Tumour, narrow pelvis and surgery specific factors for total mesorectal excision quality and morbidity following rectal cancer resection.

BACKGROUND: Pelvic anatomy is critical in challenging rectal resections. This study investigated how pelvic anatomy relates to total mesorectal excision (TME) quality, anastomotic leakage rate, and long-term oncological outcomes. METHODS: Patients undergoing elective rectal cancer resection from 2008 to 2017 in an Austrian institution were retrospectively reviewed regardless of the surgical approach. CT scans were analysed for pelvic measurements and volumes. The primary outcomes of interest were the correlation between pelvic dimensions and the TME quality and anastomotic leakage. Subanalysis was done by surgical approach (open, laparoscopic, transanal TME). Secondary outcomes were overall and disease-free survivals. RESULTS: Among 154 eligible patients, 112 were included. The angle between pubic symphysis and promontory significantly correlated with worse TME grades (TME grade 1: mean(s.d.) 102.7(5.7)°; TME grade 2: 92.0(4.4)°; TME grade 3: 91.4(3.6)°; P < 0.001). A significantly lower distance between tumour and circumferential resection margin (CRM) was observed in grade 3 resections, whereas no difference appeared in grade 1 and grade 2 resection (TME grade 1: mean(s.d.) 11.92(9.4) mm; TME grade 2: 10.8(8.1) mm; TME grade 3: 3.1(4.1) mm; P = 0.003). The anastomotic leakage rate was significantly higher in case of a lower CRM (patients with anastomotic leakage: mean(s.d.) 6.8(5.8) mm versus others: 12.6(9.8) mm, P = 0.027), but not associated with pelvimetry measurements. The transanal TME (TaTME) subgroup displayed a wider angle between the pubic symphysis and promontory, younger age and improved TME quality compared to others (respectively, mean TME grades in TaTME versus open versus laparoscopic: 1.0 ± 0.0, 1.5 ± 0.7 and 1.3 ± 0.5, P = 0.013). Finally, oncological survival was not impacted by pelvic measurements or worse TME quality. CONCLUSION: The angle between the pubic symphysis and promontory and the distance between tumour and CRM were associated with worse TME grades. The anastomotic leakage was associated with a lower CRM but not with pelvimetric measures.

Sarcopenic Obesity Is a Risk Factor for Worse Oncological Long-Term Outcome in Locally Advanced Rectal Cancer Patients: A Retrospective Single-Center Cohort Study.

BACKGROUND: Malnutrition and skeletal muscle waste (sarcopenia) are known as predictive factors for a poor postoperative outcome. Paradoxically, obesity seems to be associated with a survival advantage in wasting diseases such as cancer. Thus, the interpretation of body composition indices and their impact on rectal cancer therapy has become more and more complex. The aim of this study was to evaluate body composition indices in locally advanced rectal cancer patients prior to therapy and their impact on short- and long-term outcomes. METHODS: Between 2008 and 2018, 96 patients were included in this study. Pre-therapeutic CT scans were used to evaluate visceral and subcutaneous fat mass, as well as muscle mass. Body composition indices were compared to body mass index, morbidity, anastomotic leakage rate, local recurrency rate, and oncological long-term outcomes. RESULTS: Increased visceral fat (p < 0.01), subcutaneous fat (p < 0.01), and total fat mass (p = 0.001) were associated with overweight. Skeletal muscle waste (sarcopenia) (p = 0.045), age (p = 0.004), comorbidities (p < 0.01), and sarcopenic obesity (p = 0.02) were significantly associated with increased overall morbidity. The anastomotic leakage rate was significantly influenced when comorbidities were present (p = 0.006). Patients with sarcopenic obesity showed significantly worse disease-free (p = 0.04) and overall survival (p = 0.0019). The local recurrency rate was not influenced by body composition indices. CONCLUSION: Muscle waste, older age, and comorbidities were demonstrated as strong risk factors for increased overall morbidity. Sarcopenic obesity was associated with worse DFS and OS. This study underlines the role of nutrition and appropriate physical activity prior to therapy.

Are risk factors for anastomotic leakage influencing long-term oncological outcomes after low anterior resection of locally advanced rectal cancer with neoadjuvant therapy? A single-centre cohort study.

PURPOSE: Anastomotic leakage (AL) poses the most serious problem following low anterior resection in patients with rectal cancer independent of surgical approach or technique. The aim of this study was to evaluate risk factors for the occurrence of AL and how they affect the oncological long-term outcome of patients who received neoadjuvant therapy. METHODS: A single centre cohort study of 163 consecutive locally advanced rectal cancer patients (cT3, cT4, N +) that received neoadjuvant therapy followed by resection with primary anastomosis between January 1998 and December 2020 were included in this study. Short- and long-term findings were compared between patients with AL (Leakage +) and without AL (Leakage -). RESULTS: A complete follow-up was obtained from 163 patients; thereby, 33 patients (20%) developed an AL. We observed more patients with comorbidities (38% vs. 61%, p = 0.049) which developed a leakage in the course. Permanent stoma rate (36% vs. 18%, p = 0.03) was higher, and time between primary operation and stoma reversal was longer (219 days [172-309] vs. 93 days [50-182], p < 0.001) in this leakage group as well. Tumour distance lower than 6 cm from the anal verge (OR: 2.81 [95%CI: 1.08-7.29], p = 0.04) and comorbidities (OR: 2.22 [95%CI: 1.01-4.90], p = 0.049) was evaluated to be independent risk factors for developing an AL after rectal cancer surgery. Oncological outcome was not influenced by AL nor by other associated risk factors. CONCLUSION: We could clearly detect the distance of tumour from the anal verge and comorbidities independent risk factors for the occurrence of AL. Oncological findings and long-term outcome were not influenced by these particular risk factors.

Is Robotic Assisted Colorectal Cancer Surgery Equivalent Compared to Laparoscopic Procedures during the Introduction of a Robotic Program? A Propensity-Score Matched Analysis.

BACKGROUND: Robotic surgery represents a novel approach for the treatment of colorectal cancers and has been established as an important and effective method over the last years. The aim of this work was to evaluate the effect of a robotic program on oncological findings compared to conventional laparoscopic surgery within the first three years after the introduction. METHODS: All colorectal cancer patients from two centers that either received robotic-assisted or conventional laparoscopic surgery were included in a comparative study. A propensity-score-matched analysis was used to reduce confounding differences. RESULTS: A laparoscopic resection (LR Group) was performed in 82 cases, and 93 patients were treated robotic-assisted surgery (RR Group). Patients' characteristics did not differ between groups. In right-sided resections, an intracorporeal anastomosis was significantly more often performed in the RR Group (LR Group: 5 (26.31%) vs. RR Group: 10 (76.92%), p = 0.008). Operative time was shown to be significantly shorter in the LR Group (LR Group: 200 min (150-243) vs. 204 min (174-278), p = 0.045). Conversions to open surgery did occur more often in the LR Group (LR Group: 16 (19.51%) vs. RR Group: 5 (5.38%), p = 0.004). Postoperative morbidity, the number of harvested lymph nodes, quality of resection and postoperative tumor stage did not differ between groups. CONCLUSION: In this study, we could clearly demonstrate robotic-assisted colorectal cancer surgery as effective, feasible and safe regarding postoperative morbidity and oncological findings compared to conventional laparoscopy during the introduction of a robotic system.

Short- and Long-Term Outcome of Laparoscopic- versus Robotic-Assisted Right Colectomy: A Systematic Review and Meta-Analysis.

Background: There is a rapidly growing literature available on right hemicolectomy comparing the short- and long-term outcomes of robotic right colectomy (RRC) to that of laparoscopic right colectomy (LRC). The aim of this meta-analysis is to revise current comparative literature systematically. Methods: A systematic review of comparative studies published between 2000 to 2021 in PubMed, Scopus and Embase was performed. The primary endpoint was postoperative morbidity, mortality and long-term oncological results. Secondary endpoints consist of blood loss, conversion rates, complications, time to first flatus, hospital stay and incisional hernia rate. Results: 25 of 322 studies were considered for data extraction. A total of 16,099 individual patients who underwent RRC (n = 1842) or LRC (n = 14,257) between 2002 and 2020 were identified. Operative time was significantly shorter in the LRC group (LRC 165.31 min ± 43.08 vs. RRC 207.38 min ± 189.13, MD: −42.01 (95% CI: −51.06−32.96), p < 0.001). Blood loss was significantly lower in the RRC group (LRC 63.57 ± 35.21 vs. RRC 53.62 ± 34.02, MD: 10.03 (95% CI: 1.61−18.45), p = 0.02) as well as conversion rate (LRC 1155/11,629 vs. RRC 94/1534, OR: 1.65 (1.28−2.13), p < 0.001) and hospital stay (LRC 6.15 ± 31.77 vs. RRC 5.31 ± 1.65, MD: 0.84 (95% CI: 0.29−1.38), p = 0.003). Oncological long-term results did not differ between both groups. Conclusion: The advantages of robotic colorectal procedures were clearly demonstrated. RRC can be regarded as safe and feasible. Most of the included studies were retrospective with a limited level of evidence. Further randomized trials would be suitable.

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P < 0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.

A Novel Diagnostic and Prognostic Score for Abdominal Aortic Aneurysms Based on D-Dimer and a Comprehensive Analysis of Myeloid Cell Parameters.

The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors of myeloid cell activation and recruitment. To establish their marker potential, neutrophil and monocyte sub-sets were measured by flow cytometry in peripheral blood samples of 41 AAA patients and 38 healthy controls matched for age, sex, body mass index and smoking habit. Comparably, circulating factors reflecting neutrophil and monocyte activation and recruitment were assayed in plasma. Significantly elevated levels of CD16+ monocytes, activated neutrophils and newly released neutrophils were recorded for AAA patients compared with controls. In line, the monocyte chemoattractant C-C chemokine ligand 2 and myeloperoxidase were significantly increased in patients' plasma. The diagnostic value was highest for myeloperoxidase, a mediator which is released by activated neutrophils as well as CD16+ monocytes. Multivariable regression models using myeloid activation markers and routine laboratory parameters identified myeloperoxidase and D-dimer as strong independent correlates of AAA. These two biomarkers were combined to yield a diagnostic score which was subsequently challenged for confounders and confirmed in a validation cohort matched for cardiovascular disease. Importantly, the score was also found suited to predict rapid disease progression. In conclusion, D-dimer and myeloperoxidase represent two sensitive biomarkers of AAA which reflect distinct hallmarks (thrombus formation and inflammation) of the pathomechanism and, when combined, may serve as diagnostic and prognostic AAA score warranting further evaluation.