Does robotic TME bring difference in lymph node yield and quality of TME?

BACKGROUNDS: Oncological outcomes of the robotic low anterior rectal resection with total mesorectal excision (TME) are still under discussion. Few studies have proven that robotic TME (rTME) is a safe and equivalent method for treatment of rectal carcinoma. But there is almost no comparison between the rTME and conventional TME in terms of the number of lymph nodes obtained and the quality of the TME. METHODS: A single institution retrospective study was designed in a cohort of 261 patients. Cohort was divided into two groups depending on the type of surgery (rTME versus TME) and within these two groups, patients were divided according to whether they underwent neoadjuvant chemoradiation (nCHRT) or did not. The primary objective of the study was to compare obtained number of the lymph nodes in specimen. Secondary objectives were comparison of the quality of the TME and the number of positive circumferential resection margins. RESULTS: Results of the study have shown no significant difference in number of the lymph nodes obtained by the rTME and TME. There was no difference in the quality of the TME, neither in the group with the previous nCHRT nor in the group without a nCHRT. CONCLUSION: With results from the study we consider the rTME to be non-inferior to the conventional TME. Therefore, at least identical oncological results can be expected in patients treated by the rTME.

Should minimally invasive approaches in rectal surgery be regarded as a key element of modern enhanced recovery perioperative care?

INTRODUCTION: The aim of study was to assess the impact of an enhanced recovery after surgery (ERAS) protocol and minimally invasive approaches on short-term outcomes in rectal surgery. PATIENTS AND METHODS: A consecutive series of patients that underwent open or minimally invasive rectal resections in a single institution between January 2015 and April 2020 were included in the study. An ERAS program was introduced in April 2016. The study cohort was divided into three groups: open surgery without ERAS, open surgery with ERAS, and minimally invasive surgery with ERAS. Outcome measures compared were recovery parameters, surgical stress parameters, 30-day morbidity and mortality, oncological radicality and length of hospital stay. RESULTS: A total of 202 patients were included: 43 in the open non-ERAS group, 92 in the open ERAS group and 67 in the minimally invasive ERAS group. All recovery parameters apart from postoperative nausea and vomiting were significantly improved in both ERAS groups. Surgical stress parameters, prolonged postoperative ileus, and hospital stay were significantly reduced in the minimally invasive ERAS group. The overall 30-day morbidity and mortality and oncological radicality did not significantly differ among the three groups. CONCLUSIONS: Minimally invasive approaches and enhanced recovery care in rectal surgery improve short-term outcomes. Their combination leads to an improvement in recovery parameters and a reduction of prolonged postoperative ileus and hospital stay.

Monitoring of Early Changes of Circulating Tumor DNA in the Plasma of Rectal Cancer Patients Receiving Neoadjuvant Concomitant Chemoradiotherapy: Evaluation for Prognosis and Prediction of Therapeutic Response.

Introduction: Patients with locally advanced rectal cancer (LARC) are undergoing neoadjuvant chemoradiotherapy (NCRT) prior to surgery. Although in some patients the NCRT is known to prevent local recurrence, it is also accompanied by side effects. Accordingly, there is an unmet need to identify predictive markers allowing to identify non-responders to avoid its adverse effects. We monitored circulating tumor DNA (ctDNA) as a potential liquid biopsy-based biomarker. We have investigated ctDNA changes plasma during the early days of NCRT and its relationship to the overall therapy outcome. Methods and Patients: The studied cohort included 36 LARC patients (stage II or III) undergoing NCRT with subsequent surgical treatment. We have detected somatic mutations in tissue biopsies taken during endoscopic examination prior to the therapy. CtDNA was extracted from patient plasma samples prior to therapy and at the end of the first week. In order to optimize the analytical costs of liquid-biopsy testing, we have utilized a two-level approach in which first a low-cost detection method of denaturing capillary electrophoresis was used followed by examination of initially negative samples by a high-sensitivity BEAMING assay. The ctDNA was related to clinical parameters including tumor regression grade (TRG) and TNM tumor staging. Results: We have detected a somatic mutation in 33 out of 36 patients (91.7%). Seven patients (7/33, 21.2%) had ctDNA present prior to therapy. The ctDNA positivity before treatment reduced post-operative disease-free survival and overall survival by an average of 1.47 and 1.41 years, respectively (p = 0.015, and p = 0.010). In all patients, ctDNA was strongly reduced or completely eliminated from plasma by the end of the first week of NCRT, with no correlation to any of the parameters analyzed. Conclusions: The baseline ctDNA presence represented a statistically significant negative prognostic biomarker for the overall patient survival. As ctDNA was reduced indiscriminately from circulation of all patients, dynamics during the first week of NCRT is not suited for predicting the outcome of LARC. However, the general effect of rapid ctDNA disappearance apparently occurring during the initial days of NCRT is noteworthy and should further be studied.

The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome.

Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.

Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA.

BACKGROUND: One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a "liquid (re)biopsy" it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient's body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence. AIM: To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer. METHODS: A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient. RESULTS: Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers. CONCLUSION: ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.