Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. MethodsWe did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. FindingsWe included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58•0%) were male. Median gestational age at birth was 38 weeks (IQR 36-39) and median bodyweight at presentation was 2•8 kg (2•3-3•3). Mortality among all patients was 37 (39•8%) of 93 in low-income countries, 583 (20•4%) of 2860 in middle-income countries, and 50 (5•6%) of 896 in high-income countries (p<0•0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90•0%] of ten in lowincome countries, 97 [31•9%] of 304 in middle-income countries, and two [1•4%] of 139 in high-income countries; p≤0•0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2•78 [95% CI 1•88-4•11], p<0•0001; middle-income vs high-income countries, 2•11 [1•59-2•79], p<0•0001), sepsis at presentation (1•20 [1•04-1•40], p=0•016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4-5 vs ASA 1-2, 1•82 [1•40-2•35], p<0•0001; ASA 3 vs ASA 1-2, 1•58, [1•30-1•92], p<0•0001]), surgical safety checklist not used (1•39 [1•02-1•90], p=0•035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1•96, [1•4...
Background/Aim: Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability. Materials and Methods: A total of 717 patients with CRLM who underwent hepatic resection +/-RFA at two tertiary institutions between 09/01/2000-12/01/2015 were eligible for inclusion in this study. Results: Among patients with <4 lesions (n=568), OS in the resection + RFA group (n=48) was significantly worse than in the resection alone group (n=520) (5-year OS: 34.4 % versus 58.9%, p=0.007). Conversely, in patients with ≥4 lesions, OS in the resection + RFA (n=68) and resection alone(n=81) groups were not significantly different (5-year OS: 31.9% versus 34.1%, p=0.48). In patients with <4 lesions, carcinoembryonic antigen (CEA) ≥30 ng/ml, extrahepatic metastasis, preoperative chemotherapy and resection + RFA were independently associated with poor prognosis. Interestingly, in patients with ≥4 lesions, positive primary lymph nodes, KRAS mutation, CEA ≥30 ng/ml and extrahepatic metastasis were independent predictors of poor prognosis; however, the combination of hepatic resection with RFA was not associated with worse survival (p=0.93). Conclusion: Although surgeons should always strive for R0 resection when feasible, combined resection and RFA may be a viable alternative for CRLM patients with a large number of tumors. Currently, the principal treatment strategy for patients with colorectal cancer liver metastasis (CRLM) is systemic chemotherapy, while hepatic resection can further improve survival in carefully selected patients (1-5). On the contrary, many reports concur that radio-frequency ablation (RFA) results in inferior outcomes than hepatic resection in patients with CRLM and should only be employed when surgical resection cannot be performed (6-9). Nonetheless, the presence of extensive metastatic tumor number in the liver, (especially four or more lesions) often precludes a curative hepatic resection due to either technical challenges or inadequate remnant liver function and is a wellknown poor prognostic factor (4, 5, 10-12). In fact, historically, specifically ≥4 CRLM, was considered to be a contraindication for liver resection (13, 14). Similarly, a study on a contemporary cohort (treated after 2005) demonstrated that the prognosis of patients with ≥4 CRLM who undergo surgery has not improved despite the development of modern chemotherapies (14). Interestingly, our group and others have demonstrated that hepatectomy + RFA may achieve long-term outcomes that are comparable to hepatectomy alone (15, 16). Nonetheless, the impact of combined resection and RFA on survival among patients with different levels of tumor number 6353 This article is freely accessible online.
Background: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.Methods: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.Results: 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P = 0.01) and wtKRAS status remained independently associated with a major response (P = 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P = 0.023).Conclusions: Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.
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