Real world propensity score matched analysis evaluating the influence of en-bloc vs. non en-bloc techniques, energy and instrumentation on enucleation outcomes for large and very large prostates.

PURPOSE: The primary aim of the study was to evaluate if en-bloc vs. non en-bloc made a difference to intra-, peri- and post-operative surgical outcomes of anatomical endoscopic enucleation (AEEP) in large (> 80 cc) and very large prostates (> 200 cc). The secondary aim was to determine the influence of energy and instruments used. METHODS: Data of patients with > 80 cc prostate who underwent surgery between 2019 and 2022 were obtained from 16 surgeons across 13 centres in 9 countries. Propensity score matching (PSM) was used to reduce confounding. Logistic regression was performed to evaluate factors associated with postoperative urinary incontinence (UI). RESULTS: 2512 patients were included with 991 patients undergoing en-bloc and 1521 patients undergoing non-en-bloc. PSM resulted in 481 patients in both groups. Total operation time was longer in the en-bloc group (p < 0.001), enucleation time was longer in the non en-bloc group (p < 0.001) but morcellation times were similar (p = 0.054). Overall, 30 day complication rate was higher in the non en-bloc group (16.4% vs. 11.4%; p = 0.032). Rate of late complications (> 30 days) was similar (2.3% vs. 2.5%; p > 0.99). There were no differences in rates of UI between the two groups. Multivariate analysis revealed that age, Qmax, pre-operative, post-void residual urine (PVRU) and total operative time were predictors of UI. CONCLUSIONS: In experienced hands, AEEP in large prostates by the en-bloc technique yields a lower rate of complication and a slightly shorter operative time compared to the non en-bloc approach. However, it does not have an effect on rates of post-operative UI.

One-Year Outcomes of Transurethral Treatment of Bladder Neck Stenosis Following Transurethral Resection of the Prostate. Results from a Large, Multicenter Series.

Purpose: To assess management and outcomes of bladder neck stenosis (BNS) post-transurethral resection of the prostate (TURP) in 12 centers. Patients and Methods: A retrospective analysis of patients who underwent transurethral BN incision for stenosis following TURP from January 2015 and January 2023 was performed. Inclusion criteria included endoscopic diagnosis of BNS associated with obstruction and/or lower urinary tract symptoms. Data are presented as median and interquartile range. Two distinct univariable logistic regression analyses were performed to identify factors associated with overall urinary incontinence and recurrent stenosis. Results: Three hundred and seventy-two men were included. 95.2% of patients developed BNS following bipolar TURP. 21.0% of patients were on an indwelling catheter before BNS incision. Bipolar electrocautery was the most commonly employed energy for incision (66.5%). Collings knife was the most commonly employed (61.2%) instrument for incision, followed by end-firing holmium lasering (35.3%). Median operation time was 30 (25-45) minutes. The overall complication rate was 12.4%, with 19 (5.1%) patients suffering from acute urinary retention, 6 (1.6%) patients requiring prolonged irrigation due to persistent hematuria, and a surgical hemostasis was necessary in 8 cases (2.2%). Overall postoperative incontinence rate was 17.2%, with urge incontinence accounting for the most common type (45.3%). Incontinence lasted more than 3 months in 9/46 (14.3%) patients. Recurrent BNS occurred in 29 (7.8%) patients and was managed by re-endoscopic incision in 21 (5.6%) patients and dilatation only in 6 (1.6%) patients. Two (0.5%) patients underwent urethroplasty for recalcitrant stenosis. Logistic regression analysis showed that Collings knife was associated with higher odds of having postoperative incontinence (OR 3.93 95% CI 1.45-11.13, p=0.008) and BN recurrence (OR 3.589 95% CI 1.157-15.7, p=0.047). Conclusion: Transurethral BN incision provides satisfactory short-term results with an acceptable rate of complications.

Influence of Prostate Volume on the Incidence of Complications and Urinary Incontinence Following Thulium Fiber Laser Enucleation of the Prostate: Results from Multicenter, Real-world Experience of 2732 patients.

Background: The use of the new thulium fiber laser in enucleation of the prostate (ThuFLEP) has been introduced recently. Objective: To evaluate complications and urinary incontinence (UI) after ThuFLEP in small and large prostate volume (PV). Design setting and participants: We retrospectively reviewed patients who underwent ThuFLEP in six centers (from January 2020 to January 2023). The exclusion criteria were concomitant lower urinary tract surgery, previous prostate/urethral surgery, prostate cancer, and pelvic radiotherapy. Outcome measurements and statistical analysis: Patients were divided into two groups: group 1: PV ≤80 ml; group 2: PV >80 ml. Univariable and multivariable logistic regression analyses were performed to evaluate the independent predictors of overall UI. Results and limitations: There were 1458 patients in group 1 and 1274 in group 2. There was no significant difference in age. The median PV was 60 (61-72) ml in group 1 and 100 (90-122) ml in group 2. En bloc enucleation was employed more in group 1, while the early apical release technique was used more in group 2. The rate of prolonged irrigation for hematuria, urinary tract infection, and acute urinary retention did not differ significantly. Blood transfusion rate was significantly higher in group 2 (0.5% vs 2.0%, p = 0.001). There was no significant difference in the overall UI rate (12.3% in group 1 vs 14.7% in group 2, p = 0.08). A multivariable regression analysis showed that preoperative postvoiding urine residual (odds ratio 1.004, 95% confidence interval 1.002-1.007, p < 0.01) was the only factor significantly associated with higher odds of UI. A limitation of this study was its retrospective nature. Conclusions: Complications and UI rates following ThuFLEP were similar in patients with a PV up to or larger than 80 ml except for the blood transfusion rate that was higher in the latter. Patient summary: In this study, we looked at outcomes after thulium fiber laser in enucleation of the prostate stratified by PV. We found that blood transfusion was higher in men with PV >80 ml, but urinary incontinence was similar.

Incidence of complications and urinary incontinence following endoscopic enucleation of the prostate in men with a prostate volume of 80 ml and above: results from a multicenter, real-world experience of 2512 patients.

PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.

The Association of Polish Surgeons (APS) clinical guidelines for the use of laparoscopy in the management of abdominal emergencies. Part II.

Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. The recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The second part of the guidelines covers sections 6 to12 and the following challenges for surgical practice: acute appendicitis, acute mesenteric ischemia, abdominal injuries, bowel obstruction, diverticulitis, laparoscopy in pregnancy and postoperative complications requiring a reoperation.

Patient-reported pain associated with grid-based transperineal magnetic resonance imaging (MRI)/ultrasound (US) software fusion biopsy of the prostate under local anesthesia: a multicenter experience.

Background: Biopsy by transperineal (TP) approach is recommended standard for prostate cancer (PC) diagnosis. To avoid pain, patients undergoing TP biopsy may be offered sedation or general anesthesia. Our aim was to investigate the degree of patient-reported pain for magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy of the prostate being performed under local anesthesia (LA) and to study for possible factors associated with increased risk of significant pain (SP) in this setting. Methods: In this retrospective observational study, we reviewed data of consecutive patients without a prior diagnosis of PC who underwent MRI/US software fusion biopsy of the prostate under LA with lidocaine at two centers between May 2020 and April 2022, and who reported their periprocedural pain on a Wong-Baker FACES Pain Rating Scale (0-10). We defined SP as reported pain score of 6-10. Patient and procedure characteristics together with SP were studied for interdependencies. Results: A total of 299 patients were included. Median pain score was 2 (interquartile range: 2-4), with SP having been reported by 55 (18.4%) patients. Among patient characteristics, only age demonstrated association with SP [odds ratio (OR), per 10 years =0.53, 95% confidence interval (CI): 0.35-0.80, P=0.003] and patients aged 62 or above were significantly less likely to report SP (OR =0.33, 95% CI: 0.18-0.60, P<0.001). Conclusions: Performing TP MRI/US fusion prostate biopsy under LA is associated with low rates of SP, with the risk being significantly lower in older men. The results of this study can serve as evidence resource for preprocedural counselling in patients especially concerned about the risk of pain.

The Association of Polish Surgeons (APS) clinical guidelines for the use of laparoscopy in the management of abdominal emergencies. Part I.

Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The first part of the guidelines covers 5 sections and the following challenges for surgical practice: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia and acute cholecystitis. Contraindications for laparoscopy and the ERAS program are discussed.

Predictors of Clinically Significant Prostate Cancer in Patients with PIRADS Categories 3-5 Undergoing Magnetic Resonance Imaging-Ultrasound Fusion Biopsy of the Prostate.

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.

Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer.

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

Serum and Erythrocyte Antioxidant Defense in Colorectal Cancer Patients during Early Postoperative Period: Potential Modifiers and Impact on Clinical Outcomes.

A better understanding of antioxidant status, its modifiers, and its effect on clinical outcomes in patients undergoing colorectal cancer surgery is needed for effective antioxidant-based interventions. The objectives of this cohort study were: to determine baseline serum (total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP); n = 72) and erythrocyte (superoxide dismutase (SOD) and glutathione peroxidase (GPx); n = 47) antioxidant capacity and time-course during the 72 h postoperative period, to identify potential modifiers, and to establish impact on clinical outcomes. Older patients with comorbidities had lower baseline FRAP. TAC was inversely and SOD directly correlated with inflammatory markers. Cancer pathology affected GPx (lower in advanced and more aggressive cancers) and SOD (higher in advanced cancers). Surgical intervention induced a transient increase in FRAP and TAC with greater FRAP elevation in older, obese patients with several comorbidities. SOD activity significantly increased while GPx non-significantly decreased between 8 and 24 h post-incision. Poorer health status was associated with an increase in SOD and a decrease in GPx at 72 h. Clinical manifestation of postoperative ileus was preceded by decreased TAC at 24 h and an increase in SOD between 8 and 24 h and anastomotic leak was manifested by diminished SOD at 72 h compared to activities at 8 and 24 h. The time-frame between 8 and 24 h post-incision might be the most critical regarding oxidant/antioxidant balance and therefore the best suited for antioxidant-based intervention.

Sex, Type of Surgery, and Surgical Site Infections Are Associated with Perioperative Cortisol in Colorectal Cancer Patients.

Excessive endocrine response to trauma negatively affects patients' well-being. Cortisol dynamics following robot-assisted colorectal surgery are unknown. We aimed at determining the impact of cancer pathology and surgery-related factors on baseline cortisol levels and analyzed its time-profile in colorectal cancer patients undergoing open or robot-assisted surgery. Cortisol levels were measured using liquid chromatography quadrupole time-of-flight mass spectrometry. Baseline cortisol was not associated with any patient- or disease-related factors. Post-surgery cortisol increased by 36% at 8 h and returned to baseline on postoperative day three. The cortisol time profile was significantly affected by surgery type, estimated blood loss, and length of surgery. Baseline-adjusted cortisol increase was greater in females at hour 8 and in both females and patients from open surgery group at hour 24. Solely in the open surgery group, cortisol dynamics paralleled changes in interleukin (IL)-1ß, IL-10, IL-1ra, IL-7, IL-8 and tumor necrosis factor (TNF)-α but did not correlate with changes in IL-6 or interferon (IFN)-γ at any time-point. Cortisol co-examined with C-reactive protein was predictive of surgical site infections (SSI) with high accuracy. In conclusion, patient's sex and surgery invasiveness affect cortisol dynamics. Surgery-induced elevation can be reduced by minimally invasive robot-assisted procedures. Cortisol and C-reactive protein as SSI biomarkers might be of value in the evaluation of safety of early discharge of patients.

Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial.

OBJECTIVE: To assess non-inferiority of s.c. to i.v. CT-P13 in RA. METHODS: Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46-54) then PFS (W56-64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: -0.6). RESULTS: Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. CONCLUSION: CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings.

Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs' expression is worth exploration.

Simultaneous LC-MS/MS-Based Quantification of Free 3-Nitro-l-tyrosine, 3-Chloro-l-tyrosine, and 3-Bromo-l-tyrosine in Plasma of Colorectal Cancer Patients during Early Postoperative Period.

Quantification with satisfactory specificity and sensitivity of free 3-Nitro-l-tyrosine (3-NT), 3-Chloro-l-tyrosine (3-CT), and 3-Bromo-l-tyrosine (3-BT) in biological samples as potential inflammation, oxidative stress, and cancer biomarkers is analytically challenging. We aimed at developing a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for their simultaneous analysis without an extract purification step by solid-phase extraction. Validation of the developed method yielded the following limits of detection (LOD) and quantification (LOQ) for 3-NT, 3-BT, and 3-CT: 0.030, 0.026, 0.030 ng/mL (LODs) and 0.100, 0.096, 0.098 ng/mL (LOQs). Coefficients of variation for all metabolites and tested concentrations were <10% and accuracy was within 95-105%. Method applicability was tested on colorectal cancer patients during the perioperative period. All metabolites were significantly higher in cancer patients than healthy controls. The 3-NT was significantly lower in advanced cancer and 3-BT showed a similar tendency. Dynamics of 3-BT in the early postoperative period were affected by type of surgery and presence of surgical site infections. In conclusion, a sensitive and specific LC-MS/MS method for simultaneous quantification of free 3-NT, 3-BT, and 3-CT in human plasma has been developed.

In pursuit of COVID-19 surgical risk stratification to manage a limited workforce and supplies in minimally invasive surgery.

The protective barriers used so far in surgery do not provide adequate protection against SARS-CoV-2 virus, and reinforced protective equipment is needed. The rapid increase in the number of patients and the worldwide panic associated with the increasingly low availability of protective equipment has resulted in a shortage of protective equipment in many hospitals. Appropriatepersonal protective equipment must be provided so that the surgical team proceeding to surgery is not excluded from the further struggle for patients' health, especially in MIS. Reckless and excessive use of maximum protective equipment may result in a severe shortage of these products when the number of infected persons requiring surgery increases. The use of a structured infection risk scheme for medical staff, depending on the results of reverse transcription polymerase chain reaction assays and COVID-19 symptoms, combined with the division of protection equipment into three groups, allows easy selection of an appropriate clothing scheme for the clinical setting.

L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs.

L-arginine/nitric oxide pathway metabolites are altered in colorectal cancer (CRC). We evaluated underlying changes in pathway enzymes in 55 paired tumor/tumor-adjacent samples and 20 normal mucosa using quantitative-PCR and assessed the impact of classic and novel oxicam analogues on enzyme expression and intracellular metabolite concentration (LC-MS/MS) in Caco-2, HCT116, and HT-29 cells. Compared to normal mucosa, ARG1, PRMT1, and PRMT5 were overexpressed in both tumor and tumor-adjacent tissue and DDAH2 solely in tumor-adjacent tissue. Tumor-adjacent tissue had higher expression of ARG1, DDAH1, and DDAH2 and lower NOS2 than patients-matched tumors. The ARG1 expression in tumors increased along with tumor grade and reflected lymph node involvement. Novel oxicam analogues with arylpiperazine moiety at the thiazine ring were more effective in downregulating DDAHs and PRMTs and upregulating ARG2 than piroxicam and meloxicam. An analogue distinguished by propylene linker between thiazine's and piperazine's nitrogen atoms and containing two fluorine substituents was the strongest inhibitor of DDAHs and PRMTs expression, while an analogue containing propylene linker but no fluorine substituents was the strongest inhibitor of ARG2 expression. Metabolic reprogramming in CRC includes overexpression of DDAHs and PRMTs in addition to ARG1 and NOS2 and is not restricted to tumor tissue but can be modulated by novel oxicam analogues.

L-Arginine/NO Pathway Metabolites in Colorectal Cancer: Relevance as Disease Biomarkers and Predictors of Adverse Clinical Outcomes Following Surgery.

The L-Arginine/NO pathway is involved in carcinogenesis and immunity. Its diagnostic and prognostic value in colorectal cancer (CRC) was determined using tandem mass spectrometry in 199 individuals (137 with CRC) and, during a three-day follow up, in 60 patients undergoing colorectal surgery. Citrulline was decreased and asymmetric (ADMA) and symmetric (SDMA) dimethylarginines and dimethylamine (DMA) were increased in CRC. The DMA increase corresponded with CRC advancement while arginine, ADMA, and SDMA levels were higher in left-sided cancers. Arginine, citrulline, ADMA, and DMA dropped and SDMA increased post incision. Females experienced a more substantial drop in arginine. The arginine and ADMA dynamics depended on blood loss. The initial SDMA increase was higher in patients requiring transfusions. Postoperative dynamics in arginine and dimethylarginines differed in robot-assisted and open surgery. Concomitant SDMA, citrulline, and DMA quantification displayed a 92% accuracy in detecting CRC. Monitoring changes in arginine, ADMA, and SDMA in the early postoperative period predicted postoperative ileus with 84% and surgical site infections with 90% accuracy. Changes in ADMA predicted operative morbidity with 90% and anastomotic leakage with 77% accuracy. If positively validated, L-arginine/NO pathway metabolites may facilitate CRC screening and surveillance, support differential diagnosis, and assist in clinical decision-making regarding patients recovering from colorectal surgery.

Guidelines for the management of surgical departments in non-uniform hospitals during the COVID-19 pandemic.

In the last several weeks we have been witnessing the exponentially progressing pandemic SARS-CoV-2 coronavirus. As the number of people infected with SARS-CoV2 escalates, the problem of surgical management of patients requiring urgent surgery is increasing. Patients infected with SARS-CoV2 virus but with negative test results will appear in general hospitals and may pose a risk to other patients and hospital staff. Health care workers constitutes nearly 17% of infected population in Poland, therefore early identification of infected people becomes a priority to protect human resources and to ensure continuity of the access to a surgical care. Both surgical operations, and endoscopic procedures are considered as interventions with an increased risk of infection. Therefore, determining the algorithm becomes crucial for qualifying patients for surgical treatment, but also to stratify the risk of personnel being infected during surgery and to adequately protect staff. Each hospital should be logistically prepared for the need to perform urgent surgery on a patient with suspected or confirmed infection, including personal protective equipment. Limited availability of the equipment, working under pressure and staff shortages in addition to a highly contagious pathogen necessitate a pragmatic management of human resources in health care. Instant synchronized action is needed, and clear uniform guidelines are essential for the healthcare system to provide citizens with the necessary surgical care while protecting both patients, and staff. This document presents current recommendations regarding surgery during the COVID-19 pandemic in Poland.

Risk factors in reoperations in colorectal surgery.

BACKGROUND: Reoperations in colorectal surgery are usually a consequence of major surgical complications. Recently, the rate of reoperation has been proposed as a marker of surgical performance. Yet, the incidence of re-intervention varies significantly in literature, ranging from 5.2% to 13%. Therefore, in this study we investigated 30-day reoperation rates and made an attempt to identify risk factors of re-intervention following colorectal resection at our institution. METHODS: This is a retrospective study of patients who had undergone colorectal resection at a single institution from 2013 to 2017. Univariate and multivariate analysis of predicting factors were performed. RESULTS: Out of 464 patients included, 51 required reoperations (11%). The most common causes of reoperations were anastomotic leakage, postoperative bleeding, and wound dehiscence. In univariate analysis the age of the patient and location of the tumor were related to an increased rate of reoperation. In multivariate analysis patients older than 75 (OR = 2.1; 95%CI = 1.1-3.9) and tumors sited in the rectum (OR = 2.66; 95%CI = 1.4-5) were associated with an increased risk of re-intervention. Patients who required postoperative re-intervention stayed in hospital longer (14 vs. 6 days, P < 0.0001) and had higher mortality (9.8% vs. 1.2%, P = 0.002). CONCLUSIONS: Our study shows that reoperation rates that follow colorectal surgery are frequently undervalued. In our series, 11% of patients required an unplanned return to the operative room. Patient's age and rectal tumors were the two independent factors that affect the rate of reoperation. Novel aspect: Data concerning reoperation rates in colorectal surgery is varying and most reports have shown the incidence of re-intervention to be as low as 5-7%. Our study demonstrates that reoperations after curative surgery for colorectal cancer are more frequent and may occur in over a tenth of total patients operated on.

Distinct Chemokine Dynamics in Early Postoperative Period after Open and Robotic Colorectal Surgery.

Stress response to robot-assisted colorectal surgery is largely unknown. Therefore, we conducted a prospective comparative nonrandomized study evaluating the perioperative dynamics of chemokines: IL-8/CXCL8, MCP-1/CCL2, MIP-1α/CCL3, MIP-1ß/CCL4, RANTES/CCL5, and eotaxin-1/CCL11 in 61 colorectal cancer patients following open colorectal surgery (OCS) or robot-assisted surgery (RACS) in reference to clinical data. Postoperative IL-8 and MCP-1 increase was reduced in RACS with a magnitude of blood loss, length of surgery, and concomitant up-regulation of IL-6 and TNFα as its independent predictors. RANTES at 8 h dropped in RACS and RANTES, and MIP1α/ß at 24 h were more elevated in RACS than OCS. IL-8 and MCP-1 at 72 h remained higher in patients subsequently developing surgical site infections, in whom a 2.6- and 2.5-fold increase was observed. IL-8 up-regulation at 24 h in patients undergoing open procedure was predictive of anastomotic leak (AL; 94% accuracy). Changes in MCP-1 and RANTES were predictive of delayed restoration of bowel function. Chemokines behave differently depending on procedure. A robot-assisted approach may be beneficial in terms of chemokine dynamics by favoring Th1 immunity and attenuated angiogenic potential and postoperative ileus. Monitoring chemokine dynamics may prove useful for predicting adverse clinical events. Attenuated chemokine up-regulation results from less severe blood loss and diminished inflammatory response.