[Advances in lung cancer diagnosis and treatment - a review].

Lung cancer is the second and third most common cancer in Iceland for females and males, respectively. Although the incidence is declining, lung cancer still has the highest mortality of all cancers in Iceland. Symptoms of lung cancer can be specific and localized to the lungs, but more commonly they are unspecific and result in significant diagnostic delay. Therefore, majority of lung cancer patients are diagnosed with non-localized disease. In recent years, major developments have been made in the diagnosis and treatment of lung cancer. Positive emission scanning (PET) and both transbroncial (EBUS) or transesophageal ultrasound (EUS) biopsy techniques have resulted in improved mediastinal staging of the disease and minimal invasive video-assisted thoracic surgery (VATS) has lowered postoperative complications and shortened hospital stay. Technical developments in radiotherapy have benefitted those patients who are not candidates for curative surgery. Finally, and most importantly, recent advances in targeted chemotherapeutics and development of immunomodulating agents have made individual tailoring of treatment possible. Recent screening-trials with low-dose computed tomography show promising results in lowering mortality. This evidence-based review focuses on the most important developments in the diagnosis and treatment of lung cancer, and includes Icelandic studies in the field.

[Outcome of Icelandic patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) abroad].

BACKGROUND: Peritoneal carcinomatosis is a known complication of colorectal cancer and has long been considered very difficult to manage. The survival has been reported to be under two years after systemic chemotherapy with or without palliative surgery. The most recent method of treatment is compiled of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and has been suggested to significantly increase survival. The aim of this study was to research the cases of Icelandic patients undergoing this treatment overseas and the impact it has had on their disease. METHODS: A retrospective study of all Icelandic patients who have undergone CRS-HIPEC treatment abroad 2008-2017. Information was retrieved from medical records and from registry of the Icelandic Health Insurance committee of medical treatments abroad. RESULTS: A total of 11 patients have undergone CRS-HIPEC treatment after having received their initial treatment in Landspitali University Hospital. All of the surgeries were performed in the United States by the same surgeon in the years 2008-2017. The group consists of 10 women and 1 man with a mean age of 53 years. The cause of peritoneal carcinomatosis was appendiceal cancer for 7 patients (67%) and colon cancer for 3 patients (27%). One patient had a primary malignancy of the peritoneum, mesothelioma. Three patients suffered complications within 30 days of surgery, 2 had infection and 1 had an anastomotic leak. Another patient had a late complication of bowel stenosis and later a fistula. Five patients have completed their five year observation period post surgery without diagnosis of recurrence and mean follow-up time was 44 months. Out of 11 patients, 10 are still alive. Five have been diagnosed with recurrence of disease. CONCLUSION: Icelandic patients who have undergone CRS-HIPEC treatment have in most cases done well and survival is comparable to other studies. Half of the survivors did not have recurrence of disease within 5 years of surgery. Prognosis has improved since the introduction of this treatment and every reason to keep sending selected Icelandic patients abroad to receive it.

The challenge of implementing Less is More medicine: A European perspective.

The concept of Less is More medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health, tackling the erroneous assumption that more care is always better. In response, several medical societies across the world launched quality-driven campaigns ("Choosing Wisely") and published "top-five lists" of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures. However, barriers and challenges for the implementation of Less is More medicine have been identified in several European countries, where overuse is rooted in the culture and demanded by a society that requests certainty at almost any cost. Patients' high expectations, physician's behavior, lack of monitoring and pernicious financial incentives have all indirect negative consequences for medical overuse. Multiple interventions and quality-measurement efforts are necessary to widely implement Less is More recommendations. These also consist of a top-five list of actions: (1) a novel cultural approach starting from medical graduation courses, up to (2) patient and society education, (3) physician behavior change with data feedback, (4) communication training and (5) policy maker interventions. In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine. This project will constitute part of the future agenda of the European Federation of Internal Medicine.

Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood.

BACKGROUND: Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. METHODS: We performed genome-wide association studies of serum levels of AFP (N = 22,686), carcinoembryonic antigen (N = 22,309), cancer antigens 15.3 (N = 7,107), 19.9 (N = 9,945), and 125 (N = 9,824), and ALP (N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry. RESULTS: We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels. CONCLUSIONS: Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood. IMPACT: Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers.

Risk-Stratified Initial Salvage Therapy for Relapsed or Refractory Metastatic Germ Cell Tumors.

BACKGROUND: Salvage treatment with either conventional-dose chemotherapy (CDCT) or high-dose chemotherapy with autologous stem cell transplantation (HDCT) offers curative potential for patients with relapsed or refractory germ cell tumor (GCT). However, the optimal initial salvage strategy remains controversial, and the criteria for appropriate patient selection are not clear. METHODS: This was a retrospective analysis of the clinical outcomes for GCT patients receiving initial salvage therapy using a risk-stratified treatment approach. In general, patients with favorable-risk disease received CDCT with 4 cycles of paclitaxel, ifosfamide, and cisplatin, while patients with unfavorable-risk disease received HDCT per institutional protocol. The prognostic validity of the International Germ Cell Cancer Collaborative Group (IGCCCG) and the International Prognostic Factors Study Group (IPFSG) risk groups were evaluated in this context. RESULTS: Thirty-seven patients received initial salvage therapy. Twenty-four patients (65%) achieved a favorable response (including complete response to chemotherapy alone, complete response after post-chemotherapy surgical resection, or partial response with negative tumor markers). The favorable response rates for the CDCT and HDCT treatment groups were 69% and 62%, respectively. After a median follow-up of 31 months, the median survival for CDCT-treated patients has not been reached, and the median survival for the HDCT-treated group was 24 months. Both the International Germ Cell Cancer Collaborative Group and the International Prognostic Factors Study Group risk groups were significantly associated with progression-free survival (log-rank P = .009 and P = .039, respectively). CONCLUSIONS: Patients with favorable prognostic features may achieve durable remissions without requiring high-dose salvage chemotherapy. However, the criteria for optimal patient selection remain unclear, and these findings further support the need for a definitive randomized trial.

Cardiometabolic and skeletal risk factors in black men with prostate cancer starting androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. METHODS: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between -1 to -2.5 and osteoporosis when T scores ≤-2.5. RESULTS: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. CONCLUSIONS: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.

Evaluating the safety and efficacy of axitinib in the treatment of advanced renal cell carcinoma.

Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor-α, and c-kit. Phase I studies demonstrated 5 mg twice daily as the recommended starting dose with notable effects seen in renal cell carcinoma, an observation confirmed in Phase II trials. The trial of comparative effectivess of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS) was an international randomized Phase III study designed for registration purposes, compared axitinib to sunitinib. This trial randomized 723 patients with metastatic kidney cancer to axitinib or sunitinib in the second-line setting and demonstrated a median progression-free survival of 6.7 months for axitinib versus 4.7 months for sorafenib (P<0.0001). Clinical benefit was detected regardless of prior therapy, but no overall survival benefit has been observed. Axitinib is well tolerated without a significant effect on quality of life. The most common grade 3 toxicities are hypertension (16%), diarrhea (11%), and fatigue (11%), with other notable side effects being anorexia, nausea, hand-foot syndrome, and rash. Patients who developed diastolic blood pressure >90 mmHg were noted to have significantly longer median overall survival and overall response rates when compared to normotensive patients. Therefore, the manufacturer recommends escalating the twice-daily dose to 7 mg and 10 mg, as tolerated, if there is no significant increase in blood pressure on treatment. Currently, axitinib is approved for use in the second-line setting for patients with metastatic renal cell carcinoma. Research is ongoing in other disease settings.

Palliative care and advance care planning for patients with advanced malignancies.

Patients diagnosed with an advanced cancer frequently have a very limited life expectancy and need to understand their prognosis in order to make good choices about care. Advance care planning (ACP) is an important aspect of this care but can be especially difficult to address. Most patients and families prefer direct and honest communication, but they may interpret the information they are given in very different ways. In addition, oncologists strive to communicate honestly and sensitively, but often struggle with the best approach. Finally, standardization of ACP is challenging because patients have highly individualized values, traditions and social and family dynamics that guide their preferences. Palliative Care is a rapidly growing field that specializes in communication and patient-centered approaches to care. Treatment of patients with advanced or metastatic cancer should prioritize early discussions of ACP to ensure high quality end-of-life care. When available, this care should be delivered through careful integration with palliative care specialists.

[Yellow nail syndrome]. / Heilkenni gulra nagla.

We describe a 77 year old man with a prior history of recurrent airway infections, who presented with a history of cough, dyspnea and increased mucous production that had lasted several months. On chest X-ray a pleural effusion was observed. Subsequent thoracocentesis demonstrated an exudate with predominant eosinophils. An infectious cause was ruled out. The pleural effusion subsequently recurred and he was admitted for pleural biopsy, which revealed chronic pleuritis. On physical examination yellow nails on fingers and toes were noted. Subsequently, after exclusion of other diseases, a diagnosis of yellow nails syndrome was established. He was treated with corticosteroids, which were tapered over 6 months. One year later the eosinophilia had subsided, however the pleural effusion remained, although on a much smaller scale.

Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake.

CONTEXT: Adequate vitamin D status for optimum bone health has received increased recognition in recent years; however, the ideal intake is not known. Serum 25-hydroxyvitamin D is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. OBJECTIVE: To investigate the relative importance of high calcium intake and serum 25-hydroxyvitamin D for calcium homeostasis, as determined by serum intact parathyroid hormone (PTH). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 2310 healthy Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65 years, or 70-85 years) and recruited from February 2001 to January 2003. They were administered a semi-quantitative food frequency questionnaire, which assessed vitamin D and calcium intake. Participants were further divided into groups according to calcium intake (<800 mg/d, 800-1200 mg/d, and >1200 mg/d) and serum 25-hydroxyvitamin D level (<10 ng/mL, 10-18 ng/mL, and >18 ng/mL). MAIN OUTCOME MEASURE: Serum intact PTH as determined by calcium intake and vitamin D. RESULTS: A total of 944 healthy participants completed all parts of the study. After adjusting for relevant factors, serum PTH was lowest in the group with a serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25-hydroxyvitamin D level (<10 ng/mL), calcium intake of less than 800 mg/d vs more than 1200 mg/d was significantly associated with higher serum PTH (P = .04); and at a calcium intake of more than 1200 mg/d, there was a significant difference between the lowest and highest vitamin D groups (P = .04). CONCLUSIONS: As long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. Vitamin D supplements are necessary for adequate vitamin D status in northern climates.