Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations
Objective surgical process will doubtless cure resectable carcinoma (PaC) and considerably prolong survival in some patients. This large-scale international study aimed to research variations in surgical process for political action committee in Europe and USA and determinants for its usage.
Design knowledge from six European population-based cancer registries and therefore the North American country police investigation, medicine, and finish Results Program information throughout 2003–2016 were analysed. Age-standardised surgical process rates for overall and stage I–II PaCs were computed. Associations between surgical process and demographic and clinical parameters were assessed exploitation multivariable logistical regression models.
Results a complete of 153 698 records were analysed. In population-based registries in 2012–2014, surgical process rates ranged from thirteen.2% (Estonia) to twenty one.2% (Slovenia) overall and from thirty four.8% (Norway) to sixty eight.7% (Denmark) for stage I–II tumours, with nice international variations. throughout 2003–2014, surgical process rates solely magnified in USA, Netherlands and Scandinavian country. surgical process was considerably less often performed with a lot of advanced growth stage (ORs for stage III and IV versus stage I–II tumours: zero.05–0.18 and 0.01–0.06 across countries) and increasing age (ORs for patients 70–79 and ≥80 versus those [1]
Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer
Purpose
Germline variants in double-strand DNA injury repair (dsDDR) genes (e.g., BRCA1/2) incline to duct gland glandular cancer (PDAC) and should predict sensitivity to platinum-based therapy and poly(ADP) carbohydrate enzyme (PARP) inhibitors. we have a tendency to wanted to see the prevalence and significance of germline cancer status cistron variants in PDAC with paired corporal and survival analyses.
Methods
Using a bespoke next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC observed while not preselection for unsound options (e.g., young age,
personal/family history). All known variants were assessed for pathogenicity. Outcomes were analyzed exploitation multivariable-adjusted Cox proportional hazards regression.
Results
We found that 28/289 (9.7%; ninety five confidence interval [CI] half dozen.5–13.7%) patients carried infective/likely pathogenic germline variants, together with twenty one (7.3%) dsDDR cistron variants (3 BRCA1, 4 BRCA2, fourteen alternative dsDDR genes [ATM, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C]), three kill syndrome, and four alternative genes (APC p.I1307K, CDKN2A, TP53). corporal sequencing and assay known second hits within the tumour in 12/27 (44.4%) patients with germline variants (1 failing sequencing). Compared with noncarriers, patients with germline dsDDR cistron variants had superior overall survival (hazard magnitude relation [HR] zero.54; ninety five CI zero.30–0.99; P = 0.05).
Conclusion
Nearly tenth of PDAC patients harbor germline variants, though the bulk lack corporal second hits, the therapeutic significance of that warrants any study. [2]
Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX
Objective: The aim of this study was to see (1) whether or not surgical factors will predict resectability of borderline resectable (BR) and domestically advanced (LA) duct gland ductal carcinoma (PDAC) when neoadjuvant FOLFIRINOX, (2) that patients may enjoy adjuvant medical care, and (3) survival variations between resected BR/LA patients World Health Organization received neoadjuvant FOLFIRINOX and direct resected patients.
Background: Patients with BR/LA PDAC are usually treated with FOLFIRINOX to get a margin-negative surgical operation, nevertheless choice of patients for surgical operation remains difficult.
Methods: Clinicopathologic knowledge of PDAC patients surgically explored between 04/2011-11/2016 in an exceedingly single establishment were retrospectively collected.
Results: Following neoadjuvant FOLFIRINOX, 141 patients were surgically explored (BR: forty nine, LA: 51%) and one hundred ten (78%) were resected. Resected patients had lower surgical CA 19-9 levels (21 vs forty U/mL, P = 0.03) and smaller tumors on surgical X-raying (CT) scan (2.3 vs 3.0 cm, P = 0.03), however no predictors of resectability were known. Median overall survival (OS) was thirty four.2 months from identification for all FOLFIRINOX patients and thirty seven.7 months for resected patients. Among resected patients, surgical CA 19-9 >100 U/mL and >8 months between identification and surgery expected a shorter operative disease-free survival (DFS); Charlson comorbidity index >1, surgical CA 19-9 >100 U/mL and neoplasm size (>3.0 cm on CT or >2.5 cm on pathology) expected cut OS. DFS and OS were considerably higher for BR/LA PDAC patients treated with neoadjuvant FOLFIRINOX compared with direct resected patients (DFS: twenty nine.1 vs 13.7, P < 0.001; OS: thirty seven.7 vs 25.1 months from identification, P = 0.01).
Conclusion: BR/LA PDAC patients with no progression on neoadjuvant FOLFIRINOX ought to be offered surgical exploration. Except size, ancient pathological parameters fail to predict survival among resected FOLFIRINOX patients. Resected FOLFIRINOX patients have survival that seems to be superior than that of resectable patients World Health Organization go on to surgery. [3]
Family history of cancer, Ashkenazi Jewish ancestry, and pancreatic cancer risk
Background
Individuals with a case history of cancer is also at inflated risk of carcinoma. Jew soul (AJ) people carry inflated risk for carcinoma and different cancer sorts.
Methods
We examined the association between case history of cancer, AJ heritage, and incident carcinoma in forty nine 410 male participants of the possible Health Professionals Follow-up Study. Hazard ratios (HRs) were calculable victimisation multivariable-adjusted Cox proportional hazards models.
Results
During 1.1 million person-years (1986–2016), 452 participants developed carcinoma. inflated risk of carcinoma was discovered in people with a case history of exocrine gland (HR, 2.79; ninety five confidence interval [CI], 1.28–6.07) or carcinoma (HR, 1.40; 95% CI, 1.01–1.94). There was a trend towards higher risk of carcinoma in regard to a case history of large intestine cancer (HR, 1.21; 95% CI, 0.95–1.55) or AJ heritage (HR, 1.29; 95% CI, 0.94–1.77). the chance was extremely elevated among AJ men with a case history of breast or large intestine cancer (HR, 2.61 [95% CI, 1.41–4.82] and 1.92 [95% CI, 1.05–3.49], respectively).
Conclusion
Family history of carcinoma was related to inflated risk of this malignancy. case history of breast or large intestine cancer was related to the inflated risk among AJ men. [4]
Kaurenoic Acid Isolated from the Root Bark of Annona senegalensis Induces Cytotoxic and Antiproliferative Effects against PANC-1 and HeLa cells
Aims: Cancer is one in all the leading causes of death worldwide with Associate in Nursing calculable half dozen.7 million deaths and twenty four.6 million individuals living with cancer in 2002. Presently, there’s a world increase in prevalence, mortality and health burden of assorted malignancies. World Health Organization (WHO) report projected that cancer prevalence rates might any increase by fiftieth to fifteen million new cases within the year 2020. The bioactivity guided isolation of the bioactive constituent and its characterization, liable for the antiepileptic drug effects of the foundation bark extract of A. senegalensis yielded kaur-16-en-19-oic acid (KA). Therefore, the aim of this study was to guage the anti-proliferative activity of kaurenoic acid from A. senegalensis on designated neoplastic cell lines.
Study Design: The study was designed to establish the antiproliferative and cytotoxic effects of kaurenoic acid, a diterpenoid isolated from the foundation bark of Nigerian magnoliid dicot genus senegalensis (Annonaceae).
Place and period of Study: Department of medical specialty and pharmacological medicine, college of Pharmaceutical Sciences, University of African nation, Nsukka, Nigeria, between October 2010 and Gregorian calendar month, 2012.
Methodology: Human embryonic urinary organ cells expressing SV40 massive T-antigen (293 T), duct gland tumor (PANC-1) and Henrietta Lacks’ cervical (HeLa) cell lines were employed in the study exploitation customary MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazoliumbromide, assay methodology.
Results: Kaurenoic acid (KA) exhibited cytotoxic effects against the cells with calculable IC50 values of zero.93, 0.74 and 0.52 M concentrations for 293 T, Hel and PANC-1 cells severally. this is often a sign of the doable potentials of Hindu deity within the treatment of cervical and duct gland cancers.
Conclusions: Kaurenoic acid (KA), a diterpenoid, possesses antiproliferative impact against Hel and PANC-1 cell lines, and will be the metastatic tumor constituent within the root bark extract of A. senegalensis with potentials as a lead within the chemical synthesis of ordinary anti cancer agents. [5]
Reference
[1] Huang, L., Jansen, L., Balavarca, Y., Molina-Montes, E., Babaei, M., Van Der Geest, L., Lemmens, V., Van Eycken, L., De Schutter, H., Johannesen, T.B. and Fristrup, C.W., 2019. Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. Gut, 68(1), pp.130-139. (Web Link)
[2] Yurgelun, M.B., Chittenden, A.B., Morales-Oyarvide, V., Rubinson, D.A., Dunne, R.F., Kozak, M.M., Qian, Z.R., Welch, M.W., Brais, L.K., Da Silva, A. and Bui, J.L., 2019. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genetics in Medicine, 21(1), p.213. (Web Link)
[3] Michelakos, T., Pergolini, I., Fernández-del Castillo, C., Honselmann, K.C., Cai, L., Deshpande, V., Wo, J.Y., Ryan, D.P., Allen, J.N., Blaszkowsky, L.S. and Clark, J.W., 2019. Predictors of resectability and survival in patients with borderline and locally advanced pancreatic cancer who underwent neoadjuvant treatment with FOLFIRINOX. Annals of surgery, 269(4), pp.733-740. (Web Link)
[4] Family history of cancer, Ashkenazi Jewish ancestry, and pancreatic cancer risk
Tsuyoshi Hamada, Chen Yuan, Matthew B. Yurgelun, Kimberly Perez, Natalia Khalaf, Vicente Morales-Oyarvide, Ana Babic, Jonathan A. Nowak, Douglas A. Rubinson, Marios Giannakis, Kimmie Ng, Peter Kraft, Meir J. Stampfer, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino & Brian M. Wolpin
British Journal of Cancer (2019) (Web Link)
[5] C. Okoye, T., A. Akah, P., S. Nworu, C. and C. Ezike, A. (2014) “Kaurenoic Acid Isolated from the Root Bark of Annona senegalensis Induces Cytotoxic and Antiproliferative Effects against PANC-1 and HeLa cells”, European Journal of Medicinal Plants, 4(5), pp. 579-589. doi: 10.9734/EJMP/2014/6926. (Web Link)