Surgical Antimicrobial Prophylaxis in Low-Risk Cholecystectomies is Associated with Fewer Surgical Site Infections: Nationwide Cohort Study in Switzerland.

OBJECTIVE: To assess whether administration of surgical antimicrobial prophylaxis (SAP) versus absence of SAP is associated with a decreased risk of surgical site infections (SSI) after low-risk cholecystectomies (LR-CCE). SUMMARY BACKGROUND DATA: Current guidelines do not recommend routine SAP administration prior to LR-CCE. METHODS: This cohort study included adult patients who underwent LR-CCE and were documented by the Swissnoso SSI surveillance system between 1/2009-12/2020 at 66 Swiss hospitals. LR-CCE was specified as elective endoscopic surgery, age <70, no active cholecystitis, ASA score <3, operating time <120 minutes without implantation of foreign material. Exposure was defined as the administration of cefuroxime or cefazoline ± metronidazole within 120 minutes prior to incision versus no SAP administration. Our main outcome was occurrence of SSI until day 30. Logistic regression models were used to adjust for institutional, patient, and perioperative variables. RESULTS: Of 44 682 surveilled adult cholecystectomy patients, 12 521 (8 726 women [69.7%]; median [IQR] age, 49.0 [38.1-58.2] years), fulfilled inclusion criteria. SSI was identified in 143 patients (1.1%). SAP was administered in 9 269 patients (74.0%) and was associated with a lower SSI rate (adjusted odds ratio [aOR], 0.50; 95% CI, 0.35-0.70; P < 0.001). The number needed to treat to prevent one SSI episode is 100. CONCLUSIONS: The overall LR-CCE SSI rate was 1.1%. SAP was associated with a 50% lower overall SSI rate. Patients undergoing LR-CCE may benefit from routine surgical antimicrobial prophylaxis.

Machine learning-based preoperative analytics for the prediction of anastomotic leakage in colorectal surgery: a swiss pilot study.

BACKGROUND: Anastomotic leakage (AL), a severe complication following colorectal surgery, arises from defects at the anastomosis site. This study evaluates the feasibility of predicting AL using machine learning (ML) algorithms based on preoperative data. METHODS: We retrospectively analyzed data including 21 predictors from patients undergoing colorectal surgery with bowel anastomosis at four Swiss hospitals. Several ML algorithms were applied for binary classification into AL or non-AL groups, utilizing a five-fold cross-validation strategy with a 90% training and 10% validation split. Additionally, a holdout test set from an external hospital was employed to assess the models' robustness in external validation. RESULTS: Among 1244 patients, 112 (9.0%) suffered from AL. The Random Forest model showed an AUC-ROC of 0.78 (SD: ± 0.01) on the internal test set, which significantly decreased to 0.60 (SD: ± 0.05) on the external holdout test set comprising 198 patients, including 7 (3.5%) with AL. Conversely, the Logistic Regression model demonstrated more consistent AUC-ROC values of 0.69 (SD: ± 0.01) on the internal set and 0.61 (SD: ± 0.05) on the external set. Accuracy measures for Random Forest were 0.82 (SD: ± 0.04) internally and 0.87 (SD: ± 0.08) externally, while Logistic Regression achieved accuracies of 0.81 (SD: ± 0.10) and 0.88 (SD: ± 0.15). F1 Scores for Random Forest moved from 0.58 (SD: ± 0.03) internally to 0.51 (SD: ± 0.03) externally, with Logistic Regression maintaining more stable scores of 0.53 (SD: ± 0.04) and 0.51 (SD: ± 0.02). CONCLUSION: In this pilot study, we evaluated ML-based prediction models for AL post-colorectal surgery and identified ten patient-related risk factors associated with AL. Highlighting the need for multicenter data, external validation, and larger sample sizes, our findings emphasize the potential of ML in enhancing surgical outcomes and inform future development of a web-based application for broader clinical use.

Systematic identification of novel cancer genes through analysis of deep shRNA perturbation screens.

Systematic perturbation screens provide comprehensive resources for the elucidation of cancer driver genes. The perturbation of many genes in relatively few cell lines in such functional screens necessitates the development of specialized computational tools with sufficient statistical power. Here we developed APSiC (Analysis of Perturbation Screens for identifying novel Cancer genes) to identify genetic drivers and effectors in perturbation screens even with few samples. Applying APSiC to the shRNA screen Project DRIVE, APSiC identified well-known and novel putative mutational and amplified cancer genes across all cancer types and in specific cancer types. Additionally, APSiC discovered tumor-promoting and tumor-suppressive effectors, respectively, for individual cancer types, including genes involved in cell cycle control, Wnt/ß-catenin and hippo signalling pathways. We functionally demonstrated that LRRC4B, a putative novel tumor-suppressive effector, suppresses proliferation by delaying cell cycle and modulates apoptosis in breast cancer. We demonstrate APSiC is a robust statistical framework for discovery of novel cancer genes through analysis of large-scale perturbation screens. The analysis of DRIVE using APSiC is provided as a web portal and represents a valuable resource for the discovery of novel cancer genes.

The prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on CD8+ density.

BACKGROUND: Tumor infiltration with cytotoxic CD8+ T-cells is associated with a favorable outcome in several neoplasms, including thyroid cancer. The chemokine axis CXCR4/SDF-1 correlates with more aggressive tumors, but little is known concerning the prognostic relevance in relation to the tumor immune microenvironment of differentiated thyroid cancer (DTC). METHODS: A tissue microarray (TMA) of 37 tumor specimens of primary DTC was analyzed by immunohistochemistry (IHC) for the expression of CD8+, CXCR4, phosphorylated CXCR4 and SDF-1. A survival analysis was performed on a larger collective (n = 456) at RNA level using data from The Cancer Genome Atlas (TCGA) papillary thyroid cancer cohort. RESULTS: Among the 37 patients in the TMA-cohort, the density of CD8+ was higher in patients with less advanced primary tumors (median cells/TMA-punch: 12.5 (IQR: 6.5, 12.5) in T1-2 tumors vs. 5 (IQR: 3, 8) in T3-4 tumors, p = 0.05). In the TCGA-cohort, CXCR4 expression was higher in patients with cervical lymph node metastasis compared to N0 or Nx stage (CXCR4high/low 116/78 vs. 97/116 vs. 14/35, respectively, p = 0.001). Spearman's correlation analysis of the TMA-cohort demonstrated that SDF-1 was significantly correlated with CXCR4 (r = 0.4, p = 0.01) and pCXCR4 (r = 0.5, p = 0.002). In the TCGA-cohort, density of CD8+ correlated with CXCR4 and SDF-1 expression (r = 0.58, p < 0.001; r = 0.4, p < 0.001). The combined marker analysis of the TCGA cohort demonstrated that high expression of both, CXCR4 and SDF-1 was associated with reduced overall survival in the CD8 negative TCGA cohort (p = 0.004). CONCLUSION: These findings suggest that the prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on the density of CD8 positive T-lymphocytes. Further studies with larger sample sizes are needed to support our findings and inform future investigations of new treatment and diagnostic options for a more personalized approach for patients with differentiated thyroid cancer.

Continuously sutured versus linear-stapled anastomosis in robot-assisted hybrid Ivor Lewis esophageal surgery following neoadjuvant chemoradiotherapy: a single-center cohort study.

BACKGROUND: Esophageal cancer surgery is technically highly demanding. During the past decade robot-assisted surgery has successfully been introduced in esophageal cancer treatment. Various techniques are being evaluated in different centers. In particular, advantages and disadvantages of continuously sutured (COSU) or linear-stapled (LIST) gastroesophageal anastomoses are debated. Here, we comparatively analyzed perioperative morbidities and short-term outcomes in patients undergoing hybrid robot-assisted esophageal surgery following neoadjuvant chemoradiotherapy (nCRT), with COSU or LIST anastomoses in a single center. METHODS: Following standardized, effective, nCRT, 53 patients underwent a hybrid Ivor Lewis robot-assisted esophagectomy with COSU (n = 32) or LIST (n = 21) gastroesophageal anastomoses. Study endpoints were intra- and postoperative complications, in-hospital morbidity and mortality. Duration of operation, intensive care unit (ICU) and overall hospital stay were also evaluated. Furthermore, rates of rehospitalization, endoscopies, anastomotic stenosis and recurrence were assessed in a 90-day follow-up. RESULTS: Demographics, ASA scores and tumor characteristics were comparable in the two groups. Median duration of operation was similar in patients with COSU and LIST anastomosis (467 vs. 453 min, IQR 420-521 vs. 416-469, p = 0.0611). Major complications were observed in 4/32 (12.5%) and 4/21 (19%) patients with COSU or LIST anastomosis, respectively (p = 0.697). Anastomotic leakage was observed in 3/32 (9.3%) and 2/21 (9.5%) (p = 1.0) patients with COSU or LIST anastomosis, respectively. Pleural empyema occurred in 1/32 (3.1%) and 2/21 (9.5%) (p = 0.555) patients, respectively. Mortality was similar in the two groups (1/32, 3.1% and 1/21, 4.7%, p = 1.0). Median ICU stay did not differ in patients with COSU or LIST anastomosis (p = 0.255), whereas a slightly, but significantly (p = 0.0393) shorter overall hospital stay was observed for COSU, as compared to LIST cohort (median: 20 vs. 21 days, IQR 17-22 vs. 18-28). CONCLUSIONS: COSU is not inferior to LIST in the performance of gastroesophageal anastomosis in hybrid Ivor Lewis operations following nCRT.

Laparoscopic versus robotic-assisted, left-sided colectomies: intra- and postoperative outcomes of 683 patients.

BACKGROUND: Robotic-assisted colorectal surgery has gained more and more popularity over the last years. It seems to be advantageous to laparoscopic surgery in selected situations, especially in confined regions like a narrow male pelvis in rectal surgery. Whether robotic-assisted, left-sided colectomies can serve as safe training operations for less frequent, low anterior resections for rectal cancer is still under debate. Therefore, the aim of this study was to evaluate intra- and postoperative results of robotic-assisted laparoscopy (RAL) compared to laparoscopic (LSC) surgery in left-sided colectomies. METHODS: Between June 2015 and December 2019, 683 patients undergoing minimally invasive left-sided colectomies in two Swiss, high-volume colorectal centers were included. Intra- and postoperative outcome parameters were collected and analyzed. RESULTS: A total of 179 patients undergoing RAL and 504 patients undergoing LSC were analyzed. Baseline characteristics showed similar results. Intraoperative complications occurred in 0.6% of RAL and 2.0% of LSC patients (p = 0.193). Differences in postoperative complications graded Dindo ≥ 3 were not statistically significant (RAL 3.9% vs. LSC 6.3%, p = 0.227). Occurrence of anastomotic leakages showed no statistically significant difference [RAL n = 2 (1.1%), LSC n = 8 (1.6%), p = 0.653]. Length of hospital stay was similar in both groups. Conversions to open surgery were significantly higher in the LSC group (6.2% vs.1.7%, p = 0.018), while stoma formation was similar in both groups [RAL n = 1 (0.6%), LSC n = 5 (1.0%), p = 0.594]. Operative time was longer in the RAL group (300 vs. 210.0 min, p < 0.001). CONCLUSION: Robotic-assisted, left-sided colectomies are safe and feasible compared to laparoscopic resections. Intra- and postoperative complications are similar in both groups. Most notably, the rate of anastomotic leakages is similar. Compared to laparoscopic resections, the analyzed robotic-assisted resections have longer operative times but less conversion rates. Further prospective studies are needed to confirm the safety of robotic-assisted, left-sided colectomies as training procedures for low anterior resections.

Robot-assisted vs. laparoscopic repair of complete upside-down stomach hiatal hernia (the RATHER-study): a prospective comparative single center study.

BACKGROUND: Complete upside-down stomach (cUDS) hernias are a subgroup of large hiatal hernias characterized by high risk of life-threatening complications and technically challenging surgical repair including complex mediastinal dissection. In a prospective, comparative clinical study, we evaluated intra- and postoperative outcomes, quality of life and symptomatic recurrence rates in patients with cUDS undergoing robot-assisted, as compared to standard laparoscopic repair (the RATHER-study). METHODS: All patients with cUDS herniation requiring elective surgery in our institution between July 2015 and June 2019 were evaluated. Patients undergoing primary open surgery or additional associated procedures were not considered. Primary endpoints were intra- and postoperative complications, 30-day morbidity, and mortality. During the 8-53 months follow-up period, patients were contacted by telephone to assess symptoms associated to recurrence, whereas quality of life was evaluated utilizing the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) questionnaire. RESULTS: A total of 55 patients were included. 36 operations were performed with robot-assisted (Rob-G), and 19 with standard laparoscopic (Lap-G) technique. Patients characteristics were similar in both groups. Median operation time was 232 min. (IQR: 145-420) in robot-assisted vs. 163 min. (IQR:112-280) in laparoscopic surgery (p < 0.001). Intraoperative complications occurred in 5/36 (12.5%) cases in the Rob-G group and in 5/19 (26%) cases in the Lap-G group (p = 0.28). No conversion was necessary in either group. Minor postoperative complications occurred in 13/36 (36%) Rob-G patients and 4/19 (21%) Lap-G patients (p = 0.36). Mortality or major complications did not occur in either group. Two asymptomatic recurrences were observed in the Rob-G group only. No patient required revision surgery. Finally, all patients expressed satisfaction for treatment outcome, as indicated by similar GERD-HRQL scores. CONCLUSION: While robot-assisted surgery provides additional precision, enhanced visualization, and greater feasibility in cUDS hiatal hernia repair, its clinical outcome is at least equal to that obtained by standard laparoscopic surgery.

From open Ivor Lewis esophagectomy to a hybrid robotic-assisted thoracoscopic approach: a single-center experience over two decades.

PURPOSE: Robotic-assisted procedures are increasingly used in esophageal cancer surgery. We compared postoperative complications and early oncological outcomes following hybrid robotic-assisted thoracoscopic esophagectomy (Rob-E) and open Ivor Lewis esophagectomy (Open-E), performed in a single mid-volume center, in the context of evolving preoperative patient and tumor characteristics over two decades. METHODS: We evaluated prospectively collected data from a single center from 1999 to 2020 including 321 patients that underwent Ivor Lewis esophagectomy, 76 underwent Rob-E, and 245 Open-E. To compare perioperative outcomes, a 1:1 case-matched analysis was performed. Endpoints included postoperative morbidity and 30-day mortality. RESULTS: Preoperative characteristics revealed increased rates of adenocarcinomas and wider use of neoadjuvant treatment over time. A larger number of patients with higher ASA grades were operated with Rob-E. In case-matched cohorts, there were no differences in the overall morbidity (69.7% in Rob-E, 60.5% in Open-E, p value 0.307), highest Clavien-Dindo grade per patient (43.4% vs. 38.2% grade I or II, p value 0.321), comprehensive complication index (median 20.9 in both groups, p value 0.401), and 30-day mortality (2.6% in Rob-E, 3.9% in Open-E, p value 1.000). Similar median numbers of lymph nodes were harvested (24.5 in Rob-E, 23 in Open-E, p value 0.204), and comparable rates of R0-status (96.1% vs. 93.4%, p value 0.463) and distribution of postoperative UICC stages (overall p value 0.616) were observed. CONCLUSIONS: Our study demonstrates similar postoperative complications and early oncological outcomes after Rob-E and Open-E. However, the selection criteria for Rob-E appeared to be less restrictive than those of Open-E surgery.

From laparoscopic to robotic-assisted Heller myotomy for achalasia in a single high-volume visceral surgery center: postoperative outcomes and quality of life.

BACKGROUND: Laparoscopic (LSC) Heller myotomy (HM) is considered the standard procedure for the treatment of achalasia. Robotic platforms, established over the last years, provide important advantages to surgeons, such as binocular 3-dimensional vision and improvement of fine motor control. However, whether perioperative outcomes and long-term results of robotic-assisted laparoscopic (RAL) HM are similar or even superior to LSC technique, especially concerning long-term follow-up, is still debated. Therefore, the aim of the present study was to evaluate intra- and postoperative results as well as long-term quality of life after RAL compared to LSC surgery for achalasia in a single high-volume visceral surgery center. METHODS: Between August 2007 and April 2020, 43 patients undergoing minimally invasive HM for achalasia in a single high-volume Swiss visceral surgery center, were included in the present study. Intra- and postoperative outcome parameters were collected and evaluated, and a long-term follow-up was performed using the gastroesophageal-reflux disease health-related quality of life (GERD-Hr-QuoL) questionnaire. RESULTS: A total of 11 patients undergoing RAL and 32 undergoing LSC HM were analyzed. Baseline demographics and clinical characteristics were similar. A trend (p = 0.052) towards a higher number of patients with ASA III score treated with RAL was detectable. Operation time was marginally, but significantly, shorter in LSC (140 min, IQR: 136-150) than in RAL (150 min, IQR: 150-187, p = 0.047). Postoperative complications graded Clavien-Dindo ≥ 3 were only observed in one patient in each group. Length of hospital stay was similar in both groups (LSC: 11 days, IQR: 10-13 vs. RAL: 11 days, IQR: 10-14, p = 0.712). Long-term follow-up (LSC: median 89 months, vs. RAL: median 28 months, p = 0.001) showed comparable results and patients from both groups expressed similar levels of satisfaction (p = 0.181). CONCLUSIONS: LSC and RAL HM show similar peri- and postoperative results and a high quality of life, even in long-term (> 24 months) follow-up. Prospective, randomized, controlled multicenter trials are needed to overcome difficulties associated to small sample sizes in a rare condition and to confirm the equality or demonstrate the superiority of robotic-assisted procedures for achalasia. Meanwhile, the choice of the treatment technique could be left to the operating surgeon's preferences.

MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease.

BACKGROUND: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. PATIENTS AND METHODS: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. RESULTS: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056-0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049-0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. CONCLUSIONS: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality.

BACKGROUND: Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. METHODS: One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. RESULTS: Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401-8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. CONCLUSIONS: High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

Nestin and CD34 expression in colorectal cancer predicts improved overall survival.

BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.

Long-term urogenital assessment after elective laparoscopic sigmoid resection for diverticulitis: a comparison between central and peripheral vascular resection.

AIM: Increasing attention has been given to postoperative gastrointestinal functional outcome and quality of life after sigmoid resection for diverticulitis. Conversely, very little has been described about postoperative urogenital functional outcome and even less about its potential relationship to the type of vascular approach. The aim of this study was to evaluate whether central ligation of the inferior mesenteric artery (IMA) compared with peripheral dissection could impair urinary and sexual function in the long term. METHOD: Patients undergoing elective laparoscopic sigmoid resection for diverticulitis from 2004 to 2017 were retrospectively analysed. They were asked to complete the American Urological Association Symptom Index (AUASI) questionnaire. Men received the five-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Patients were then divided according to the type of vascular resection. RESULTS: A response rate of the 36.4% to the AUASI and 43.8% to the IIEF-5 questionnaires was achieved. Three hundred and twenty four patients with a mean age of 62 ± 9.85 years were analysed for their urinary function (IMA preserved n = 217; IMA resected n = 107) in a median follow-up of 87 months. Furthermore, 115 men with a mean age of 60 ± 8.97 years were investigated for their sexual function (IMA preserved n = 80; IMA resected n = 35) in a median follow-up of 89 months. No difference (AUASI: 8 ± 6.32 IMA preserved vs. 7 ± 6.26 IMA resected, P = 0.204; IIEF-5: 15 ± 7.67 IMA preserved vs. 15 ± 8.61 IMA resected, P = 0.674) was found regarding the type of vascular approach during sigmoid resection. CONCLUSIONS: No association was found between the type of vascular approach and the long-term urogenital functional outcome in patients undergoing sigmoid resection for diverticulitis.

Optimising functional outcomes in rectal cancer surgery.

BACKGROUND: By improved surgical technique such as total mesorectal excision (TME), multimodal treatment and advances in imaging survival and an increased rate of sphincter preservation have been achieved in rectal cancer surgery. Minimal-invasive approaches such as laparoscopic, robotic and transanal-TME (ta-TME) enhance recovery after surgery. Nevertheless, disorders of bowel, anorectal and urogenital function are still common and need attention. PURPOSE: This review aims at exploring the causes of dysfunction after anterior resection (AR) and the accordingly preventive strategies. Furthermore, the indication for low AR in the light of functional outcome is discussed. The last therapeutic strategies to deal with bowel, anorectal, and urogenital disorders are depicted. CONCLUSION: Functional disorders after rectal cancer surgery are frequent and underestimated. More evidence is needed to define an indication for non-operative management or local excision as alternatives to AR. The decision for restorative resection should be made in consideration of the relevant risk factors for dysfunction. In the case of restoration, a side-to-end anastomosis should be the preferred anastomotic technique. Further high-evidence clinical studies are required to clarify the benefit of intraoperative neuromonitoring. While the function of ta-TME seems not to be superior to laparoscopy, case-control studies suggest the benefits of robotic TME mainly in terms of preservation of the urogenital function. Low AR syndrome is treated by stool regulation, pelvic floor therapy, and transanal irrigation. There is good evidence for sacral nerve modulation for incontinence after low AR.

Predictive model estimating the decrease of postoperative gastrointestinal quality of life index (GIQLI) in patients after elective laparoscopic sigmoid resection for diverticular disease.

BACKGROUND: Growing consideration in quality of life (QoL) has changed the therapeutic strategy in patients suffering from diverticular disease. Patients' well-being plays a crucial role in the decision-making process. However, there is a paucity of studies investigating patients' or surgery-related factors influencing the postoperative gastrointestinal function. The aim of this study was to investigate in a predictive model patients or surgical variables that allow better estimation of the postoperative gastrointestinal QoL. METHODS: This observational study retrospectively analyzed patients undergoing elective laparoscopic sigmoidectomy for diverticulitis between 2004 and 2017. The one-time postoperative QoL was assessed with the gastrointestinal quality of life index (GIQLI) in 2019. A linear regression model with stepwise selection has been applied to all patients and surgery-related variables. RESULTS: Two hundred seventy-two patients with a mean age of 62.30 ± 9.74 years showed a mean GIQLI of 116.39±18.25 at a mean follow-up time of 90.4±33.65 months. Women (n=168) reported a lower GIQLI compared to male (n=104; 112.85±18.79 vs 122.11±15.81, p<0.001). Patients with pre-operative cardiovascular disease (n=17) had a worse GIQLI (106.65 ±22.58 vs 117.08±17.66, p=0.010). Finally, patients operated less than 5 years ago (n=63) showed a worse GIQLI compared to patients operated more than 5 years ago (n=209; 111.98±19.65 vs 117.71±17.63, p=0.014). CONCLUSIONS: Female gender and the presence of pre-operative cardiovascular disease are predictive for a decreased postoperative gastrointestinal QoL. Furthermore, patients' estimation of gastrointestinal functioning seems to improve up to 5 years after surgery.

Short- and long-term outcomes for primary anastomosis versus Hartmann's procedure in Hinchey III and IV diverticulitis: a multivariate logistic regression analysis of risk factors.

PURPOSE: The management of perforated diverticulitis with generalized peritonitis is still controversial and no preferred standardized therapeutic approach has been determined. We compared surgical outcomes between Hartmann's procedure (HP) and primary anastomosis (PA) in patients with Hinchey III and IV perforated diverticulitis. METHODS: Multicenter retrospective analysis of 131 consecutive patients with Hinchey III and IV diverticulitis operated either with HP or PA from 2015 to 2018. Postoperative morbidity was compared after adjustment for known risk factors in a multivariate logistic regression. RESULTS: Sixty-six patients underwent HP, while PA was carried out in 65 patients, 35.8% of those were defunctioned. HP was more performed in older patients (74.6 vs. 61.2 years, p < .001), with Hinchey IV diverticulitis (37% vs. 7%, p < .001) and in patients with worse prognostic scores (P-POSSUM Physiology Score, p < .001, Charlson Comorbidity Index p < .001). Major morbidity and mortality were higher in HP compared to PA (30.3% vs. 9.2%, p = .002 and 10.6% vs. 0%, p = .007, respectively) with lower stoma reversal rate (43.9% vs. 86.9%, p < .001). In a multivariate logistic regression, PA was independently associated with lower postoperative morbidity and mortality (OR 0.24, 95% CI 0.06-0.96, p = .044). CONCLUSIONS: In comparison to PA, HP is associated with a higher morbidity, higher mortality, and a lower stoma reversal rate. Although a higher prevalence of risk factors in HP patients may explain these outcomes, a significant increase in morbidity and mortality persisted in a multivariate logistic regression analysis that was stratified for the identified risk factors.

Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer.

OBJECTIVES: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. METHODS: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients' survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. RESULTS: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. CONCLUSIONS: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease.

Background: Metastatic disease in colorectal cancer represents a major cause of significant cancer-associated morbidity and mortality. L1CAM is a stem cell marker, cell adhesion molecule, belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAM) and it is aberrantly expressed in several different types of human solid tumors. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer.Patients and methods: Surgical specimens of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry and the results were correlated with clinical and survival data.Results: L1CAM expression was significantly correlated with advanced stage of disease (p < .001), higher T classification (p = .040), the presence of lymph node (p < .001) and distant metastasis (p = .011). Patients displaying high L1CAM expression demonstrated a dismal three-year progression free survival (29.7% vs 87.1%, p < .001) and five-year overall survival (39.9% vs 87.7%, p < .001). Multivariate analysis using Cox proportional hazard models revealed high L1CAM expression as a prognostic marker of dismal progression free (HR 0.187, 95%CI = 0.075-0.467, p < .0001) and overall survival (HR 0.154, 95%CI = 0.049-0.483, p = .001) independent of other clinicopathological characteristics. Subgroup analysis comprised of patients with early stage disease only presented as well significantly worse progression free and overall survival when L1CAM exhibited high expression.Conclusions: Colorectal cancer patients displaying high expression of L1CAM harbor high risk for metastasis already in early stage disease identifying therefore a group of patients prone to dismal prognosis.

Role of lymphadenectomy in resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) remains one of the most devastating malignant diseases, predicted to become the second leading cause of cancer-related death by 2030. Despite advances in surgical techniques and in systemic therapy, the 5-year relative survival remains a grim 9% for all stages combined. The extent of lymphadenectomy has been discussed intensively for decades, given that even in early stages of PC, lymph node (LN) metastasis can be detected in approximately 80%. PURPOSE: The primary objective of this review was to provide an overview of the current literature evaluating the role of lymphadenectomy in resected PC. For this, we evaluated randomized controlled studies (RCTs) assessing the impact of extent of lymphadenectomy on OS and studies evaluating the prognostic impact of anatomical site of LN metastasis and the impact of the number of resected LNs on OS. CONCLUSIONS: Lymphadenectomy plays an essential part in the multimodal treatment algorithm of PC and is an additional therapeutic tool to increase the chance for surgical radicality and to ensure correct staging for optimal oncological therapy. Based on the literature from the last decades, standard lymphadenectomy with resection of at least ≥ 15 LNs is associated with an acceptable postoperative complication risk and should be recommended to obtain local radicality and accurate staging of the disease. Although radical surgery including appropriate lymphadenectomy of regional LNs remains the only chance for long-term tumor control, future studies specifically assessing the impact of neoadjuvant therapy on extraregional LNs are warranted.

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

BACKGROUND: Despite improvements in therapy of colorectal cancer, some patients will present occurrence of recurrence either locally or distantly. Tumor metastasis constitutes the major cause of cancer-associated morbidity and mortality. Nectin-1 belongs to the family of immunoglobulin-like cell adhesion molecules that contribute to the formation of cell-cell adhesions and regulate a series of cellular activities including cell polarization, differentiation, movement, proliferation, and survival. Expression of Nectin-1 in malignant tumors has been associated with aggressive tumor phenotypes. OBJECTIVES: The aim of the present study was to assess Nectin-1 expression patterns in colorectal cancer and to investigate its clinical significance. METHODS: Nectin-1 expression was assessed via immunohistochemistry in surgical specimens of a cohort comprised of 111 patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data. Progression-free survival was defined as the primary outcome of the present study. RESULTS: Nectin-1 was strongly expressed in the cytoplasm of colorectal cancer cells. High Nectin-1 expression was associated with advanced stage of disease (p = 0.012) and lymph node metastasis (p = 0.007). Progression-free survival of patients exhibiting high expression of Nectin-1 in the first 36 months after surgery was significantly worse compared to patients with low expression of Nectin-1 (55.7%, 95% CI = 47-70, vs. 82.1%, 95% CI = 69-93, p = 0.014) and independent of other clinicopathological characteristics (HR = 0.389, 95% CI = 0.156-0.972, p = 0.043). CONCLUSION: Nectin-1 expression in colorectal cancer is associated with a significantly worse 3-year progression-free survival identifying therefore a group of patients with high risk for early disease recurrence.