Heath-related quality of life (HRQoL) among survivors with unresectable locally-advanced non-small cell lung cancer (LA-NSCLC) treated with radiotherapy and chemotherapy still is not clear. The current study w...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 2 Δεκεμβρίου 2017
Health-related quality of life in long-term survivors of unresectable locally advanced non-small cell lung cancer
Health-related quality of life in long-term survivors of unresectable locally advanced non-small cell lung cancer
Heath-related quality of life (HRQoL) among survivors with unresectable locally-advanced non-small cell lung cancer (LA-NSCLC) treated with radiotherapy and chemotherapy still is not clear. The current study w...
http://ift.tt/2npqccn
Fragmentation level determines mitochondrial damage response and subsequently the fate of cancer cells exposed to carbon ions
Although mitochondria are known to play an important role in radiation-induced cellular damage response, the mechanisms of how radiation elicits mitochondrial responses are largely unknown.
http://ift.tt/2npm5wK
Clinical evaluation of atlas and deep learning based automatic contouring for lung cancer
Contouring of organs at risk (OARs) is an important but time consuming part of radiotherapy treatment planning. The aim of this study was to investigate whether using institutional created software-generated contouring will save time if used as a starting point for manual OAR contouring for lung cancer patients.
http://ift.tt/2zHT41e
Interobserver variability in the delineation of the primary lung cancer and lymph nodes on different four-dimensional computed tomography reconstructions
The study compared interobserver variation in the delineation of the primary tumour (GTVp) and lymph nodes (GTVln) between three different 4DCT reconstruction types; Maximum Intensity Projection (MIP), Mid-Ventilation (Mid-V) and Mid-Position (Mid-P).
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Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence
Abstract
Background
Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence.
Methods
We conducted a nested case–control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: − 11 to − 8, − 7 to − 4, and − 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia).
Results
Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the − 3 to 0 interval, OR was 1.97 (95% CI 1.32–2.93) for 110–125 mg/dL and 3.17 (95% CI 2.09–4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24–3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87–6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction = .06).
Conclusion
Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.
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Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence
Abstract
Background
Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence.
Methods
We conducted a nested case–control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: − 11 to − 8, − 7 to − 4, and − 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia).
Results
Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the − 3 to 0 interval, OR was 1.97 (95% CI 1.32–2.93) for 110–125 mg/dL and 3.17 (95% CI 2.09–4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24–3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87–6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction = .06).
Conclusion
Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.
http://ift.tt/2zHkt3a
Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells
Pharmacology-based target identification has become a novel strategy leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer acti...
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Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?
Abstract
Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.
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Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?
Abstract
Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.
http://ift.tt/2zL04du
[Stereotactic body radiation therapy for oligometastatic prostate cancer].
[Stereotactic body radiation therapy for oligometastatic prostate cancer].
Bull Cancer. 2017 Nov 27;:
Authors: Bibault JE
Abstract
INTRODUCTION: The first line treatment of metastatic prostate cancer is medical or surgical androgen-deprivation. This treatment however has significant side effects that can affect the patients' quality of life. For oligometastatic patients, a new therapeutic approach, focusing on local treatment of metastases, is emerging.
METHODS: A systematic review of studies published on Stereotactic Body Radiation Therapy (SBRT) for oligometastatic prostate cancer was performed using results from search request on MEDLINE.
RESULTS: Treatment regimens vary from a single fraction of 20Gy (bone lesions) to ten fractions for a total dose of 64Gy (visceral metastases). Local control is 95.5 to 100% at 2 years with grade 1 and 2 toxicities around 10%, without any grade 3 side effects. These retrospective studies show the feasibility and very low toxicity of SBRT for this population of patients. The effect of SBRT on disease-free or global survival and quality of life has not been assessed. Several prospective trials (STOMP & ORIOLE) are underway.
CONCLUSION: Treating patients with up to five prostate cancer metastases is efficient and has a low toxicity. Prospective trials should identify which patients, if any, really benefit from this approach.
PMID: 29191358 [PubMed - as supplied by publisher]
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Angiomatosis of the uterus, cervix and fallopian tubes: a rare and benign cause of intractable, heavy menstrual bleeding
Angiomatosis of the uterus, cervix and fallopian tubes is a rare and benign entity that has not been reported in the literature previously. We present a case of a 27-year-old patient with severe and intractable heavy menstrual bleeding unresponsive to all conservative and conventional forms of treatment. Following a laparoscopic hysterectomy, the histopathological finding of angiomatosis, a vascular abnormality in the uterus, cervix and fallopian tubes, provided a plausible explanation in this situation.
http://ift.tt/2j86InY
Severe recurrent hypothermia in an elderly patient with refractory mania associated with atypical antipsychotic, valproic acid and oxcarbazepine therapy
Hypothermia is a rare but serious condition that has been associated with various psychiatric medications. We present a 76-year-old woman with refractory mania who developed multiple episodes of severe hypothermia associated with several psychiatric medications including olanzapine, quetiapine, valproic acid and oxcarbazepine. These episodes resolved following discontinuation of the agents. The patient had never experienced hypothermia before, despite having been on these or similar agents for many years. With traditional treatments for mania not feasible, other medications were used to treat her including lithium, clonazepam, gabapentin and the novel protein kinase c inhibitor tamoxifen. The regimen resulted in some success and importantly, without triggering hypothermia. This case alerts clinicians to the rare side effect of hypothermia in response to various psychiatric medications, the fact that patients can suddenly develop this intolerance and suggests possible medications that may be used safely without triggering hypothermia.
http://ift.tt/2BtsXeZ
Bilateral ocular surface squamous neoplasia with bilateral periocular basal cell carcinoma in a case of xeroderma pigmentosum
Xeroderma pigmentosum (XP) is an autosomal recessive disorder associated with multiple oculocutaneous manifestations.We discuss a unique case of XP having bilateral ocular surface squamous neoplasia (OSSN) and periocular basal cell carcinoma. In the right eye, a large OSSN mass involving the ocular surface extensively along with intraocular invasion was noted, whereas in the left eye, the tumour mass was involving the limbus, and extending up to three clock hours. Because of extensive disease in the right eye, orbital exenteration was performed, and for the left eye, a wide excision of the mass with triple freeze thaw cryo application to the margins followed by amniotic membrane grafting was done. Basal cell carcinoma was noted around the medial canthus on both sides. The right-sided basal cell carcinoma was treated by wide excision followed by a forehead rotation flap and the left-sided lesion was managed with topical 5% imiquimod cream.
http://ift.tt/2j9BSLJ
Volvulus of a wandering pelvic spleen: CT diagnosis with 3D reformatted illustration
Description
A 55-year-old woman was admitted at the hospital for acute abdominal pain, nausea, vomiting and loss of appetite. The unique relevant information of her previous clinical story was an aberrant location of the spleen in the pelvis. This was detected with sonography (US), 24 years before, in relation to the same clinical presentation followed by a rapid spontaneous resolution. Present blood tests were normal. An abdominal US of the abdomen was then performed, confirming the pelvic location of the spleen. The ectopic spleen was homogeneous, and any other relevant findings were noted. A multislice CT of the abdomen was required to exclude splenic infarct and to detect another cause of the abdominal pain missed with US.
The CT showed a whirloop configuration of the splenic vascular pedicle, with absence of ischaemic changes of the splenic parenchyma (figure 1). Volvulus of a wandering pelvic spleen (WS)...
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Leg length discrepancy: the importance of a complete history and examination
A 26-year-old woman with a 1-year history of right knee pain had failed to respond to analgesia and activity modification in the community. Her general practitioner referred her to the orthopaedic department for specialist review. A thorough history revealed that she had multiple orthopaedic interventions as a child. The patient had significant postoperative infection of the left knee following knee surgery at 7 years of age. Examination demonstrated the presence of a limp, scoliosis and suspected leg length discrepancy. Plain film radiography confirmed the presence of leg length discrepancy, with the right limb measuring 30 mm longer than the left. The leg length discrepancy was likely secondary to a growth arrest of the left knee following the postoperative infection in childhood. The patient was managed with physiotherapy and heel raises and received regular orthopaedic follow-up.
http://ift.tt/2j92893
Challenging and uncommon diagnosis of long-evolution ascites
This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years with worsening in the last year with severe ascites development. Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil count >250 cells/µL. Ascitic fluid cytology revealed reactive mesothelial hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose positron emission tomography/CT showed 'omental cake' pattern suggesting peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop adhesions and necrosis with whitish exudate in the right pelvic excavation. Biochemical/cytological/histological/microbiological study only revealed reactive mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A second exploratory laparoscopy with liver and peritoneal biopsies and appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary mesothelioma. The patient was referred for intraperitoneal chemotherapy and is undergoing monthly therapeutic paracentesis.
http://ift.tt/2BsXPMz
Rupture of the posterior cul-de-sac during trial of labour after caesarean section
Rupture of the vaginal wall in unobstructed labour is a rare entity in the developed world. This case report describes rupture of the posterior cul-de-sac in a healthy 34-year-old multiparous woman attempting trial of labour after caesarean section. The woman presented to the labour ward at term with spontaneous onset of contractions. In the second stage of labour, the woman experienced sudden severe abdominal pain, different in character from the contraction pain. Therefore, the baby was delivered by ventouse extraction. As the woman continued to experience severe immobilising abdominal pain during the hospital stay, a CT scan was performed which revealed a haematoma and free fluid at the right side of the uterus. A laparotomy was performed 3 days postdelivery, during which a rupture of the posterior cul-de-sac was found and closed with a continuous suture. The woman was discharged 3 days after laparotomy in good clinical condition.
http://ift.tt/2j94yVh
Carcinoma en cuirasse
We present a case of carcinoma en cuirasse as a presentation of advanced lobular breast carcinoma. On further investigation, she was found to have metastasis to her liver and bone. We report this case to highlight the phenomenon of cutaneous metastasis. It is important to consider this diagnosis as an initial manifestation of breast cancer, but rarely, it can also be associated with other adenocarcinomas, for example, carcinoma of lung, kidney or gastrointestinal tract.
http://ift.tt/2BsXNUX
The telescoping aorta: a case of circumferential aortic dissection with intimo-intimal intussusception into the left ventricle
Description
A 67-year-old man with history of tobacco smoking presents to the emergency department with sudden onset, retrosternal chest pain radiating to the neck and associated with diaphoresis and nausea. On examination, his blood pressure was 106/42 mm Hg, pulse of 73 beat/min. He was pale, diaphoretic with IV/VI diastolic blowing murmur of unknown chronicity heard at the left sternal border. His distal pulses were faint but symmetric in all extremities. No marfanoid features. ECG showed sinus rhythm with ST segment elevation in leads aVR and V1, with widespread ST segment depression (figure 1). He underwent emergent coronary angiogram with initial diagnosis of acute coronary syndrome and impending cardiogenic shock. Angiogram revealed type-A aortic dissection extending to the aortic arch with concomitant aortic regurgitation (AR) (videos 1 and 2). On prompt recognition of aortic dissection, he was transferred to the operating room for emergent surgical repair. Intraoperative transoesophageal...
http://ift.tt/2j94xkb
Neck mass: an obstructive cause of respiratory distress with medical management
Congenital goitre is a known cause of hypothyroidism in newborn. Congenital goitre can be due to defective synthesis of thyroxine or administration of antithyroid drugs to the mother during pregnancy. In this case report, we report an instance of a preterm male infant with antenatally detected goitre presenting as a neck mass with congenital hypothyroidism. Hormonal replacement therapy was started immediately after birth which lead to resolution of the mass and normalisation of thyroid function.
http://ift.tt/2BsXMjR
Haemorrhagic conversion of infectious myelitis in an immunocompromised patient
A 28-year-old man recently diagnosed with HIV (CD4 19 cells/mm3, viral load 3.6 million copies/mL, not on highly active antiretroviral therapy on initial diagnosis at outside hospital), disseminated histoplasmosis, shingles and syphilis presented with paraplegia developing over 3 days. Spine MRI demonstrated a longitudinally extensive cord lesion extending from C3 to the tip of the conus. Brain MRI was consistent with meningoencephalitis. Cerebrospinal fluid findings were notable for positive varicella zoster virus (VZV) and cytomegalovirus (CMV) PCRs as well as a Venereal Disease Research Laboratory titre of 1:2. Patient was started on treatment for VZV and CMV meningoencephalitis, neurosyphilis and high-dose steroids for infectious myelitis. Repeat spine MRI demonstrated subacute intramedullary haemorrhage of the cervical cord. He was ultimately discharged to a skilled nursing facility for long-term intravenous antiviral therapy and rehabilitation. After 59 days in the hospital, his neurological exam remained grossly unchanged, with flaccid paraplegia and lack of sensation to fine touch in his lower extremities.
http://ift.tt/2j9JC0t
Perforated neuroenteric cyst masquerading as congenital pulmonary airway malformation
A 3-month-old child was presented with haemoptysis with respiratory distress. Imaging was suggestive of a cavitary lesion in the lung with surrounding consolidation. Diagnosis of a primary lung pathology like congenital pulmonary airway malformation was considered. Based on clinical suspicion and prior experience, a Tc-99m pertechnetate radionuclide study was performed, which clinched the diagnosis of foregut duplication cyst. Intraoperative findings confirmed the presence of a neuroenteric cyst. The child remains asymptomatic on follow-up awaiting neurosurgical intervention for the intraspinal component of the cyst.
http://ift.tt/2Bt6Tkv
Retrovesical malignant fibrous histiocytoma: a rare tumor
Malignant fibrous histiocytoma (MFH) originating from the retrovesical space is a very rare tumour. A 61-year-old man presented to our hospital with complaints of retention of urine and burning sensation during micturition since 6 months. CT scan abdomen showed a large retrovesical mass between the urinary bladder and rectum, measuring 11x9x12 cm, displacing the urinary bladder. Serum PSA (Prostate Specific Antigen) value was within normal range. Biopsy from retrovesical mass and immunohistochemistry was suggestive of MFH. Wide excision of the retrovesical mass was done. Histopathology confirmed the diagnosis of MFH. He received adjuvant radiotherapy. He is on regular follow-up since the last 2 years after radiotherapy with no signs and symptoms of disease recurrence.
http://ift.tt/2j7g2bW
Deadly combination: Clostridium septicum and colorectal malignancy
Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This case outlines an initial presentation of colonic malignancy as gas gangrene from C.septicum infection.
A 69-year-old man presented with abdominal pain, vomiting and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed caecal thickening and subcutaneous emphysema overlying the left flank. Clinically, he became haemodynamically unstable. Examination revealed crepitus overlying the left flank in keeping with gas gangrene. The patient required immediate surgical debridement. Tissue specimens cultured C.septicum. Following a complicated postoperative period, he was transferred to the plastic surgery team for further tissue debridement and reconstruction. A colonoscopy was later performed which was suspicious for malignancy. Colorectal multidisciplinary team discussion is awaited.
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Atrial myxoma: an unusual aetiology for exertional dyspnoea and palpitation
Description
A 67-year-old woman had recently emigrated from the Dominican Republic where, many years prior, she had been evaluated for 'tachycardias' and had unrevealing monitors. She was well until 6 months prior to admission when she started to experience unpredictable, generally exertional palpitations, dyspnoea and left arm discomfort. There was no history of antecedent anxiety. Examination was notable for a 3/6 systolic murmur heard from apex to base and radiating to the neck that ultimately decreased with Valsalva manoeuvre, consistent with aortic sclerosis that was also seen on her echocardiogram. ECG showed normal sinus rhythm, significant left ventricular hypertrophy with strain and question of a right atrial abnormality. Transthoracic echo, for the murmur, showed a 3 cm highly mobile atrial mass, sometimes crossing the mitral valve, and aortic sclerosis (online ). Catheterisation showed unremarkable coronary arteries and no vascular attachments to the mass. Cardiac MRI showed a large mobile and multilobulated...
http://ift.tt/2j7g03O
Preoperative simulation unveiled undetected surgical difficulties in a case of cochlear implantation
We herein report a case in which extensive preparation changed a difficult-to-treat patient into an easy one. We performed a revision cochlear implantation on a patient whose first procedure had been aborted due to unidentified difficulties. During a series of thorough three-dimensional simulations, we found that the patient in question had a normal cochlea but the cochlea was placed in an unusual position and orientation. This condition is difficult to detect on standard preoperative radiographic images. Through this simulation, we were able to propose a surgical plan to avoid making the same mistakes as the first surgeon. We present this case not as a rare difficult case of an unfortunate patient but instead emphasise the importance of performing surgical simulation and looking for non-obvious difficulties. This case is an example of the success that can be achieved with such extensive preparation.
http://ift.tt/2BrPE30
Artery of Percheron ischaemic stroke revealed by brain MRI DWI/ADC sequences
Description
A 71-year-old Caucasian female patient presented with acute onset of visual disturbance, gait difficulties and fluctuation of consciousness.
Her medical history included artery hypertension, previous cardiac valve replacement with mechanical prosthesis, in treatment with oral anticoagulant.
An emergency CT scan resulted negative for acute lesions, haematological exams were normal, international normalised ratio (INR) was >2.5. The EKG revealed high-frequency atrial fibrillation, not previously known.
At the neurological examination, the patient presented drowsiness, easily resolved by verbal stimulus, bilateral divergent diplopia, with eye movements possible only horizontally and severe postural instability with retropulsion.
On the day after the onset of neurological symptoms, the patient underwent brain MRI without gadolinium. Axial fluid attenuation inversion recovery (FLAIR) sequences revealed diffuse cerebral vasculopathy in the bilateral white matter without evidence of acute lesions (figure 1). Diffusion-weighted imaging (DWI) sequences revealed the presence of recent ischaemic lesions in the territory of the artery...
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Nivolumab-induced polyarthritis
Description
A 48-year-old Japanese woman with non-small cell lung adenocarcinoma (cT3N2M1b) received nivolumab (an immune checkpoint inhibitor) at a dosage of 3 mg/kg every 2 weeks. Treatment with nivolumab was effective. The primary tumour as well as metastases to the lymph nodes and spine almost completely disappeared, as shown on positron emission tomography-CT before treatment (figure 1A) and 4 months after treatment (figure 1B). However, she developed sustained pain and swelling in the shoulders and knees bilaterally after only one infusion of nivolumab, and active inflammation was detected in the shoulder joints bilaterally (figure 1B). She had no personal and family histories of autoimmune disease. Serum C-reactive protein level was 2.1 mg/L. Serum matrix metalloproteinase-3 was elevated at 209 ng/mL (normal <60). Antinuclear antibody, rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative. Ultrasonography confirmed shoulder tenosynovitis and bursitis (figure 2). The arthritis responded...
http://ift.tt/2BuhuMi
Systemic lupus erythematosus (SLE): an unusual cause of ileocolic intussusception
Intussusception is a rare diagnosis in adults. Gastrointestinal involvement is not unusual in systemic lupus erythematosus (SLE).1 A case of intussusception as first presenting symptom of SLE is described. A 50-year-old woman of Chinese origin came to the emergency room with symptoms of high fever, nausea, vomiting and weight loss of 10 kg. Three months before, an episode with abdominal pain due to ileal invagination in the colon occurred. Laboratory analysis showed: thrombocytopaenia, lymphopaenia, positive antinuclear antibody, antidouble-stranded DNA, Coombs tests and low C3 in combination with an active urine sediment and proteinuria. CT and positron emission tomography scan showed lymphadenopathy, but no other abnormalities. Axillar lymph node biopsy showed no abnormalities. The diagnosis new-onset SLE was made. Prednisone treatment was started and soon thereafter tapered, azathioprine and hydroxychloroquine were added. During follow-up, the SLE remained in remission. SLE is a rare cause of ileocolic intussusception and ileocolic intussusception may be the first presenting symptom.
http://ift.tt/2j7fPpa
Pretargeting of internalizing trastuzumab and cetuximab with a 18 F-tetrazine tracer in xenograft models
Abstract
Background
Pretargeting-based approaches are being investigated for radioimmunoimaging and therapy applications to reduce the effective radiation burden to the patient. To date, only a few studies have used short-lived radioisotopes for pretargeting of antibodies, and such examples with internalizing antibodies are even rarer. Herein, we have investigated pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab and trastuzumab.
Results
Bioorthogonal reaction between tetrazine and trans-cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a fluorine-18 (t ½ = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab was administered 24, 48, or 72 h prior to the injection of tracer to A431 or BT-474 tumour-bearing mice, respectively. With cetuximab, the highest tumour-to-blood ratios were achieved when the lag time between antibody and tracer injections was 72 h. With trastuzumab, no difference was observed between different lag times. For both antibodies, the tumour could be clearly visualized in the PET images with the highest tumour uptake of 3.7 ± 0.1%ID/g for cetuximab and 1.5 ± 0.1%ID/g for trastuzumab as quantified by ex vivo biodistribution. In vivo IEDDA reaction was observed in the blood for both antibodies, but with trastuzumab, this was to a much lower degree than with cetuximab.
Conclusions
We could successfully visualize the tumours by using cetuximab and trastuzumab in pretargeted PET imaging despite the challenging circumstances where the antibody is internalized and there is still some unbound antibody circulating in the blood flow. This clearly demonstrates the potential of a pretargeted approach for targeting internalizing antigens and warrants development of pharmacokinetic optimization of the biorthogonal reactants to this end.
http://ift.tt/2iDlaaI
Pretargeting of internalizing trastuzumab and cetuximab with a 18 F-tetrazine tracer in xenograft models
Abstract
Background
Pretargeting-based approaches are being investigated for radioimmunoimaging and therapy applications to reduce the effective radiation burden to the patient. To date, only a few studies have used short-lived radioisotopes for pretargeting of antibodies, and such examples with internalizing antibodies are even rarer. Herein, we have investigated pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab and trastuzumab.
Results
Bioorthogonal reaction between tetrazine and trans-cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a fluorine-18 (t ½ = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab was administered 24, 48, or 72 h prior to the injection of tracer to A431 or BT-474 tumour-bearing mice, respectively. With cetuximab, the highest tumour-to-blood ratios were achieved when the lag time between antibody and tracer injections was 72 h. With trastuzumab, no difference was observed between different lag times. For both antibodies, the tumour could be clearly visualized in the PET images with the highest tumour uptake of 3.7 ± 0.1%ID/g for cetuximab and 1.5 ± 0.1%ID/g for trastuzumab as quantified by ex vivo biodistribution. In vivo IEDDA reaction was observed in the blood for both antibodies, but with trastuzumab, this was to a much lower degree than with cetuximab.
Conclusions
We could successfully visualize the tumours by using cetuximab and trastuzumab in pretargeted PET imaging despite the challenging circumstances where the antibody is internalized and there is still some unbound antibody circulating in the blood flow. This clearly demonstrates the potential of a pretargeted approach for targeting internalizing antigens and warrants development of pharmacokinetic optimization of the biorthogonal reactants to this end.
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Serum lipids and risk of obesity-related cancers in postmenopausal women
Abstract
Purpose
Obesity, which is commonly accompanied by dyslipidemia, is associated with an increased risk of certain cancers. However, the association of serum lipids with specific obesity-related cancers is unclear.
Methods
We examined the association of baseline lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) with risk of developing seven obesity-related cancers in a subcohort of 24,208 participants in the Women's Health Initiative. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of lipids with cancers of the breast, colorectum, pancreas, endometrium, ovary, and kidney, and multiple myeloma.
Results
Total cholesterol and LDL-C showed no association with these outcomes. HDL-C was inversely associated, and triglycerides were positively associated, with several cancers. However, after adjustment for other lipids or insulin, consideration of preclinical disease, and exclusion of women taking statins, most associations were attenuated and no longer significant. Only the inverse association of HDL-C with pancreatic cancer (HR for highest vs. lowest quartile 0.52, 95% CI 0.32–0.85, p for trend 0.007) and the positive association of triglycerides with kidney cancer (HR for highest vs. lowest quartile 3.21, 95% CI 1.63–6.33, p for trend = 0.0001) remained significant. However, the inverse association of HDL-C with pancreatic cancer was no longer significant when women who lost substantial weight before diagnosis were excluded.
Conclusions
Our results suggest that when possible sources of confounding and bias are taken into account there are few robust associations of lipids with obesity-related cancers.
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Serum lipids and risk of obesity-related cancers in postmenopausal women
Abstract
Purpose
Obesity, which is commonly accompanied by dyslipidemia, is associated with an increased risk of certain cancers. However, the association of serum lipids with specific obesity-related cancers is unclear.
Methods
We examined the association of baseline lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) with risk of developing seven obesity-related cancers in a subcohort of 24,208 participants in the Women's Health Initiative. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of lipids with cancers of the breast, colorectum, pancreas, endometrium, ovary, and kidney, and multiple myeloma.
Results
Total cholesterol and LDL-C showed no association with these outcomes. HDL-C was inversely associated, and triglycerides were positively associated, with several cancers. However, after adjustment for other lipids or insulin, consideration of preclinical disease, and exclusion of women taking statins, most associations were attenuated and no longer significant. Only the inverse association of HDL-C with pancreatic cancer (HR for highest vs. lowest quartile 0.52, 95% CI 0.32–0.85, p for trend 0.007) and the positive association of triglycerides with kidney cancer (HR for highest vs. lowest quartile 3.21, 95% CI 1.63–6.33, p for trend = 0.0001) remained significant. However, the inverse association of HDL-C with pancreatic cancer was no longer significant when women who lost substantial weight before diagnosis were excluded.
Conclusions
Our results suggest that when possible sources of confounding and bias are taken into account there are few robust associations of lipids with obesity-related cancers.
http://ift.tt/2zWRwV6
Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival
Abstract
Background
The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies.
Methods
A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan–Meier survival analysis was used to determine overall and recurrence-free survival rates.
Results
Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%).
Conclusions
The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.
http://ift.tt/2iaYhHP
New laparoscopic procedure for left-sided pancreatic cancer—artery-first approach laparoscopic RAMPS using 3D technique
Abstract
Background
For left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the "artery-first approach") has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC. However, owing to several technical difficulties in this procedure, its application remains uncommon. Moreover, the artery-first approach in L-RAMPS has not been reported. Here, we developed the artery-first approach L-RAMPS for left-sided PDAC and have presented the same in this report.
Case presentation
Between June 2014 and July 2015, 16 patients with left-sided PDAC were referred to our division for pancreatic resection. The following technique was used for performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After opening the omental bursa, only the middle segment of the pancreas was initially separated from both the left renal vein and the SMA. We termed this procedure as the "artery-first approach using a dome-shaped dorsomedial dissection (3D) technique." This 3D technique enabled the interruption of the entire arterial supply to the specimen while preserving the venous drainage through the splenic vein for preventing venous congestion. The technique also contributed to the early detection of no tumor infiltration into the SMA and the early determination of posterior dissection plane. After pancreatic neck transection, the splenic artery and vein were divided. Finally, the pancreatic tail and spleen were dissected in a right-to-left direction. All operations were completed without any intraoperative complications. The median blood loss and retrieved lymph node count were 75 mL and 37, respectively, which were superior to those reported by other previous studies on L-RAMPS. All resection margins were free of carcinoma. No severe postoperative complications were observed.
Conclusions
The artery-first approach L-RAMPS using 3D technique is safe and feasible to perform. The significance of our proposed procedure is minimal blood loss and precise lymphadenectomy. Therefore, this novel technique may become the preferred treatment for left-sided PDAC in selected cases.
http://ift.tt/2jEZmbh
Evaluation of the new TNM-staging system for thymic malignancies: impact on indication and survival
Abstract
Background
The objective of this study is the evaluation of the Masaoka-Koga and the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposal for the new TNM-staging system on clinical implementation and prognosis of thymic malignancies.
Methods
A retrospective study of 76 patients who underwent surgery between January 2005 and December 2015 for thymoma. Kaplan–Meier survival analysis was used to determine overall and recurrence-free survival rates.
Results
Indication for surgery was primary mediastinal tumor (n = 55), pleural manifestation (n = 17), or mediastinal recurrence (n = 4) after surgery for thymoma. Early Masaoka-Koga stages I (n = 9) and II (n = 14) shifted to the new stage I (n = 23). Advanced stages III (Masaoka-Koga: n = 20; ITMIG/IASLC: n = 17) and IV (Masaoka-Koga: n = 33; ITMIG/IASLC: n = 35) remained nearly similar and were associated with higher levels of WHO stages. Within each staging system, the survival curves differed significantly with the best 5-year survival in early stages I and II (91%). Survival for stage IV (70 to 77%) was significantly better compared to stage III (49 to 54%). Early stages had a significant longer recurrence-free survival (86 to 90%) than advanced stages III and IV (55 to 56%).
Conclusions
The proportion of patients with IASLC/ITMIG stage I increased remarkably, whereas the distribution in advanced stages III and IV was nearly similar. The new TNM-staging system presents a clinically useful and applicable system, which can be used for indication, stage-adapted therapy, and prediction of prognosis for overall and recurrence-free survival.
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New laparoscopic procedure for left-sided pancreatic cancer—artery-first approach laparoscopic RAMPS using 3D technique
Abstract
Background
For left-sided pancreatic ductal adenocarcinoma (PDAC), radical antegrade modular pancreatosplenectomy (RAMPS) is a reasonable surgical approach for tumor-free margin resection and systemic lymph node clearance. In pancreaticoduodenectomy for PDAC, the superior mesenteric artery (SMA)-first approach (or the "artery-first approach") has become the standard procedure. With improvements in laparoscopic instruments and techniques, some surgeons attempted to apply laparoscopic RAMPS (L-RAMPS) for carefully selected patients with left-sided PDAC. However, owing to several technical difficulties in this procedure, its application remains uncommon. Moreover, the artery-first approach in L-RAMPS has not been reported. Here, we developed the artery-first approach L-RAMPS for left-sided PDAC and have presented the same in this report.
Case presentation
Between June 2014 and July 2015, 16 patients with left-sided PDAC were referred to our division for pancreatic resection. The following technique was used for performing L-RAMPS on 3 of the 16 patients (19%). Six trocars were placed. After opening the omental bursa, only the middle segment of the pancreas was initially separated from both the left renal vein and the SMA. We termed this procedure as the "artery-first approach using a dome-shaped dorsomedial dissection (3D) technique." This 3D technique enabled the interruption of the entire arterial supply to the specimen while preserving the venous drainage through the splenic vein for preventing venous congestion. The technique also contributed to the early detection of no tumor infiltration into the SMA and the early determination of posterior dissection plane. After pancreatic neck transection, the splenic artery and vein were divided. Finally, the pancreatic tail and spleen were dissected in a right-to-left direction. All operations were completed without any intraoperative complications. The median blood loss and retrieved lymph node count were 75 mL and 37, respectively, which were superior to those reported by other previous studies on L-RAMPS. All resection margins were free of carcinoma. No severe postoperative complications were observed.
Conclusions
The artery-first approach L-RAMPS using 3D technique is safe and feasible to perform. The significance of our proposed procedure is minimal blood loss and precise lymphadenectomy. Therefore, this novel technique may become the preferred treatment for left-sided PDAC in selected cases.
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Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials
Abstract
Background
Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients' decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial.
Methods/design
Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients' understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes.
Discussion
PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers.
Trial registration
Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).
http://ift.tt/2jFbnNP
Prevalence of incidental breast cancer and precursor lesions in autopsy studies: a systematic review and meta-analysis
Abstract
Background
Autopsy studies demonstrate the prevalence pool of incidental breast cancer in the population, but estimates are uncertain due to small numbers in any primary study. We aimed to conduct a systematic review of autopsy studies to estimate the prevalence of incidental breast cancer and precursors.
Methods
Relevant articles were identified through searching PubMed and Embase from inception up to April 2016, and backward and forward citations. We included autopsy studies of women with no history of breast pathology, which included systematic histological examination of at least one breast, and which allowed calculation of the prevalence of incidental breast cancer or precursor lesions. Data were pooled using logistic regression models with random intercepts (non-linear mixed models).
Results
We included 13 studies from 1948 to 2010, contributing 2363 autopsies with 99 cases of incidental cancer or precursor lesions. More thorough histological examination (≥20 histological sections) was a strong predictor of incidental in-situ cancer and atypical hyperplasia (OR = 126·8 and 21·3 respectively, p < 0·001), but not invasive cancer (OR = 1·1, p = 0·75). The estimated mean prevalence of incidental cancer or precursor lesion was 19·5% (0·85% invasive cancer + 8·9% in-situ cancer + 9·8% atypical hyperplasia).
Conclusion
Our systematic review in ten countries over six decades found that incidental detection of cancer in situ and breast cancer precursors is common in women not known to have breast disease during life. The large prevalence pool of undetected cancer in-situ and atypical hyperplasia in these autopsy studies suggests screening programs should be cautious about introducing more sensitive tests that may increase detection of these lesions.
http://ift.tt/2jFbkBD
Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma
Abstract
Background
Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients.
Methods
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression.
Results
Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1–6.1), p = 0.029.
Conclusion
We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.
http://ift.tt/2iaMYiC
Characteristics and outcome in patients with non-specific symptoms and signs of cancer referred to a fast track cancer patient pathway; a retrospective cohort study
Abstract
Background
In 2012 a new cancer patient pathway for patients with non-specific symptoms and signs of cancer (NSSC-CPP) was introduced in Denmark. Limited information is available about the patients referred to the NSSC-CPP and the investigational course. The aim was to describe the population and the investigational course, estimate the prevalence of cancer and one-year mortality, and identify factors associated with a subsequent cancer diagnosis in patients referred to the NSSC-CPP.
Method
This cohort study included patients with at least one visit at the NSSC-CPP at North Zealand Hospital in Denmark (NOH) from October 1st 2013 to September 30th 2014. Data was based on retrospective reviews of the patient files. Logistic regression identified factors associated with a subsequent cancer diagnosis. Multivariate analyses were adjusted by age, gender, smoking status and alcohol consumption. Kaplan-Meier survival plots were made at one-year follow-up.
Results
Eight hundred twenty-five patients were included with a median age of 67 years, 47.4% were male. Prevalence of cancer within one year was 16.7% (138/825). 70.3% (97/138) were solid cancers and 29.7% (41/138) were haematological cancers. During the investigational course 76.7% went through advanced diagnostic imaging (ultrasound, CT, FDG-PET/CT or MRI). Anaemia (OR1.63 CI1.02–2.60), leucocytosis (OR 2.06 CI 1.34–3.15), thrombocytopenia (OR 4.13 CI 2.02–8.47) and elevated LDH (OR 1.64 CI 1.07–2.52) and CRP (OR 2.56 CI 1.66–3.95) were associated with a cancer diagnosis when adjusting for possible confounders. No single non-specific symptom was significantly associated with a cancer diagnosis. One-year mortality for those diagnosed with cancer was 44.2%.
Conclusion
The prevalence of cancer matches that of another NSSC-CPP in Denmark. Deviations in basic biochemistry were associated with a higher probability of underlying cancer and could possibly raise the level of suspicion of malignancy among physicians. High one-year mortality was seen amongst patients diagnosed with cancer.
http://ift.tt/2jD7VTV
Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials
Abstract
Background
Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients' decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial.
Methods/design
Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients' understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes.
Discussion
PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers.
Trial registration
Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).
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Prevalence of incidental breast cancer and precursor lesions in autopsy studies: a systematic review and meta-analysis
Abstract
Background
Autopsy studies demonstrate the prevalence pool of incidental breast cancer in the population, but estimates are uncertain due to small numbers in any primary study. We aimed to conduct a systematic review of autopsy studies to estimate the prevalence of incidental breast cancer and precursors.
Methods
Relevant articles were identified through searching PubMed and Embase from inception up to April 2016, and backward and forward citations. We included autopsy studies of women with no history of breast pathology, which included systematic histological examination of at least one breast, and which allowed calculation of the prevalence of incidental breast cancer or precursor lesions. Data were pooled using logistic regression models with random intercepts (non-linear mixed models).
Results
We included 13 studies from 1948 to 2010, contributing 2363 autopsies with 99 cases of incidental cancer or precursor lesions. More thorough histological examination (≥20 histological sections) was a strong predictor of incidental in-situ cancer and atypical hyperplasia (OR = 126·8 and 21·3 respectively, p < 0·001), but not invasive cancer (OR = 1·1, p = 0·75). The estimated mean prevalence of incidental cancer or precursor lesion was 19·5% (0·85% invasive cancer + 8·9% in-situ cancer + 9·8% atypical hyperplasia).
Conclusion
Our systematic review in ten countries over six decades found that incidental detection of cancer in situ and breast cancer precursors is common in women not known to have breast disease during life. The large prevalence pool of undetected cancer in-situ and atypical hyperplasia in these autopsy studies suggests screening programs should be cautious about introducing more sensitive tests that may increase detection of these lesions.
from Cancer via ola Kala on Inoreader http://ift.tt/2jFbkBD
via IFTTT
Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma
Abstract
Background
Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients.
Methods
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression.
Results
Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1–6.1), p = 0.029.
Conclusion
We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.
from Cancer via ola Kala on Inoreader http://ift.tt/2iaMYiC
via IFTTT
Characteristics and outcome in patients with non-specific symptoms and signs of cancer referred to a fast track cancer patient pathway; a retrospective cohort study
Abstract
Background
In 2012 a new cancer patient pathway for patients with non-specific symptoms and signs of cancer (NSSC-CPP) was introduced in Denmark. Limited information is available about the patients referred to the NSSC-CPP and the investigational course. The aim was to describe the population and the investigational course, estimate the prevalence of cancer and one-year mortality, and identify factors associated with a subsequent cancer diagnosis in patients referred to the NSSC-CPP.
Method
This cohort study included patients with at least one visit at the NSSC-CPP at North Zealand Hospital in Denmark (NOH) from October 1st 2013 to September 30th 2014. Data was based on retrospective reviews of the patient files. Logistic regression identified factors associated with a subsequent cancer diagnosis. Multivariate analyses were adjusted by age, gender, smoking status and alcohol consumption. Kaplan-Meier survival plots were made at one-year follow-up.
Results
Eight hundred twenty-five patients were included with a median age of 67 years, 47.4% were male. Prevalence of cancer within one year was 16.7% (138/825). 70.3% (97/138) were solid cancers and 29.7% (41/138) were haematological cancers. During the investigational course 76.7% went through advanced diagnostic imaging (ultrasound, CT, FDG-PET/CT or MRI). Anaemia (OR1.63 CI1.02–2.60), leucocytosis (OR 2.06 CI 1.34–3.15), thrombocytopenia (OR 4.13 CI 2.02–8.47) and elevated LDH (OR 1.64 CI 1.07–2.52) and CRP (OR 2.56 CI 1.66–3.95) were associated with a cancer diagnosis when adjusting for possible confounders. No single non-specific symptom was significantly associated with a cancer diagnosis. One-year mortality for those diagnosed with cancer was 44.2%.
Conclusion
The prevalence of cancer matches that of another NSSC-CPP in Denmark. Deviations in basic biochemistry were associated with a higher probability of underlying cancer and could possibly raise the level of suspicion of malignancy among physicians. High one-year mortality was seen amongst patients diagnosed with cancer.
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"Anticancer Res"[jour]; +80 new citations
80 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/12/01
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells
Abstract
Background
Pharmacology-based target identification has become a novel strategy leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities; however, the underlying mechanisms remain unclear. The current study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy.
Methods
The anti-metastasis ability of EA was validated by MMTV-PyMT mice and in vitro cell models. Drug affinity responsive target stability (DARTS) was utilized to identify ACTN4 as the direct target of EA. The metastatic regulated function of ACTN4 were assessed by cancer stem cells (CSCs)-related assays, including mammosphere formation, tumorigenic ability, reattachment differentiation, and signaling pathway analysis. The mechanisms of ACTN4 on β-catenin stabilization were investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The clinical significance of ACTN4 was based on human tissue microarray (TMA) analysis and The Cancer Genome Atlas (TCGA) database exploration.
Results
EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, and was accompanied by a limited CSC population. ACTN4 knockdown resulted in the blockage of malignant cell proliferation, colony formation, and ameliorated metastasis potency. ACTN4-positive CSCs exhibited a higher ESA+ proportion, increased mammosphere-formation ability, and enhanced in vivo tumorigenesis ability. Mechanism exploration revealed that interruption of ACTN4/β-catenin interaction will result in the activation of β-catenin proteasome degradation. Increased ACTN4 expression was directly associated with the advanced cancer stage, an increased incidence of metastasis, and poor overall survival period.
Conclusions
Taken together, our results suggest that ACTN4 plays an important role in breast CSCs-related metastasis and is a novel therapeutic target of EA treatment.
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Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells
Abstract
Background
Pharmacology-based target identification has become a novel strategy leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities; however, the underlying mechanisms remain unclear. The current study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy.
Methods
The anti-metastasis ability of EA was validated by MMTV-PyMT mice and in vitro cell models. Drug affinity responsive target stability (DARTS) was utilized to identify ACTN4 as the direct target of EA. The metastatic regulated function of ACTN4 were assessed by cancer stem cells (CSCs)-related assays, including mammosphere formation, tumorigenic ability, reattachment differentiation, and signaling pathway analysis. The mechanisms of ACTN4 on β-catenin stabilization were investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The clinical significance of ACTN4 was based on human tissue microarray (TMA) analysis and The Cancer Genome Atlas (TCGA) database exploration.
Results
EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, and was accompanied by a limited CSC population. ACTN4 knockdown resulted in the blockage of malignant cell proliferation, colony formation, and ameliorated metastasis potency. ACTN4-positive CSCs exhibited a higher ESA+ proportion, increased mammosphere-formation ability, and enhanced in vivo tumorigenesis ability. Mechanism exploration revealed that interruption of ACTN4/β-catenin interaction will result in the activation of β-catenin proteasome degradation. Increased ACTN4 expression was directly associated with the advanced cancer stage, an increased incidence of metastasis, and poor overall survival period.
Conclusions
Taken together, our results suggest that ACTN4 plays an important role in breast CSCs-related metastasis and is a novel therapeutic target of EA treatment.
http://ift.tt/2jE89Kl
Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated with an increased local failure rate following conventional therapy
Abstract
Studies on melanoma brain metastases (MBM) with regard to mutational status are lacking. We investigated the outcomes of MBM in molecularly characterized patients for BRAF and NRAS mutations receiving conventional treatment. We investigated associations between outcomes [competing risk of local and distant brain failure (LF, DF) and overall survival (OS)] and clinical/pathological features of patients with known mutation status following initial treatment of MBM. Competing risk analysis was performed using the methods of Fine and Gray. We identified 235 patients with MBM diagnosed from 2005 to 2011. Mutation prevalence was BRAF non-V600K 98 (42%), BRAF V600K 34 (14%), NRAS 43 (18%), and wild-type for both genes (WT) 60 (26%) patients. Six month cumulative incidence LF rates were 3% for combined SRS or surgery with adjuvant radiation, 18% for surgery, 18% for SRS, 60% for WBRT, and 67% for systemic therapy. On multivariate analysis, only mutation status and initial treatment type were found to be independent predictors of local control. As compared to WT, NRAS (HR 2.58, 95% CI 1.18–5.67, p = 0.02) and BRAF V600K (HR 2.83, 95% CI 1.23–6.47, p = 0.01) mutational status were statistically significant while BRAF non-V600K status was not statistically significant (p = 0.23). Mutation status was not associated with DF or OS. BRAF V600K and NRAS mutation status predict increased LF following conventional treatments for MBM. These data can inform the design and interpretation of future MBM trials.
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Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated with an increased local failure rate following conventional therapy
Abstract
Studies on melanoma brain metastases (MBM) with regard to mutational status are lacking. We investigated the outcomes of MBM in molecularly characterized patients for BRAF and NRAS mutations receiving conventional treatment. We investigated associations between outcomes [competing risk of local and distant brain failure (LF, DF) and overall survival (OS)] and clinical/pathological features of patients with known mutation status following initial treatment of MBM. Competing risk analysis was performed using the methods of Fine and Gray. We identified 235 patients with MBM diagnosed from 2005 to 2011. Mutation prevalence was BRAF non-V600K 98 (42%), BRAF V600K 34 (14%), NRAS 43 (18%), and wild-type for both genes (WT) 60 (26%) patients. Six month cumulative incidence LF rates were 3% for combined SRS or surgery with adjuvant radiation, 18% for surgery, 18% for SRS, 60% for WBRT, and 67% for systemic therapy. On multivariate analysis, only mutation status and initial treatment type were found to be independent predictors of local control. As compared to WT, NRAS (HR 2.58, 95% CI 1.18–5.67, p = 0.02) and BRAF V600K (HR 2.83, 95% CI 1.23–6.47, p = 0.01) mutational status were statistically significant while BRAF non-V600K status was not statistically significant (p = 0.23). Mutation status was not associated with DF or OS. BRAF V600K and NRAS mutation status predict increased LF following conventional treatments for MBM. These data can inform the design and interpretation of future MBM trials.
http://ift.tt/2nkVEsb
Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis
Abstract
Background
Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients.
Cases presentation
In this report we present our experience in 8 patients with acute or chronic GVHD with refractoriness to steroids and extracorporeal photopheresis treated with ruxolitinib. Three patients had acute GVHD (1 pulmonary, 2 cutaneous, 1 multi-systemic) and 5 had chronic GVHD (3 cutaneous); 85% obtained an overall response and 50% a complete response with a tolerable toxicity profile.
Conclusions
In our series, Ruxolitinib was very active as a rescue therapy for patients with acute or chronic GVHD refractory to standard treatment.
http://ift.tt/2j9PnuO
Compassionate use of ruxolitinib in acute and chronic graft versus host disease refractory both to corticosteroids and extracorporeal photopheresis
Abstract
Background
Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients.
Cases presentation
In this report we present our experience in 8 patients with acute or chronic GVHD with refractoriness to steroids and extracorporeal photopheresis treated with ruxolitinib. Three patients had acute GVHD (1 pulmonary, 2 cutaneous, 1 multi-systemic) and 5 had chronic GVHD (3 cutaneous); 85% obtained an overall response and 50% a complete response with a tolerable toxicity profile.
Conclusions
In our series, Ruxolitinib was very active as a rescue therapy for patients with acute or chronic GVHD refractory to standard treatment.
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Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis
Abstract
Metastasis has intrigued researchers for more than 100 years. Despite the development of technologies and therapeutic strategies, metastasis is still the major cause of cancer-related death until today. The famous "seed and soil" hypothesis is widely cited and accepted, and it still provides significant instructions in cancer research until today. To our knowledge, there are few reviews that comprehensively and correlatively focus on both the seed and soil factors involved in cancer metastasis; moreover, despite the fact that increasingly underlying mechanisms and concepts have been defined recently, previous perspectives are appealing but may be limited. Hence, we reviewed factors involved in cancer metastasis, including both seed and soil factors. By integrating new concepts with the classic hypothesis, we aim to provide a comprehensive understanding of the "seed and soil" hypothesis and to conceptualize the framework for understanding factors involved in cancer metastasis. Based on a dynamic overview of this field, we also discuss potential implications for future research and clinical therapeutic strategies.
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Factors involved in cancer metastasis: a better understanding to “seed and soil” hypothesis
Abstract
Metastasis has intrigued researchers for more than 100 years. Despite the development of technologies and therapeutic strategies, metastasis is still the major cause of cancer-related death until today. The famous "seed and soil" hypothesis is widely cited and accepted, and it still provides significant instructions in cancer research until today. To our knowledge, there are few reviews that comprehensively and correlatively focus on both the seed and soil factors involved in cancer metastasis; moreover, despite the fact that increasingly underlying mechanisms and concepts have been defined recently, previous perspectives are appealing but may be limited. Hence, we reviewed factors involved in cancer metastasis, including both seed and soil factors. By integrating new concepts with the classic hypothesis, we aim to provide a comprehensive understanding of the "seed and soil" hypothesis and to conceptualize the framework for understanding factors involved in cancer metastasis. Based on a dynamic overview of this field, we also discuss potential implications for future research and clinical therapeutic strategies.
http://ift.tt/2ANw8BT
DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies
Abstract
The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them 'age acceleration'. We aimed to assess associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma, nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450K Beadchip assay with cancer risk (N=3,216 cases) and survival (N=1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15 to 30% for the fourth vs. first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors. This article is protected by copyright. All rights reserved.
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Testicular orphan receptor 4 promotes tumor progression and implies poor survival through AKT3 regulation in seminoma
Abstract
Seminoma is recognized as the most common testicular germ cell tumor which mainly occurs in the 15-35-year-old young men worldwide. Early studies have indicated that testicular nuclear receptor 4 (TR4) firstly cloned from testis is involved in the invasion and metastasis of several human tumors, however, little attention is paid to the function of TR4 in Seminoma. Our Immunohistochemical (IHC) staining results showed that patients who underwent advanced stage tended to higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced Overall Survival in seminoma patients. In vitro MTS, western blot and transwell assays after manipulating TR4 expression in Tcam-2 cells revealed that TR4 induced epithelial-to-mesenchymal transition (EMT) and promoted Tcam-2 cells proliferation and invasion. Mechanism dissection demonstrated that AKT3, a critical component in the signaling pathway, played a crucial role in mediating TR4-promoted Tcam-2 cells proliferation and invasion. We further revealed TR4 modulated AKT3 at the transcriptional level via chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the AKT3 siRNA blocked the function of TR4. Overall, these findings firstly elucidate TR4 is a novel prognostic marker and plays a critical role in the metastatic capacity of Tcam-2 cells by EMT regulation and consequently targeting TR4-AKT3 pathway may serve as a potential therapeutic approach for seminoma.
This article is protected by copyright. All rights reserved.
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DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies
Abstract
The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them 'age acceleration'. We aimed to assess associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma, nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450K Beadchip assay with cancer risk (N=3,216 cases) and survival (N=1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15 to 30% for the fourth vs. first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors. This article is protected by copyright. All rights reserved.
http://ift.tt/2BCwc4D
Testicular orphan receptor 4 promotes tumor progression and implies poor survival through AKT3 regulation in seminoma
Abstract
Seminoma is recognized as the most common testicular germ cell tumor which mainly occurs in the 15-35-year-old young men worldwide. Early studies have indicated that testicular nuclear receptor 4 (TR4) firstly cloned from testis is involved in the invasion and metastasis of several human tumors, however, little attention is paid to the function of TR4 in Seminoma. Our Immunohistochemical (IHC) staining results showed that patients who underwent advanced stage tended to higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced Overall Survival in seminoma patients. In vitro MTS, western blot and transwell assays after manipulating TR4 expression in Tcam-2 cells revealed that TR4 induced epithelial-to-mesenchymal transition (EMT) and promoted Tcam-2 cells proliferation and invasion. Mechanism dissection demonstrated that AKT3, a critical component in the signaling pathway, played a crucial role in mediating TR4-promoted Tcam-2 cells proliferation and invasion. We further revealed TR4 modulated AKT3 at the transcriptional level via chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the AKT3 siRNA blocked the function of TR4. Overall, these findings firstly elucidate TR4 is a novel prognostic marker and plays a critical role in the metastatic capacity of Tcam-2 cells by EMT regulation and consequently targeting TR4-AKT3 pathway may serve as a potential therapeutic approach for seminoma.
This article is protected by copyright. All rights reserved.
http://ift.tt/2jDqPdn
Total Mercury Determination in Muscle and Liver Tissue Samples from Brazilian Amazon Fish Using Slurry Sampling
Abstract
This paper presents a slurry sampling method for total mercury determination by graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from the Amazon. The tissue samples were lyophilized and macerated, and then the slurry samples were prepared by putting 20 mg of tissue, added to a solution containing Triton X-100, Suprapur HNO3, and zirconium nitrate directly in sampling vials of a spectrometer. Mercury standard solutions were prepared under the same conditions as the slurry samples. The slurry samples and the mercury standard solutions were sonicated for 20 s. Twenty microliters of slurry samples were injected into the graphite tube, which contained an internal wall lined with tungsten carbide. Under these conditions, it was possible to thermally stabilize the mercury up to an atomization temperature of 1700 °C. The method was validated by mercury determination in reference materials DORM-4 and DOLT-4. The LOD and LOQ were 0.014 and 0.045 mg kg−1, respectively, and recovery percentages in relation to the concentration values were certified in the order of 98%.
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Seleno-compounds and Carnosic Acid Added to Diets with Rapeseed and Fish Oils Affect Concentrations of Selected Elements and Chemical Composition in the Liver, Heart and Muscles of Lambs
Abstract
The objective of our studies was to investigate effects of carnosic acid (CA), selenized yeast (SeY) and selenate (SeVI) added to the diet including rapeseed oil (RO) and fish oil (FO) on concentrations of elements, fatty acids (FAs), tocopherols, cholesterol, and malondialdehyde in the liver, heart, musculus longissimus dorsi (MLD), and musculus biceps femoris (MBF) of lambs. Lambs were fed diets: group I—the basal diet (BD) with RO; group II—BD with RO and FO; group III—BD with RO, FO, and CA; group IV—BD with RO, FO, CA, and SeY; group V—BD with RO, FO, CA, and SeVI. The diets with Se compounds increased Se concentrations in all tissues compared with other diets. The diet with SeVI increased Cd, Sb, and Pb concentrations in the liver compared to groups I, II, and IV. The diets containing Se compounds increased Sb and Pb concentrations in MBF compared to groups I and II. All diets with CA reduced As, Sb, and Pb concentrations in MLD compared to groups I and II. All diets with FO increased concentrations of FAs and malondialdehyde in the liver compared to group I. All diets with FO decreased FAs concentrations in MBF compared to group I. The diets containing CA with/without Se compounds increased malondialdehyde concentrations in MBF compared to groups I and II. The diet with Se compounds reduced malondialdehyde concentrations in MLD compared to group II. All diets with FO changed concentrations of tocopherols and cholesterol in all tissues compared to group I. Our study showed that the addition of SeY or SeVI to the experimental diet increased the concentration of Se in all assayed tissues of lambs without adversely influencing performance or causing physiological disorders in internal organs. Both, SeY or SeVI added to the experimental diet decreased the oxidative stress and the concentrations of As, Sb, and Pb in MLD compared with the diets containing RO, irrespective of the presence of FO (groups I and II). Our study provides useful knowledge for nutritionists carrying out further investigations aimed at improving farm animal health, performance, and the nutritional quality of animal products for humans.
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Magnesium in Breast Cancer: What Is Its Influence on the Progression of This Disease?
Abstract
Breast cancer is a disease of high mortality, characterized by the progressive accumulation of mutations that contribute to the uncontrolled development of breast tissue cells. Literature shows that disturbances in mineral homeostasis, such as magnesium, may interfere with tumor progression. The objective of this study is to provide updated information about magnesium's role in the pathogenesis of breast cancer. A review of literature was carried out from a search for articles in the PubMed and CAPES Periodicals databases published between 1995 and 2016 with the cross-references of the descriptors "magnesium," "breast neoplasms," and "oxidative stress" and the corresponding words in Portuguese. We included studies on the metabolism and bioavailability of magnesium and studies related to breast cancer and excluded articles in which only the abstract was available, dissertations, theses, articles involving adjuvant and/or neoadjuvant therapies, and supplementation of minerals in breast cancer patients. Magnesium is a mineral that participates in the metabolism of various nutrients and nucleic acids. In the presence of breast cancer, neoplastic cells increase the expression of magnesium transport channels, which raises the intracellular concentration of the mineral, contributing to tumor growth through its function of increasing energy demand. The data obtained in this review illustrates the influence of magnesium on the progression of breast cancer. However, the existing data are scarce and inconsistent, which demonstrates a need for further studies on the subject with a goal to have better control of the disease.
from Cancer via ola Kala on Inoreader http://ift.tt/2zI867e
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Total Mercury Determination in Muscle and Liver Tissue Samples from Brazilian Amazon Fish Using Slurry Sampling
Abstract
This paper presents a slurry sampling method for total mercury determination by graphite furnace atomic absorption spectrometry (GFAAS) in tissue of fish from the Amazon. The tissue samples were lyophilized and macerated, and then the slurry samples were prepared by putting 20 mg of tissue, added to a solution containing Triton X-100, Suprapur HNO3, and zirconium nitrate directly in sampling vials of a spectrometer. Mercury standard solutions were prepared under the same conditions as the slurry samples. The slurry samples and the mercury standard solutions were sonicated for 20 s. Twenty microliters of slurry samples were injected into the graphite tube, which contained an internal wall lined with tungsten carbide. Under these conditions, it was possible to thermally stabilize the mercury up to an atomization temperature of 1700 °C. The method was validated by mercury determination in reference materials DORM-4 and DOLT-4. The LOD and LOQ were 0.014 and 0.045 mg kg−1, respectively, and recovery percentages in relation to the concentration values were certified in the order of 98%.
http://ift.tt/2jFoT46
Seleno-compounds and Carnosic Acid Added to Diets with Rapeseed and Fish Oils Affect Concentrations of Selected Elements and Chemical Composition in the Liver, Heart and Muscles of Lambs
Abstract
The objective of our studies was to investigate effects of carnosic acid (CA), selenized yeast (SeY) and selenate (SeVI) added to the diet including rapeseed oil (RO) and fish oil (FO) on concentrations of elements, fatty acids (FAs), tocopherols, cholesterol, and malondialdehyde in the liver, heart, musculus longissimus dorsi (MLD), and musculus biceps femoris (MBF) of lambs. Lambs were fed diets: group I—the basal diet (BD) with RO; group II—BD with RO and FO; group III—BD with RO, FO, and CA; group IV—BD with RO, FO, CA, and SeY; group V—BD with RO, FO, CA, and SeVI. The diets with Se compounds increased Se concentrations in all tissues compared with other diets. The diet with SeVI increased Cd, Sb, and Pb concentrations in the liver compared to groups I, II, and IV. The diets containing Se compounds increased Sb and Pb concentrations in MBF compared to groups I and II. All diets with CA reduced As, Sb, and Pb concentrations in MLD compared to groups I and II. All diets with FO increased concentrations of FAs and malondialdehyde in the liver compared to group I. All diets with FO decreased FAs concentrations in MBF compared to group I. The diets containing CA with/without Se compounds increased malondialdehyde concentrations in MBF compared to groups I and II. The diet with Se compounds reduced malondialdehyde concentrations in MLD compared to group II. All diets with FO changed concentrations of tocopherols and cholesterol in all tissues compared to group I. Our study showed that the addition of SeY or SeVI to the experimental diet increased the concentration of Se in all assayed tissues of lambs without adversely influencing performance or causing physiological disorders in internal organs. Both, SeY or SeVI added to the experimental diet decreased the oxidative stress and the concentrations of As, Sb, and Pb in MLD compared with the diets containing RO, irrespective of the presence of FO (groups I and II). Our study provides useful knowledge for nutritionists carrying out further investigations aimed at improving farm animal health, performance, and the nutritional quality of animal products for humans.
http://ift.tt/2kdqdyP
Magnesium in Breast Cancer: What Is Its Influence on the Progression of This Disease?
Abstract
Breast cancer is a disease of high mortality, characterized by the progressive accumulation of mutations that contribute to the uncontrolled development of breast tissue cells. Literature shows that disturbances in mineral homeostasis, such as magnesium, may interfere with tumor progression. The objective of this study is to provide updated information about magnesium's role in the pathogenesis of breast cancer. A review of literature was carried out from a search for articles in the PubMed and CAPES Periodicals databases published between 1995 and 2016 with the cross-references of the descriptors "magnesium," "breast neoplasms," and "oxidative stress" and the corresponding words in Portuguese. We included studies on the metabolism and bioavailability of magnesium and studies related to breast cancer and excluded articles in which only the abstract was available, dissertations, theses, articles involving adjuvant and/or neoadjuvant therapies, and supplementation of minerals in breast cancer patients. Magnesium is a mineral that participates in the metabolism of various nutrients and nucleic acids. In the presence of breast cancer, neoplastic cells increase the expression of magnesium transport channels, which raises the intracellular concentration of the mineral, contributing to tumor growth through its function of increasing energy demand. The data obtained in this review illustrates the influence of magnesium on the progression of breast cancer. However, the existing data are scarce and inconsistent, which demonstrates a need for further studies on the subject with a goal to have better control of the disease.
http://ift.tt/2zI867e
Histopathological analysis of meningioma and its variants: A study of fifty cases
Indian Journal of Cancer 2017 54(1):313-315
BACKGROUND: The study was conducted to know the various histopathological variants of meningiomas, the age incidence and sex ratio. MATERIALS AND METHODS: A retrospective and prospective analysis of all the samples sent for histopathology for 2 years during June 2013–May 2015 was done to diagnose meningioma and its variants. Cases were analyzed in detail about the complete clinical history, exact location, and clinical and radiological diagnosis. The majority of the cases were clinically and radiologically diagnosed as meningioma. RESULTS: Of 50 cases which were diagnosed as meningiomas, 21 were meningothelial variant, 15 were psammomatous, 8 were fibroblastic, 4 were transitional, and 1 case each of anaplastic and atypical variant. The most common age group was between 41 and 50 years. The youngest age group was 16 years and oldest was 70. The male:female ratio was 1:1.5. CONCLUSION: The majority of the meningiomas have been observed between 41 and 50 years. Their proper recognition is therefore important to allow appropriate treatment. Histopathological study plays a major role by which we can diagnose the lesion. Meningiomas typically develop in middle-aged individuals and occur more frequently in women than men. These lesions may also occur in children.
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Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A single-institution experience from South India
Indian Journal of Cancer 2017 54(1):228-230
Wide use and incorporation of newer diagnostic tools in the management of metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of personalized treatment of this disease. With the wide use of polymerase chain reaction and fluorescence in situ hybridization increasing number of patients are being diagnosed with dual and complex mutations posing a new challenge in the management of patient with metastatic NSCLC. In this article, we would like to bring forth six such cases and the varied responses to the current available treatment in patients with complex and dual mutations. The appropriate management in these groups of patients is yet to be standardized.
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Is pulmonary metastasectomy beneficial in head and neck squamous cell carcinoma? A review of literature
Indian Journal of Cancer 2017 54(1):2-5
Metastatic head and neck squamous cell carcinoma (HNSCC) has traditionally carried a dismal prognosis; however with advances in care, it has been shown that pulmonary metastasectomy is a viable therapeutic option in selected patients, palliating symptoms and improving survival. With the increasing incidence of human papilloma virus-related HNSCC and better availability of minimal access surgery, there is a need to better understand the role of pulmonary metastasectomy in the treatment of HNSCC. This article summarizes the literature on indications, results, surgical options and approaches, clinical dilemmas, and controversies associated with pulmonary metastasectomy in HNSCC, to identify suitable candidates and optimize outcomes.
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Testicular seminoma: Are clinical features and treatment outcomes any different in India?
Indian Journal of Cancer 2017 54(1):385-387
AIM: This study aims to identify clinical features, treatment outcomes, and prognostic factors for relapse and survival in patients with testicular seminoma. MATERIALS AND METHODS: Retrospective analysis of all patients with pure seminoma treated at our center during over a decade (January 2005–December 2014) was carried out. Patient demographics, tumor characteristics, and treatment details and pattern of recurrence were recorded in a structured format, and disease-free survival and overall survival were calculated. RESULTS: Sixty-three patients' case records were included in the analysis. Ten patients developed disease in the undescended testis. All patients underwent orchiectomy as the initial treatment procedure. Majority of the patients were Stage I (57.14%) followed by Stage II (39.6%). Among the patients with Stage I, 55.5% received adjuvant chemotherapy while 22.2% received adjuvant radiation and the rest opted for surveillance. The compliance for active surveillance was very poor. Among patients with Stage II disease, majority (80%) were treated with adjuvant chemotherapy and the rest with radiation. At a median follow-up of 49 months, there were four recurrences of which three were salvaged successfully, and one patient remained alive with disease. There were no disease-related deaths. CONCLUSIONS: Testicular seminoma remains to be relatively low and majority of them presented with Stage I disease and single agent carboplatin appeared to be the preferred adjuvant treatment. Advanced disease patients were treated with etoposide and cisplatin/bleomycin, etoposide and cisplatin chemotherapy and the clinical outcome is comparable with the Western literature.
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