Impact of microsatellite status in early-onset colonic cancer

Background The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Methods Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. Results A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Conclusion Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers. Data on 650 patients aged less than 50 years diagnosed with stage I-III colonic cancer and undergoing surgery with curative intent were collected, and the impact of microsatellite instability (MSI) on clinicopathological features and disease-specific outcomes was assessed. Patients with early-onset disease had a high risk of MSI and defined genetic conditions. Those with MSI tumours had more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

The place of Somali in the resistance of Ethiopia against the Italian colonial forces in the Ogaden, 1915 to 1941

The study investigated the role of Somalis in Ethiopia’s struggle against Italian colonial forces in the Ogaden region from 1915 to 1941, which has been overlooked in existing literature. The research was conducted using an exploratory design and qualitative data obtained from primary records, oral evidence, and secondary sources. The relationship between Ethiopia and Italian forces in the Ogaden frontiers from 1915 to 1935 was characterized by tensions due to Italian incursions and Ethiopian resistance. The Somali people, who considered the Italians as threats to their socio-economic wellbeing, resisted the invasion of their territories in the Ogaden from 1915 onwards. They played a crucial role in the Ethiopian resistance by providing information, logistics, and combatants. Notable figures such as Omer Semeter, Ali Nur, Erzi Jama, Sultan Bede, Hussein Elmie, Ahmed Hashi, and Mahamud Ebrahim organized the Somalis in the resistance against the Italian colonial forces. Although there are pieces of literature related to Ethiopia’s resistance against Italian colonial forces, most of them are geographically confined to the north and temporally limited from 1935 to 1941. Moreover, existing literature on Ethiopian resistance in the Ogaden mainly focuses on defensive wars headed by higher nobles. This study reveals historical realities that have been made invisible in historical literature by highlighting the contributions of local peoples of the Ogaden who participated in the resistance against Italian invasion.</p

Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis.

OBJECTIVES: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC ß-lactamase. METHODS: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum ß-lactam/ß-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. REGISTRATION: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). RESULTS: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. CONCLUSIONS: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems

Impact of microsatellite status in early-onset colonic cancer

Background: The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Methods: Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. Results: A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Conclusion: Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes