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Background: Colorectal cancer (CRC) incidence and mortality in those aged 50 years and above have decreased over the last 2 decades. However, there is a rising incidence in CRC among individuals under 50 years of age, termed early-onset colorectal cancer (EOCRC). EOCRC patients are more advanced stage at diagnosis and may suffer more psychosocial, emotional and financial distress., Objective: Our study examines the epidemiological shifts of CRC in Singapore, a multiethnic country., Methods: CRCs diagnosed at age 20 and above from 1968 to 2019 were identified from the Singapore Cancer Registry. Patient characteristics included gender, ethnicity and age of diagnosis of CRC. Population information was obtained from the Department of Statistics Singapore. Age specific incidence rates (ASR) and age standardized incidence rates (ASIR) were calculated. The cohort was divided into 3 age groups: 20 - 49, 50 - 64 and ≥65 years. Temporal trends of incidence rates were modelled with Joinpoint Regression. Birth cohort models were fitted using the National Cancer Institute (NCI) age-period-cohort analysis tool. Cancer-specific survival analysis was performed with Cox proportional hazards model., Results: 53044 CRCs were included, and 6183 (11.7%) adults aged 20 to 49 years were diagnosed with EOCRC. ASR of EOCRC rose from 5 in 1968 to 9 per 100,000 in 1996 at 2.1% annually and rose to 10 per 100,000 in 2019 at 0.64% annually. The ASR for CRC among adults 50 to 64 years rose at 3% annually from 1968 to 1987 and plateaued from 1987 while the ASR for adults aged 65 and above rose at 4.1% from 1968 to 1989 and 1.3% annually from 1989 to 2003 but decreased from 2003 onwards at 1% annually. There is a continued rise in the ASR of EOCRC among males (APC: 1.5%) compared to females (APC: 0.41%) and a significant increase in APC for early-onset rectal cancer at 1.5% yearly. Compared to the 1950 - 1954 birth reference cohort, the 1970 - 1984 birth cohort had a significantly higher incidence rate ratio (IRR) of 1.17 - 1.36 for rectal cancer while there was no significant change for colon cancer in later cohorts. There were differences in CRC trends across the 3 ethnic groups. Malays had a rapid and persistent rise in ASR of CRC across all age groups (APC: 2- 3%) while amongst young Chinese, only the ASR of rectal cancer is increasing (APC: 1.5%). EOCRC patients had better survival compared to patients diagnosed at 65 years and above (HR 0.73, 95% CI 0.67 - 0.79, P <0.001) after adjusting for covariates., Conclusions: The rise in incidence of rectal cancer among young adults especially among Chinese and Malays in Singapore highlights the need for further research to diagnose CRC earlier and reduce cancer-related morbidity and mortality.

Health system expenditure on cancer drugs is rising rapidly in many countries given the high-priced novel treatments as well as the increasing usage due to a growing and ageing global population. The cost of cancer care continues to outstrip other diseases and it presents a global challenge to treatment access and cancer outcomes. Substantial variability exists in drug pricing across Asia, with low- or middle-income countries being heavily impacted. There is an urgent need to practice value-based pricing for oncology drugs. This will incentivize development of higher-value medicine and eliminate waste. Value-based assessments, financing infrastructure to assist appropriate prioritization, establishing domestic innovation and productive capabilities and reducing the unit economics of care are some of the measures that Asian countries should take towards ensuring universal health coverage for cancer care. Asia will need to keep driving cost management measures that are focused on drug pricing and simultaneously, should be encouraged to explore other interventions including centralising expertise for high "learning curve" efficiencies like chimeric antigen receptor (CAR)-T cell therapy. There is a call for more international collaboration within Asia and a continuous need to engage the public within each country, in order to ensure equitable access to effective cancer medications.

The field of onco-microbiome is rapidly expanding. Multiple studies have shown the crucial role of gut microbiota in the regulation of nutrient metabolism, immunomodulation and protection against pathogens. Tools for manipulating the gut microbiota include dietary modification and faecal microbiota transfer. Accumulating evidence has also documented the application of specific intestinal microbiome in cancer immunotherapy, notably in enhancing the efficacy of immune checkpoint inhibitors. The aim of this review is to focus on the East Asian microbiome and to provide a current overview of microbiome science and its clinical application in cancer biology and immunotherapy., Competing Interests: None

Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide. Classically, HCC develops in genetically susceptible individuals who are exposed to risk factors, especially in the presence of liver cirrhosis. Significant temporal and geographic variations exist for HCC and its etiologies. Over time, the burden of HCC has shifted from the low-moderate to the high sociodemographic index regions, reflecting the transition from viral to nonviral causes. Geographically, the hepatitis viruses predominate as the causes of HCC in Asia and Africa. Although there are genetic conditions that confer increased risk for HCC, these diagnoses are rarely recognized outside North America and Europe. In this review, we will evaluate the epidemiologic trends and risk factors of HCC, and discuss the genetics of HCC, including monogenic diseases, single-nucleotide polymorphisms, gut microbiome, and somatic mutations., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors., Methods: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm 3 ), neutropenia (absolute neutrophils < 2000/mm 3 ), and thrombocytopenia (platelets < 140 000/mm 3 )., Results: Two hundred and thirty-five CRS-HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0-16 days), 0 day (0-2 days), and 1 day (1-2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1-3 days), 1 day (1-2days), and 3 days (range 0-16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105-0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression., Conclusion: Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS-HIPEC., (© 2019 John Wiley & Sons Australia, Ltd.)

Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy.

Aim: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is known to improve survival in selected patients with peritoneal metastasis. However, there is limited data supporting the role of CRS and HIPEC in elderly patients (≥65 years old)., Methods: A retrospective review of a prospectively maintained database of patients who underwent CRS-HIPEC between April 2001 and July 2015 from a single institution was performed. Patients were divided into two groups non-elderly (<65 years old), and elderly (≥65 years old). Clinico- pathological parameters, morbidity and overall (OS) and disease-free survival (DFS) of the patients were compared., Results: A total of 177 patients (median age 52, range 9-74) underwent CRS-HIPEC with curative intent. There were 159 non-elderly patients and 18 elderly patients. Median PCI scores were 12 (0-39) for the non- elderly patients and 11 (1-29) for the elderly patients (p=0.77). High-grade complications occurred in 39 non-elderly patients (24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non-elderly patients (38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day (p=0.69). There was no difference in the 30-day mortality between the two groups (0% vs. 0%, p=1). After a median follow-up of 16 months for all patients, there was no difference in 5-years OS (51.0% vs. 59.6%, p=0.88) and 5-years DFS (23.3% vs. 53.3%, p=0.60) between non-elderly and elderly patients., Conclusions: Surgical outcomes after CRS-HIPEC do not differ significantly between non-elderly and elderly patients. Hence, age should not be a contraindication in selecting patients for CRS and HIPEC., (© 2017 John Wiley & Sons Australia, Ltd.)

Purpose: Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS)., Methods: A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed., Results: The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003-0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients., Conclusions: OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.