Antinuclear antibodies and cancer: A literature review

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Alexandru Vlagea, Sandra Falagan, Gerardo Gutiérrez-Gutiérrez, Juan Moreno-Rubio, María Merino, Francisco Zambrana, Enrique Casado, María Sereno
Antinuclear antibodies (ANAs) are a spectrum of autoantibodies targeted to various nuclear and cytoplasmic components of the cells. They are very useful as serological markers for different autoimmune disease, like systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), scleroderma, polymyositis, or mixed connective tissue disease. In these years, an increasing attention has been focussed in the relationship between tumours and autoimmunity. Different authors have demonstrated that ANAs are presented, not only in autoimmune diseases, also in serum of patients with different types of cancers. These data suggested that ANAs could be involved in the pathogenesis of cancer as well as other premalignant disease. In this review, we are going to describe all data reported about the presence of these antibodies in samples from patients with cancer as well as the potential role of some of these proteins in early detection and prognosis.



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The unfolded protein response as a target for anticancer therapeutics

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Mengxiong Wang, Mary E. Law, Ronald K. Castellano, Brian K. Law
The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells, responsible for protein synthesis, folding, sorting, and transportation. ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein. Tumor microenvironmental conditions, such as nutrient deprivation, hypoxia, and oxidative stress perturb protein folding and trigger chronic ER stress. Cancer cells can tolerate mild ER stress, however, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death. Based on this rationale, many drugs have been developed for triggering irremediable ER stress in cancer cells by targeting various processes in the secretory pathway. This review discusses the mechanisms of protein targeting to the ER, the key signaling cassettes that are involved in the ER stress response, and their correlation with cancer formation and progression. Importantly, this review discusses current experimental and FDA approved anti-cancer drugs that induce ER stress, and emerging targets within the secretory pathway for the development of new anticancer drugs.



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Systemic therapy for intermediate and advanced hepatocellular carcinoma: Sorafenib and beyond

Publication date: July 2018
Source:Cancer Treatment Reviews, Volume 68
Author(s): Jean-Luc Raoul, Masatoshi Kudo, Richard S. Finn, Julien Edeline, Maria Reig, Peter R. Galle
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can be prevented. Sorafenib-related AEs have been identified as clinical biomarkers for sorafenib efficacy. Healthcare professionals have become more efficient in managing AEs, identifying patients who are likely to benefit from treatment, and assessing response to treatment, resulting in a trend towards increased overall survival in the sorafenib arms of clinical studies. The rapidly changing treatment landscape due to the emergence of new treatment options (sorafenib and lenvatinib equally effective in first line; regorafenib, cabozantinib, and ramucirumab showing OS benefit in second line with nivolumab approved by the FDA based on response rate) underscores the importance of re-assessing the role of the first approved systemic agent in HCC, sorafenib.



https://ift.tt/2kuAdAN

Asymptomatic Pulmonary Artery Intimal Sarcoma with Chest Wall Metastasis as an Initial Manifestation: An Autopsy Case

Pulmonary artery intimal sarcoma (PAIS) is a rare mesenchymal malignancy arising in the pulmonary trunk or proximal pulmonary artery and shows intraluminal growth. Clinical manifestations in PAIS are predominantly related to the pulmonary artery embolism, so cases with initial symptoms related to an extrapulmonary metastasis are unusual. The present report describes an 82-year-old man without any cardiopulmonary symptoms who was detected with an abnormal shadow on chest radiography during a routine health checkup. Contrast medium-enhanced chest computed tomography revealed an enhancing mass in the right pulmonary artery, pulmonary nodules, and a chest wall tumor corresponding to the abnormal shadow observed using chest radiography. A core needle biopsy for the chest wall tumor determined a pathological diagnosis of unclassified sarcoma. The patient was diagnosed with PAIS on the basis of clinical, radiological, and pathological correlations. He was scheduled to receive supportive care, but died of respiratory failure 1 year from the first visit. An autopsy revealed the pleomorphic sarcoma occupying the entire lumen of the right pulmonary artery with the only site of extrapulmonary metastasis in the chest wall. We should be aware of rare cases of asymptomatic PAIS found through routine health checkups.

https://ift.tt/2IOpgbV

Delineation guideline for the para-aortic lymph node region in cervical cancer

We read with great interest the paper entitled, "An atlas to aid delineation of para-aortic lymph node region in cervical cancer: Design and validation of contouring guidelines," which addresses guidelines for delineating the para-aortic lymph node (PAN) clinical target volume (CTV) in patients with cervical cancer [1]. The authors evaluated 21 patients with 39 pathological PANs identified via positron emission tomography–computed tomography (PET-–CT) and used asymmetrical margins to expand the aorta and inferior vena cava (IVC) and create a CTV with more favourable PAN coverage.

https://ift.tt/2LvYP8s

Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy

To report the primary endpoint of a randomized trial comparing pain response following palliative stereotactic body radiation therapy (SBRT) versus conventionally-fractionated 3D-conformal radiotherapy (3DCRT) for previously untreated spinal metastases.

https://ift.tt/2INLk2d

Prevalence of lung cancer in Isfahan Province, Iran

Publication date: June 2018
Source:Journal of the Egyptian National Cancer Institute, Volume 30, Issue 2
Author(s): Zahra Tolou_Ghamari
ObjectiveTo describe for the first time period prevalence (PP) and incidence rate (Ir) for patients with lung cancer in Isfahan Province/Iran.DesignData associated to the Surveillance, Epidemiology, and End Results; (SEER) was collected from the Isfahan Cancer Registry from March 2011 to March 2015. Lung cancer was distinguished by the related established topography code. PP and Ir were calculated and expressed per 100,000 persons.ResultsIn all, 548 females and 1399 males were identified. For the total population the PP was calculated as 39.1 (distinguished as: 30.7 for bronchus and lung, 7.9 for larynx and 0.5 for trachea). This value corresponded to a PP of 55.3 for males and 22.3 for females (p < 0.001). Irs versus mortality rates were calculated for each year, i.e. 2011–2012, 2012–2013, 2013–2014, and 2014–2015, as 9.3 vs 6.3, 10.1 vs 6.6, 9.9 vs 6.3, 9.6 vs 6.4, respectively. The mean (SD, range) age of the patients was 65.8 (14.7, 1–103) years. In relation to the age of study population, lung cancer occurred in 94% of patients aged between 40 and 90 years.ConclusionThe PP for lung cancer in male population was 2.5 times higher than females. There was a 3.2% increase in the Irs over the study period. To facilitate early diagnosis for better management associated to pharmacotherapy or surgical care, our findings emphasized the advantage of further research and greater effort toward environmental, job related exposure, genetic and geographical factors in Isfahan Province/Iran.



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First experience of the Egyptian National Cancer Institute using the robot-assisted laparoscopic approach in radical hysterectomies for cervical cancer

Publication date: June 2018
Source:Journal of the Egyptian National Cancer Institute, Volume 30, Issue 2
Author(s): Ashraf Saad Zaghloul, Ahmed Mahmoud El-Minawi, Mohamed Atef ElKordy, Amr Kamal Younes, Ahmed Mostafa Mahmoud, Waleed Mohamed Fadlalla, Gamal Amira Mohamed
Aim of workRobotics in surgery led to an improvement of visualization, a better handling of tissues and better suturing. This study aimed to document the first experience of the Egyptian National Cancer Institute (NCI) using the robot-assisted laparoscopic approach in radical hysterectomies for cervical cancer and to highlight observed advantages, disadvantages, morbidity and oncological outcomes.Patients and methodsData of cases that had either early cervical cancer (stage IB-IIA1 with a tumor ≥2 cm) or locally advanced cervical cancer (Stage IIA2-IIB after chemo-radiotherapy) were collected prospectively. Study patients underwent robotic radical hysterectomies for their cervical cancers at the NCI, Cairo University, between January 1, 2015 and December 31, 2016. For each patient, duration of surgery, amount of blood loss, and intra-operative complications were recorded. Similarly, the duration of postoperative hospital-stay, analgesia used and post-operative gastrointestinal recovery were documented. Pathological assessment of safety margins and the lymph nodes number yield were also assessed.ResultsTwenty patients underwent robotic radical hysterectomy during the study period. Twelve cases had early cervical cancer while 8 suffered locally advanced disease. The mean procedure time was 319 (range 240–560) minutes; the mean blood loss was 309 (range 150–600) ml. Three cases had bladder injuries during their procedures. The median hospital stay was 6 (range 4–10) days. One case had a positive margin. The median of lymph nodes yield number was 15 (range 10–25). Follow-up ranged 9–31 months, with only one case developing local recurrence.ConclusionRobotic radical hysterectomy is a feasible approach with a tolerable rate of complications.



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Role of hydroxyurea as an adjuvant treatment after Gamma knife radiosurgery for atypical (WHO grade II) meningiomas

Publication date: June 2018
Source:Journal of the Egyptian National Cancer Institute, Volume 30, Issue 2
Author(s): Khalid Abdel Karim, Amr El Shehaby, Reem Emad, Wael Reda, Manal El Mahdy, Ramy Ghali, Ahmed Nabeel




https://ift.tt/2GTd83h

Rare presentation of rickettsial infection as purpura fulminans: a case report

Purpura fulminans is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly ...

https://ift.tt/2saYKPC

A pilot study of prostate cancer knowledge among African American men and their health care advocates: implications for screening decisions

Abstract

Purpose

Prostate cancer (PCa) is the second leading cause of cancer death in U.S. men [American Cancer Society (ACS)], most often affecting men age 50 and older. The study provides information about factors that influence rural AA men in their decision to undergo screening for PCa with a specific focus on PCa knowledge among AA men and their health care advocates.

Methods

A longitudinal quantitative study included AA males and their health care advocates. Participants were from three Alabama rural counties. Measures included demographics, PCa knowledge, decisional conflict, and health literacy scales.

Results

Thirty-three men with a mean age of 54.61 and 35 health care advocates were included in the study. PROCASE Knowledge Index measure results indicate a lack of PCa knowledge among both male primary participants and their advocates. The knowledge of AA men in the study was somewhat low, with individuals correctly answering approximately six questions out of ten at multiple time points (baseline total M = 6.42, SD = 1.52). Decisional conflict responses at 12 months (38.64) were lower than at baseline (M = 62.88) and at 6 months (M = 58.33), p < .005.

Conclusion

Health care advocates of the 33 male participants were usually women, spouses, or significant others, supporting the vital role women play in men's health specifically in rural underserved communities. Low overall PCa knowledge, including their risk for PCa, among these participants indicates a need for PCa and screening educational interventions and dialogue that include males and their significant others.

https://ift.tt/2Lz9q2C

Lung cancer incidence trends in Uruguay 1990–2014: An age-period-cohort analysis

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Rafael Alonso, Marion Piñeros, Mathieu Laversanne, Carina Musetti, Mariela Garau, Enrique Barrios, Freddie Bray
BackgroundUruguay, a country with one of the highest lung cancer rates worldwide, initiated a series of comprehensive anti-smoking measures in 2005. We assess the tobacco control policies in the context of cohort-driven lung cancer incidence trends over a 25-year period, providing baseline predictions to 2035.MethodsUsing data from the National Cancer Registry of Uruguay, an age-period-cohort analysis of trends 1990–2014 was performed. The NORDPRED package was used to predict the annual number of new cases of lung cancer and incidence rates up to 2035.ResultsIn men, age-standardised (world) rates declined from a peak of 165.6 in 1995 to 103.1 by 2014, translating to a 70% reduction in the risk of lung cancer in men born in 1970 relative to the early-1940s. In females, rates increased steadily from 18.3 in 1991 to 30.0 by 2014, with successive increases in risk among generations of women born 1940–1960. There is however evidence of a decline in observed rates in women born recently. Extrapolations of the trends indicate an 8% reduction in the mean number of new lung cancer cases in men by 2035, but a 69% increase in women.ConclusionDespite observed and predicted reductions in lung cancer incidence in Uruguayan men, rates among women are set to continue to increase, with a large rise in the annual number of female lung cancer diagnoses expected before 2035. There are signals of a diminishing risk among recent generations of women born after 1960. The current analysis provides important baseline information in assessing the future impact of the recent tobacco control initiatives in Uruguay.



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Has cancer survival improved for older people as for younger people? New South Wales, 1980–2012

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Ming Li, Stephen Morrell, Nicola Creighton, Hanna Tervonen, Hui You, David Roder, David Currow
BackgroundCancer survival has improved markedly in Australia for all ages but it is still lower in older patients. We hypothesize that the survival gap by age has increased. Our rationale is that treatment constraints in older people and potentially their limited participation in trials may have limited opportunities for survival gain.MethodsPost-diagnostic five-year cancer-specific mortality rates were analysed by age group for cancers recorded on the NSW Cancer Registry. Live cases were censored on December 31st, 2012. Hazards ratios (HRs) were obtained from proportional hazards regression for 1990-99 and 2000-12 diagnostic periods, using 1980-89 as the reference, adjusting for socio-demographic factors, degree of cancer spread, and for all cancers combined, for cancer sites.ResultsFive-year mortality reduced by diagnostic period for all cancers collectively from 53% in 1980-89 to 33% in 2000-12, with decreases for separate cancer sites. Adjusted HRs (95% confidence intervals) were 0.78 (0.77, 0.80) for 1990-99 and 0.61 (0.58, 0.63) for 2000-12 for all cancers combined. The downward trend in HRs was smaller for the 80+ year age group, leading to significantly higher HRs of 0.83 (0.81, 0.87) and 0.73 (0.70, 0.76) for 1990-99 and 2000-12 respectively. Results were similar using competing risk regression and 5-year rather than 10-year age strata.ConclusionThe reduction in cancer mortality was smaller in older people, as seen in the USA. Research is needed to achieve the best trade-offs between cancer control and harm avoidance in older people. Multidisciplinary teams have an important contribution to make.



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Analysis of incidence, mortality and survival for pancreatic and biliary tract cancers across Europe, with assessment of influence of revised European age standardisation on estimates

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Pamela Minicozzi, Tiziana Cassetti, Claudia Vener, Milena Sant
BackgroundPancreatic (PC) and biliary tract (BTC) cancers have higher incidence and mortality in Europe than elsewhere. We analysed time-trends in PC/BTC incidence, mortality, and survival across Europe. Since the European standard population (ESP) was recently revised to better represent European age structure, we also assessed the effect of adopting the revised ESP to age-standardise incidence and mortality data.MethodsWe analysed PCs/BTCs (≥15 years) diagnosed in 2000–2007 and followed-up to end of 2008, in 29 European countries across five regions: UK/Ireland, and northern, central, southern, and eastern Europe. Incidence, mortality, and 5-year relative survival were compared between regions, by age, sex, and period of diagnosis.ResultsVariation in age-standardised incidence (PC 12–15/100,000; BTC 2–6) and mortality (PC 10–14; BTC 1–5) was modest. Eastern Europe had highest incidence and mortality, and lowest survival; northern and southern Europe had highest age-specific incidence (most age groups) for PC and BTC, respectively. Incidence and survival increased slightly from 2000 to 2007, particularly in elderly patients and women, but survival remained poor (≤8% for PC; 13–18% for BTC). Use of the revised ESP for age-standardisation did not impact European regional incidence and mortality rankings.ConclusionPoor survival for PC and BTC, together with increasing incidence, indicate that action is required. Countries with higher incidence had higher risk factor frequency, suggesting that prevention initiatives targeting risk factors should be promoted. Improvements in diagnosis and treatment are also required. Our results provide a baseline from which to monitor evolution of the PC/BTC burden in Europe.



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Temporal trends in competing mortality from second and subsequent primary cancers, 1980–2014: An Australian population-based study

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Yuanzi Ye, Petr Otahal, Karen E. Wills, Amanda L. Neil, Alison J. Venn
BackgroundSubsequent primary cancers (SPCs) compete with first cancers and non-cancer events as the primary cause of death among cancer patients. We aimed to assess temporal trends in SPC mortality since 1980 among adult-onset cancer patients in competing risk models.MethodsPatients registered with a first cancer in the population-based Tasmanian Cancer Registry, Australia, between 1980–2009 were followed up to December 2014. Cumulative incidence function (CIF) was used to estimate the cumulative incidence of cause-specific deaths in the presence of competing risks. The hazard ratios of SPC-specific deaths were assessed in two regression models: subdistribution hazard ratios from competing risk models (SHRs) and hazard ratios from Cox models (CHRs).ResultsOverall, 5339 (9.3%) of 57,288 patients developed SPCs and 2494 died from SPCs during the follow-up. While the cumulative incidence of first cancer deaths at 5, 10, 15 and 20-years gradually decreased over periods of first cancer diagnosis, the cumulative incidence of SPC deaths did not. The SHRs for SPC-specific deaths increased from the reference period 1980–1984 to a peak for first cancers diagnosed in 1995–1999 (SHR = 1.18, 95%CI 1.03–1.35), before a decrease in 2005–2009 (SHR = 0.82, 95%CI 0.70-0.95) in competing risk models. However, this pattern was not consistent in CHRs. For individuals with specific first cancers, those with a first prostate cancer in 1995–1999 ha d the greatest SPC mortality risk (SHR = 2.08, 95%CI 1.29–3.36).ConclusionCompeting risk models, but not Cox models, demonstrated temporal increases in SPC-specific mortality. Greater detection of non-fatal first prostate cancers appears to have contributed to this trend.



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Determinants of cancer treatment and mortality in older cancer patients using a multi-state model: Results from a population-based study (the INCAPAC study)

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Angéline Galvin, Catherine Helmer, Gaëlle Coureau, Brice Amadeo, Pierre Joly, Camille Sabathé, Alain Monnereau, Isabelle Baldi, Muriel Rainfray, Pierre Soubeyran, Fleur Delva, Simone Mathoulin-Pélissier
IntroductionSeveral studies have reported disparities in the care management and survival of older cancer patients. The aim of our study was to identify determinants of treatment administration in this population of cancer patients aged over 65 years taking into account competing risks of death.MethodsThe INCAPAC study is a population-based study. Four cancer registries and three prospective cohort studies on older subjects (age ≥65 years) from Gironde, a French department, were merged to identify older cancer patients. We used a non-parametric multi-state model including three states (cancer, treatment and all-cause death). This model allowed studying determinants of treatment administration (all treatments including curative, symptomatic and palliative treatments) and mortality considering that patients can move from cancer state to death state, either directly or through the treatment phase. Studied variables were demographic and socioeconomic-, cancer-, health-, and geriatric-related.ResultsA total of 450 patients were included in the analyses. They were mainly aged 85 and over, men and educated. Among included patients, 372 (83%) received cancer treatment. In the final multivariate model, dementia was associated with a lower likelihood of receiving cancer treatment (HR = 0.68, 95% CI = 0.47–0.99). In treated patients, age, sex, comorbidities, dependency and stage at diagnosis were associated to all-cause mortality, and in untreated patients, diagnosis of dementia and stage at diagnosis were associated to mortality.ConclusionFurther studies are necessary to understand the impact of geriatric impairments on treatment administration and to develop clinical practice guidelines.



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Review of methodological challenges in comparing the effectiveness of neoadjuvant chemotherapy versus primary debulking surgery for advanced ovarian cancer in the United States

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Ashley L. Cole, Anna E. Austin, Ryan P. Hickson, Matthew S. Dixon, Emma L. Barber
Randomized trials outside the U.S. have found non-inferior survival for neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) for advanced ovarian cancer (AOC). However, these trials reported lower overall survival and lower rates of optimal debulking than U.S. studies, leading to questions about generalizability to U.S. practice, where aggressive debulking is more common. Consequently, comparative effectiveness in the U.S. remains controversial. We reviewed U.S. comparative effectiveness studies of NACT versus PDS for AOC. Here we describe methodological challenges, compare results to trials outside the U.S., and make suggestions for future research. We identified U.S. studies published in 2010 or later that evaluated the comparative effectiveness of NACT versus PDS on survival in AOC through a PubMed search. Two independent reviewers abstracted data from eligible articles. Nine of 230 articles were eligible for review. Methodological challenges included unmeasured confounders, heterogeneous treatment effects, treatment variations over time, and inconsistent measurement of treatment and survival. Whereas some limitations were unavoidable, several limitations noted across studies were avoidable, including conditioning on mediating factors and immortal time introduced by measuring survival beginning from diagnosis. Without trials in the U.S., non-randomized studies are an important source of evidence for the ideal treatment for AOC. However, several methodological challenges exist when assessing the comparative effectiveness of NACT versus PDS in a non-randomized setting. Future observational studies must ensure that treatment is consistent throughout the study period and that treatment groups are comparable. Rapidly-evolving oncology data networks may allow for identification of treatment intent and other important confounders.



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Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Noah C. Peeri, Jordan H. Creed, Gabriella M. Anic, Reid C. Thompson, Jeffrey J. Olson, Renato V. LaRocca, Sajeel A. Chowdhary, John D. Brockman, Travis A. Gerke, L. Burton Nabors, Kathleen M. Egan
BackgroundSelenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse.MethodsIn a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study.ResultsNone of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70).ConclusionThe present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.



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Avoidable colorectal cancer cases in Denmark – The impact of red and processed meat

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Sofia Lourenço, Vibeke Berglund Gunge, Therese M.-L. Andersson, Camilla Liv Erthmann Andersen, Anne-Sofie Q. Lund, Brian Køster, Gitte Laub Hansen
BackgroundHigh red and processed meat intakes are associated with increased colorectal cancer (CRC) risk. The effect of eliminating or reducing red and processed meat consumption on CRC burden was not previously quantified in Denmark. The aim of this study was to calculate the possible effects of reductions in red and processed meat consumption on future CRC incidence in the Danish adult population.MethodsUnder six scenarios of prevalence exposure (meat consumption) the number of CRC cases in Denmark for a 30-year period (2016-2045) was estimated and compared to the projected number of CRCs if the prevalence of meat consumption remains constant. Data was obtained from the NORDCAN register, Statistics Denmark, and from the Danish dietary survey data (DANSDA). Analyses were conducted using the Prevent model.ResultsDuring the 30-year period, a total of 36,767 (19.8%) CRC cases out of 185,937 expected could be avoided in Denmark by eliminating the consumption of both red and processed meat. For the same period, a modest reduction in both red and processed meat consumption could lead to the prevention of 16,964 (9.1%) CRC cases. The greatest reductions were seen among men, and the highest impact was estimated for the elimination or reduction of processed meat consumption.ConclusionDecreased red and processed meat consumption could reduce the burden of CRC markedly in Denmark. These results can assist public health planners and help highlight the important role of a modest but realistic reduction in meat consumption in the prevention of CRC.



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A prospective study of cancer survivors and risk of sepsis within the REGARDS cohort

Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Justin Xavier Moore, Tomi Akinyemiju, Alfred Bartolucci, Henry E. Wang, John Waterbor, Russell Griffin
BackgroundHospitalized cancer patients are nearly 10 times more likely to develop sepsis when compared to patients with no cancer history. We compared the risk of sepsis between cancer survivors and no cancer history participants, and examined whether race was an effect modifier.MethodsWe performed a prospective analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We categorized participants as "cancer survivors" or "no cancer history" derived from self-reported responses of being diagnosed with any cancer, excluding non-melanoma skin cancer. We defined sepsis as hospitalization for a serious infection with ≥2 systemic inflammatory response syndrome criteria. We performed Cox proportional hazard models to examine the risk of sepsis after cancer (adjusted for sociodemographics, health behaviors, and comorbidities), and stratified by race.ResultsAmong 29,693 eligible participants, 2959 (9.97%) were cancer survivors, and 26,734 (90.03%) were no cancer history participants. Among 1393 sepsis events, the risk of sepsis was higher for cancer survivors (adjusted HR: 2.61, 95% CI: 2.29–2.98) when compared to no cancer history participants. Risk of sepsis after cancer survivorship was similar for Black and White participants (p value for race and cancer interaction = 0.63).ConclusionIn this prospective cohort of community-dwelling adults we observed that cancer survivors had more than a 2.5-fold increased risk of sepsis. Public health efforts should attempt to mitigate sepsis risk by awareness and appropriate treatment (e.g., antibiotic administration) to cancer survivors with suspected infection regardless of the number of years since cancer remission.



https://ift.tt/2KUiWvU

Primary gastric melanoma: a rare presentation

Description

A man in his early 50s presented to the emergency department with complaints of abdominal pain and dark tarry stools. He reported 3/10 burning left upper quadrant abdominal pain that started 2 days before. The pain radiated to the epigastric region and the patient was unsure what exacerbates or relieves the pain. Starting around the same time, the patient had 8 to 10 black tarry stools daily, which were loose in consistency, which were coming out of his ostomy bag. Review of systems was positive for weakness, fatigue, nausea, abdominal pain and change in stools. The patient has a history of T4 caecal adenocarcinoma with metastasis to bladder diagnosed in 2014, for which he underwent right hemicolectomy, low anterior resection, radical cystectomy and colostomy with urostomy that was reversed 2 years later. He also underwent chemotherapy/radiation therapy with (FIFLORI) leucovorin calcium (folinic acid), fluorouracil and irinotecan hydrochloride. Vitals showed a temperature of 97.5°F, pulse...

https://ift.tt/2KWmv4Z

Coronary artery fistula and mid-cavitary obstructive hypertrophic cardiomyopathy: a rare association

We report a case of a 60-year-old man with a history of angina on exertion (New York Heart Association Class II) who was found to have mid-cavitary obstructive hypertrophic cardiomyopathy on two-dimensional echocardiography and whose coronary angiogram showed right coronary artery–left ventricular fistula, with no significant coronary atherosclerosis suggestive of ischaemic heart disease. The patient was started on beta-blocker therapy, and on follow-up his angina improved. The patient had a benign course and did not have any progressive heart failure or acute coronary syndrome on follow-up. This case report highlights a rare association of mid-cavitary obstructive hypertrophic cardiomyopathy with coronary artery fistula.

https://ift.tt/2LzwFt4

Personalised 3D-printed model of a chest-wall chondrosarcoma to enhance patient understanding of complex cardiothoracic surgery

Description

Novel technologies, such as additive manufacturing (also termed three-dimensional (3D) printing), play an important role in surgical planning. Their role in enhancing a patient's understanding of their medical condition and increasing their satisfaction with their treatment is also gaining increased attention in medicine and surgery. As an illustration, we describe the case of a 65-year-old Caucasian man who presented with left-sided anterior chest-wall pain which was associated with a visible palpable lump. He had a body mass index of 27 kg/m², and CT of the thorax demonstrated a 62 mm x 60 mm x 48 mm tumour involving multiple structures, including the left fourth to sixth ribs, costal cartilages and the pericardium overlaying the right ventricle (figure 1). Transthoracic echocardiography showed normal ventricular function without any indication of tumour infiltration into the myocardium.

Figure 1

Axial (right) and sagittal (left) CT slices of the thorax demonstrating a large chondrosarcoma...

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Neisseria meningitidis sepsis in a patient with acute epiglottitis and respiratory failure

A 78-year-old female patient presented to our emergency department with a 5-day history of throat pain, hoarseness and a progressive and dolorous submandibular swelling. Due to non-conclusive clinical examination and the stable but visibly affected patient, we performed a neck CT scan with intravenous contrast, which showed the thumbprint sign typical for acute epiglottitis. Within minutes, the patient's condition deteriorated and the patient was close to respiratory exhaustion. As intubation was severely complicated by massive swelling of the supraglottic soft tissue, the patient went into hypoxaemia and eventually cardiac arrest. After initiating reanimation protocol, eventually the airway was secured and Return of spontaneous circulation (ROSC) achieved after around 5 min. The initially sampled blood cultures revealed Neisseria meningitidis bactera emia and the patient was successfully treated accordingly. In patients with swelling of the upper airway, rapid clinical deterioration is possible. Diagnostics should not delay therapy, including administration of empiric antibiotics, steroids and intubation.

https://ift.tt/2JcomFD

Right-sided hydrothorax: a peritoneal dialysis dilemma

We present a 23-year-old female patient with a chief complaint of progressively worsening dyspnoea of 2 days duration. Her medical history was significant for end stage renal disease secondary to membranoproliferative glomerulonephritis. A peritoneal dialysis (PD) catheter was placed 8 weeks prior to admission. She did not miss any of the PD sessions prior to this admission. Vital signs were significant for hypoxemia. Physical examination was remarkable for right-sided basilar crackles with no other signs of fluid overload. A chest X-ray demonstrated the presence of a large right-sided pleural effusion. Right-sided thoracentesis was performed, with subsequent pleural fluid analysis concerning for a pleuroperitoneal leak. CT peritoneography performed confirming the diagnosis as contrast material leaked through the inferior vena cava (IVC) diaphragmatic foramen into the right pleural space. Surgical intervention was deferred in light of the close proximity of the defect to the IVC. The patient was transitioned to haemodialysis for temporary cessation of PD.

https://ift.tt/2KWKgd2

Successful pregnancies and reduced treatment requirement while breast feeding in a patient with congenital hypoparathyroidism due to homozygous c.68C>A null parathyroid hormone gene mutation

A female patient with consanguineous parents presented at the age of 4 with isolated hypoparathyroidism due to a parathyroid hormone (PTH) gene mutation. She was managed with alfacalcidol and calcium supplements, and developed normally. Her consanguineous parents described symptoms suggestive of hypocalcaemia but had normal serum calcium and low normal PTH levels. A molecular diagnosis obtained in her adulthood revealed the presence of homozygous point mutation (c.68C>A) in exon 2 introducing a premature stop codon resulting in a non-functional precursor protein. This mutation has been reported only once before. Our patient remained on stable doses of alfacalcidol during pregnancy, but stopped all supplementation while breast feeding. This case confirms that alternative mechanisms (likely breast-derived parathyroid hormone-related protein) contribute to calcium homeostasis during breast feeding. Heterozygotes for the c.68C>A mutation may have latent hypoparathyroidism and maintain calcium homeostasis except during prolonged hypocalcaemia. This would suggest incomplete dominance, or a dose effect of the wild-type PTH allele.

https://ift.tt/2LvmE0g

Chronic pancreatitis with Bochdalek hernia causing right-sided pleural effusion in a previously asymptomatic adult

A 41-year-old man with a medical history of chronic back pain, seizure disorder, alcohol and tobacco abuse presented with acute shortness of breath. Chest X-ray showed a large right-sided pleural effusion. Pleural fluid analysis was significant for an elevated amylase level, suggestive of pleural effusion secondary to pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) revealed a persistent right-sided pleural effusion in connection with a right pararenal space fluid collection via a Bochdalek hernia. An endoscopic ultrasound found hyperechoic strands and foci, and pancreatic parenchyma consistent with chronic pancreatitis, as well as a pseudocyst in the pancreatic head. A chest tube was ultimately placed to continuously drain the pleural effusion. The patient was discharged and was referred to gastroenterology for outpatient follow-up. This case illustrates a rare presentation of chronic pancreatitis with a Bochdalek hernia as a right-sided pleural effusion in a patient who was previously asymptomatic.

https://ift.tt/2KSAhp5

Thromboatheromatous coarctation of the aorta diagnosed with intraoperative TOE during emergent open aneurysm clipping

A woman in her 50s presenting for emergent intracranial surgery was discovered to have a large incongruity in blood pressure between her right arm and her other extremities. Intraoperative rescue transoesophageal echocardiography (TOE) revealed a large thromboatheromatous burden in her descending aorta resulting in a functional coarctation. Usually diagnosed via CT imaging, we present what we believe to be the first published case diagnosed intraoperatively using TOE. After the diagnosis was made, blood pressure goals were adjusted to provide sufficient perfusion distally and her surgery was completed otherwise uneventfully.

https://ift.tt/2LxRHIU

Synchronous oesophageal and gastric sarcomatoid carcinoma: first reported case in Australia

A 75-year-old retired teacher presents with dysphagia and weight loss for a duration of 6 months. Her gastroscopy showed two synchronous submucosal masses. A 7 cm polypoid mass was seen at the distal oesophagus, arising from a thick stalk and a 4 cm mass seen at the cardia. The biopsies showed high-grade sarcomatoid cancer. Staging CT scan and Positron Emission Tomography scan did not show any distant metastasis except a lesion in the rectum that was subsequently found to be tubulovillous adenoma on transanal excision. The patient was managed with Ivor Lewis oesophagectomy. The biopsies of resection specimen showed spindle cell/sarcomatoid carcinoma with a component of poorly differentiated neuroendocrine carcinoma in oesophageal tumour and a small component of conventional invasive squamous cell carcinoma in tumour at cardia. The patient recovered well after surgery. Since then, she has completed adjuvant chemoradiotherapy. No recurrence has been noted in 10 months follow-up.

https://ift.tt/2KYfi4n

Bronchiolitis obliterans organising pneumonia as an initial manifestation in a patient with systemic lupus erythematosus: a rare presentation

Bronchiolitis obliterans organising pneumonia as an initial manifestation of systemic lupus erythematosus (SLE) is a rare and uncommon presentation. We describe a case of SLE presenting with shortness of breath, found to have pneumothorax, bilateral nodular infiltrates along with pleural effusions and pericardial effusion. Work-up suggested a diagnosis of active SLE with anaemia, thrombocytopenia, positive antinuclear antibodies (ANAs) and positive anti-double-stranded DNA. On retrospective review of patient records, from 8 years prior to presentation, lung biopsy histology consistent with bronchiolitis obliterans organising pneumonia with positive ANA serology was found, without any further autoimmune work-up. In our opinion, bronchiolitis obliterans organising pneumonia was the index presentation of SLE. Treatment with steroids and subsequent management with immunosuppressive therapy could have prevented subsequent hospitalisations. Prompt work-up for autoimmune diseases should be considered in patients with positive ANA and histological evidence of bronchiolitis obliterans organising pneumonia.

https://ift.tt/2LyS1qO

Spinal tophaceous gout presenting in a young adult without pain

A 26-year-old man with a medical history of gout and morbid obesity presented with a 7-day history of decreased sensation to light touch and temperature from the feet to the level of the nipples. He also noted incomplete voiding. Laboratory investigations showed an elevated serum uric acid level (10.4 mg/dL, reference range: 3.8–8.7 mg/dL) as well as negative rapid plasma reagin and rheumatoid factor. MRI showed inflammatory changes on multiple spinal levels. Laminectomy was performed, with follow-up biopsy revealing multiple multinucleated giant cells and monosodium urate (MSU) crystals. He was ultimately diagnosed with spinal gout. Patient's symptoms did not resolve immediately after surgery. Yet with the administration of intravenous glucocorticoids and a course of non-steroidal anti-inflammatory drugs, he slowly regained sensation, leaving the hospital with complete resolution of symptoms.

https://ift.tt/2KWLzsi

Metastatic ductal carcinoma of the breast to colonic mucosa

Breast cancer is the most common malignancy among women, while invasive ductal carcinoma is the most common type of invasive breast cancer. Metastatic spread to the colon and rectum in breast cancer is rare. This report describes a case of a 69-year-old woman with metastatic ductal breast cancer to the rectosigmoid, presenting as an incidental finding on screening colonoscopy. The breast carcinoma was first diagnosed 2 years prior. Colonic biopsies from colonoscopy confirmed metastatic adenocarcinoma consistent with a breast primary. Ultimately her clinical condition worsened as she developed malignant ascites, a small bowel obstruction, and new bone metastases, and the patient succumbed to her illness. Cases of metastatic breast cancer to the gastrointestinal tract have predominantly been lobular breast carcinoma. Increased awareness of colonic metastasis may lead to more accurate diagnosis and earlier systemic treatment.

https://ift.tt/2LxvcU9

Foreign body urethra misdiagnosed as stricture leading to inadequate management and prolonged treatment duration: a lesson to learn

Misdiagnosis of a urethral foreign body (FB) as urethral stricture leads to inadequate management and prolonged treatment duration. A 55-year-old male patient was referred with complaints of difficulty in voiding and poor urinary stream for 2 months. He initially presented at a primary healthcare centre and was misdiagnosed as urethral stricture and was scheduled for urethroplasty. Surprisingly, intraoperative cystourethroscopy performed by us revealed that the urethra had been obstructed by an FB. The FB was gently pushed into the bladder and retrieved. The postoperative course was uneventful. The present case represents a rare occurrence of polyembolokoilamania or insertion of a FB into any bodily orifice for sexual gratification.

https://ift.tt/2KSsOGD

Approach to rectal foreign body: an unusual presentation

Foreign bodies in the rectum are commonly confronted worldwide in the surgical emergency. Such a situation arises either accidentally or for autoerotic purposes. A wide variety of foreign objects have been reported in the literature and this usual object would add to the reports for its unusual location. We report a case of a 26-year-old young man with accidental insertion of hand shower in the rectum and no signs of any active bleed or peritonism. Extraction was done successfully in the operating room under general anaesthesia, with an uneventful postprocedure period and the patient was discharged after 48 hours of observation. Rectal foreign bodies can be of wide variety and can lead to life-threatening conditions. An orderly approach is required for diagnosis, management and evaluation in the postprocedure period.

https://ift.tt/2Lwfo40

Mycobacterium avium intracellulare infection complicated by allergic bronchopulmonary aspergillosis in a non-asthmatic patient

Allergic bronchopulmonary aspergillosis (ABPA) most often develops in patients with asthma or cystic fibrosis. We present a 91-year-old non-asthmatic patient with pre-existing Mycobacteriumavium complex (MAC) infection who got diagnosed with ABPA. Treatment of the two conditions can be challenging as immunosuppression with steroids for treatment of ABPA may exacerbate the underlying MAC infection. Treatment with steroids and antibiotics resulted in significant improvement in the patient's condition.

https://ift.tt/2KUT17m

Uterine torsion and subsequent rupture in a gravid bicornuate uterus associated with an elevated alpha-fetoprotein

Uterine torsion is a rare obstetric complication with a non-specific presentation. We describe a patient with a bicornuate uterus and a pregnancy complicated by a markedly elevated second-trimester maternal serum alpha-fetoprotein (MSAFP), intermittent pelvic pain and fetal growth restriction. At 24 weeks gestational age, she presented to labour and delivery with an acute abdomen. A subsequent exploratory laparotomy revealed torsion and rupture of her right uterine horn. Uterine torsion can be difficult to diagnose because it is not associated with specific symptoms or characteristic imaging findings. In patients with a bicornuate uterus who present with abdominal pain, an elevated mid-trimester MSAFP may be a harbinger of placental ischaemia as a result of uterine torsion.

https://ift.tt/2LxuZQR

Disseminated coccidioidomycosis masquerading as recurrent lymphoma

Description

Infection with Coccidioides immitis, a soil-dwelling fungus endemic to the American Southwest, may have protean manifestations in immunocompromised patients who reside in1 2 or who have travelled to3 that region. We report a patient whose abnormal PET/CT scan raised concern for recurrent lymphoma but instead was due to disseminated coccidioidomycosis.

A 62-year-old woman was diagnosed with ileocaecal marginal zone lymphoma (MZL) after presenting with iron-deficiency anaemia and faecal occult blood. Ten years earlier, she underwent allogeneic haematopoietic cell transplantation for acute myeloid leukaemia (AML). She had recurrent cutaneous chronic graft-versus-host-disease (CGVHD); 50 months before the diagnosis of MZL, she completed a 9-month course of prednisone (50 mg every other day) and did not receive any further corticosteroid therapy. At the time of diagnosis of MZL, the patient was receiving twice-monthly extracorporeal photopheresis (ECP), which had been initiated 1 year earlier for the most...

https://ift.tt/2KX3UWq

Seronegative enteropathy and malnutrition: a diagnostic challenge

A 21-year-old woman presented with a 2-week history of vomiting, diarrhoea and epigastric pain, with 9 kg weight loss over the last two months. Laboratory tests were normal with negative coeliac serology. Duodenal biopsies revealed total villous atrophy, crypt hypertrophy and intraepithelial lymphocytosis. A diagnosis of seronegative coeliac disease was made, and she started a gluten-free diet. However, she did not respond and her weight fell to 30.6 kg (body mass index 11), becoming dependent on parenteral nutrition. Her diagnosis was reconsidered and the histology reviewed. The histopathological features were of severe active chronic duodenitis. By diagnosis of exclusion, with the absence of other clear pathology, she was treated as Crohn's disease. She responded to third-line therapy with biologics. In this case, the patient had refractory villous atrophy and the mucosal features, in addition to response with anti-tumour necrosis factor therapy, suggest inflammatory bowel disease, although not with complete diagnostic certainty.

https://ift.tt/2LxuNkB

Renal ultrasound imaging in a preterm infant with a persistently elevated C reactive protein

Description 

A preterm infant born at 25+5 weeks gestation was being treated for late onset sepsis on day 30. She had just recovered from an episode of necrotising enterocolitis, requiring a 14-day course of intravenous antibiotics. She was on biphasic non-invasive respiratory support and fully enterally fed on expressed breast milk. During this time, she was noted to have a rising C reactive protein (to maximum of 114 mg/L), high white cell count (highest count 26.2x10⁹/L) and thrombocytopaenia (lowest count 63x10⁹/L), in spite of being treated with second-line intravenous broad-spectrum antibiotics (meropenem and vancomycin) for 14 days. She did not receive antifungal prophylaxis during her admission. Blood and cerebrospinal fluid cultures showed no growth. Urinalysis showed no growth on bacterial and fungal culture and no filamentous fungi were noted on microscopy. She remained clinically well. A cranial and abdominal ultrasound scan was  undertaken on day 35. The abdominal ultrasound revealed a...

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Anomalous origin of the coronary artery from the pulmonary artery in a 33-year-old man

Description 

A 33-year-old man, without prior history of coronary artery disease, was referred to a catheterisation laboratory with a diagnosis of non-ST elevation myocardial infarction. Coronary angiogram showed a dilated, dominant right coronary artery of normal origin with multiple collaterals draining to the left coronary system (figure 1A,B) and a coronary 'steal' phenomenon into the pulmonary artery (PA). Left main coronary artery (LMA) was not visualised on contrast injection into the aortic root (figure 1B). Ventriculogram showed ejection fraction of 40%–45% and anterior wall hypokinesis. Subsequent three-dimensional heart computer tomogram revealed anomalous origin of the LMA from PA, (figure 1C), confirming the diagnosis of anomalous origin of the coronary artery from the pulmonary artery (ALCAPA).

Figure 1

(A) Left anterior oblique (LAO) view. Large dominating RCA with extensive collaterals to the left coronary system. (B) Failure to visualise left coronary artery...

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Increasing preoperative body size in breast cancer patients between 2002 and 2016: implications for prognosis

Abstract

Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24–99-year-old primary breast cancer patients (n = 640) in Sweden 2002–2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002–2016 (p_trends < 0.0001). Of these, a breast volume ≥ 850 mL was associated with the strongest recurrence-risk (adjusted hazard ratio [_adjHR] 1.67; 95% CI 1.17–2.39), especially combined with waist circumference ≥ 80 cm (_adjHR 2.07; 95% CI 1.25–3.44), while BMI ≥ 25 kg/m² or large waist circumference conferred almost a twofold risk for death (both Log-Rank p ≤ 0.0001). Chemotherapy seemed to counteract the negative impact of a high BMI or large waist circumference on OS. Large breast volume was the strongest predictor for recurrence in all treatment groups. In conclusion, preoperative BMI, waist circumference, and breast volume increased between 2002 and 2016. Larger body size negatively impacted breast cancer-free interval and OS. If confirmed, body measurements may help select patients requiring more individualized treatment.

https://ift.tt/2J7w8jT

An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer

https://ift.tt/2INoxHY

The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model

https://ift.tt/2IJhG2l

Gene expression and prognosis of NOX family members in gastric cancer

https://ift.tt/2IMFl1R

Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer

https://ift.tt/2xfWBqD

Sedation for gastrointestinal endoscopy in Australia: what is the same and what is different?

Purpose of review The purpose of this article is to review the practice of sedation for adults having gastrointestinal endoscopy in Australia and to compare it with practice in other countries. Recent findings The practice of sedation for endoscopy in Australia is dominated by anaesthesiologists, who have a preference for deep propofol-based sedation. The recent literature includes a number of guidelines for sedation developed by multidisciplinary groups, anaesthesiologists and gastroenterologists in Australia and other countries. The appropriate health practitioner to provide deep sedation and general anaesthesia, to use propofol for sedation and to manage higher risk patients remains controversial. The estimated risks associated with endoscopy vary by provider, sedation technique and study design (prospective or retrospective, single- or multicentre). New airway management techniques are being investigated that may be useful in patients at high risk of hypoventilation and hypoxia. Summary Endoscopy sedation is safe but more high-quality, multicentre observer-blinded randomized controlled trials are required. Correspondence to Kate Leslie, AO, FAHMS, Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, VIC 3050, Australia. Tel: +61 3 93427540; e-mail: kate.leslie@mh.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Measuring quality of recovery in perioperative clinical trials

Purpose of review Perioperative studies increasingly report patient-centered outcomes, but few provide a valid, global measure of a patient's health status after surgery and anesthesia. This review considers three quality of recovery (QoR) scales. Recent findings The 9-item (QoR Score), 15-item (QoR-15), and 40-item (QoR-40) QoR scales have been extensively validated in perioperative settings, and have also been used as outcome measures in numerous surgery and anesthesia studies. A range of clinical trials are presented to illustrate the value of the QoR scales in perioperative medicine research. Summary The QoR Score, QoR-15, and QoR-40 are valid and recommended endpoints for perioperative clinical trials, and there is guidance as to what constitutes a minimal clinically important difference. These recovery scales are sensitive to a change in health status and, as numerical data, optimize statistical power when used in the design of a clinical trial. They are closely correlated with conventional measures of outcome such as analgesic consumption, pain scores, nausea and vomiting, and hospital stay. Although conventional measures may be considered patient-centered, each are incomplete by themselves. QoR scores provide a meaningful overall evaluation of a patient's recovery after surgery and anesthesia. Correspondence to Paul S. Myles, Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Road, Melbourne 3004, VIC, Australia. Tel: +61 39076 2000; fax: +61 39076 2813; e-mail: p.myles@alfred.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Inhibition of survivin enhances radiosensitivity of esophageal cancer cells by switching radiation-induced senescence to apoptosis

https://ift.tt/2GRdBTU

The outcome to axitinib or everolimus after sunitinib in metastatic renal cell carcinoma

We aimed to investigate the different outcomes in patients with metastatic renal cell carcinoma treated with second-line axitinib or everolimus after sunitinib. Patients treated in 16 oncological centres in Italy were included, and those receiving axitinib or everolimus from January 2013 onwards were analysed for outcomes. Descriptive statistical tests were used to highlight differences between groups. The Kaplan–Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Data on 634 patients with metastatic renal cell carcinoma treated with first-line sunitinib have been obtained. A total of 182 patients received a second-line therapy with everolimus (79 patients, 43%) or axitinib (103 patients, 57%), respectively. The median PFS was 4.6 [95% confidence (CI): 2.6–6.5] months for patients treated with everolimus and 5.5 (95% CI: 4.3–6.7) months for patients treated with axitinib (P=0.7). The median OS was 13.9 (95% CI: 10.4–17.4) months for patients treated with everolimus and 12.0 (95% CI: 7.9–16.2) months for patients treated with axitinib (P=0.3). No differences were found based on length of first-line treatment. Major limitations are the retrospective nature of the study and the lack of a prospective evaluation of the progression. This study reports no significantly differences between everolimus and axitinib in terms of both PFS and OS. Furthermore, the length of first-line treatment cannot be used as such a predictive factor and cannot suggest the use of a molecule compared with another. Correspondence to Roberto Iacovelli, MD, PhD, Medical Oncology Unit, Integrated University Hospital of Verona (AOUI), Piazzale L.A. Scuro 10, 37134 Verona, Italy Tel: +39 045 812 115; fax: +39 045 802 7410; e-mail: roberto.iacovelli@aovr.veneto.it Received December 19, 2017 Accepted March 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Dabrafenib and trametinib treatment-associated fevers in metastatic melanoma causing extreme elevation in procalcitonin in the absence of infection

Febrile illnesses are common in the management of metastatic solid organ malignancies. Traditionally they occur in the setting of immunosuppression and neutropenia owing to cytotoxic therapy necessitating consideration of systemic infections. Systemic markers of inflammation, such as C-reactive protein and procalcitonin (PCT), may be used to assist in determining the aetiology of a fever in such patients. Newer anticancer therapies may cause significant noninfectious fevers and may result in a rise in inflammatory markers, despite the absence of an infection. We present a case of a critically unwell febrile patient being treated with dabrafenib and trametinib for advanced melanoma. The patient had an extreme elevation in PCT in the absence of infection. We discuss the presentation of fevers related to dabrafenib and trametinib therapy in the management of advanced melanoma, and the utility of PCT in the management of fevers in advanced solid organ malignancies. Correspondence to Samantha E. Bowyer, MBBS (Hons), DMedSci, FRACP, St John of God Subiaco Hospital, Suite C202, 12 Salvado Road, Subiaco, Western Australia 6008, Australia Tel: +61 893 826 111; fax: +61 864 659 250; e-mail: tim@drtimclay.com.au Received March 5, 2018 Accepted May 10, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)–poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy

Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core–shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)–poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)–poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy. Correspondence to Mingzhi Zhang, PhD, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe Road, No. 1, Erqi Square, Zhengzhou 450000, People's Republic of China Tel/fax: +86 371 6697 0906; e-mail: mingzhi_zhang1@163.com or Correspondence to Yonggang Shi, MSc, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe Road, No. 1, Erqi Square, Zhengzhou 450000, People's Republic of China Tel/fax: +86 371 6697 0906; e-mail: shiyong737@126.com Received October 20, 2017 Accepted March 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands

There is little evidence on the costs associated with the route of administration of oncology drugs. We investigated time and resource use for hospitals and patients and compared healthcare and societal costs for intravenous (IV) and subcutaneous (SC) administration of trastuzumab and rituximab. Data for the preparation and administration of both drugs were collected at the hospital pharmacy and at the oncology day care unit. Patients completed a questionnaire for obtaining information on societal costs (productivity losses, informal care and traveling expenses). A total of 126 patients were recruited in six hospitals; 82 received trastuzumab (37 IV and 45 SC) and 44 received rituximab (23 IV and 21 SC). The costs per administration (including societal cost but excluding drug costs) were €167 and €264 for IV and €76 and €146 for SC trastuzumab and rituximab, respectively. The costs for SC administration were lower in all categories. The largest cost component was related to time spent at the day care unit (overhead costs). This resulted in savings of €47 for SC trastuzumab and €69 for SC rituximab. The costs related to time of healthcare professionals was €9 lower for both drugs. The costs for consumables resulted in another €12 savings. Societal costs were €22 lower for SC trastuzumab and €28 lower for SC rituximab. Although administration costs are relatively a small part of the total costs, important savings can be generated by switching to an SC route of administration especially because a large number of patients receive oncology drugs and patients receive more than one administration. Correspondence to Margreet G. Franken, PhD, Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands Tel: +31 10 408 1372; e-mail: franken@imta.eur.nl Received January 10, 2018 Accepted April 24, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical management of a pituitary gland metastasis from clear cell renal cell carcinoma

In very few years, several treatments have significantly improved the prognosis of patients with metastatic renal cell carcinoma (RCC). Despite this, the clinical outcomes of specific subgroups of patients including those with central nervous metastases still remain poor. In this population, a very infrequent and poorly described site of metastases is the pituitary gland. Because of the important endocrinal function and the anatomic site of this specific organ, clinical management of this complication requires several additional precautions compared with other central nervous metastases. Here, we describe a case of a single pituitary metastasis from clear cell RCC in a patient who showed a surprising progression-free survival and overall survival to sunitinib first-line treatment. Because of the uncommon clinical course of the disease of our patient and the atypical site of metastases, we want also to underline the importance of further investigation of molecular pathways associated with a favorable prognosis in patients with metastatic clear cell RCC. *Vincenzo Di Nunno and Veronica Mollica contributed equally to the writing of this article. Correspondence to Francesco Massari, MD, Division of Oncology, Sant'Orsola-Malpighi Hospital, Via Albertini n.15, 40138 Bologna, Italy Tel: +39 051 214 2223; fax: +39 051 636 2764; e-mail: fmassari79@gmail.com Received March 4, 2018 Accepted April 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2GPVWvz

9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma

Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD-8, and 9-ING-41) suppressed the growth of neuroblastoma cells, whereas 9-ING-41, a clinically relevant small-molecule GSK-3β inhibitor with broad-spectrum preclinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and an increase in neuroblastoma cell apoptosis. Mouse xenograft studies showed that the combination of clinically relevant doses of CPT-11 and 9-ING-41 led to greater antitumor effect than was observed with either agent alone. These data support the inclusion of patients with advanced neuroblastoma in clinical studies of 9-ING-41, especially in combination with CPT-11. Correspondence to Andrew P. Mazar, PhD, Monopar Therapeutics, Inc. 5 Revere Drive, Suite 200, Northbrook, IL 60062, USA Tel: +1 847 388 0349 x403; e-mail: mazar@monopartx.com Received March 23, 2018 Accepted May 1, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Survival outcomes in patients with non-small-cell lung cancer treated with erlotinib

Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment of advanced stage (IIIB or IV) NSCLC (August 2008). In the pivotal trial supporting initial subsidy, erlotinib increased overall survival (OS) by 2 months compared with placebo (adjusted hazard ratio, 0.70; 95% confidence interval: 0.58–0.85). We examined the effectiveness of erlotinib in a 'real-world' setting by measuring survival outcomes in NSCLC patients treated in two tertiary metropolitan public hospitals in Queensland. We extracted data from the electronic oncology prescribing system (CHARM) for NSCLC patients prescribed erlotinib (1 September 2009 to 1 February 2015). Survival estimates and analyses were generated using Kaplan–Meier curves. 134 patients received at least one dose of erlotinib during the study period. At the date of data extraction 113 patients had died. The median patient age was 64 years and 55% were men. The median duration of treatment was 2.0 months. The median OS was 5.8 months. The median progression-free survival (time from start of erlotinib to disease progression or death from any cause) was 3.6 months. The use of erlotinib in the two Queensland sites was consistent with the pivotal trial used to support subsidy. The median OS was somewhat less than the trial (5.8 vs. 6.7 months), which could be because of the hospital cohort including frailer patients who were unsuitable for parenteral chemotherapy, and the mixed epidermal growth factor receptor mutation status of the hospital cohort. Correspondence to Samantha A. Hollingworth, BSc, MPH, PhD, School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba QLD 4102, Australia Tel: +61 733 461 981; fax: +61 733 461 999; e-mail: s.hollingworth@uq.edu.au Received October 24, 2017 Accepted April 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2sgnrt9

Promising effects of eribulin for cystic lung metastases of epithelioid sarcoma: a case report

Epithelioid sarcoma (ES) is a rare and aggressive type of soft tissue sarcoma with resistance to systemic chemotherapy. Therefore, new treatment options are required for patients with advanced ES. Eribulin is a novel potential treatment option for patients with inoperative sarcoma. We herein report a case of a 27-year-old Japanese man with cystic lung metastases from an ES in the left forearm, resulting in long-term stable disease. A solid, metastatic sarcomatous nodule appeared in the right lung, as shown by computed tomography, within the first 2 months after surgery. After the lung metastasis was detected, he underwent a total of 37 cycles of chemotherapy in six regimens. However, multiple cystic lung metastases had progressed in segments S6 and S9/10; hence, eribulin treatment was initiated. After two courses of eribulin, the excess fluid density material in the cystic metastases was completely absorbed, and an additional four courses of treatment resulted in shrinkage of the cystic metastases. These effects lasted for 13 months without severe adverse effects. Cystic lung metastases are an extremely rare consequence of soft tissue sarcoma, and eribulin is one of the most promising options for the treatment of advanced ES. Correspondence to Tadashi Iwai, MD, Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka 545-8585, Japan Tel: +81 666 453 851; fax: +81 666 466 260; e-mail: qq329xpd@opal.ocn.ne.jp Received March 27, 2018 Accepted May 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Use of pertuzumab and trastuzumab during pregnancy

Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy. Correspondence to Nilgun Yildirim, MD, Department of Medical Oncology, Dr Ersin Arslan Training and Research Hospital, Gaziantep 27000, Turkey Tel: +90 342 221 0700/+90 505 254 3251; fax: +90 342 221 0142; e-mail: drnilgunsari@yahoo.com Received February 21, 2018 Accepted May 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Turning cancer's metabolic plasticity into fragility- an evolving paradigm

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Identification of a novel GREM1 duplication in a patient with multiple colon polyps

Abstract

Hereditary mixed polyposis syndrome (HMPS) is a hereditary syndrome that is characterized by multiple colon polyps of mixed pathologic subtypes and an increased risk for colorectal cancer. A 40 kb duplication in the 5′ regulatory region of the GREM1 gene was recently found to be the causal mutation in a subset of Ashkenazi Jewish families with HMPS. Given this discovery, the GREM1 5′ regulatory region is now analyzed on many different multi-gene cancer panels, however the data on duplications distinct from the 40 kb duplication remains minimal. Herein we report a novel 24 kb tandem duplication of the 5′ regulatory region of GREM1 in a patient without Ashkenazi Jewish heritage, who had a family history that was concerning for Lynch syndrome and satisfied Amsterdam II criteria. This is only the third reported GREM1 duplication separate from the 40 kb Ashkenazi Jewish duplication, and is the only reported duplication to selectively involve exon 1 of GREM1. This finding supports comprehensive testing of the GREM1 regulatory region in families of all ethnicities with multiple colon polyps or colon cancer, and when Lynch syndrome is suspected.

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Atraumatic splenic rupture secondary to abscess in a hemodialysis patient: a rare and fatal cause of acute abdomen diagnosed late

Abstract

Splenic abscess is a very rare condition in the general population. It is more likely to develop in association with underlying comorbidities and trauma. More attention should be paid in patients with immunosuppression, diabetes mellitus, and congenital or acquired immunocompromise. Splenic rupture secondary to nontraumatic abscess causing acute abdomen is a rarer condition. Herein, we report a 55-year-old hemodialysis patient who presented with signs and symptoms of late generalized peritonitis. The patient was operated under emergency conditions and diagnosed with splenic abscess rupture, for which splenectomy with drainage procedure was performed. In such patients, the morbidity and mortality rates vary depending on the intraoperative and postoperative risks.

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Gastric hibernoma: a novel location and presentation of a rare tumor

Abstract

We present a case of gastric hibernoma, an unusual tumor with a location novel to the literature. A 39-year-old female presented with one year of upper gastrointestinal bleeding and dysphagia. Gastroenterology performed an esophagogastroduodenoscopy with ultrasound and identified a 6 cm mass within the muscularis propria of the antrum. Computed tomography demonstrated a 9.7 × 7.8 × 4.8 cm³ heterogeneous antral mass with internal septa. A distal gastrectomy with Bilroth I gastroduodenostomy was performed with 4 cm proximal and 2 cm distal margins. Excision was appropriate to make the diagnosis, exclude malignancy, and remove a symptomatic mass. Hibernoma was confirmed by histopathology. These are rare tumors of brown fat named for their resemblance to the thermogenic tissue found in hibernating animals. They typically present as a slowly enlarging mass of the thigh or shoulder. To our knowledge, this is the first presentation of a hibernoma as a submucosal gastric mass.

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Phosphaturic mesenchymal tumor, an unusual localization in head and neck

Abstract

Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated with tumor-induced osteomalacia involving bone and soft tissue that produces paraneoplastic hypophosphatemic osteomalacia. The common physiologic defect in this conditions involves an impairment in renal tubular phosphate reabsorption with a downregulation of renal 1α-hydroxylase activity, while calcium metabolism remains essentially unaffected. Microscopic features consist of spindle cells, multinucleated giant cells and calcifications embedded in a chondromyxoid matrix with variable cellularity and prominent vascularity. Approximately 95% of PMTs involve the extremities and appendicular skeleton, with only 5% occurring in the head and neck region. Localization in the head and neck is pretty uncommon, nose and paranasal sinuses are preferentially affected. Due to its rarity, the purpose of the study was to report a new case of PMT whose locations in temporomandibular joint was never reported in literature.

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The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Abstract

Background

Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.

Methods

We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.

Results

We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.

Conclusions

Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

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ESPR 2018

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