Risk factors, histopathological landscape, biomarkers, treatment patterns and survival of early-onset colorectal cancer: A narrative review.

Early-onset colorectal cancer (EOCRC) incidence has increased in most Western countries over the last decade, with Australia at the forefront. Recent literature has thus focused on characterizing EOCRC from later-onset colorectal cancer (LOCRC). Earlier exposure to modifiable risk factors resulting in gut dysbiosis has been linked with EOCRC development. EOCRCs have more aggressive histopathological features with somatic mutations resulting in pro-inflammatory tumor microenvironments. There is a tendency to treat EOCRCs with multimodal chemotherapeutic regimens and more extensive surgery than LOCRCs with conflicting postoperative outcomes and survival data. Current research is limited by a lack of Australasian studies, retrospective study designs, and heterogeneous definitions of EOCRC. Future research should address these and focus on investigating the role of immunotherapies, establishing minimally invasive diagnostic biomarkers and nomograms, and evaluating the survival and functional outcomes of EOCRC.

The health-related quality of life of early-onset colorectal cancer patients: an Australian cross-sectional study.

AIM: Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire. RESULTS: A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group. CONCLUSIONS: HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research.

Surgical and survival outcomes of early-onset colorectal cancer patients: a single-centre descriptive Australian study.

BACKGROUND: Early-onset colorectal cancer (EOCRC) incidence is increasing in Australia. However, no Australian studies have reported on EOCRC patients' surgical management and survival patterns. METHODS: A retrospective study of 111 EOCRC patients treated at the Royal Prince Alfred Hospital (RPAH), Sydney, Australia between January 2013 and December 2021 was performed. RPAH is a quaternary referral centre for pelvic exenteration (PE) and cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). RESULTS: Most patients had left-sided tumours (76.58%) and stage IV disease at the time of presentation (37.85%). 27.93% of patients underwent either CRS/HIPEC and PE and 72.07% of patients underwent other colorectal resections of which the most common was low anterior resection (19.82%). A stoma was fashioned in 50.54% of patients. Complications occurred in 54.95% of patients of which most were Clavien-Dindo grade II (47.54%). Absolute 1-, 3- and 5-year time intervals were 93.69%, 87.39% and 85.48%. Disease-free and overall survival were poorer in stage IV patients who had PE, followed by CRS/HIPEC then other colorectal resections (P < 0.001 and P = 0.003). CONCLUSIONS: Stoma formation, PE and CRS/HIPEC and minor postoperative complications were common in our EOCRC cohort. Despite this, the 5-year absolute survival rate was acceptable. Thus, an aggressive surgical approach in EOCRC patients at a quaternary referral centre may be feasible at the cost of greater postoperative morbidity. This information is imperative in the surgical consent and preoperative counselling of EOCRC patients and highlights the need for further research to assess the postoperative functional outcomes and quality of life of EOCRC patients.

Increased Incidence of Liver Metastases in Colorectal Versus Appendiceal Adenocarcinoma Peritonectomy Patients Despite Equivocal Survival.

BACKGROUND/AIM: Colorectal adenocarcinoma (CRAdenoCa) and appendiceal adenocarcinoma (AAdenoCa) are diseases of the same histopathological type that metastasise to the liver and peritoneum. In selected subgroups, peritonectomy and heated intraperitoneal chemotherapy (HIPEC) may be indicated as part of the multimodal treatment plan. However, literature comparing the survival outcomes and preoperative tumour activity and burden of CRAdenoCa and AAdenoCa peritonectomy patients without synchronous liver metastases (sLM) is scarce. Little is also known about the comparative incidence of sLM and metachronous LM (mLM) between CRAdenoCa and AAdenoCa peritonectomy patients. This study aimed to clarify the above. PATIENTS AND METHODS: A retrospective cohort study of 684 CRAdenoCa and AAdenoCa primary peritonectomy patients between 2001-2021 was conducted at St George Hospital in Sydney, Australia. RESULTS: Median overall survival (years) was equivocal between CRAdenoCa and AAdenoCa peritonectomy patients (1.7 vs. 1.9, p=0.35). Peritoneal cancer index and preoperative carcinoembryonic antigen (CEA) were significantly elevated (25 vs. 9, p<0.0001 and 7.9 vs. 5, p=0.0080) in AAdenoCa versus CRAdenoCa peritonectomy patients without sLM. The incidence of sLM and mLM was increased in CRAdenoCa peritonectomy patients (24% vs. 3.1%, p<0.0001 and 26% vs. 10%, p=0.0001). CONCLUSION: This study demonstrates similar survival outcomes between CRAdenoCa and AAdenoCa peritonectomy patients. Despite elevated preoperative tumour burden and biological activity in AAdenoCa patients, CRAdenoCa patients had higher rates of sLM and mLM. Further studies are warranted to validate and identify cellular and molecular targets that increase CRAdenoCa's ability to metastasise to the liver.

Strangulated interstitial interparietal hernia following lower segment caesarean section: a case report.

Interparietal hernias are rare and occur most commonly in the long-term postoperative setting following abdominopelvic surgery. This case report describes the development of a strangulated interparietal hernia through a defect in the posterior rectus sheath 4 days post-lower segment caesarean section (LSCS) in a 36-year-old female. Whilst she had an acute abdomen, she did not have a palpable incisional hernia. Her interparietal hernia was identified via a computed tomography scan of her abdomen and pelvis. She underwent a midline laparotomy where ischaemic small bowel was found within her hernia. This was resected and she had an unremarkable recovery. This case is the first of its kind and highlights the diagnostic challenge of interparietal hernias in acute postoperative patients as well as the importance of having a low threshold for suspicion for complicated interparietal hernias in patients with an acute abdomen following LSCS.

Early-onset colorectal cancer: why it should be high on our list of differentials.

BACKGROUND: Early-onset colorectal cancer (EOCRC) (<50 years) incidence has increased in Australia and worldwide. However, the diagnosis of EOCRC is often delayed. Recent research has discovered some differences from later-onset colorectal cancer (LOCRC) (>50 years). An awareness of the unique features of EOCRC is crucial to reduce time from symptom onset to diagnosis. METHODS: A literature search was conducted on electronic databases (MEDLINE, EMBASE and Cochrane Library) using the search terms "early onset colorectal cancer" or "young onset colorectal cancer." RESULTS: The American Cancer Society has reduced the colorectal cancer screening initiation age to 45 for average-risk adults whilst screening programmes in the United Kingdom and Australia remain unchanged with initiation at 60 and 50, respectively. Exposures resulting in dysbiosis (obesity, westernised diet, alcohol, antibiotic and sugar-sweetened beverage consumption) have been linked with increased EOCRC risk. EOCRC is often left-sided presenting with rectal bleeding, altered bowel habit and constitutional symptoms. EOCRC is more commonly sporadic than hereditary, harbouring different genetic mutations than LOCRC. Comparative survival outcomes of EOCRC and LOCRC are conflicting with studies suggesting either better or poorer survival. Young patients better tolerate treatment-related toxicities, which may account for their improved survival despite comparatively advanced stages and poorer histopathological features at diagnosis. CONCLUSION: Current EOCRC literature is limited by American-focused datasets and heterogenous EOCRC definitions and study designs (the greatest strength of evidence exists for EOCRC risk factor studies comprised of large retrospective cohorts). There is minimal research into the quality of life and surgical outcomes of EOCRC patients, and this area warrants further investigation.

Comparison of neutrophil to lymphocyte ratio and prognostic nutritional index with other clinical and molecular biomarkers for prediction of glioblastoma multiforme outcome.

OBJECTIVE: Pre- and post-operative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) and other prognostic clinicopathological variables were correlated with progression free survival (PFS) and overall survival (OS) of Glioblastoma Multiforme (GBM) patients. METHODS: GBM patients (n = 87, single-centre, recruited 2013-2019) were retrospectively divided into low and high groups using literature-derived cut-offs (NLR = 5.07, PNI = 46.97). Kaplan-Meier survival curves and log rank tests assessed PFS and OS. Univariate and multivariate analyses identified PFS and OS prognosticators. RESULTS: High vs low post-operative PNI cohort was associated with longer PFS (279 vs 136 days, p = 0.009), but significance was lost on multivariate analysis. Post-operative ECOG (p = 0.043), daily dexamethasone (p = 0.023) and IDH mutation (p = 0.046) were significant on multivariate analysis for PFS. High pre- and post-operative PNI were associated with improved OS (384 vs 114 days, p = 0.034 and 516 vs 245 days, p = 0.001, respectively). Low postoperative NLR correlated with OS (408 vs 249 days, p = 0.029). On multivariate analysis using forward selection process, extent of resection (EOR) (GTR vs biopsy, p = 0.004 and STR vs biopsy, p = 0.011), and any previous surgery (p = 0.014) were independent prognostic biomarkers for OS. On multivariate analysis of these latter variables with literature-derived prognostic biomarkers, EOR remained significantly associated with OS (p = 0.037). CONCLUSIONS: EOR, followed by having any surgery prior to GBM, are the most significant independent predictors of GBM patient's OS. Post-operative ECOG, daily dexamethasone and IDH mutation are independent prognostic biomarkers for PFS. PNI may be superior to NLR. Post- vs pre-operative serum inflammatory marker levels may be associated with survival.

A phase I, nonrandomized controlled trial demonstrating the novel technique of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy utilizing warm humidified carbon dioxide insufflation.

AIM: The aim of this work was to report on the safety and feasibility of warm humidified CO2 (WHCO2 ) insufflation during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Ten consecutive patients with histologically confirmed peritoneal cancer were enrolled in this phase I pilot nonrandomized controlled trial. They were alternately assigned to CRS and HIPEC with WHCO2 versus standard procedure. WHCO2 was delivered at 10 L/min, a pressure of 4.5 bar, 37ºC and 98% relative humidity during CRS using the HumiGardTM system. HIPEC was performed with an open abdomen using the Coliseum technique at 42ºC for 60 min. All patients were admitted to the intensive care unit and commenced on total parenteral nutrition postoperatively. Surface and core temperatures were measured every 30 min using an infrared camera and nasopharyngeal probe, respectively. Clinicopathological, intra- and postoperative details were collated between groups, and median surface and core temperatures were statistically compared. RESULTS: Surface and core temperatures were generally higher in the WHCO2 group. Core temperature at 120 and 180 min was significantly higher in the WHCO2 versus the non-WHCO2 group (p = 0.028 and 0.008, respectively). There was a significant linear relationship between core and surface temperature at 30, 60, 90, 120, 150 and 180 min (p = 0.033, 0.004, 0.007, 0.021, 0.009 and 0.006, respectively). The peritoneal cancer index was lower but the estimated blood loss was higher in the non-WHCO2 than the WHCO2 group. CONCLUSION: WHCO2 in CRS and HIPEC appears to be safe and feasible. An appropriately powered phase II trial will be required to determine if WHCO2 is associated with improved intra- and postoperative outcomes.

The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients.

Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12-15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication.