Clinical Oncology

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study n the original publication, in a title of Table 2

Novel therapeutic strategy based on genetic and epigenetic abnormalities for myeloid neoplasms

FDG-PET might not contribute to improving survival in patients with locally advanced inoperable esophageal cancer Abstract Background In Japan, positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) has been covered by the national health insurance for esophageal cancer since 2006. FDG-PET is commonly performed in advanced esophageal cancer. The aim of this study was to determine the effect of FDG-PET on survival in patients with locally advanced inoperable esophageal cancer. Methods We retrospectively reviewed all patients with cT4 and without M1 esophageal cancer on CT in our institution between 2000 and 2014, and data for 78 patients who meet the eligibility criteria described below were used for analysis in this study. The eligibility criteria included (1) cT4 esophageal cancer without distant metastases or M1 lymph node metastasis (UICC 2002), (2) histologically proven squamous cell carcinoma, (3) 20–79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with 50 Gy or more, and (6) no other active malignant tumor during treatment. Results Two patients were excluded because abdominal lymph node metastases or neck lymph node metastases were detected by FDG-PET. In 78 eligible patients, FDG-PET was not performed before treatment in 41 of the 78 patients and was performed in the other patients. The median observation period was 68 months. The 3-year and 5-year overall survival rates in 78 patients were 36.9% and 30.8%, respectively. There was no significant difference in overall survival or progression-free survival between patients in whom FDG-PET was performed and those in whom FDG-PET was not performed (12.0 months vs. 11.0 months, p = 0.920 and 6.0 months vs. 6.0 months, p = 0.844, respectively). Conclusions Compared with only CT, additional information from FDG-PET is not associated with improving survival in patients with locally advanced esophageal cancer. Our results suggest that FDG-PET might not have much meaning for survival in locally advanced esophageal cancer.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study Abstract Background The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. Methods We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. Results The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030–2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). Conclusion Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma Abstract Background Osteosarcoma (OS) is the most common malignant bone tumor in young adults and adolescents with approximately 3 million new cases annually. Due to the lack of sensitive and specific diagnostic biomarkers, although OS patients are curable after surgical resection, many patients suffer from metastasis or recurrence. This study aimed to investigate whether circulating microRNAs (miRNAs) could serve as biomarkers for the diagnosis of OS. Materials and methods Healthy individuals and OS patients enrolled in this study came from Nanjing First Hospital. First, candidate miRNAs were selected by integrated analysis of two GEO datasets and a publicly available miRNA dataset. The expression of these miRNAs in tissues and serum samples were subsequently examined through qRT-PCR. The diagnostic utility of these differential miRNAs was examined by using receiver operating characteristic (ROC) curve analysis. Finally, the potential signaling pathways associated with candidate miRNAs were searched through online tools. Results Four miRNAs (miR-487a, miR-493-5p, miR-501-3p and miR-502-5p) were selected to further investigate their diagnostic potential for OS. We discovered miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were upregulated in OS tissues and serums. Besides, miR-487a, miR-493-5p, miR-501-3p and miR-502-5p in peripheral blood of OS patients were tumor-derived. The area under the ROC curve (AUC) was 0.83 (95% CI 0.71–0.97) for miR-487a, 0.79 (95% CI 0.66–0.93) for miR-493-5p, 0.82 (95% CI 0.68–0.95) for miR-501-3p, 0.83 (95% CI 0.72–0.95) for miR-502-5p, and 0.89 (95% CI 0.78–1.0) for miRNAs combination. Conclusion Circulating miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were novel potential diagnostic biomarkers of OS.

Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma Abstract Background Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. Materials and methods The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III–IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. Results The median age of patients with PmOC and MmOC was 55 (18–81) and 51 years (30–82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303–3.654), P = 0.0036]. Conclusion The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

Removal of the entire internal iliac vessel system is a feasible surgical procedure for locally advanced ovarian carcinoma adhered firmly to the pelvic sidewall Abstract Background Ovarian carcinomas sometimes grow in the pelvic cavity, adhering firmly to the pelvic sidewall. These cases are often considered as inoperable or result in the incomplete resection because the tumors are not mobile. We performed en bloc resection of the tumors along with the entire internal iliac vessel system to achieve complete resection. Methods Twenty of 237 consecutive patients with FIGO stage II–IV ovarian, fallopian tubal, or primary peritoneal carcinoma who underwent cytoreductive surgery at Chiba University Hospital between January 2008 and December 2016 had locally advanced tumors adhered firmly to the pelvic sidewall. We performed isolation of the tumors from the pelvic sidewall using the following procedure: the trunk of internal iliac vessels, the obturator vessels, the inferior gluteal and internal pudendal vessels were isolated and divided. The tumor together with the entire internal iliac vessel system was isolated from the sacral nerve plexus and piriform muscle. We examined the surgical outcomes, perioperative complications, and prognosis for the patients who underwent this procedure. Results All patients successfully underwent complete resection, resulting in no gross residual disease in the pelvic cavity. There was no mortality within 90 days postoperatively. Two patients had Grade IIIb complications, comprising wound dehiscence and vesicovaginal fistula. Recurrence occurred in nine of the patients. However, no recurrence was observed in the pelvic sidewall. The median progression-free survival was 43 months. Conclusions Removal of the entire internal iliac vessel system is feasible for the complete resection of locally advanced ovarian carcinomas adhered firmly to the pelvic sidewall.

Precision medicine and novel molecular target therapies in acute myeloid leukemia: the background of hematologic malignancies (HM)-SCREEN-Japan 01 Abstract The development of allogeneic hematopoietic-stem-cell transplantation has improved the prognosis of younger acute myeloid leukemia (AML) patients. However, the outcome of older AML patients remains poor. The majority of AML patients are elderly. For elderly AML patients unfit for intensive chemotherapy, less toxic single agent that targets a specific gene mutation or combination therapy with a single agent is needed. The role of chromosomal abnormalities and genetic mutations in leukemia has become more apparent, and detailed prognostic stratification based on the type of genetic mutation has been established. Next-generation sequencing (NGS) has been used for gene analysis of AML. In the future, the evaluation of biologically homogeneous population on the basis of chromosomal abnormalities and gene mutations will lead to a paradigm shift that will help in the development of optimized therapy. As rapid diagnosis of gene mutations is required by the clinical physicians to decide on induction therapy, it is important to have a swift turnaround time for comprehensive DNA sequencing to provide actionable data to clinical physicians. It is required to conduct a feasibility study to evaluate the turnaround time from sending the specimens to receiving the results while maintaining the quality of the specimens contributing to gene analysis. To detect infrequent gene mutations, investigators need to perform multicenter studies and/or cooperative-group trials with a certain sample size to examine the frequency of the gene mutations in elderly AML patients, enabling sufficient statistical power for meaningful comparisons.

Bortezomib-based strategy with autologous stem cell transplantation for newly diagnosed multiple myeloma: a phase II study by the Japan Study Group for Cell Therapy and Transplantation (JSCT-MM12) Abstract Background The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance. Methods Sixty-four symptomatic patients aged between 20 and 65 years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1 year. Results Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41 months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group. Conclusions The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.

Genetic abnormalities and pathophysiology of MDS Abstract Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies characterized by peripheral blood cytopenia and dishematopoiesis and frequently progress to acute myeloid leukemia. Genetic defects play a major role in pathogenesis of MDS, including cytogenetic abnormalities, gene mutations, and abnormal gene expression. Chromosomal abnormalities have been detected in approximately 50–60% of MDS patients, including the deletions of chromosome 5q and 7q, trisomy 8, and complex karyotypes. Newer genomic technologies, such as single-nucleotide polymorphism array and next-generation sequencing, revealed the heterozygous deletions resulting in haploinsufficient gene expression (e.g., CSNK1A1, DDX41 on chromosome 5, CUX1, LUC7L2, EZH2 on chromosome 7) involved in the pathogenesis of MDS. In addition, recurrent somatic mutations in more than 50 genes have been identified in 80–90% of MDS. The most recurrent genetic mutations are involved in the RNA splicing (e.g., SF3B1, SRSF2, U2AF1, ZRSR2, LUC7L2, DDX41) and epigenetic modifications, such as histone modification (e.g., ASXL1, EZH2) and DNA methylation (e.g., TET2, DNMT3A, IDH1/IDH2). TP53 mutation is associated with aggressive disease and frequently coincides with deletion of chromosome 5q. This review summarizes the recent progress in molecular pathogenesis of MDS. A better understanding of the specific subgroups of MDS patients will also aid in the development of new therapeutic approach for MDS.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Supportive Care

Special Articles: Managing Cancer Pain - Key Issues and Lessons Learned to Optimize Patient Care

The first online conference for breast cancer survivors—SURVIVA 2018: an innovative information tool Abstract Purpose The implementation of a new online conference tool, with the goal of providing competent answers, information, and support from experts in their fields, about diagnosis, treatment, and rehabilitation in breast cancer patients. Methods The implementation process and data of the first online conference are described. Results Following the idea and initiative of a breast cancer survivor, and under the umbrella of a leading oncologist in breast cancer treatment, and with the cooperation of further leading experts in the fields, plus their therapeutic teams, the new online conference SURVIVA 2018 was implemented as an innovative platform—free of charge, online, and with easy and anonymous access—to provide breast cancer survivors with in-depth information and help from the leading Austrian experts in their fields. This first online conference for German-speaking breast cancer survivors is an innovative and modern concept, which seems to have been very well accepted. Conclusion This concept could also be of interest to survivors of other cancer entities.

Modeling cancer pain: "the times they are a-changin'"

Pain and related complaints in patients with acute leukemia: time for simultaneous care in hemato-oncology Abstract This commentary deals with the need of an early integration between hematologist and palliative care specialists as well as pain therapists as a routine basis in order to ensure the best management of patients affected by acute leukemia from the onset of the disease and in the stages of causal therapy. This strategy could limit the burden of painful symptoms and, in addition, avoid unnecessary suffering to patients, ensuring the best conditions for optimal outcome of these patients with extremely high clinical complexity and symptomatology who receive intensive treatments or who are managed with novel treatment approaches.

Opening up disruptive ways of management in cancer pain: the concept of multimorphic pain Abstract Purpose Following a series of articles reviewing the basics of cancer pain management, in this article, we develop the guiding principle of our philosophy: the concept of multimorphic pain and how to integrate it as the innovative cornerstone of supportive care in cancer. Method Critical reflection based on literature analysis and clinical practice. Results This model aims to break with standard approaches, offering a more dynamic and exhaustive vision of cancer pain as a singular clinical entity, taking into account its multimorphic characteristics (cancer pain experience can and will change during cancer: aetiology, physiopathology, clinical presentation and consequences of pain) and the disruptive elements that can occur to influence its evolution (cancer evolution, concomitant treatments, pain from associated diseases, comorbidities and complications, or modifications in the environment). Our model establishes the main key stages for interdisciplinary management of cancer pain: Early, personalised management that is targeted and multimodal; Identification, including in advance, of potential disruptive elements throughout the care pathway, using an exhaustive approach to all the factors influencing pain, leading to patient and caregiver education; Optimal analgesic balance throughout the care pathway; Integration of this concept into a systemic early supportive care model from the cancer diagnosis. Conclusions Given the difficulties still present in the management of pain in cancer, and whilst cancer is often considered as a chronic condition, the concept of multimorphic pain proposes a practical, optimised and innovative approach for clinicians and, ultimately, for patients experiencing pain.

Fatigue in survivors of malignant melanoma and its determinants: a register-based cohort study Abstract Purpose Fatigue has found increasing attention as a debilitating and lasting condition of cancer patients. However, it has remained unclear to what degree long-term survivors of malignant melanoma suffer from fatigue. Therefore, this study aimed to determine fatigue and its link with quality of life, aftercare behavior, and mental and physical symptoms among melanoma survivors. Methods A register-based sample of 684 long-term survivors an average of 8.4 (SD = 1.72; range 5.67–12.17) years after diagnosis was compared to 2049 participants from a representative survey by the Multidimensional Fatigue Inventory. In a hierarchical linear regression, statistical predictors for fatigue were ascertained. Results Overall fatigue was not increased in melanoma survivors except for younger melanoma survivors under 40 years. As in the general population, fatigue increased with age, and it was higher in women compared to men. Fatigue was associated with decreased quality of life, reduced functioning, and increased physical and mental symptoms. Substantial predictors (30% explained variance) were higher age, additional chronic illness, self-blame, detrimental interactions and lack of social support, and also fear of recurrence. There was neither an effect of medical parameters (clinical stage, time since diagnosis) nor of participation in follow-up care. Conclusions Fatigue needs to be taken seriously in the aftercare of melanoma survivors as it is associated with multiple functional and quality of life impairments and heightened distress. Reduction of fatigue in melanoma patients should address younger survivors (under 40 years) and older survivors (over 60 years) with additional chronic illness and focus on illness coping and social support.

A cross-sectional, comparative, syndromic description of oncological mixed pain in Medical Oncology units in Spain Abstract Objective The reason cancer pain remains prevalent and hard to classify may be partially explained by the failure to identify neuropathic mechanisms. The objective of this research was to identify the syndromes of cancer pain that may be particularly hard to manage due to their mixed pathophysiology. Design A series of 384 patients who had cancer of any type, at any stage, and suffered from chronic pain (symptom onset > 3 months) were assessed during a routine return visit in Spain. Medical oncologists indicated the presence and pathophysiology of 33 predefined pain syndromes on a per-patient basis. This information was then measured against clinical, psychosocial, and health care-related data to determine which syndromes pose particular challenges. Results The mean (standard deviation) age of patients was 61.6 (12.6) years, 49.7% were women. Most (82%) had advanced metastatic disease, 68.7% were on second-line or palliative therapies. The worst syndrome was nociceptive, pure neuropathic, and mixed in 34.6, 26.9, and 38.6% of patients, respectively. Any syndrome could be of mixed pathophysiology. Only 10 syndromes were common (≥ 5% of patients). Syndromes related to malignant bone pain and involvement of chest wall structures were the most frequent. Certain syndromes (including tumor-related bone pain, chemotherapy-induced peripheral neuropathies, paraneoplastic pain syndromes, and malignant neuralgias or injury to cranial nerves) can be particularly challenging when they have a mixed pathophysiology, because the neuropathic component is rarely or unevenly considered. Conclusions Virtually all cancer pain syndromes can present mixed pathophysiology. Certain syndromes can include neuropathic components that are frequently overlooked.

A nationwide survey of adherence to analgesic drugs among cancer patients in Taiwan: prevalence, determinants, and impact on quality of life Abstract Purpose Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan. Methods Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky's four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses. Results Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all p < 0.05). Age ≥ 50 years, head and neck or hematological malignancies, cancer-related pain, patients who agreed or strongly agreed that the side effects of analgesic drugs were tolerable, and patients who disagreed or strongly disagreed that the dosing schedule could be flexibly self-adjusted to deal with the actual pain were predictors of good adherence to analgesic drugs. Conclusions Awareness of the clinical factors associated with adherence to analgesic drugs may help clinicians to identify cancer patients at a greater risk of non-adherence, reinforce optimal pain management, and improve the QoL by enhancing adherence to pain medications.

Association between glycemic control, age, and outcomes among intensively treated patients with acute myeloid leukemia Abstract Purpose To investigate the impact of hyperglycemia and glycemic variability during intensive acute myeloid leukemia therapy (AML) on outcomes by age. Methods Retrospective study of 262 consecutive patients with newly diagnosed AML hospitalized for intensive induction. Hyperglycemia was assessed by mean blood glucose (BG) (mg/dL) during hospitalization and glycemic variability was determined by the standard deviation (SD) of mean BG. Outcomes were complete remission ± incomplete count recovery (CR + CRi), and overall survival (OS). We used logistic regression to evaluate CR + CRi, and Cox proportional hazard models for OS, stratified by age (< 60 vs ≥ 60 years). Results Older patients (N = 138, median age 70) had higher baseline comorbidity (CCI > 1 60.1% vs 25.8%) and prevalence of diabetes (20.3% vs 7.3%) compared to younger (N = 124, median age 47). The mean ± SD number of BG values obtained per patient during hospitalization was 61 ± 71. The mean (± SD) glucose (mg/dL) during hospitalization was 121.7 (25.9) in older patients (≥ 60 years) versus 111.6 (16.4) in younger. In older patients, higher mean glucose and greater glycemic variability were associated with lower odds of remission (OR 0.80, 95% CI 0.69–0.93 and OR 0.73, 95% CI 0.61–0.88 respectively, per 10-unit increase) and higher mortality rates (HR 1.13, 95% CI 1.05–1.21 and HR 1.17, 95% CI 1.09–1.26, respectively, per 10-unit increase) in multivariate analyses. Conclusions Our observations that hyperglycemia and increased glycemic variability were associated with lower remission rates and increased mortality in older patients suggest glycemic control may be a potentially modifiable factor to improve AML outcomes.

Physical problems, functional limitations, and preferences for physical therapist-guided exercise programs among Dutch patients with metastatic breast cancer: a mixed methods study Abstract Purpose In this study we aimed (1) to identify the most prevalent physical symptoms and functional limitations that limit physical activity of patients with palliative treatment for metastatic breast cancer (MBC) and (2) to identify their preferences for exercise-based physical therapy programs, as a first step towards the development of physical therapist (PT)-guided exercise programs for patients with MBC. Methods We performed a mixed-method study that comprised a cross-sectional survey and two focus group sessions among patients with MBC. Survey results were analyzed using descriptive statistics. The focus groups were audio-taped, transcribed verbatim, and analyzed independently by two researchers, using directed content analysis. Results A total of 114 women (response rate 61%) completed the survey (mean age 63.5, SD 10.2). Eighty-six percent of the women reported at least some level of physical problems limiting their ability to be physically active, of whom 46% reported substantial problems. The most prevalent problems were fatigue, painful joints, painful muscles, and shortness of breath. Uptake of exercise appeared to be limited. Exercise preferences varied strongly. Fifty-three percent indicated a preference for some form of PT-supervision, and 34% for a prolonged period of time (> 8 weeks). Focus group results clarified that patients' preferences for supervision, by PTs with special qualifications in oncology, were related to feelings of insecurity about their ability to self-manage physical functioning. Conclusions Patients with MBC experience a broad range of physical health problems that limit their ability to be physically active. While preferences vary strongly, patients with MBC would value the availability of high quality, PT-guided, tailored exercise programs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Klinische Endokrinologie und Stoffwechsel

Angst vor Hypoglykämien gefährdet das Erreichen der Therapieziele

Editorial

Primärer Hyperparathyreoidismus Zusammenfassung Der primäre Hyperparathyreoidismus (pHPT) ist eine relativ häufige endokrine Erkrankung. Die Unterscheidung zwischen „asymptomatischem pHPT" und „asymptomatischem pHPT mit begleitenden, oft stummen Komplikationen" muss gründlich untersucht und herausgearbeitet werden, damit die beste weitere Vorgehensweise für den Patienten festgelegt werden kann. Die Standardtherapie bei symptomatischen Patienten ist die Operation, ebenso bei vielen Patienten mit asymptomatischem pHPT, wenn erfüllte Leitlinienkriterien ein solches Vorgehen unterstützen. Mit dem Cholin- und Methionin-PET(Positronen-Emissions-Tomographie)/CT(Computertomographie) sowie der Radiofrequenzablation (nur in ausgewählten Fällen) haben sich in den letzten Jahren sowohl diagnostische als auch therapeutische Möglichkeiten zugunsten der Betroffenen weiter verbessert.

Störungen der Pubertätsentwicklung

Mitochondrialer Diabetes Zusammenfassung Die genetische Heterogenität von Diabetes mellitus ist groß, neben „Typ 1 und Typ 2" sind gut 50 weitere Subtypen definiert. Monogenetischen Formen kommt aufgrund ihrer hohen Penetranz, des meist jugendlichen Manifestationsalters sowie der assoziierten Komorbiditäten und Implikationen hinsichtlich Familienscreening ein großer Stellenwert zu. Eine wichtige Untergruppe stellt „mitochondrialer Diabetes" dar, dem eine Störung auf Ebene der mitochondrialen Atmungskette mit daraus resultierender Dysfunktion der Betazellen zugrunde liegt. Die wichtigste Ursache im Erwachsenenalter ist die „MELAS-Mutation" 3243A→G der mitochondrialen DNA. In unselektionierten Diabetespopulationen reicht ihre Prävalenz von 0.1% bis 3%, eingeschränktes Hörvermögen ist häufig Teil dieses Syndroms. Mitochondriopathien sind notorisch vielgestaltig, was die Diagnosestellung oft gravierend erschwert. Wenn normalgewichtige Patienten im jüngeren Erwachsenenalter Diabetes entwickeln und sich in der maternalen Familienanamnese prämature Schwerhörigkeit oder Anhaltspunkte für eine Multisystemerkrankung finden, sollte an diese Diabetesform gedacht und eine molekulargenetische Abklärung veranlasst werden.

Hyperglykämie erfolgreich behandeln

Primäre kongenitale Hypothyreose

Herausfordernde Levothyroxinsubstitutionstherapie während einer Schwangerschaft

Hyponatriämie/Hypernatriämie – Diagnose und Therapie basierend auf der Analyse von physiologischen Regulationsmechanismen Zusammenfassung Hypo- und Hypernatriämien sind Störungen des Wasserhaushalts und können nur durch eine erhebliche Beeinträchtigung von dessen Regulationsmechanismen entstehen. Hypernatriämien entwickeln sich durch eine Reduktion des Durstempfindens oder prinzipiell der Möglichkeit zu trinken und werden von einer Störung der Harnkonzentrationsmechanismen oder den Verlust von hypotonen Flüssigkeiten begleitet. Eine Substitution dieser Verluste von hypotonen Körperflüssigkeiten durch isotone oder hypertone Lösungen erhöht die Wahrscheinlichkeit des Auftretens einer Hypernatriämie. Für die Entstehung einer Hyponatriämie ist eine (in)adäquate Ausschüttung von Vasopressin verantwortlich, da dies zu einer Retention von Wasser ohne Natrium führt. Die Zufuhr von hypotonen Lösungen in Kombination mit einer niedrigen Zufuhr an osmotisch aktiven Substanzen kann ebenfalls eine Hyponatriämie verursachen. Für die Differenzialdiagnose der Dysnatriämien ist neben der Erhebung des Volumenstatus auch eine Analyse der renalen Natrium- und Wasserausscheidung eine Notwendigkeit. Diese Analyse basiert auf den physiologischen Grundprinzipien der Regulation des Wasserhaushalts. Erst diese exakte Erhebung der Grundlage für das Auftreten einer Dysnatriämie macht eine adäquate Therapie möglich.

Intrathyreoidales hormoninaktives Nebenschilddrüsenkarzinom

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Oral Oncology

Intraoperative flow cytometry for head and neck lesions. Assessment of malignancy and tumour-free resection margins  Available Online 02 July 2019  George Vartholomatos, Lentiona Basiari, George Exarchakos, Ioannis Kastanioudakis, Ioannis Komnos, Maria Michali, Georgios S. Markopoulos, Anna Batistatou, Alexandra Papoudou-Bai, George A. Alexiou

Tongue cancer: A discrete oral cavity subsite  Available Online 02 July 2019  Sameep S. Shetty, Akshay Kudpaje, Rama Jayaraj, Vishal Rao, Prit Kiran Shah  select article Tongue cancer: A discrete oral cavity subsite CorrespondenceNo access Tongue cancer: A discrete oral cavity subsite Sameep S. Shetty, Akshay Kudpaje, Rama Jayaraj, Vishal Rao, Prit Kiran Shah In Press, Corrected Proof, Available online 2 July 2019 Purchase PDF select article Intraoperative flow cytometry for head and neck lesions. Assessment of malignancy and tumour-free resection margins CorrespondenceAbstract only Intraoperative flow cytometry for head and neck lesions. Assessment of malignancy and tumour-free resection margins George Vartholomatos, Lentiona Basiari, George Exarchakos, Ioannis Kastanioudakis, ... George A. Alexiou In Press, Corrected Proof, Available online 2 July 2019 Purchase PDF Abstract Head and neck cancer poses a significant health problem worldwide. We set out to investigate the value of rapid intraoperative cell cycle analysis by flow cytometry for the intraoperative characterization of head and neck lesions and surgical margins. Seventy patients with head and neck lesions suspicious of malignancy were included in the study. There were 31 neoplastic and 39 benign lesions. Flow cytometry permitted the intraoperative detection of neoplastic lesions within 6 min with high sensitivity and specificity based on cell cycle fractions. In the cases in which surgical margins were assessed, intraoperative flow cytometry had complete concordance with pathology. Intreoperative flow cytometry is a novel promising technique for rapid intraoperative characterization of malignancy and tumour free resection margins in head and neck lesions. select article Cowden's syndrome: A case report CorrespondenceNo access Cowden's syndrome: A case report Zhongfeng Liu, Qi Wang, Jun Li In Press, Corrected Proof, Available online 28 June 2019 Purchase PDF select article Agreement between skeletal muscle mass measurements using computed tomography imaging and magnetic resonance imaging in head and neck cancer patients CorrespondenceNo access Agreement between skeletal muscle mass measurements using computed tomography imaging and magnetic resonance imaging in head and neck cancer patients N. Chargi, E. Ansari, L.F.J. Huiskamp, G. Bol, R. de Bree In Press, Corrected Proof, Available online 26 June 2019 Purchase PDF select article Medication related osteonecrosis of jaw in a leukemia patient undergoing systemic arsenic trioxide therapy: A rare case report CorrespondenceAbstract only Medication related osteonecrosis of jaw in a leukemia patient undergoing systemic arsenic trioxide therapy: A rare case report Mathangi Kumar, Ravindranath Vineetha, Adarsh Kudva In Press, Corrected Proof, Available online 26 June 2019 Purchase PDF Abstract Osteonecrosis of the jaw is a potential side effect of certain pharmaceutical agents used in the field of medicine. Early diagnosis and effective management of this condition can be challenging to the clinicians. Bisphosphonates and other anti-angiogenic agents are the most common drugs that are attributed to cause medication-related osteonecrosis of the jaw. In the past, arsenic-based compounds were commonly used local agents for pulp devitalization therapy. Arsenic is also one of the components of the chemotherapeutic regimen in the management of refractory leukemia. Although local diffusion of the arsenic compounds is known to cause osteonecrosis, there are no reports of the same caused by its systemic administration. Here, we present the first ever case of mandibular bone necrosis in a patient with acute promyelocytic leukemia who underwent systemic arsenic trioxide therapy. select article Limiting radiotherapy field to ipsilateral side only in unresected lateralised HPV positive N2b squamous cell carcinoma of the tonsil CorrespondenceNo access Limiting radiotherapy field to ipsilateral side only in unresected lateralised HPV positive N2b squamous cell carcinoma of the tonsil Muhammad Shahid Iqbal, Josef Kovarik, Charles Kelly In Press, Corrected Proof, Available online 12 June 2019 Purchase PDF select article Conceptual interpretation of findings on systematic review and meta-analysis of altered-fractionation radiotherapy improves local control in the early-stage glottic carcinoma CorrespondenceNo access Conceptual interpretation of findings on systematic review and meta-analysis of altered-fractionation radiotherapy improves local control in the early-stage glottic carcinoma Rama Jayaraj, Chellan Kumarasamy, Shanthi Sabarimurugan, Madurantakam Royam Madhav, ... Siddhartha Baxi In Press, Corrected Proof, Available online 7 June 2019 Purchase PDF select article Together consideration of microenvironment and tumor cells: Analysis of papers published in Oral Oncology CorrespondenceNo access Together consideration of microenvironment and tumor cells: Analysis of papers published in Oral Oncology Gargi S. Sarode, Sachin C. Sarode, Nilookumari Choudhary, Nilesh Kumar Sharma, ... Shankargouda Patil In Press, Corrected Proof, Available online 7 June 2019 Purchase PDF select article Corrigendum to 'Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis'. [Oral Oncol. 85 (2018) 60–67] ErratumFull text access Corrigendum to 'Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis'. [Oral Oncol. 85 (2018) 60–67] Jie Jane Chen, Jeremy P. Harris, Christina S. Kong, John B. Sunwoo, ... Wendy Y. Hara In Press, Corrected Proof, Available online 4 June 2019 Download PDF select article Resolution without surgery of an advanced stage of medication-related osteonecrosis of the jaw (MRONJ) in a patient who could not suspend her treatment for osteoporosis CorrespondenceNo access Resolution without surgery of an advanced stage of medication-related osteonecrosis of the jaw (MRONJ) in a patient who could not suspend her treatment for osteoporosis Ana Karina Sarmiento L. In Press, Corrected Proof, Available online 4 June 2019 Purchase PDF