Obesity Significantly Affects the Incidence of Hepatic Injury in Patients with Colorectal Liver Metastasis

Objective: Surgical resection is the mainstay treatment for colorectal liver metastasis. In unresectable cases, chemotherapy is used to transform the tumor into resectable lesions, with related concerns about toxicity to nontumoral liver parenchyma. Liver toxicity, including steatosis, steatohepatitis, and sinusoidal dilation, has been reported. However, these changes are difficult to histologically distinguish from non-alcoholic fatty liver disease, which is commonly found in populations and attributed mainly to metabolic syndrome. The aim of this study was to investigate the factors associated with liver injury in patients with colorectal liver metastasis. Methods: This retrospective study included patients who underwent hepatic resection for colorectal liver metastasis at Siriraj Hospital during the 2006 to 2013 study period. Patient demographic data, clinical characteristics, and histologic changes related to liver injury were collected and analyzed. Results: Ninety-two patients (50 men, 42 women) were included, with a mean age of 59.4 years (range: 48.5-70.3). Forty-four patients (47.8%) received preoperative chemotherapy (CMT). Incidence of liver injury was not significantly different between the CMT and non-CMT groups (65.9% vs. 62.5%; p=0.902). However, incidence of liver injury was significantly higher in obese patients than in non-obese patients (82.8% vs. 55.6%; p=0.022, odds ratio=3.95). In multivariate analysis, obesity (BMI ≥25 kg/m2) was the only factor significantly associated with liver injury in patients with colorectal liver metastasis. Conclusion: Of the ten factors evaluated for association in this study, including preoperative chemotherapy, obesity was the only factor found to be significantly associated with liver injury in patients with colorectal liver metastasis

Early-Onset Signet-Ring Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in the United States. While a decline has been observed in the older population, the occurrence of CRC in the adolescent and young adult (AYA) population has increased over the past two decades. The histopathologic characteristics and clinical behavior of CRC in AYA patients have been shown to be distinct from those of CRC in older adults. The rarer subtypes of CRC such as mucinous adenocarcinoma and signet-ring cell carcinoma are associated with a poorer prognosis compared to the more common subtypes. Here we report a case of a 20-year-old man who was diagnosed with stage IVB (T4 N2 M1, with peritoneal carcinomatosis) signet-ring cell adenocarcinoma of the colon. The scarcity of information on these rarer subtypes merits further study and investigation

The <i>KRAS</i>-Mutant Consensus Molecular Subtype 3 Reveals an Immunosuppressive Tumor Microenvironment in Colorectal Cancer

Colorectal cancers (CRC) with KRAS mutations (KRASmut) are frequently included in consensus molecular subtype 3 (CMS3) with profound metabolic deregulation. We explored the transcriptomic impact of KRASmut, focusing on the tumor microenvironment (TME) and pathways beyond metabolic deregulation. The status of KRASmut in patients with CRC was investigated and overall survival (OS) was compared with wild-type KRAS (KRASwt). Next, we identified CMS, and further investigated differentially expressed genes (DEG) of KRASmut and distinctive pathways. Lastly, we used spatially resolved gene expression profiling to define the effect of KRASmut in the TME regions of CMS3-classified CRC tissues. CRC patients with KRASmut were mainly enriched in CMS3. Their specific enrichments of immune gene signatures in immunosuppressive TME were associated with worse OS. Activation of TGFβ signaling by KRASmut was related to reduced pro-inflammatory and cytokine gene signatures, leading to suppression of immune infiltration. Digital spatial profiling in TME regions of KRASmut CMS3-classified tissues suggested up-regulated genes, CD40, CTLA4, ARG1, STAT3, IDO, and CD274, that could be characteristic of immune suppression in TME. This study may help to depict the complex transcriptomic profile of KRASmut in immunosuppressive TME. Future studies and clinical trials in CRC patients with KRASmut should consider these transcriptional landscapes