Colorectal cancer (CRC) is a leading cause of death worldwide, despite progress made in detection and management through surgery, chemotherapy, radiotherapy, and immunotherapy. Novel therapeutic agents have improved survival in both the adjuvant and advanced disease settings, albeit with an increased risk of toxicity and cost. However, metastatic disease continues to have a poor long-term prognosis and significant challenges remain due to late stage diagnosis and treatment failure. Biomarkers are a key tool in early detection, prognostication, survival, and predicting treatment response. The past three decades have seen advances in genomics and molecular pathology of cancer biomarkers, allowing for greater individualization of therapy with a positive impact on survival outcomes. Clinically useful predictive biomarkers aid clinical decision making, such as the presence of KRAS gene mutations predicting benefit from epidermal growth factor receptor (EGFR) inhibiting antibodies. However, few biomarkers have been translated into clinical practice highlighting the need for further investigation. We review a range of protein, DNA and RNA-based biomarkers under investigation for diagnostic, predictive, and prognostic properties for CRC. In particular, long non-coding RNAs (lncRNA), have been investigated as biomarkers in a range of cancers including colorectal cancer. Specifically, we evaluate the potential role of lncRNA plasmacytoma variant translocation 1 (PVT1), an oncogene, as a diagnostic, prognostic, and therapeutic biomarker in colorectal cancer.

Pilonidal sinus disease is chronic acquired condition leading to significant morbidity and associated healthcare costs. Several techniques have been described to manage this condition with no treatment gaining universal acceptance. With the shift towards minimally invasive surgery, Video Assisted-Ablation of Pilonidal Sinus (VAAPS) and Endoscopic Pilonidal Sinus Treatment (EPiST) have gained prominence. The aim of this review is to analyse current treatment modalities and the evidence for endoscopic pilonidal sinus surgery.

Acute appendicitis (AA) is one of the most common acute general surgical presentations affecting 7% of the population at some point in their lifetime. The ability to assess the risk of complicated appendicitis (CA) from uncomplicated appendicitis (UA) in acute appendicitis (AA) could reduce the associated morbidity and mortality. The value of platelet lymphocyte ratio (PLR) as an inflammatory marker increases when its fluctuations are interpreted along with other complementary hematologic indices, such as neutrophil-to-lymphocyte ratio (NLR), which provides additional information about the disease activity. Hence, we postulated that NLR and/or PLR could serve as a potential surrogate marker in assessing the severity of AA. This study aims to investigate the use of PLR and/or NLR as a surrogate biomarker in differentiating uncomplicated from complicated appendicitis. This retrospective study was conducted at Russells Hall Hospital from January 1, 2017, to December 31, 2020. Data of all patients over age 16 years that had histologically confirmed appendicitis were retrieved. NLR and PLR were calculated from the admission hemogram, and the ratios were compared between uncomplicated (UA) or complicated appendicitis (CA). Cut-off values were calculated using the summarized ROC curve; in addition, the sensitivity and specificity with 95% confidence intervals were determined using SPSS 25.0 (IBM Corp., Armonk, NY). A total of 799 patients were analyzed, of which 469 (58.7%) were female. The median age was 31.2 years. The difference between NLR and PLR within the two appendicitis groups was significant (P=0.05; Kruskal-Wallis). Cohen’s kappa (degree of inter-rater agreement) between NLR and PLR showed a moderate agreement of 0.589 (P<0.001). We equally demonstrated an exponential relationship between PLR and NLR (R² =0.510, P<0.05). For UA, the area under the curve (AUC) and the cut-off for NLR and PLR were 0.715, 4.75 with a confidence interval (CI) of 0.678-0.653 and 0.632, 155 with a CI of 0.591-0.672, respectively. For CA, using NLR and PLR, the AUC and cut-off were 0.727, 6.96 with a CI of 0.687-0.768 and 0.653, 180.5 with a CI of 0.602-0.703, respectively; all were significant with a P of <0.001. NLR and PLR are a reliable, less cumbersome surrogate biomarker for assessing the severity of acute appendicitis.

The ability to predict risk of perforation in acute appendicitis (AA) could direct timely management and reduce morbidity. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are surrogate severity markers in infections. This study investigates the use of PLR and NLR as a marker for distinguishing uncomplicated (UA) and complicated appendicitis (CA) in children. This retrospective single-center study collected data between January 1, 2014, and December 31, 2020. Children between five and 17 years of age with histologically confirmed appendicitis were included. Cut-off values for NLR and PLR were determined by employing the receiver operating characteristic (ROC) curve with sensitivity and specificity in addition to regression analysis. A total of 701 patients were included with a median age of 13 years. Out of which 52% of the cohort was female. The difference between the NLR and PLR ratios between UA and CA was significant (p=0.05, Kruskal-Wallis). For UA, the area under the ROC curve (AUC) and cut-off for NLR and PLR were 0.741, 3.80 with 95% CI of 0.701-0.781 and 0.660, 149.25 with 95% CI of 0.618-0.703, respectively. In CA, using NLR and PLR, AUC and cut-off were 0.776, 8.86 with 95%CI of 0.730-0.822 and 0.694, 193.67 with 95%CI of 0.634-0.755, respectively. All were significant with p<0.001. NLR and PLR are reliable, synergistic markers predicting complicated appendicitis which can guide non-operative management in children.

The clinical diagnosis of complicated acute cholecystitis (CAC) remains difficult with several pathological or ultrasonography criteria used to differentiate it from uncomplicated acute cholecystitis (UAC). This study aims to evaluate the use of combined inflammatory markers C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) as surrogate markers to differentiate between UAC and CAC. We identified 600 consecutive patients admitted with biliary symptoms during an acute surgical take from our electronic prospectively maintained database over a period of 55 months. Only patients undergoing emergency cholecystectomy performed during the index admission were included. The primary outcome was the finding of CAC versus UAC. A total of 176 patients underwent emergency laparoscopic cholecystectomy (ELC) during the index admission, including 118 (67%) females with a median age of 51 years (range: 21-97 years). The proportion of UAC (130 [74%]) and CAC (46 [26%]) was determined along with demographic data. Multivariate regression analysis showed that patient’s age (OR=1.047; p=0.003), higher CRP (OR=1.005; p=0.012) and NLR (OR=1.094; p=0.047) were significant independent factors associated with severity of cholecystitis. Receiver operating characteristic (ROC) analysis for CRP showed an AUC (area under the curve) of 0.773 (95% CI: 0.698- 0.849). Using a cut-off value of 55 mg/L for CRP, the sensitivity of CAC was 73.9% and specificity was 73.1% in predicting CAC. The median post-operative length of stay was four days. The conversion rate from laparoscopic cholecystectomy to open surgery was 2% (4/176), and 5% (9/176) patients suffered post-operative complications with no mortality at 30 days. CRP, NLR and age were independent factors associated with the severity of acute cholecystitis. NLR and CRP can be used as surrogate markers to predict patients at risk of CAC during emergency admission, which can inform future guidelines. Moreover, ELC for CAC can be safely performed under the supervision of dedicated upper GI surgeons.

There is increasing evidence in a range of cancer types that the microbiome plays a direct role in modulating the anti-cancer immune response both at the gut level and systemically. Differences in the gut microbiota have been shown to correlate with differences in immunotherapy responses in a range of non-gastrointestinal tract cancers. DNA mismatch repair-deficient (dMMR) colorectal cancer (CRC) is radically different to DNA mismatch repair-proficient (pMMR) CRC in clinical phenotype and in its very good responses to immunotherapy. While this has usually been thought to be due to the high mutational burden in dMMR CRC, the gut microbiome is radically different in dMMR and pMMR CRC in terms of both composition and diversity. It is probable that differences in the gut microbiota contribute to the varied responses to immunotherapy in dMMR versus pMMR CRC. Targeting the microbiome offers a way to boost the response and increase the selection of patients who might benefit from this therapy. This paper reviews the available literature on the role of the microbiome in the response to immunotherapy in dMMR and pMMR CRC, explores the potential causal relationship and discusses future directions for study in this exciting and rapidly changing field.