Last century, the major problem in the treatment of rectal cancer was the very high local recurrence rate after surgery. Local recurrence rates of 30–50% were common and resulted in a very poor ...quality of life and short survival of patients with rectal cancer. Treatment of these local recurrences is difficult and often mutilating. In 1986, the landmark paper by Phil Quirke and others 1 described that involvement of the radial surgical margin, or circumferential resection margin (CRM), was the main cause of local recurrence. This finding, together with the excellent clinical results by Bill Heald and others with a new surgical technique 2, total mesorectal excision (TME), caused a major change in the treatment and prognosis of rectal cancer patients.
Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm with dismal prognosis. Insights into the molecular basis of ACC can pave the way for the application of more effective, personalized ...therapies and detection of patients with hereditary predisposition.
Molecular analysis revealed a germline BRCA2 (and CHEK2) mutation in a patient with a rare pancreatic ACC with extensive intraductal growth. Somatic loss of the wild-type BRCA2 allele in the tumor indicated the causal relationship of ACC with the germline defect. A thorough literature review identified another nine ACCs associated with germline BRCA2 mutation and two ACCs associated with germline BRCA1 mutation, resulting in a prevalence of BRCA1/2 germline mutations in almost 7% of ACCs. Moreover, somatic BRCA1/2 alterations are reported in 16% of sporadic ACCs. Overall, about one fifth (22%) of all pancreatic ACCs exhibit BRCA1/2 deficiency.
This study underscores the important role of BRCA1/2 mutations in pancreatic ACC. All ACC patients should undergo genetic testing for BRCA1/2 mutations to identify carriers of pathogenic variants. This will allow to select patients that can benefit from targeted therapies directed against BRCA1/2-deficient tumors and is also crucial as a referral to genetic screening for the relatives of affected individuals carrying germline BRCA1/2 alterations.
Abbreviations: ACC: acinar cell carcinoma; HBOC: Hereditary Breast and Ovarian Cancer; LOH: loss of heterozygosity; PARP: poly (ADP-ribose) polymerase; PDAC: pancreatic ductal adenocarcinoma; PP: pancreatic panniculitis; SD: standard deviation; WES: whole-exome sequencing.
Aim
This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care.
...Method
Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I–III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011–2015). Separate analyses were performed for cT1–3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses.
Results
A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1–3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1–3 Dutch population.
Conclusion
Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer.
Background: Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed ...against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. Patients and methods: The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. Results: Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). Conclusions: We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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