The utility of ctDNA in colorectal cancer with peritoneal metastases.

BACKGROUND: The development of peritoneal metastases (PM) in patients with colorectal cancer (CRC) connotates a poor prognosis. Circulating tumour (ctDNA) is a promising tumour biomarker in the management CRC. This systematic review aimed to summarize the role of ctDNA in patients with CRC and PM. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic review of the literature until June 2022 was performed. Studies reporting on the utility of ctDNA in colorectal PM were included. A total of eight eligible studies were identified including a total of 167 patients. RESULTS: The findings from this review suggest an evolving role for ctDNA in CRC with PM. ctDNA can be isolated from both plasma and peritoneal fluid, with peritoneal fluid preferred as the liquid biopsy of choice with higher mutation detection rates. Concordance rates between tissue and plasma/peritoneal ctDNA mutation detection can vary, but is generally high. ctDNA has a potential role in monitoring anti-EGFR treatment response and resistance, as well as in predicting future prognosis and recurrence. The detection of ctDNA in plasma of patients with isolated PM is also possibly suggestive of occult systemic disease, and patients exhibiting such ctDNA positivity may benefit from systemic treatment. Limitations to ctDNA mutation detection may include the size of peritoneal lesions, as well as the fact that PM poorly shed ctDNA. CONCLUSION: While these findings are promising, further large-scale studies are needed to better evaluate the utility of ctDNA in this subset of patients.

Comparison of colorectal cancer outcomes in young adults and octogenarians.

BACKGROUND: This study aimed to characterise the outcomes associated with colorectal cancer (CRC), comparing young adults (<50 years), patients of screening age (50-79 years), and octogenarians (>80 years). METHODS: All consecutive CRC resections with curative intent were recruited into this study from a prospectively maintained CRC database at a tertiary academic centre. RESULTS: A total of 745 eligible cases were identified. Five-year survival in young adults was poorer than that of patients of screening age. Young adults had the highest incidence of rectal cancer resections, and presented with the most advanced tumour stages. Independent associations for poorer survival in young adults were increased nodal stage, the presence of distal metastases, and loss of MLH1/PMS2 staining on immunohistochemistry. Young adults had similar survival to octogenarians, when comparing patients treated with curative intent, regardless of oncological treatment.

Retained fecalith following laparoscopic appendectomy.

It is important to identify a retained fecalith and remove that infective nidus to decrease the morbidity in patients undergoing laparoscopic appendectomy for perforated appendicitis.

Rate of anastomotic leak following right hemicolectomy by general surgical trainees.

PURPOSE: Performing a right hemicolectomy (RH) is a core technical competency for general surgical trainees. There is a concern that anastomotic leaks occur more frequently when patients are operated on by trainees rather than by surgeons. This study aims to analyse the quality of care outcomes after RH, stratified by the experience level of the operator. METHODS: Patients were retrospectively recruited from the Bi-National Colorectal Cancer Audit (BCCA) Registry, from 2007 to 2018. All patients who underwent a RH for colorectal cancer were eligible. The primary outcome measure was anastomotic leak rate. RESULTS: A total of 6548 eligible right hemicolectomies were identified, with 74% being performed by consultants, 12% by fellows, and 14% by surgical trainees. The overall incidence of an anastomotic leak was 2.1%, with the highest rate of 3.7% noted among supervised registrars. Positive resection margin rate was the highest among unsupervised trainees at 10.5%, as compared with 4.3% among consultants. Anastomotic leak, anastomotic bleeding, prolonged ileus, and pneumonia occurred significantly less frequently with consultant surgeons, as compared with trainees. Independent risk factors for anastomotic leak were urgent surgery, extended right hemicolectomy, conversion to open surgery, and a lower level of operator seniority. Two independent risk factors were identified for inpatient mortality-a high ASA score (III and above) and urgent surgery. CONCLUSION: RH is a common operative procedure in general surgical training. Data from this study may assist with the structuring of surgical training programmes, aimed at maximising both patient safety and trainee professional development and education.

Safety of laparoscopic appendicectomy during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Acute appendicitis is the most common non-obstetric surgical presentation during pregnancy. There were concerns that laparoscopic appendicectomy increases the risk of foetal loss compared to an open approach. Therefore, with recent advances in perioperative care, it is likely the risk has changed. Here, we performed an updated meta-analysis assessing the safety of laparoscopic appendicectomy in pregnant women. METHODS: A meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was undertaken between 2000 and 2017 on Ovid Medline and Embase. The primary outcome measures were foetal loss and preterm delivery, whereas secondary outcome measures were operative time and hospital length of stay. A random-effect model was performed to pool odds ratio (OR) and standardized mean difference (SMD). RESULTS: Seventeen observational studies were included, with 1886 patients in the laparoscopic and 4261 patients in the open group. Comparing laparoscopic versus open appendicectomy, there were 54 (5.96%) and 136 (3.73%) foetal losses, respectively. However, preterm delivery was much higher in the open approach (8.99%) compared to laparoscopic approach (2.84%). Pooled OR for foetal loss was 1.84 (95% confidence interval (CI) 1.31-2.58, P < 0.001), whereas OR for preterm delivery was 0.39 (95% CI 0.27-0.55, P < 0.001). There was no significant difference between both approaches for operative time (SMD -0.07; 95% CI -0.43 to 0.30, P = 0.71) or hospital length of stay (SMD -0.34; 95% CI -0.83 to 0.16, P = 0.18). CONCLUSION: In a pooled analysis of level III evidence, laparoscopic appendicectomy posed a higher risk of foetal loss but lower risk of preterm delivery. Caution and informed consent are crucial when offering a laparoscopic approach.

Correction to: Short-term outcome of emergency colorectal cancer surgery: results from Bi-National Colorectal Cancer Audit.

The publisher regret that a typographical error was present in the Table 1 of the original version of this article. The value "20,032" should have been "2" in the Variable column under T stage. The correct table is now presented correctly in this article.

Short-term outcome of emergency colorectal cancer surgery: results from Bi-National Colorectal Cancer Audit.

BACKGROUNDS: A significant number of patients with colorectal cancer will have an emergency presentation requiring surgery. This study aims to evaluate short-term outcomes for patients undergoing emergency colorectal cancer surgery in Australasia. METHODS: All consecutive CRC from the Bi-National Colorectal Cancer Audit Database was interrogated from 2007 to 2016. Short-term outcomes including length of stay, complication rate and mortality rate were compared between the emergency and elective groups. Logistic regression analysis was performed to identify independent predictors for inpatient mortality. A predictive model for inpatient mortality was constructed using these variables, and its accuracy was then validated by the Bootstrap re-sampling method. RESULTS: Of 15,676 colorectal cancer cases identified, 13.6% were emergency cases. The emergency group had a higher rate of surgical and medical complications (26.7% vs 22.6%, p < 0.001; 22.8 vs 13.8%, p < 0.001, respectively). Higher inpatient mortality rate was also observed in the emergency group (3.4% vs 2.6%, p = 0.023). Independent predictors for inpatient survival included age, American Society Anaesthesiologists score, emergency surgery and tumour stage. In addition, postoperative complications such as anastomotic leak (odds ratio [OR] 3.78, p < 0.001), sepsis (OR 2.85, p < 0.001) and medical complications (OR 13.88, p < 0.001) had a significant impact in survival in the emergency group. Receiver operating characteristics curve for inpatient mortality was 0.913. CONCLUSION: Emergency colorectal cancer surgery carries significant morbidity and mortality. Recognition of the increasing rate of postoperative complications may help minimise the detrimental impact of this event on overall outcomes.

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

BACKGROUND: Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. OBJECTIVE: The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. DESIGN: A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. SETTINGS: This study is based on a binational colorectal cancer audit database. PATIENTS: Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. RESULTS: A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). LIMITATIONS: This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. CONCLUSIONS: The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Tumor-Infiltrating Lymphocyte Function Predicts Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

PURPOSE: The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB). PATIENTS AND METHODS: Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti-programmed cell death protein 1 [anti-PD-1] antibody) response was also assessed in a subset of patient specimens. RESULTS: Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423]; p < .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti-PD-1 antibody exposure. CONCLUSION: Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.