Addition of adjuvant hepatic artery infusion to systemic chemotherapy following resection of colorectal liver metastases is associated with reduced liver-related mortality.

BACKGROUND: After resection of colorectal liver metastases (CRLM), recurrent disease in the liver is a major cause of death but may be reduced with the addition of adjuvant hepatic arterial infusion (HAI) chemotherapy to systemic chemotherapy (SYS). OBJECTIVE: This study investigates organ-specific causes of death in patients receiving adjuvant HAI and SYS compared to adjuvant SYS alone. METHODS: Between 2000 and 2007, patients undergoing complete CRLM resection were identified from a prospectively maintained liver resection database and categorized as receiving HAI + SYS or SYS only. Using newly constructed definitions, mortality was attributed to specific organs (liver, lung, peritoneum, and brain) or infection. Univariate models and cumulative incidence functions were generated using competing risk methods. RESULTS: Of 361 eligible patients, 208 (57.6%) received HAI + SYS and 153 (42.4%) received SYS. The median follow up among survivors was 142 months (range = 12-217 months). Ten-year overall survival was 50.6% in the HAI + SYS group compared to 30.9% in those receiving SYS (P = .004). The 5-year cumulative incidence of liver-related mortality was 6.8% in the HAI + SYS group compared to 14.3% in the SYS group (P = .007). CONCLUSION: The addition of HAI to SYS after CRLM resection is associated with a 50% reduction in liver-related mortality at 5 years.

Treatment of colorectal cancer in Sub-Saharan Africa: Results from a prospective Nigerian hospital registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Mortality for CRC is improving in high income countries, but in low and middle income countries, rates of disease and death from disease are rising. In Sub-Saharan Africa, the ratio of CRC mortality to incidence is the highest in the world. This study investigated the nature of CRC treatment currently being offered and received in Nigeria. METHODS: Between April 2013 and October 2017, a prospective study of consecutively diagnosed cases of CRC was conducted. Patient demographics, clinical features, and treatment recommended and received was recorded for each case. Patients were followed during the study period every 3 months or until death. RESULTS: Three hundred patients were included in our analysis. Seventy-one percent of patients received a recommended surgical operation. Of those that didn't undergo surgery as recommended, 37% cited cost as the main reason, 30% declined due to personal reasons, and less than 5% absconded or were lost to follow up. Approximately half of patients (50.5%) received a chemotherapy regimen when it was recommended, and 4.1% received radiotherapy when this was advised as optimal treatment. With therapy, the median overall survival for patients diagnosed with stage III and stage IV CRC was 24 and 10.5 months respectively. Overall, we found significantly better median survival for patients that received the recommended treatment (25 vs 7 months; P < .01). CONCLUSIONS: A number of patients were unable to receive the recommended treatment, reflecting some of the burden of untreated CRC in the region. Receiving the recommended treatment was associated with a significant difference in outcome. Improved healthcare financing, literacy, training, access, and a better understanding of tumor biology will be necessary to address this discrepancy.

A symptom-based model to predict colorectal cancer in low-resource countries: Results from a prospective study of patients at high risk for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) rates in low-resource countries, which typically lack CRC screening programs, are rising. This study determined whether a risk model for patients with rectal bleeding could identify patients with curable CRC. METHODS: This prospective, cross-sectional study evaluated a model constructed from data from 1 hospital and validated at 2 other hospitals. The primary endpoint was the ability of the model to predict CRC, as diagnosed by colonoscopy, from clinical characteristics. The secondary endpoint was to determine the percentage of patients who had CRC. RESULTS: Consecutive patients who were 45 years old or older and had self-reported rectal bleeding for more than 1 week were evaluated. From January 2014 to July 2016, 362 patients answered a questionnaire and underwent colonoscopy. In the validation cohort, 56% of patients with rectal bleeding, weight loss, and changes in bowel habits had CRC, whereas 2% of patients with bleeding alone did. Overall, 18.2% of the patients had CRC, and 8.6% had adenomas. The proportion of CRC patients with potentially curable stage II or III disease was 74%, whereas the historical rate was 36%. The combination of rectal bleeding with both symptoms significantly predicted CRC in the validation set (odds ratio, 12.8; 95% confidence interval, 4.6-35.4; P < .001). CONCLUSIONS: In low-resource settings, patients with rectal bleeding, weight loss, and changes in bowel habits should be classified as high risk for CRC. Patients with a high risk score should be prioritized for colonoscopy to increase the number of patients diagnosed with potentially curable CRC. Cancer 2018;124:2766-2773. © 2018 American Cancer Society.

Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma.

BACKGROUND: Preoperative serum inflammatory markers have been correlated with outcome after resection of hepatocellular carcinoma (HCC), but studies have had conflicting results. This study aimed to evaluate the association of six inflammatory markers with recurrence-free survival (RFS), overall survival (OS), and microvascular invasion (MVI), a well-known prognostic factor. METHODS: This study investigated 370 patients who underwent resection of HCC from 1992 to 2016, retrospectively evaluating their inflammatory indices and individual components including their neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase-to-neutrophil ratio index (ANRI). Uni- and multivariate analyses were performed to evaluate these markers for RFS, OS, and MVI. RESULTS: The median RFS was 23 months, and the median OS was 60 months. Factors independently associated with worse RFS were higher PLR and alpha-fetoprotein level, male gender, and the presence of MVI as well as multiple nodules. Factors independently associated with worse OS were higher PLR and international normalized ratio, male gender, older age, presence of MVI and multiple nodules, larger tumor, presence of cirrhosis, and absence of steatosis. The study identified MVI in 47% of the patients. Lower level of albumin, higher level of alpha-fetoprotein, and larger tumor on preoperative imaging were independently associated with MVI. CONCLUSIONS: This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care.

PURPOSE: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management. EXPERIMENTAL DESIGN: The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome. RESULTS: Colorectal genomic subtype prediction was primarily influenced by mutations in APC and PIK3CA, tumor mutational burden, and DNA mismatch repair (MMR)-deficiency signature. Pancreatic genomic-subtype prediction was dictated by KRAS gene alterations, particularly KRAS G12D, KRAS G12R, and KRAS G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the MDM2 gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability. CONCLUSIONS: The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.

Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.