected. Subjective outcome measures, objective voice analysis parameters, and swallowing studies were annotated. RESULTS: Sixty-one patients underwent IL for the management of laryngeal dysfunction. Lung cancer was the most common cancer diagnosis (39.3%), and 52% of patients had thoracic malignancies. All patients had a self-reported improvement in vocal function with a single injection, and 55 patients (90%) reported lasting effects at 3 months. In patients with pre- and postoperative voice analysis, phonatory function increased from 5.0 to 10.5 s, more than twofold improvement compared with baseline functioning. Seventy-one percent of patients who aspirated before injection no longer required a modified diet. There were no major complications. CONCLUSIONS: Interventions to improve the QoL in oncology patients continue to evolve. We report significant improvements in both subjective and objective measures of laryngeal function after IL for vocal fold dysfunction that are both immediate and sustained. We conclude that IL is a safe and efficacious procedure for the treatment of laryngeal dysfunction in oncology patients, resulting in palliation and improved QoL.

Reversal of transtentorial herniation with hypertonic saline.

OBJECTIVE: To evaluate the role of 23.4% saline in the management of transtentorial herniation (TTH) in patients with supratentorial lesions. METHODS: Consecutive patients with clinically defined TTH treated with 23.4% saline (30 to 60 mL) were included in a retrospective cohort. Factors associated with successful reversal of TTH were determined. RESULTS: Seventy-six TTH events occurred in 68 patients admitted with intracerebral hemorrhage (n = 29), subarachnoid hemorrhage (n = 16), stroke (n = 8), brain tumor (n = 8), subdural hematoma (n = 5), epidural hematoma (n = 1), and meningitis (n = 1). In addition to 23.4% saline, TTH management included hyperventilation (70% of events), mannitol (57%), propofol (62%), pentobarbital (15%), ventriculostomy drainage (27%), and decompressive hemicraniectomy (18%). Reversal of TTH occurred in 57/76 events (75%). Intracranial pressure decreased from 23 +/- 16 mm Hg at the time of TTH to 14 +/- 10 mm Hg at 1 hour (p = 0.002), and 11 +/- 12 mm Hg at 24 hours (p = 0.001) among 22 patients with intracranial pressure monitors. Reversal of TTH was predicted by a >/=5 mmol/L rise in serum sodium concentration (p = 0.001) or an absolute serum sodium of >/=145 mmol/L (p = 0.007) 1 hour after 23.4% saline. Adverse effects included transient hypotension in 13 events (17%); no evidence of central pontine myelinolysis was detected on post-herniation MRI (n = 18). Twenty-two patients (32%) survived to discharge, with severe disability in 17 and mild to moderate disability in 5. CONCLUSION: Treatment with 23.4% saline was associated with rapid reversal of transtentorial herniation (TTH) and reduced intracranial pressure, and had few adverse effects. Outcomes of TTH were poor, but medical reversal may extend the window for adjunctive treatments.

CT assessment of vocal cord medialization.

BACKGROUND AND PURPOSE: Unilateral vocal cord paralysis (UVCP) occurs after iatrogenic injury or disease process and is associated with dysphonia and aspiration. Various surgical options are available for treatment of UVCP, including vocal cord medialization thyroplasty and injection laryngoplasty. These augmentative procedures improve phonation and airway protection. Our purpose was to demonstrate the CT appearance of implants used for the treatment of UVCP. METHODS: Twelve patients treated surgically for UVCP were studied with helical CT. The vocal cords were augmented by using Silastic implants (n = 7), polytetrafluoroethylene (Gore-Tex) implants (n = 2), Teflon injections (n = 2), or fat injection (n = 1). Augmented vocal cords were characterized by size, shape, and Hounsfield units (HU). Two other patients with failed medialization thyroplasty were evaluated for the position of the extruded implant relative to the paralyzed vocal cord. RESULTS: The 7 Silastic implants were triangular and hyperattenuated (293.4 +/- 90.4 HU). The 2 Gore-Tex implants were heterogeneous with lobulated medial margins and were hyperattenuating (320 and 414 HU). The injected materials demonstrated ovoid/masslike configurations: the 2 Teflon injections were hyperattenuated (107 and 429 HU), and the fat injection was hypoattenuated (-102 HU). Inferior displacement of the implant was demonstrated relative to the true vocal cord in 2 patients with failed Silastic thyroplasties. CONCLUSION: CT can distinguish various types of vocal cord augmentation. Silastic implants are recognized by their characteristic triangular configuration. The Gore-Tex implants had unique heterogeneous attenuation with lobulated medial margins. Fat and Teflon injections both appear ovoid/masslike. Teflon injection should not be mistaken for tumor.

Magnetic resonance-guided biliary drainage in a patient with malignant obstructive jaundice and thrombocytopenia.

In a patient suffering from malignant obstructive jaundice and thrombocytopenia, magnetic resonance imaging (MRI) was used to guide percutaneous transhepatic biliary drainage, to avoid blind puncture of the bile ducts using fluoroscopy. The first puncture approach was successful, and an MRI-visible guide wire and drainage catheter were inserted successfully within 35 min. The course after the intervention was uneventful, and the patient's fever and itching improved. MRI guidance facilitated optimal procedure planning and high puncture accuracy.

Progesterone: a novel adjunct to intravesical chemotherapy.

OBJECTIVE: To investigate the effect of progesterone on multidrug-resistant urothelial cell lines, as the failure of intravesical chemotherapeutic drugs is often caused by multidrug resistance (MDR), mediated by the drug efflux pump P-glycoprotein (PGP), the function of which can be down-regulated by various compounds including steroid hormones. MATERIALS AND METHODS: Two urothelial cell lines (RT112S and MGH-U1S) and their MDR sublines (RT112R, to cisplatin; and MGH-U1R, a cell line expressing PGP) were used to assess the cytotoxic effects of progesterone, epirubicin and their combination. Cytotoxicity was assessed using a tetrazolium-based assay and in situ confocal microscopy. RESULTS: Cell lines sensitive to epirubicin (MGH-U1S, RT112S and RT112R) required a much lower dose of epirubicin to kill half the cells than did the MDR cell line. Progesterone was intrinsically cytotoxic to all cell lines with little difference among them. Combined therapy had no cumulative effect on epirubicin-sensitive cell lines, but reversed MDR in the MGHU1R cell line, both assessed by confocal microscopy and by the tetrazolium assay. CONCLUSIONS: Progesterone can reverse MDR in urothelial cells in vitro. This, combined with its effects on cell differentiation and apoptosis, together with its safety and tolerability compared to other MDR agents, suggests it may be a valuable adjunct to intravesical chemotherapy.

Sexual dysfunction after treatment for testicular cancer: a systematic review.

OBJECTIVES: We aimed to assess the nature and risk of sexual dysfunction in men after treatment for testicular cancer. METHOD: Systematic review of sexual dysfunction in men treated for testicular cancer. The odds ratio or proportions of subjects with reduced sexual drive, erectile dysfunction or orgasmic/ejaculatory dysfunction was calculated. RESULTS: A detailed review of 79 of the 227 citations was conducted. The highest level of evidence found, were controlled studies. Six controlled studies examined sexual function in 709 patients after they had received treatment. Seven uncontrolled studies examined sexual function in 337 subjects before and after treatment for testicular cancer. Most studies were limited by low response rates, use of unvalidated questionnaires and inclusion of a variety of treatment modalities. Few assessed psychological function and none examined its possible interaction with sexual dysfunction. Meta-analysis of the controlled studies indicated significantly reduced or absent orgasm (OR=4.62, 95% CI=2.47-8.63) together with erectile (OR=2.47, 95% CI=1.54-3.96) and ejaculatory dysfunction (OR=28.57, 95% CI=1.75-464.78) up to 2 years after treatment. Effects on sexual function were less consistent in the uncontrolled studies. CONCLUSIONS: The controlled studies indicate that sexual dysfunction persists for up to 2 years after treatment. However, better evidence is needed in studies that control for the impact of the testicular cancer, the treatment modality and psychological reactions to both.

The development and validation of a dysphagia-specific quality-of-life questionnaire for patients with head and neck cancer: the M. D. Anderson dysphagia inventory.

OBJECTIVE: To design a reliable and validated self-administered questionnaire whose purpose is to assess dysphagia's effects on the quality of life (QOL) of patients with head and neck cancer. DESIGN: Cross-sectional survey study. METHODS: Focus groups were convened for questionnaire development and design. The M. D. Anderson Dysphagia Inventory (MDADI) included global, emotional, functional, and physical subscales. One hundred consecutive adult patients with a neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Speech pathologists completed the Performance Status Scale for each patient. Validity and reliability properties were calculated. Analysis of variance was used to assess how well the MDADI discriminated between groups of patients. RESULTS: The internal consistency reliability of the MDADI was calculated using the Cronbach alpha coefficient. The Cronbach alpha coefficients of the MDADI subscales ranged from 0.85 to 0.93. Test-retest reliability coefficients of the subscales ranged from 0.69 to 0.88. Spearman correlation coefficients between the MDADI subscales and the SF-36 subscales demonstrated construct validity. Patients with primary tumors of the oral cavity and oropharynx had significantly greater swallowing disability with an adverse impact on their QOL compared with patients with primary tumors of the larynx and hypopharynx (P<.001). Patients with a malignant lesion also had significantly greater disability than patients with a benign lesion (P<.001). CONCLUSIONS: The MDADI is the first validated and reliable self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer. Standardized questionnaires that measure patients' QOL offer a means for demonstrating treatment impact and improving medical care. The development and validation of the MDADI and its use in prospective clinical trials allow for better understanding of the impact of treatment of head and neck cancer on swallowing and of swallowing difficulty on patients' QOL.

Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols.

Development of effective chemopreventive agents against prostate cancer (CaP) for humans requires conclusive evidence of their efficacy in animal models that closely emulates human disease. The autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops metastatic CaP, is one such model that mimics progressive forms of human disease. Employing male TRAMP mice, we show that oral infusion of a polyphenolic fraction isolated from green tea (GTP) at a human achievable dose (equivalent to six cups of green tea per day) significantly inhibits CaP development and increases survival in these mice. In two separate experiments, the cumulative incidence of palpable tumors at 32 weeks of age in 20 untreated mice was 100% (20 of 20). In these mice, 95% (19 of 20), 65% (13 of 20), 40% (8 of 20), and 25% (5 of 20) of the animals exhibited distant site metastases to lymph nodes, lungs, liver, and bone, respectively. However, 0.1% GTP (wt/vol) provided as the sole source of drinking fluid to TRAMP mice from 8 to 32 weeks of age resulted in (i) significant delay in primary tumor incidence and tumor burden as assessed sequentially by MRI, (ii) significant decrease in prostate (64%) and genitourinary (GU) (72%) weight, (iii) significant inhibition in serum insulin-like growth factor-I and restoration of insulin-like growth factor binding protein-3 levels, and (iv) marked reduction in the protein expression of proliferating cell nuclear antigen (PCNA) in the prostate compared with water-fed TRAMP mice. The striking observation of this study was that GTP infusion resulted in almost complete inhibition of distant site metastases. Furthermore, GTP consumption caused significant apoptosis of CaP cells, which possibly resulted in reduced dissemination of cancer cells, thereby causing inhibition of prostate cancer development, progression, and metastasis of CaP to distant organ sites.