Association between microsatellite instability status and peri-operative release of circulating tumour cells in colorectal cancer

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the IsofluxTM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively

Management of sub-5 mm rectal carcinoids with lymph node metastases

Minute (<5mm) and small (5–10mm) rectal carcinoids discovered during colonoscopy are generally considered to be non-aggressive, and the management and surveillance of patients with this entity are usually limited. We present the case of a 61-year-old Chinese female with multiple sub-5mmcarcinoid tumours in the rectum without any computed tomography (CT) evidence of lymph node or distant metastases. She underwent an ultra-low anterior resection for a sessile rectal polyp with the histological appearance of a moderately differentiated adenocarcinoma. Seven foci of minute carcinoids in the rectum and perirectal lymph node metastastic spread from the carcinoid tumours were also discovered on histopathology. There were no lymph node metastases originating from adenocarcinoma. This case report and review of the literature suggests that minute rectal carcinoids are at risk of metastasizing and that these patients should be investigated for lymph node and distant metastatic spread with CT and somatostatin receptor scintigraphy or its equivalent, as this would influence prognosis and surgical management of these patients. Findings relating to lymphovascular invasion, perineural invasion, high Ki-67, mitotic rate, depth of tumour invasion, central ulceration, multifocal tumours and size are useful in predicting metastases and may be used in scoring tools. Size alone is not a good predictor of metastastic spread

Splenic vein turndown for vascular reconstruction following pancreatic cancer resection in patients with high risk profile

Introduction: Vascular reconstruction is utilized following resections for pancreatic cancers with borderline resectability. This is defined by venous or partial superior mesenteric artery (SMA) involvement, where vessels are resected en bloc to achieve an R0 resection. There are many vascular reconstruction techniques post en bloc R0 resection, each with its own complication profile. The splenic turndown technique separates the vascular anastomosis from the pancreatic anastomosis, reducing the risk of vascular disruption should a pancreatic leak occur. Case Report: This is the first report in literature of the splenic vein turndown technique being utilized for vascular reconstruction post- pancreatic resection for borderline resectable pancreatic cancer. To date, splenic vein turndown repair has only been described in a trauma setting. In this case, splenic vein turndown was preferred as the patient was on long-term corticosteroids with a high risk of anastomotic leak. Conclusion: This case report showing that splenic vein turndown technique is a feasible option for vascular reconstruction post-pancreatic resection. The main disadvantage of this technique is high risk of segmental portal hypertension if the spleen is not removed concomitantly. For this reason, its utility should be restricted to patients at high risk of pancreatic leak

The potential value of immunotherapy in colorectal cancers : review of the evidence for programmed death-1 (PD-1) inhibitor therapy

BACKGROUND: Colorectal cancers have been identified as potential targets for immunotherapy with programmed cell death-1 (PD-1) inhibitors. METHOD: English-language publications from MEDLINE and Embase evaluating PD-1/PD-L1 in the CRC tumour microenvironment and clinical trials assessing PD-1 inhibitors were included. Sixteen abstracts were screened. Fifteen met the inclusion criteria. After review of the full texts, this resulted in a final reference list of eight studies eligible for review. RESULTS: Five studies assessing PD-1/PD-L1 in CRC and three trials assessing PD-1 inhibitors were included. PD-1+ tumour infiltrating lymphocytes (TILs) and PD-L1+ cancer cells featured more prominently in MSI-H CRCs when compared with MSS CRCs, except in one study where PD-L1 expression was higher in MSS CRCs. In the three trials assessing PD-1 inhibitor, all three studies recruited metastatic CRC (mCRC) patients. One study also included recurrent CRC (rCRC). The objective response as per the Response Evaluation Criteria in Solid Tumours (RECIST) criteria was 0% (19 colorectal cancer patients, MSI status unknown) in the nivolumab study. In the pembrolizumab study, objective response to PD-1 inhibitor was 40% and 0% in MSI-H and MSS mCRCs respectively (10 patients in MSI-H group, 18 patients in MSS group). 78% of patients in the MSI-H mCRC group compared to 11% in the MSS mCRC group (p <0.005) showed no further disease progression at 12 weeks. In the nivolumab +/- ipilimumab study, objective partial response at 12 weeks to PD-1 inhibitor with or without CTLA-4 inhibitor was 25.5-33.3% and 5% in MSI-H and MSS groups respectively (100 patients in MSI-H group, 20 patients in MSS group). LIMITATIONS: Clinical trials assessing PD-1 inhibitor immunotherapy in CRC have recruited only small cohorts of metastatic CRC patients. Studies on the tumour microenvironment have been based on archival specimens with different antibody PD-1 and PD-L1 preparations for immunohistochemistry, independent from immunotherapy trials. CONCLUSIONS: Immunotherapy with PD-1 therapy has potential benefit for immunogenic MSI-H CRCs whereas there is no evidence currently suggesting immunotherapy benefit in MSS CRCs. The available data is limited, and there is no information on non-metastatic CRCs. Future trials are underway to determine its benefits