Deep learning-based classification of dermatological lesions given a limited amount of labelled data.

BACKGROUND: Artificial intelligence (AI) techniques are promising in early diagnosis of skin diseases. However, a precondition for their success is the access to large-scaled annotated data. Until now, obtaining this data has only been feasible with very high personnel and financial resources. OBJECTIVES: The aim of this study was to overcome the obstacle caused by the scarcity of labelled data. METHODS: To simulate the scenario of label shortage, we discarded a proportion of labels of the training set. The training set consisted of both labelled and unlabelled images. We then leveraged a self-supervised learning technique to pretrain the AI model on the unlabelled images. Next, we fine-tuned the pretrained model on the labelled images. RESULTS: When the images in the training dataset were fully labelled, the self-supervised pretrained model achieved 95.7% of accuracy, 91.7% of precision and 90.7% of sensitivity. When only 10% of the data were labelled, the model could still yield 87.7% of accuracy, 81.7% of precision and 68.6% of sensitivity. In addition, we also empirically verified that the AI model and dermatologists are consistent in visually inspecting the skin images. CONCLUSIONS: The experimental results demonstrate the great potential of the self-supervised learning in alleviating the scarcity of annotated data.

A MEMS nanoindenter with an integrated AFM cantilever gripper for nanomechanical characterization of compliant materials.

This work presents the development of a MEMS nanoindenter that uses exchangeable AFM probes for quasi-static nanomechanical characterization of compliant and ultra-compliant materials. While the electrostatic micro-force transducer of the MEMS nanoindenter provides a maximum indentation depth up to 9.5 µm with a maximum output force of 600 µN, experimental investigations reveal that it can achieve a depth and force resolution better than 4 pm Hz-1/2 and 0.3 nN Hz-1/2, in air for f≥ 1 Hz. A passive AFM probe gripper is integrated into the MEMS nanoindenter, allowing the nanoindenter to utilize various AFM probes as an indenter for material testing. A proof-of-principle experimental setup has been built to investigate the performance of the MEMS nanoindenter prototype. In proof-of-principle experiments, the prototype with a clamped diamond AFM probe successfully identified an atomic step (∼0.31 nm) within a Si < 111 > ultraflat sample using the scanning probe microscopy mode. The nanomechanical measurement capability of the MEMS nanoindenter prototype has been verified by means of measurements of reference polymer samples using a silicon AFM probe and by means of measurements of the elastic properties of a PDMS sample using a spherical diamond-coated AFM probe. Owing to its compact and low-cost but high-resolution capacitive readout system, this MEMS nanoindenter head can be further applied for in-situ quantitative nanomechanical measurements in AFMs and SEMs.

Lack of health insurance among juvenile offenders: a predictor of inappropriate healthcare use and reincarceration?

OBJECTIVES: Relationships between the health insurance status and healthcare use among justice-involved youths transitioning into adulthood is an underexplored topic, even if transition to adulthood is a crucial time period for healthcare outcomes. To fill in these knowledge gaps, this study had two aims: (1) to examine trajectories of health insurance coverage and healthcare use among serious juvenile offenders transitioning into adulthood; and (2) to explore associations between the lack of health insurance, healthcare use and reincarceration. STUDY DESIGN: We conducted a secondary analysis on the data of the US longitudinal Pathways to Desistance study between ages 20 and 23 years (2000-2010). METHODS: Participant data on health insurance coverage, healthcare use, reincarceration and sociodemographic variables (n = 1215) were extracted and analysed using descriptive statistics, generalized linear regressions and cross-lagged panel models. RESULTS: About half of the young offenders had no health insurance coverage or intermittent coverage between the age of 20 and 23 years. Emergency services were used (≥17.4%), notably more by insured participants and were increasingly used over time. Being uninsured at the age of 20 years was associated with reincarceration at the age of 23 years (b = -0.052, p = 0.014, odd-ratio = 0.95), but incarceration at the age of 20 years did not predict the insurance status at the age of 23 years (b = 0.009, p = 0.792). CONCLUSIONS: Serious juvenile offenders, especially if uninsured, faced major barriers to accessing health care and often reported an inappropriate healthcare use. This likely led to reincarceration. The lack of continuity of care and of access to health care may, therefore, increase health disparities, and efforts are needed to mitigate detrimental outcomes, by effective in and out of detention coordination of health insurance coverage and among health services.

Nasal protein profiles in work-related asthma caused by different exposures.

BACKGROUND: The mechanisms of work-related asthma (WRA) are incompletely delineated. Nasal cell samples may be informative about processes in the lower airways. Our aim was to determine the nasal protein expression profiles of WRA caused by different kind of exposures. METHODS: We collected nasal brush samples from 82 nonsmoking participants, including healthy controls and WRA patients exposed to (i) protein allergens, (ii) isocyanates and (iii) welding fumes the day after relevant exposure. The proteome changes in samples were analysed by two-dimensional difference gel electrophoresis, and the differentially regulated proteins found were identified by mass spectrometry. Immunological comparison was carried out using Western blot. RESULTS: We detected an average of 2500 spots per protein gel. Altogether, 228 protein spots were chosen for identification, yielding 77 different proteins. Compared to the controls, exposure to protein allergens had the largest effects on the proteome. Hierarchical clustering revealed that protein allergen- and isocyanate-related asthma had similar profiles, whereas asthma related to welding fumes differed. The highly overrepresented functional categories in the asthma groups were defence response, protease inhibitor activity, inflammatory and calcium signalling, complement activation and cellular response to oxidative stress. Immunological analysis confirmed the found abundance differences in galectin 10 and protein S100-A9 between the groups. CONCLUSIONS: Work-related asthma patients exposed to protein allergens and isocyanates elicit similar nasal proteome responses and the profiles of welders and healthy controls were alike. Revealed biological activities of the protein expression changes are associated with allergic inflammation and asthma.

A novel glycocluster molecule prevents timothy-induced allergic airway inflammation in mice.

BACKGROUND: Allergen-specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th)2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen-induced chronic allergic inflammation model in mice. METHODS: Female BALB/c mice were intranasally sensitized with 50 µL of timothy grass pollen extract (TE) twice a week for a period of 15 weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25 µg/50 µL), CpG-ODN (20 µg/50 µL) or MPLA (2 µg/50 µL). Groups of 9-10 animals per treatment were killed 24 hours after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis. RESULTS: When mice were repeatedly exposed to TE for 15 weeks, the number of eosinophils and lymphocytes increased in the BAL fluids. The eosinophil and lymphocyte counts decreased dose-dependently and were practically abolished in the mice treated with TADM. Treatments with MPLA or CpG significantly increased the numbers of neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure. CONCLUSIONS: A novel synthetic glycocluster molecule inhibited the development of grass-induced eosinophilic pulmonary inflammation in mice when administrated in the airways. This compound could be a candidate to be used either as an adjuvant in SIT or as a topical anti-inflammatory treatment.

Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

BACKGROUND: The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). METHODS: MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. RESULTS: MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). CONCLUSIONS: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

A novel mannoside-glycocluster adjuvant: Compared in vitro to CpG ODN and MPL and tested in vivo in mouse asthma model.

BACKGROUND: Allergen-specific immunotherapy balances the Th2-biased immunity towards Th1 and Treg responses. Adjuvants are used in allergen preparations to intensify the immune responses. The increased prevalence of allergies in developed societies has been associated with decreased microbial load during childhood. This has initiated a search for microbial structures to be used as adjuvants. Our study has shown that a synthetic triacedimannose (TADM) may suppress the Th2-type allergic inflammatory response. The aim of this study was to compare the properties of TADM with capacities of other adjuvants, CpG ODN and MPL, to modulate cytokine production in PBMC and regulate sensitisation in an OVA-sensitised mouse asthma model. METHODS: The effects of TADM were studied in vitro on birch stimulated PBMC cultures of birch allergic rhinitis patients with other known adjuvants. Cytokines in supernatants were measured by Luminex. Effects of TADM were analysed in vivo in a mouse model of OVA-induced allergic asthma by analysing BAL, cytokine mRNA and serum antibodies. RESULTS: TADM was the only adjuvant that significantly suppressed the production of all birch induced Th2-type cytokines. In a murine model, TADM significantly suppressed the specific IgE production and enhanced IFN-γ production. CONCLUSIONS: TADM suppresses the birch allergen induced Th2-type cytokine responses in allergic subjects more efficiently than the two other adjuvants, MPL and CpG ODN. TADM is immunomodulatory also in vivo and decreases the IgE levels and increases the IFN-γ responses in a murine model. These results suggest that TADM may be a promising candidate for novel adjuvants in immunotherapy.

[Originators and eponyms of dermatomyositis : Ernst Leberecht Wagner (1821-1888) and Heinrich Unverricht (1853-1912)]. / Erstbeschreiber und Namensgeber der Dermatomyositis : Ernst Leberecht Wagner (1821-1888) und Heinrich Unverricht (1853-1912).

Dermatomyositis is a rare muscle disease that was first described by Ernst Leberecht Wagner and Heinrich Unverricht.After providing a survey on both scientists' life works, this contribution describes the most significant subsequent works on the diagnostics and classification of clinical symptoms and the progress of the disease that the author has been observing for more than three decades.Polymyositis/dermatomyositis (also known as Unverricht-Wagner or Wagner-Unverricht syndrome) was described in two publications by Ernst Leberecht Wagner in 1863 and 1887. Wagner was - probably uniquely in Germany - consecutively professor of pathology and also, as a successor to K. A. Wunderlich, of internal medicine at the University of Leipzig. The most frequently used designation for polymyositis/dermatomyositis today was originated by Heinrich Unverricht in 1891. After his education in his home town of Breslau, Unverricht was first employed as head of the clinic for internal medicine in Jena. From 1886 he was a professor in Dorpat, but he left this university when the language of teaching was changed to Russian in 1892. Unverricht then became the first director of the newly founded Sudenburg Hospital in Magdeburg (Medical Academy from 1954 to 1991).During the subsequent decades, further medical scientists have studied the disease and brought about today's precise classification criteria for diagnostics - based on Wagner's and Unverricht's findings.

Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.

BACKGROUND: Folliculitis decalvans leads to scarring alopecia through inflammatory destruction of the hair follicle. Currently, antibiotics are most commonly used to treat this disease. However, treatment regimens with antibiotics feature a high relapse rate and encourage the development of resistant bacteria. OBJECTIVE: To evaluate the outcome of different treatment options for folliculitis decalvans. METHODS: Retrospective study to compare the efficacy of different treatment regimens in 28 patients with folliculitis decalvans. RESULTS: The success of treatment with clindamycin and rifampicin, clarithromycin, dapsone and isotretinoin was analysed. The evaluation of the combination of clindamycin and rifampicin showed the lowest success rate in achieving long-term remission, since 80% of the patients relapsed shortly after end of treatment. Clarithromycin and dapsone were more successful with long-term and stable remission rates of 33% and 43% respectively. Treatment with isotretinoin was the most successful oral treatment in our analysis with 90% of the patients experiencing stable remission during and up to two years after cessation of the treatment. CONCLUSION: The common use of antibiotics as first-line therapy in folliculitis decalvans needs to be re-evaluated critically and oral isotretinoin should be considered as valid treatment alternative.

[Drug treatment of alopecia]. / Arzneimitteltherapie der Alopezien.

BACKGROUND: Alopecia is the term used to describe hairless areas of the scalp. They can follow a specific pattern, be diffuse or circumscript. Androgenetic alopecia (AGA) follows a pattern: in men thinning of temples and vertex up to total baldness; in women thinning of the midline or parietal area. CAUSES: Lack of iron or cytostatic drugs cause diffuse alopecia, while in autoimmune diseases such as alopecia areata or lichen planus bizarre shapes of hairless areas are observed. TREATMENT: For therapy, the following medications are used: topical minoxidil solution for AGA of men and women; systemic finasteride 1 mg for men with AGA; topical diphencyprone immunotherapy for alopecia areata; systemic antimycotic agents for tinea capitis; antibiotics such as clindamycin and rifampicin for folliculitis decalvans; systemic corticosteroids and isotretinoin for folliculitis et perifolliculitis capitis abscedens et suffodiens; topical corticosteroids for lichen planus and Kossard's frontal fibrosing alopecia.

Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3.

Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the 'missing heritability' of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio = 1.66, P = 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P = 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC.

Fractionated external beam radiotherapy of skull base metastases with cranial nerve involvement.

BACKGROUND AND PURPOSE: Skull base metastases frequently appear in a late stage of various tumor entities and cause pain and neurological disorders which strongly impair patient quality of life. This study retrospectively analyzed fractionated external beam radiotherapy (EBRT) as a palliative treatment approach with special respect to neurological outcome, feasibility and acute toxicity. PATIENTS AND METHODS: A total of 30 patients with skull base metastases and cranial nerve disorders underwent EBRT with a mean total dose of 31.6 Gy. Neurological status was assessed before radiotherapy, during radiotherapy and 2 weeks afterwards categorizing orbital, parasellar, middle fossa, jugular foramen and occipital condyle involvement and associated clinical syndromes. Neurological outcome was scored as persistence of symptoms, partial response, good response and complete remission. Treatment-related toxicity and overall survival were assessed. RESULTS: Before EBRT 37 skull base involvement syndromes were determined with 4 patients showing more than 1 syndrome. Of the patients 81.1 % responded to radiotherapy with 10.8 % in complete remission, 48.6 % with good response and 21.6 % with partial response. Grade 1 toxicity of the skin occurred in two patients and grade 1 hematological toxicity in 1 patient under concurrent chemoradiotherapy. Median overall survival was 3.9 months with a median follow-up of 45 months. CONCLUSION: The use of EBRT for skull base metastases with symptomatic involvement of cranial nerves is marked by good therapeutic success in terms of neurological outcome, high feasibility and low toxicity rates. These findings underline EBRT as the standard therapeutic approach in the palliative setting.

Increasing toxicity during neoadjuvant radiochemotherapy as positive prognostic factor for patients with esophageal carcinoma.

The aim of this study was to correlate acute organ toxicity during preoperative radiochemotherapy with overall survival and tumor regression for patients with primarily operable esophageal carcinoma. From 1995 to 2002, 60 patients with primarily operable esophageal carcinoma were treated in a preoperative setting at our department. Thirty-three percent of the patients had International Union against Cancer (UICC)-stage II tumors, 62% had UICC-stage III tumors, and 5% had UICC-stage IVA tumors. All patients received irradiation (40 Gy at 2 Gy/fraction). Chemotherapy for all patients with adenocarcinoma and, from 2001, also for patients with squamous cell carcinoma consisted of two cycles, 5-fluorouracil and cisplatinum; between 1995 and 2001, patients with squamous cell carcinoma received three courses of chemotherapy (folinic acid, etoposide, 5-fluorouracil, and cisplatinum every 3 weeks) before and further cisplatinum and etoposide during radiotherapy. We found a significant correlation between acute organ toxicity and histopathological tumor regression, as well as overall survival. The probability to achieve tumor regression grade 1 after radiochemotherapy was nearly four times higher for patients with worsening of odynophagia than for those without an increase (odds ratio: 3.97). Patients with worsening of odynophagia had a 5-year overall-survival rate of 66% compared with 39% in patients without (P = 0.048). Our data indicate that normal tissue and tumor tissue may behave similar with respect to treatment response, as acute organ toxicity showed to be an independent prognostic marker in our patient population. The hypothesis should be further analyzed on biomolecular and clinical level in future clinical trials.

[Persistent tropical diseases among migrants]. / Maladies tropicates persistantes chez les migrants.

Several infectious diseases may remain a- or pauci-symptomatic for many years before causing major clinical manifestations. Migrants are particularly vulnerable to several persistent infectious diseases due to exposure in their country of origin and their specific living conditions. This article emphasizes neglected parasitic diseases among migrants, such as schistosomiasis, strongyloidiasis and Chagas disease. In the case of co-infection with HIV, hepatitis B and C, some of these persistent parasitosis may induce more significant morbidity. These aspects are particularly important to know as these diseases, both viral and parasitic, are particularly common among migrants.

Advances in quality control: mouse embryo morphokinetics are sensitive markers of in vitro stress.

STUDY QUESTION: Can time-lapse analysis of cell division timings [morphokinetics (MK)] in mouse embryos detect toxins at concentrations that do not affect blastocyst formation? SUMMARY ANSWER: An MK algorithm enhances assay sensitivity while providing results 24-48 h sooner than the traditional mouse embryo assay (MEA). WHAT IS KNOWN ALREADY: Current quality control testing methodology is sensitive but further improvements are needed to assure optimal culture conditions. MKs of embryo development may detect small variations in culture conditions. STUDY DESIGN: Cross sectional-control versus treatment. Mouse embryo development kinetics of 466 embryos were analyzed according to exposure to various concentrations of toxins and toxic mineral oil. MATERIALS, SETTING, METHODS: Cryopreserved 1-cell embryos from F1 hybrid mice were cultured with cumene hydroperoxide (CH) (0, 2, 4, 6 and 8 µM) and Triton X-100 (TX-100; 0, 0.0008, 0.0012, 0.0016 and 0.002%). Using the Embryoscope, time-lapse images were obtained every 20 min for 120 h in seven focal planes. End-points were timing and pattern of cell division and embryo development. The blastocyst rate (BR) was defined as the percentage of embryos that developed to the expanded blastocyst stage within 96 h. MAIN RESULTS AND THE ROLE OF CHANCE: BR was not affected for embryos cultured in the three lowest concentrations of CH and the four lowest concentrations of TX-100. In contrast, a unique MK model detected all concentrations tested (P < 0.05). The MK model identified toxicity in two lots of toxic mineral oil that did not affect BR (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: A limited number of toxins were used so that the results may not apply to all potential embryo toxins. A larger sample size may also demonstrate other statistically significant developmental kinetic parameters. WIDER IMPLICATIONS OF THE FINDINGS: MKs in mouse embryos are a sensitive and efficient method for quality control testing of in vitro culture conditions. BR, the end-point of traditional quality control assays, did not detect sublethal concentrations of toxins in the culture milieu in our study. This study demonstrates that temporal variation at key developmental stages reflects the quality of the culture environment. An MEA that incorporates MK will provide enhanced sensitivity and faster turn-around times.

Second primary malignancies in head and neck cancer patients: high prevalence of curable-stage disease.

BACKGROUND AND PURPOSE: Patients treated for squamous cell carcinoma of the head and neck (HNSCC) carry a high risk of second primary malignancies (SPM). Recently, computed tomography (CT) of the chest was shown to significantly decrease the risk of death due to bronchial carcinoma (BC) in a cohort of smokers whose risk of BC is increased but might be lower than that of patients previously treated for HNSCC. Thus, the present study evaluated the potential benefit of CT and other examinations in the detection of SPM in HNSCC patients. PATIENTS AND METHODS: Between July 2008 and November 2011, 118 participants underwent a prospective, systematic examination for SPM (13 women, 105 men, median age 62 years). All patients had been previously treated for HNSCC and showed no recurrence or distant metastases at the time of the study start. CT scans, ear-nose-throat endoscopy, and endoscopy of the esophagus and stomach were performed. RESULTS: Overall, 33 suspicious findings were clarified by additional investigations. In all, 26 SPM were confirmed in 21 of 118 patients (18%; 10 lung, 7 HNSCC, 3 gastrointestinal, 1 renal). Eighteen of these 21 patients (86%) underwent therapy with curative intent. CONCLUSION: The examinations revealed a high prevalence of curable stage SPM in HNSCC patients. Adapting a surveillance scheme including a chest CT is recommended.

Advances in rectal cancer: Real-world evidence suggests limited gains in prognosis for elderly patients.

BACKGROUND: Rectal cancer treatment has improved considerably due to the introduction of total meso-rectal excision, radio-chemotherapy, and high-resolution imaging. The aim of this observational cohort study was to quantify the effectiveness of these advances using high-quality data from a representative cohort of patients. METHODS: 20 281 non-metastasized cases retrieved from the Munich Cancer Registry database were divided into three time periods corresponding to before (1988-1997), partial (1998-2007), and full implementation (2008-2019) of clinical advances. Early-onset (<50 yrs.), middle-aged, elderly patient subgroups (> 70 yrs.) were compared. The overall effectiveness of evidence-based guideline adherence was also examined. RESULTS: Median survival improved by 1.5 yrs. from the first to the last time period. Relative survival increased from 74.9% (5-yr 95%CI[73.3 - 76.6]) to 79.2% (95%CI[77.8 - 80.5]). The incidence of locoregional recurrences was reduced dramatically by more than half (5-yr 17.7% (95%CI[16.5 - 18.8]); 6.7% (95%CI[6.1 - 7.3])). Gains in 5-yr relative survival were limited to early-onset and middle-aged patients with no significant improvement seen in elderly patients (Female 68.6% [63.9 - 73.3] to 67.6% [64.0 - 71.2]; Male 71.7% [65.9 - 77.4] to 74.0% [70.8 - 77.2]). CONCLUSIONS: Real-world evidence suggests that recent treatment advances have lead to an increase in prognosis for rectal cancer patients. However, more effort should be made to improve the implementation of new developments in elderly patients. Especially considering, that these cases represent a growing majority of diagnosed patients.

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer. Influence on hormone levels, quality of life, and sexual functioning.

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83 male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4 Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1 year after RCT. RESULTS: Mean dose at the testes was 3.9 Gy (range 0.28-11.98 Gy). It was higher for tumors located < 6 cm from the anocutaneous line (p < 0.05). One year after therapy, testosterone, the testosterone/LH ratio, and the FAI/LH ratio were significantly decreased (3.5-3.0 µg/l, 0.9-0.4, 7.9-4.5, respectively) while LH and FSH (4.2-8.5 IU/l, 6.0-21.9 IU/l) were increased. QoL and sexual functioning were significantly impaired. However, there was no statistical correlation between testicular radiation dose and changes in hormone levels, QoL, or sexual functioning. CONCLUSION: Multimodal treatment for rectal cancer including RCT leads to hormone level changes and to impaired QoL and sexual functioning. However, because there was no apparent correlation between the analyzed parameters, QoL is probably also influenced by other factors, e.g., psychosocial aspects.