tbuckley/cabot-search huggingface dataset:
MUTYH gene mutations in Spanish individuals with multiple colorectal adenomas without APC gene mutation.
Authors: A. I. Ferrer, M. Strunk, R. Andres, A. Ferrandez, A. Alonso, M. Fernandez, A. Tres, J. Godino
Journal: Journal of Clinical Oncology (2010)

1540 Background: Germ line mutations in the base excision repair MUTYH gene were recently implicated in recessive inheritance of multiple colorectal adenomas without APC mutations. Since the identification of polyposis associated to MUTYH mutations syndrome, different mutations have been described in diverse populations such as Caucasians, Koreans, Portuguese or Pakistanis. In Spanish population is little data about this syndrome. Our aim to describe the type of mutations and estimate its prevalence in Spanish individuals affected with colorectal adenomas with no known APC mutation. Methods: Screening for MUTYH germ line mutations was performed by denaturing liquid chromatography (DHPLC), sequencing and pyrosequencing in 50 Spanish patients with multiple colorectal adenomas with no known APC mutation. The two most prevalent mutations in Caucasian population, Y179C and G396D (previously annotated as Y165C and G382D), were also screened in 80 healthy controls. Results: Biallelic mutations were found in 6 patients (12%): 3 of them (6%) were homozygous for the G396D mutation, 2 (4%) were homozygous for the Y179C mutation, one of whom was carrying the pathogenic mutation Q338X and G396D. One patient (2%) carried a monoallelic Y179C mutation. We identified 4 patients (8%) as monoallelic carriers of unclassified variants at the moment. These variants are: R115G, R426C and P334A. In the control sample, 1 individual (1.25%) was carrier of monoallelic G396D mutation. Conclusions: The estimated prevalence of biallelic MUTYH mutation carriers in patients with colonic polyps is 12%. 50% of these mutations are due to the variant G396D and 43% to the Y179C variant. The monoallelic carrier prevalence in patients with colorectal adenomas is 2%, and the prevalence in healthy population is 1.25%. No significant financial relationships to disclose.
Tobacco smoke toxicant and carcinogen biomarkers and lung cancer susceptibility in smokers
Authors: Stephen S. Hecht, Steven G. Carmella, Sharon E. Murphy, Irina Stepanov, Silvia Balbo, Dorothy K. Hatsukami, Jian-Min Yuan, Sungship L. Park, Daniel O. Stram, Christopher Haiman, Yesha Patel, Loic Le Marchand
Journal: Journal of Thoracic Oncology (2016)
Multimedia: Textbook of Clinical Medicine for Asia
Authors: Charles F Gilks
Journal: BMJ (1999)

Eds J Y Sung, P K T Li, J E Sanderson, J Woo


Chinese University Press, $60, pp 848 




ISBN 962 201 773 8

———————

Rating: ★

This book reminds me just how advantaged we Western Europeans are in medical education. As students, we can read textbooks of medicine that are predicated on diseases common and relevant in our environment, with epidemiology, clinical features, and treatment based on information gathered from industrialised societies. Such advantages are even greater for those that have English as their first language because most medical literature uses this medium, and clinical medicine is often brought to life by colourful descriptive and vernacular phrases.

In Latin America, most of the leading US textbooks have been translated into Spanish and Portuguese, and there is a growing market in specialist texts written by “local” authors. Having contributed to one textbook on infectious diseases in Brazil, I can testify to how successful such ventures can be in harnessing regional expertise to produce a valuable national resource. In Africa one postgraduate text stands out—Parry’s superb Principles of Medicine in Africa—and is the benchmark for any attempts to capture the intricacies, subtleties, and fascination of medicine in that continent.

Those textbooks that succeed usually take as their standpoint the practice of medicine in that locality first and foremost, and then contrast this with Western (north American and European) experience where this is relevant. The reader should end up with a relevant and appropriate overview and feel for what he or she will be faced with, and which, with further experience, can be contrasted with disease patterns and management issues far away. A physician from outside the region should come away with the sense that either his or her specialist area is surprisingly similar or has intriguing and important differencs.

Against these benchmarks, how does Textbook of Clinical Medicine for Asia fare? It originates from Hong Kong but rather ambitiously aims to cover Asia. The authors are a mix of expatriate and local consultants. None of the expatriates has the feel, passion, and breadth of vision that, for example, Eldryd Parry had for Africa, and this shows. The local authors are anglocentric, approaching their chapters from a Western standpoint and then trying to contrast this with smatterings of local data and anecdote. No references from Chinese sources are cited, and I get little feel for medicine in Hong Kong, let alone South East Asia. Students may find it useful to pass exams set by their professors, but I fear it will inspire relatively few. Production of such a book is timely and would fill a gap in the literature, but this text is, sadly, quite a disappointment. I hope others will try to improve on this first effort, and learn from its shortcomings.
Abstract 21455: Histolopathologic Validation of Intravascular Ultrasound Diagnosis of a Calcified Coronary Nodule, a Type of Plaque Suspected to be Vulnerable
Authors: Jin Bae Lee, Gary S Mintz, Jennifer B Lisauskas, Jun Pu, Stephen T Sum, Sean P Madden, Allen P Burke, James Goldstein, Gregg W Stone, Renu Virmani, James E Muller Muller, Akiko Maehara
Journal: Circulation (2010)

Background: Calcified nodule is a suspected type of vulnerable plaque, accounting for approximately 3% of coronary events although its intravascular ultrasound (IVUS) and near-infrared spectroscopy...
TEMPERATURE AND METABOLISM
Journal: JAMA (1925)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Treatment of locally advanced pancreatic cancer with concurrent uftoral and radiotherapy. Results from 64 patients treated from 2001–2005
Authors: J. K. Bjerregaard, K. R. Schønnemann, H. A. Jensen, M. B. Mortensen, T. P. Hansen, P. Pfeiffer
Journal: Journal of Clinical Oncology (2008)

4624 Background: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to radiochemotherapy (RCT). LAPC is typically non-resectable due to invasion of adjacent structures, mainly the mesenteric vessels or the portal vein. Several studies have shown that a number of patients become resectable after treatment. Methods: From 2001 to 2005, we have treated 64 consecutive patients with RCT for LAPC. Patients were staged prior to RCT with endoscopic ultrasound (EUS), laparoscopic ultrasound (LUS) and/or multi-sliced CT. LUS was used in all patients prior to surgery. Patients with invasion of the celiac trunk, superior mesenteric artery/vein, portal vein or venous confluence were considered non-resectable. Treatment consisted of uftoral (UFT) (300 mg/m²/day) given orally on all radiation days. Radiation dose was 50 Gy/27 fractions. GTV was defined as tumour tissue on the therapeutic scan, including all pathological lymph nodes. CTV was defined as GTV + 2 cm. Standard 3–4 field techniques were used. Evaluation of response was performed 4–6 weeks after completion of RCT, with multi sliced CT, EUS and/or LUS. If the tumour was deemed resectable, operation was performed. Results: 64 patients were uniformly treated with RCT, 59 patients (92%) completed all 27 fractions. Toxicity was generally mild, with 10 patients (16%) experiencing toxicity CTC grade 3 or worse. One patient developed severe gastro- enteritis and died of pneumonia one week after completion of RCT. Two patients had grade 4 upper GI bleeding during and 1 week following RCT, respectively. Median survival for the entire group was 11.9 (8.7–13.3) months. Eleven patients underwent resection, leading to a resection rate of 17% following RCT with a median survival of 43.7 (22.9-nr) months in resected patients. All 11 patients had a R0 resection. One patient was resectable, but refused surgery. Median survival for the patients without resection was 9.0 (7.8–12.1) months. Conclusion: RCT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients with LAPC. R0 resection was possible in 17% leading to an impressive median survival of 43.7 months in resected patients. No significant financial relationships to disclose.
Phase II study of gefitinib and docetaxel as salvage therapy in patients (pts) with advanced pancreatic adenocarcinoma (APC)
Authors: F. Shadad, K. Matin, T. L. Evans, R. L. Volkin, G. J. Kiefer, J. J. Schlesselman, C. Cai, A. Schmotzer, S. Dranko, R. K. Ramanathan
Journal: Journal of Clinical Oncology (2006)

4120 Background: There is no standard-of-care second-line chemotherapy for APC. The combination of docetaxel and gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) shows enhanced preclinical activity compared to docetaxel alone. Docetaxel alone has activity in APC, and this phase II trial is designed to evaluate the combination. The primary endpoint is survival with an accrual goal of 45 patients to detect an improvement to 5.25 months (mo) in median survival time by one-sided log-rank test at level α = 0.05. Methods: Patients with APC and one prior chemotherapy regimen are eligible for study; EGFR over-expression is not required. Gefitinib is administered at the dose of 250 mg/day orally without interruption. The initial dose of docetaxel was 75 mg/m 2 every three weeks (one cycle), but was reduced to 60 mg/m 2 due to a high incidence of febrile neutropenia. Results: 31 pts, all with prior gemcitabine therapy, have been enrolled on study to date, with 26 evaluable for toxicity. Patient characteristics: 62% male; 92 % with ECOG performance status 0/1, 8% ECOG of 2; median age 64 years (range 47–82 years). The best response is stable disease (5 pts), median cycles administered 2 (range 1–12). Thus far the median survival time is 4.4 mo, with median time to progression of 2.5 mo. Grade (G) 3/4 febrile neutropenia occurred in 8 out of 18 pts treated at the 75 mg/m 2 dose of docetaxel; none has been seen with the 60 mg/m 2 dose. Other G 3/4 adverse events include: diarrhea (3.8%), rash (7.7%), constitutional symptoms (11.5%), and nausea (11.5%). Conclusion: The combination of gefitinib and docetaxel at 60 mg/m 2 is tolerable, with interim results showing a median survival time of 4.4 mo at this point. If the protocol’s goal of median survival time of 5.25 mo is met upon study completion, the combination may be worthy of further investigation. No significant financial relationships to disclose.
The role of EGFR in predicting clinical outcome in locally advanced rectal carcinoma treated with neoadjuvant chemoradiation
Authors: S. Mawdsley, S. Bentzen, G. Wilson, R. Glynne-Jones, F. Daley
Journal: Journal of Clinical Oncology (2004)

9592 Background: To explore the prognostic role of EGFR (epidermal growth factor receptor) expression in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation. Methods: 60 pre and post-chemoradiation tumour samples were studied. T stages : T3:21, T4:39. Median age 68 years, male: female ratio 80:20%. Median follow-up 42 months. The radiotherapy dose was 45Gy in 25 fractions over 5 weeks. 5-FU was a 60 minutes infusion days 1–5 and 29–33, at 350mg/m2, following low dose folinic acid. At 6–8 weeks following chemoradiation patients underwent surgery with curative intent. An immunohistochemical analysis was conducted to analyse EGFR expression. The primary endpoint was disease-free survival (DFS), with a secondary endpoint of overall survival (OS). Results: 65% of tumours stained for EGFR, which was predominantly cytoplasmic and there was a strong correlation between intensity and percentage of positive tumour cells (p<0.001). Expression did not significantly change following chemoradiation. EGFR correlated significantly with increasing N stage (p=0.049), suggesting a role in disease progression. EGFR expression also correlated significantly with DFS on univariate analysis, see table, and this significance remained on multivariate analysis (p=0.05). There was no effect on OS. Conclusions: The data suggests that overexpression of EGFR may correlate with disease progression; however DFS in this group improved with increasing EGFR expression. This contradicts other studies in rectal cancer; however these did not include patients receiving neoadjuvant chemoradiation. An interaction between EGFR and pre-operative 5FU chemoradiation may exist, enhancing treatment effect. Larger studies are required to elucidate the clear role of EGFR as a marker of prognosis in patients receiving different treatment modalities in this disease. No significant financial relationships to disclose.
Polymorphism of the chemokine CXCR4 to predict treatment benefit of first-line bevacizumab-based chemotherapy in patients with metastatic colorectal cancer.
Authors: Satoshi Matsusaka, Fotios Loupakis, Wu Zhang, Shu Cao, Dongyun Yang, Yan Ning, Stefan Stremitzer, Yu Sunakawa, Shinichi Yamauchi, Rita El-khoueiry, Anish Parekh, Nobuyuki Mizunuma, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

635 Background: The chemokine receptor CXCR4 and its ligand CXCL12 promote angiogenesis and the migration of tumor cells into the metastatic sites in many cancers. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor. Therefore, we analyzed the association between CXCR4/CXCL12 polymorphisms and prognosis in metastatic colorectal cancer (mCRC) patients underwent bevacizumab-based chemotherapy. Methods: This study included 144 Japanese patients (pts) for evaluation set and 424 patients from two clinical trials (204 of TRIBE arm A and 220 of PROVETTA) for validation set, with mCRC treated with bevacizumab-based chemotherapy as first line. A total of 144 Japanese pts with (male/female; 81/63, median age 61 years, median follow-up 4.2 years) and 424 pts (male/female; 252/172, median age 62 years; median follow-up time; 2.8 years) were enrolled in a pharmacogenomics translational study. Genomic DNA was extracted from the pts’ blood or tissue. One CXCR4 single nucleotide polymorphisms (SNP) (rs2228014) and two CXCL12 SNPs (rs1801157, rs3740085) were analyzed by PCR-based direct sequencing. All candidate SNPs were analyzed for association with the clinical outcome. Results: In univariate analysis, CXCR4 rs2228014 showed a significant difference in PFS [(G/G 15.3 months, any A allele 13.7 months, HR (95% CI) 1.64 (1.01-2.68), p=0.036)]. After multivariate analysis, CXCR4 rs2228014 remained to be a significant for PFS [HR (95% CI) 1.67 (1.01-2.78), p =0.046]. However, this polymorphism was not associated with tumor response and survival. In the validation cohort, pts with GG genotype had significantly longer PFS compared to those with any A allele (10.5 vs 9.6 months, HR (95% CI) 1.40 (1.02-1.93), p =0.035). CXCL12 polymorphisms were not associated with the clinical outcome. Conclusions: This study shows for the first time that CXCR4 rs2228014 may serve as a predictive marker in patients with mCRC treated with bevacizumab-based chemotherapy.
Oxaliplatin and irinotecan chemotherapy in advanced gastric cancer. Final results of a multicenter phase II trial
Authors: E. Woell, T. Kühr, W. Eisterer, K. Gattringer, R. Greil, A. Zabernigg, W. Hilbe, J. Thaler
Journal: Journal of Clinical Oncology (2006)

4070 Background: There are only limited treatment options for advanced gastric cancer. Development of new treatment options is therefore warranted. The aim of this study was to evaluate the safety, feasibility and efficacy of an outpatient Oxaliplatin/Irinotecan combination in patients suffering from unresectable, locally advanced and/or metastatic gastric cancer. Methods: The combination of Oxaliplatin 85 mg/m 2 biweekly with Irinotecan 125 mg/m 2 biweekly was chosen since it has been shown in colorectal cancer that a biweekly dose of at least 85 mg/m 2 oxaliplatin is superior to a lower dose and toxicity of Irinotecan is much lower if given fractionated into two doses. Furthermore the Irinotecan dose below MTD considers concerns about increased toxicity in gastric cancer patients. Results: 43 patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma and no previous palliative chemotherapy and/or immunotherapy were selected. Median age: 61 years (range 32–81 years), male/female ratio: 24/19, PS 0:11 patients, PS &lt;3:32 patients, locally advanced cancer 5 patients, single metastatic site: 19 patients, multiple metastases: 19 patients, previously adjuvant radiochemotherapy: 4 patients. This outpatient regimen was generally well tolerated. Frequently reported adverse events (more than 20% of patients) were grade 1 or 2 and included neutropenia (44% of patients), thrombocytopenia (30%), anemia (77%), nausea 67%), diarrhea (51%), alopecia (35%). Grade 3 and 4 toxicities included neutropenia in 2/43 pts., anemia in 3/43 pts., nausea in 2/43 pts., and diarrhea in 4/43pts. 5 patients were taken off-study due to toxicity (asthenia, nausea, reversible renal failure, diarrhea). Sensory neuropathy occurred only as grade 2 in 14%, no grade 3/4 neurotoxicity was observed. For response 38 patients are assessable with 3 pts. (8%) showing a CR, PR in 19 pts. (50%), SD in 11 pts. (29%), PD in 5 pts. (13%). Median TTP was 5.3 months and median OS 9.5 months. Conclusions: The outpatient combination of a biweekly Oxaliplatin/Irinotecan chemotherapy is well tolerated and shows a response rate within the range of other combination therapies. The favourable toxicity profile makes it an alternative 1st line regimen. [Table: see text]
Effect of monthly oral ibandronate on anastrozole-induced bone loss during adjuvant treatment for breast cancer: One-year results from the ARIBON study
Authors: J. E. Lester, S. A. Gutcher, S. P. Ellis, R. Thorpe, J. M. Horsman, J. E. Brown, O. P. Purohit, D. Dodwell, R. E. Coleman
Journal: Journal of Clinical Oncology (2007)

553 Background: The aromatase inhibitor anastrozole is a highly effective treatment for breast cancer with superior efficacy and tolerability advantages over tamoxifen. However its use is associated with significant declines in bone mineral density (BMD) with an increase in fracture risk. The ARIBON trial is a double blind, randomised, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on BMD in women taking anastrozole. The study also aims to explore the relationship between levels of biochemical markers of bone metabolism with longer term changes in BMD as measured by Dual energy Xray Absorptiometry (DXA). Methods: 131 postmenopausal, surgically treated breast cancer patients were recruited from oncology clinics in Leeds and Sheffield, UK. Following consent, baseline bone densitometry showed that 68, 50 and 13 patients were found to be normal (T &gt;-1.0), osteopenic (T -1.0 to -2.5) and osteoporotic (T &lt; -2.5) respectively. All patients were treated with anastrozole 1mg once a day and offered calcium and vitamin D supplementation. In addition, osteopenic patients were randomised on a 1:1 basis to receive either treatment with ibandronate 150 mg orally every month or placebo. Osteoporotic patients were treated with open label ibandronate orally 150mg every month. Results: After I year, osteopenic patients treated with ibandronate gained +2.78% (range -3.8, +15.1) and +1.35% (range -4.1, +5.6) at the lumbar spine and hip respectively. Patients treated with placebo however lost -2.61% (range -11.0, +2.2) at the lumbar spine and -2.34% (range -10.4, +5.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (p&lt;0.001, independent samples t-test). Patients with osteoporosis gained +5.05% (range -8.7, +15.2) at the lumbar spine and +2.62% (range -1.0, +8.6) at the hip after 1 year. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole induced bone loss and results in significant increases in BMD at the hip and lumbar spine in osteopenic and osteoporotic patients. Analysis of the biochemical markers of bone metabolism is underway and relationships between biochemical and BMD changes will be presented. No significant financial relationships to disclose.