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Long-term yield of pancreatic cancer surveillance in high-risk individuals
ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).ConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
Journal Article
In her place
Ann devoted years to her mother's care. Now, in a bid to escape the emptiness of her old flat and the paperwork caused by her death, Ann finds herself in a bar upstate. She has been so good for so long, she deserves a little fun. Justin is also grieving but his wife is still alive. She has been dying for a long time and they say she doesn't have long left. He deserves a little fun, too. Justin asks Ann to move in just a few weeks later. A million miles away from her lonely life in New York, here Ann finds a world where she is wanted and needed by both Justin and his little girl, Sophie. But just as Ann finds that she is pregnant, Justin receives news. Unexpectedly, his wife's drug trial has been a success. Deborah is coming home. Ann doesn't quite know what to do. The best news is the very worst news. And who is really the other woman in this situation?
Book
Familial Risks and Proportions Describing Population Landscape of Familial Cancer
Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20–84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.
Journal Article
If : a mother's memoir
\"An eloquent, heartfelt account of a young boy's fight with cancer and of a mother's determination and resilience, which sees their family through to his recovery. As her ten-year-old son sits at the kitchen table one evening, Lise Marzouk inspects his mouth and discovers an unusual growth, which doctors later confirm is cancerous. When he is hospitalized at the Curie Institute in Paris for lymphoma treatment, Lise finds herself torn between two worlds, one at his bedside, and the other at home with her two younger children, struggling to maintain a sense of stability in their lives. And so she writes--of their fears and doubts, but also of their moments of tenderness and joy--and through these memories, stories, and reveries, she arrives at a deeper understanding of herself as a woman, a mother, and a writer. Brimming with a rebellious sense of hope, If offers an intimate look at how a mother's love and support enabled her family to come out of a devastating experience stronger and more connected\"-- Provided by publisher.
Book
International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer
Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. Conclusions Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.
Journal Article
This ordinary stardust : a scientist's path from grief to wonder
\"A decade ago, Dr. Alan Townsend's family received two unthinkable, catastrophic diagnoses: his 4-year-old daughter and his brilliant and vivacious wife developed unrelated, life-threatening forms of brain cancer. As he witnessed his young daughter fight during the courageous final months of her mother's life, Townsend - a lifelong scientist - was indelibly altered. He began to see scientific inquiry as more than a source of answers to a given problem, but also as a lifeboat: a lens on the world that could help him find peace with the painful realities he could not change. Through scientific wonder, he found ways to bring meaning to his darkest period. At a time when society's relationship with science is increasingly polarized while threats to human life on earth continue to rise, Townsend offers a balanced, moving perspective on the common ground between science and religion through the spiritual fulfillment he found in his work. Awash in Townsend's electrifying and breathtaking prose, This ordinary stardust offers hope that life can carry on even in the face of near-certain annihilation\"-- Provided by publisher.
Book
Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)
The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.
Journal Article
The Goodbye Cancer garden
When a mother is diagnosed with breast cancer, she and her family plant a garden and watch it grow through the seasons as she undergoes treatments and gets better.
Book
Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42 103 individuals
Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. Results The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10−16), confirmed in external validation sets (Sweden p=1.2×10−6, Finland p=2×10−5). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
Journal Article