Expression of carbonic anhydrase IX suggests poor response to therapy in rectal cancer

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Colorectal cancer risk after removal of polyps in fecal immunochemical test based screening

Background: Colonoscopy surveillance intervals are based on the predicted risk of metachronous colorectal cancer (CRC) after polyp removal. However, risk estimation per polyp subtype is difficult due to the fact that many patients have multiple polyps. To enable risk estimation per polyp subtypes we examined the metachronous CRC risk of subgroups based on presence or absence of co-occurring findings. Methods: Using high-quality screening colonoscopies performed after a positive fecal immunochemical test between 2014 and 2020 within the Dutch CRC screening program, we applied Cox regression analysis to evaluate the association between findings at baseline colonoscopy and metachronous CRCs. For our primary outcome, we appointed each patient to unique subgroups based on removed polyp subtypes that were present or absent at baseline colonoscopy and used the groups without polyps as reference. High-risk subgroups were individuals with high-risk serrated polyps, defined as serrated polyp ≥10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, defined as adenoma ≥10 mm or containing high-grade dysplasia. Findings: In total 253,833 colonoscopies were included. Over a median follow-up of 36 months (IQR, 21–57), we identified 504 metachronous CRCs. Hazard ratios for metachronous CRC was 1.70 (95% CI, 1.07–2.69) for individuals with high-risk serrated polyps without high-risk adenomas, 1.22 (0.96–1.55) for individuals with high-risk adenomas without high-risk serrated polyps, and 2.00 (1.19–3.39) for individuals with high-risk serrated polyps and high-risk adenomas, compared to patients without polyps. Interpretation: Accounting for co-occurring findings, we observed an increased metachronous CRC risk for individuals that had high-risk serrated polyps with the presence of high-risk adenomas, or individuals with high-risk serrated polyps without high-risk adenomas. These findings could provide more evidence to support post-polypectomy surveillance guidelines. Funding: None.</p

Identifying Biomarkers in Lymph Node Metastases of Esophageal Adenocarcinoma for Tumor-Targeted Imaging

INTRODUCTION: Tumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC). OBJECTIVE: We performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC. METHODS: We used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells. RESULTS: EMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent. CONCLUSIONS: High expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer

Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood. Here, we explore cellular immune cell status in patients with multi-organ mCRC. We analyzed T cell infiltration in primary tumor sections, surveyed the lymphocytic landscape of liver metastases, and assessed circulating mononuclear immune cells. Besides asking whether immune cells are associated with survival at this stage of the disease, we investigated correlations between the different tissue types; as this could indicate a dominant immune phenotype. Taken together, our analyses corroborate previous observations that higher levels of CD8+ T lymphocytes link to better survival outcomes. Our findings therefore extend evidence from earlier stages of CRC to indicate an important role for cancer immunity in disease control even after metastatic spreading to multiple organs. This finding may help to improve predicting outcome of patients with mCRC and suggests a future role for immunotherapeutic strategies.</p

Can we <i>S</i>ave the rectum by watchful waiting or <i>T</i>rans<i>A</i>nal microsurgery following (chemo) <i>R</i>adiotherapy versus total mesorectal excision for early <i>RE</i>ctal <i>C</i>ancer (STAR-TREC study)?::protocol for a multicentre, randomised feasibility study

Introduction Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. Methods and analysis STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2

Metachronous peritoneal metastases in patients with pT4b colon cancer: An international multicenter analysis of intraperitoneal versus retroperitoneal tumor invasion

It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion

MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins?

Histopathological audit of positive circumferential resection margins (CRMs) can be used as a surrogate measure of the success of rectal cancer treatment. We audited CRM involvement in rectal cancer patients and the impact of the multidisciplinary team (MDT) on implementing a magnetic resonance imaging (MRI)-based preoperative treatment strategy. Data were collected on all newly diagnosed rectal cancer patients treated in our network between January 1999 and December 2002. Data were analysed for MRI prediction and histopathological assessment of CRM together with the MDT meeting treatment decisions. The CRM+ve rate of those discussed at MDT vs those not discussed were compared. We re-audited the CRM+ve rates 1 year after introducing a policy of mandatory preoperative MRI-based MDT discussion. Of the 298 patients diagnosed with rectal cancer, 39 (13%) were deemed palliative, 178 underwent surgery alone and 81 underwent neoadjuvant therapy. Of these, 62 out of 178 patients underwent surgery alone without MRI-based MDT discussion resulting in positive CRM in 16 cases (26%) as compared to 1 out of 116 (1%) in those patients with MDT discussion of MRI. Overall CRM+ve rate in all nonpalliative patients with or without MDT discussion was 12.5% (32 out of 256), significantly lower than the <20% rate (P<0.001) quoted in national guidelines. Re-audit in 98 consecutive patients following a change of policy produced a lower CRM+ve rate of 3% (1 out of 37) for all surgery alone patients and an overall CRM+ve rate of 7% (5 out of 70). In conclusion, MDT discussion of MRI and implementation of a preoperative treatment strategy results in significantly reduced positive CRM in rectal cancer patients