Incidence and risk factors for umbilical incisional hernia after reduced port colorectal surgery (SIL + 1 additional port)-is an umbilical midline approach really a problem?

PURPOSE: Umbilical midline incisions for single incision- or reduced port laparoscopic surgery are still discussed controversially because of a higher rate of incisional hernia compared to conventional laparoscopic techniques. The aim of this study was to evaluate incidence and risk factors for incisional hernia after reduced port colorectal surgery. METHODS: A total 241 patients underwent elective reduced port colorectal surgery between 2014 and 2020. Follow-up was achieved through telephone interview or clinical examination. The study collective was examined using univariate and multivariate analysis. RESULTS: A total of 150 patients with complete follow-up were included into this study. Mean follow-up time was 36 (IQR 24-50) months. The study collective consists of 77 (51.3%) female and 73 (48.7%) male patients with an average BMI of 26 kg/m2 (IQR 23-28) and an average age of 61 (± 14). Indication for surgery was diverticulitis in 55 (36.6%) cases, colorectal cancer in 65 (43.3%) patients, and other benign reasons in 30 (20.0%) cases. An incisional hernia was observed 9 times (6.0%). Obesity (OR 5.8, 95% CI 1.5-23.1, p = 0.02) and pre-existent umbilical hernia (OR 161.0, 95% CI 23.1-1124.5, p < 0.01) were significant risk factors for incisional hernia in the univariate analysis. Furthermore, pre-existent hernia is shown to be a risk factor also in multivariate analysis. CONCLUSION: We could demonstrate that reduced port colorectal surgery using an umbilical single port access is feasible and safe with a low rate of incisional hernia. Obesity and pre-existing umbilical hernia are significant risk factors for incisional hernia.

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.

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

AIMS: The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. METHODS AND RESULTS: Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. CONCLUSIONS: Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS.

The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer.

PURPOSE: This study was conducted to investigate the potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer. PATIENTS AND METHODS: Surgical specimens of 128 ypUICC (Union for International Cancer Control) stage 0-III mid-to-low rectal cancer patients were identified from a prospectively maintained colorectal cancer database and classified into two groups using the 10 high-power field average method: none/mild tumor budding (BD-0) and moderate/severe tumor budding (BD-1). Overall survival, relapse-free survival (RFS), and recurrence estimates were calculated using the Kaplan-Meier method and compared with the log-rank test. For RFS, a multivariable Cox's proportional hazards regression analysis was performed. RESULTS: No (n = 20) or mild (n = 27) tumor budding (BD-0) was identified in 47 (37%) and moderate (n = 52) or severe (n = 29) tumor budding (BD-1) in 81 (63%) surgical specimens. Positive tumor budding (BD-1) was associated with significantly reduced T­level downstaging (P < 0.001) and tumor regression (P < 0.001). After a median follow-up time of 7 years (range 2.9-146.7 months), BD-0 patients had more favorable 5­year RFS (90 vs. 71%, P = 0.02) and distant recurrence (2 vs. 12%, P = 0.03) estimates. Multivariable analyses confirmed BD-1 as a negative predictive parameter for RFS (hazard ratio = 3.44, 95% confidence interval 1.23-9.63, P = 0.018). CONCLUSIONS: Our data confirm tumor budding as a strong prognostic factor and its potential predictive value for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients. This provides the opportunity to modify and individualize neoadjuvant therapy regimens for non-responders.

HDAC-Linked "Proliferative" miRNA Expression Pattern in Pancreatic Neuroendocrine Tumors.

Epigenetic factors are essentially involved in carcinogenesis, tumor promotion, and chemoresistance. Two epigenetic key players are miRNAs and histone deacetylases (HDACs). As previously shown by own theoretical databank analysis, the crosstalk between miRNAs and HDACs is relevant in different human chronic diseases and cancerogenic pathways. We aimed to investigate a potential connection between the expression of a well-defined subset of "proliferation-associated" miRNAs and the expression of HDACs as well as clinical parameters in pancreatic neuroendocrine tumors (pNETs). MATERIALS AND METHODS: Expression levels of miRNA132-3p, miRNA145-5p, miRNA183-5p, miRNA34a-5p, and miRNA449a in 57 pNETs resected between 1997 and 2015 were measured and linked to the immunohistochemical expression pattern of members of the four HDAC classes on human tissue microarrays. All pNET cases were clinically and pathologically characterized according to published guidelines. Correlation analysis revealed a significant association between expression of specific miRNAs and two members of the HDAC family (HDAC3 and HDAC4). Additionally, a linkage between miRNA expression and clinico-pathological parameters like grading, TNM-staging, and hormone activity was found. Moreover, overall and disease-free survival is statistically correlated with the expression of the investigated miRNAs. Overall, we demonstrated that specific miRNAs could be linked to HDAC expression in pNETs. Especially miRNA449a (associated with HDAC3/4) seems to play an important role in pNET proliferation and could be a potential prognostic factor for poor survival. These first data could help, to improve our knowledge of the complex interactions of the epigenetic drivers in pNETs for further therapeutic approaches.

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells.

Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.

Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer.

BACKGROUND: Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma. OBJECTIVE: This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer. DESIGN: This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database. SETTINGS: This study was performed at a single tertiary referral center. PATIENTS: A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included. MAIN OUTCOMES MEASURES: The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates. RESULTS: Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04). LIMITATIONS: This was a retrospective study. CONCLUSIONS: Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.

First Episode of Spontaneous Pneumothorax: CT-based Scoring to Select Patients for Early Surgery.

BACKGROUND: Although recurrence of primary spontaneous pneumothorax (PSP) is frequent, guidelines do not routinely recommend surgery after first presentation. A CT-based lung dystrophy severity score (DSS) has recently been proposed to predict recurrence following conservative therapy. This study compares the DSS in surgically and conservatively treated patients. METHODS: This is a retrospective analysis of first episode PSP patients, comparing video-assisted thoracic surgery (VATS; group A) to conservative treatment with or without chest drainage (group B). CT scans were reviewed for blebs or bullae, and patients were assigned DSS values and stratified into risk groups (low and high-grade). Primary end point was ipsilateral or contralateral recurrence. RESULTS: Fifty-six patients were included, 33 received VATS and 23 conservative treatment. In total, 37.5 % experienced recurrence, with a 5-year estimated recurrence rate of 40.7 % (group A: 13.3 %; group B: 73.9 %; p < 0.001). In group B, detection of any dystrophic lesions resulted in significantly higher 5-year recurrence rates (86.7 vs. 50.0 %; p = 0.03), there was no significant difference in group A (17.7 vs. 7.7 %; p = 0.50). Greater DSS values correlated with higher 5-year recurrence rates in group B (p = 0.02), but not in group A (p = 0.90). Comparing low- and high-grade patients in group B resulted in a significant 5-year recurrence rate of 53.8 versus 100 % (p = 0.023). CONCLUSIONS: The DSS is useful to indicate VATS after the first episode. For routine application, assigning patients to low- and high-grade groups seems most practical. We recommend CT-evaluation for every PSP patient and early surgery for those with lesions exceeding one bleb. After VATS, the preoperative DSS is not beneficial in predicting recurrence.

Prolonged capnoperitoneum does not cause postoperative ileus in pigs: safety of prolonged capnoperitoneum.

INTRODUCTION: Operative time is an accepted risk factor for the development of postoperative ileus (POI). Innovative surgical procedures such as robotic surgery and natural orifice transluminal endoscopic surgery (NOTES) will be associated with longer operative times. Although intraabdominal manipulation is a major factor for POI the impact of prolonged capnoperitoneum on postoperative gastrointestinal transit time (GIT-TT) has rarely been studied. MATERIAL AND METHODS: IRB approved survival pilot study to assess postoperative GIT-TT using fecal collection and chromium-oxide (Cr2O3) labeling in pigs. Twelve female pigs were randomly assigned to three groups of four animals each. Group A received eight hours anesthesia and pressure-controlled high flow capnoperitoneum (15 mmHg), group B eight hours of anesthesia only and group C no intervention. No intraoperative manipulation. The pilot study was terminated after eight days. RESULTS: None of the animals developed POI. In Group A one animal died after eight hours of general anesthesia. No differences in postoperative fecal output, Cr2O3 excretion rate or weight gain were found. CONCLUSION: This study is the first to investigate eight hours of capnoperitoneum in a survival model. GIT-TT is not affected by prolonged capnoperitoneum in pigs. No POI occurred with prolonged capnoperitoneum. Prolonged capnoperitoneum is safe regarding postoperative gastrointestinal function in innovative surgical procedures.

Cumulative incidence of permanent stoma after sphincter preserving low anterior resection of mid and low rectal cancer.

BACKGROUND: Changes in the treatment of rectal cancer during the past decades have led to an increase in sphincter preservation with a consecutive decline in abdominoperineal resection rates. OBJECTIVE: The aim of this study was to analyze the cumulative incidence of permanent stoma in patients undergoing sphincter-preserving resection of mid and low rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2010, 125 patients with primary mid and low rectal cancer who underwent sphincter-preserving low anterior resection were included. MAIN OUTCOME MEASURES: The occurrence of a permanent stoma over time was investigated by using a Cox proportional hazards regression model and competing-risk models, with death as a competing risk. The risk factors were assessed by computing HRs and a Cox proportional hazards regression. RESULTS: After a median follow-up time of 61 months (range, 22-113), 15 of 125 patients ended up with a permanent stoma, accounting for a 5-year cumulative incidence of 6% (95% CI, 4%-11%). The reasons for obtaining a permanent stoma were anastomotic leakage (60%, 9/15), intractable fecal incontinence (27%, 4/15), and local recurrence (13%, 2/15). The Cox proportional hazards regression identified anastomotic leakage (HR, 6.10; 95% CI, 2.23-16.71; p = 0.0004) and coloanal anastomosis (HR, 4.31; 95% CI, 1.49-12.47; p = 0.007) as statistically significant risk factors. LIMITATIONS: Because of the small number of events in this sample, further investigations with a larger number of patients are required. Fecal incontinence was assessed by patient self-reported data without the use of a validated score. CONCLUSION: The 5-year cumulative incidence of a permanent stoma was 6%. Anastomotic leakage and coloanal anastomosis were identified as risk factors. These details should be considered before sphincter-preserving surgery.

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.

The SAlzburg PEritoneal SUrface CAlculator (SAPESUCA): The First Web-Based Application for Peritoneal Surface Area Quantification.

(1) Background: Peritoneal metastasized colorectal cancer is associated with a worse prognosis. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in selected patients, but standardization is lacking so far. We present the first tool enabling standardized peritoneal surface area (PSA) quantification in patients undergoing CRS and HIPEC: The SAlzburg PEritoneal SUrface CAlculator (SAPESUCA). (2) Methods: SAPESUCA was programmed using the R-Shiny framework. The application was validated in 23 consecutive colon cancer patients who received 27 closed oxaliplatin-based HIPECs between 2016 and 2020. The programming algorithm incorporates the patient's body surface area and its correlated peritoneal surface area (PSA) based on the 13 Peritoneal Cancer Index (PCI) regions. (3) Results: Patients' median age was 56 years. Median PCI was 9. SAPESUCA revealed a mean PSA of 18,613 cm2 ± 1951 of all patients before compared to 13,681 cm2 ± 2866 after CRS. The Central PCI region revealed the highest mean peritonectomy extent (1517 cm2 ± 737). The peritonectomy extent correlated significantly with PCI score and postoperative morbidity. The simulated mean oxaliplatin dose differed significantly before and after CRS (558 mg/m2 ± 58.4 vs. 409 mg/m2 ± 86.1; p < 0.0001). (4) Conclusion: SAPESUCA is the first free web-based app for standardized determination of the resected and remaining PSA after CRS. The tool enables chemotherapeutic dose adjustment to the remaining PSA.

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.

First clinical application of image-guided intraoperative electron radiation therapy with real time intraoperative dose calculation in recurrent rectal cancer: technical procedure.

Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments.

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.

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.

Prolonged Exposure to Oxaliplatin during HIPEC Improves Effectiveness in a Preclinical Micrometastasis Model.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients' samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.

How We Treat Localized Rectal Cancer-An Institutional Paradigm for Total Neoadjuvant Therapy.

Total neoadjuvant therapy (TNT)-the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery-may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians-without any claim to general validity.

Identification of Risk Factors for Sexual Dysfunction after Multimodal Therapy of Locally Advanced Rectal Cancer and Their Impact on Quality of Life: A Single-Center Trial.

PURPOSE: Sexual function is crucial for the quality of life and can be highly affected by preoperative therapy and surgery. The aim of this study was to identify potential risk factors for poor sexual function and quality of life. METHODS: Female patients were asked to complete the Female Sexual Function Index (FSFI-6). Male patients were demanded to answer the International Index of Erectile Function (IIEF-5). RESULTS: In total, 79 patients filled in the questionary, yielding a response rate of 41.57%. The proportion of women was represented by 32.91%, and the median age was 76.0 years (66.0-81.0). Sexual dysfunction appeared in 88.46% of female patients. Severe erectile dysfunction occurred in 52.83% of male patients. Univariate analysis showed female patients (OR: 0.17, 95%CI: 0.05-0.64, p = 0.01), older age (OR: 0.34, 95%CI 0.11-1.01, p = 0.05), tumor localization under 6cm from the anal verge (OR: 4.43, 95%CI: 1.44-13.67, p = 0.01) and extension of operation (APR and ISR) (OR: 0.13, 95%CI: 0.03-0.59, p = 0.01) as significant risk factors for poor outcome. Female patients (OR: 0.12, 95%CI: 0.03-0.62, p = 0.01) and tumors below 6 cm from the anal verge (OR: 4.64, 95%CI: 1.18-18.29, p = 0.03) were shown to be independent risk factors for sexual dysfunction after multimodal therapy in the multivariate analysis. Quality of life was only affected in the case of extensive surgery (p = 0.02). CONCLUSION: Higher Age, female sex, distal tumors and extensive surgery (APR, ISR) are revealed risk factors for SD in this study. Quality of life was only affected in the case of APR or ISR.