Fluorescence-guided colorectal surgery: applications, clinical results, and protocols.

In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.

Clinical Effectiveness of Fluorescence Lymph Node Mapping Using ICG for Laparoscopic Right Hemicolectomy: A Prospective Case-Control Study.

BACKGROUND: The distinction between D3 lymph nodes and actual lymphatic pathways in primary tumors can be difficult during surgery, making it challenging to confirm the completeness of D3 lymph node dissection. Fluorescence lymph node mapping (FLNM) is a promising method for lymph node visualization. PURPOSE: This study aimed to assess whether FLNM enhances the effectiveness of D3 lymph node dissection in patients with right-sided colon cancer. METHODS: Endoscopic submucosal indocyanine green injection were performed on the distal margin of the colon cancer. In an FLNM group, the lymphatic drainage pathway and distribution of D3 lymph nodes were explored. Pathological evaluations were conducted for the fluorescent D3 and non-fluorescent D3 lymph nodes. RESULTS: The FLNM group showed a significantly higher number of harvested lymph nodes in the D3 area. In stage III patients, the proportion of D3 lymph node metastasis was significantly higher in the FLNM group. The harvested D3 lymph node count showed a proportional correlation with a metastatic lymph node count of up to 15. CONCLUSION: FLNM could be considered a promising new strategy to potentially increase harvested D3 lymph node counts in colon cancer surgery.

The Safe Values of Quantitative Perfusion Parameters of ICG Angiography Based on Tissue Oxygenation of Hyperspectral Imaging for Laparoscopic Colorectal Surgery: A Prospective Observational Study.

BACKGROUND: Safe values for quantitative perfusion parameters of indocyanine green (ICG) angiography have not been fully defined, and interpretation remains at the surgeon's discretion. This prospective observational study aimed to establish the safe values for the quantitative perfusion parameters by comparing tissue oxygenation levels from HSI images in laparoscopic colorectal surgery. METHODS: ICG angiography was performed using a laparoscopic near-infrared (NIR) camera system with ICG diluted in 10 mL of distilled water. For quantitative perfusion parameters, the changes in fluorescence intensity with perfusion times were analyzed to plot a time-fluorescence intensity graph. To assess real-time tissue oxygen saturation (StO2) in the colon, the TIVITA® Tissue System was utilized for hyperspectral imaging (HSI) acquisition. The StO2 levels were compared with the quantitative perfusion parameters derived from ICG angiography at corresponding points to define the safe range of ICG parameters reflecting good tissue oxygenation. RESULTS: In the regression analysis, T1/2MAX, TMAX, slope, and NIR perfusion index were correlated with tissue oxygen saturation. Using this regression model, the cutoff values of quantitative perfusion parameters were calculated as T1/2MAX ≤ 10 s, TMAX ≤ 30 s, slope ≥ 5, and NIR perfusion index ≥50, which best reflected colon StO2 higher than 60%. Diagnostic values were analyzed to predict colon StO2 of 60% or more, and the ICG perfusion parameters T1/2MAX, TMAX, and perfusion TR showed high sensitivity values of 97% or more, indicating their ability to correctly identify cases with acceptable StO2. CONCLUSION: The safe values for quantitative perfusion parameters derived from ICG angiography were T1/2MAX ≤ 10 s and TMAX ≤ 30 s, which were associated with colon tissue oxygenation levels higher than 60% in the laparoscopic colorectal surgery.

Short-term outcomes of Early versus conventional adjuvant chemotherapy in stage III colon cancer: randomized clinical trial.

BACKGROUND: Evidence is lacking regarding the earliest timing of initiating adjuvant chemotherapy to maximize its efficacy safely. A trial was designed and conducted to evaluate the safety and oncological efficacy of early adjuvant chemotherapy compared with conventional adjuvant chemotherapy. The short-term outcomes are reported here. METHODS: A multicentre, randomized (1 : 1), open-label, phase III trial was conducted comparing early adjuvant chemotherapy with conventional adjuvant chemotherapy in patients with stage III colon cancer. Patients who underwent radical surgery who had stage III colon cancer confirmed by histopathological assessment were screened and randomized into the early adjuvant chemotherapy arm or the conventional adjuvant chemotherapy arm. The primary endpoint was 3-year disease-free survival. The adjuvant chemotherapy with FOLFOX was delivered between postoperative day 10 and 14 in the early adjuvant chemotherapy arm, and between postoperative day 24 and 28 in the conventional adjuvant chemotherapy arm. Toxicity and quality of life were evaluated. RESULTS: Between 9 September 2011 and 6 March 2020, 443 patients consented to randomization at eight sites. The intention-to-treat population included 423 patients (209 in the early adjuvant chemotherapy arm and 214 in the conventional adjuvant chemotherapy arm), and the safety population included 380 patients (192 in the early adjuvant chemotherapy arm and 188 in the conventional adjuvant chemotherapy arm). There was no statistically significant difference in overall toxicity (28.1 per cent in the early adjuvant chemotherapy arm and 28.2 per cent in the conventional adjuvant chemotherapy arm, P = 0.244), surgical complications, and quality of life between the two arms. CONCLUSION: Adjuvant chemotherapy can be safely initiated 2 weeks after surgery with toxicity and quality of life comparable to conventional adjuvant chemotherapy for stage III colon cancer.

Clinical Progression of Colorectal Resection in Gynecologic Cancer Patients: Does the Risk of Anastomotic Leakage Increase after Surgery?

OBJECTIVES: This research aimed to examine the clinicopathological results of colorectal resection in patients with advanced gynecological cancers. METHODS: We retrospectively reviewed the medical records of 104 patients with gynecological cancer who underwent colorectal resection from December 2008 to August 2020 at a single hospital (PNUYH). Using descriptive statistics, variables for risk factors and surgical complications were compared. We eliminated instances with malignancies originating from organs other than the female genitalia, benign gynecological illnesses, primary stoma formation, and any other bowel procedures outside colon resection. RESULTS: The average age of 104 patients was determined to be 62.0 years. The most prevalent gynecological cancer was ovarian cancer (85 patients, 81.7%), and the most frequent procedure was low anterior resection (80 patients, 76.9%). There were postoperative problems in 61 patients (58.7%), while there was anastomotic leaking in just 3 patients (2.9%). Among the risk factors, only preoperative albumin was statistically significant (p=0.019). CONCLUSION: Our findings imply that colorectal resection can be performed safely and effectively on individuals with advanced gynecological cancer.

Impact of non-muscle cutting periumbilical transverse incision on the risk of incisional hernia as compared to midline incision during laparoscopic colon cancer surgery: a study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Minimally invasive surgery has become popular as a surgical approach for colorectal cancer because it has fewer complications related to the abdominal incision and perioperative complications. However, the incidence of incisional hernias in laparoscopic surgery has been reported to be similar to that in open surgery. We developed a new method, the non-muscle-cutting periumbilical transverse incision, for a small incision in laparoscopic colon cancer surgery. This study aims to evaluate the effectiveness of the non-muscle-cutting periumbilical transverse incision in comparison with the midline incision in reducing the incidence of an incisional hernia in patients undergoing laparoscopic colon cancer surgery. METHODS: This is an open-label, multi-centre, parallel, superiority, and randomised trial. Altogether, 174 patients will be allocated in a 1:1 ratio to either the midline incision or the non-muscle-cutting periumbilical transverse incision group, after stratifying by the location of the tumour (right- or left-sided). The primary outcome of this study is the incidence of incisional hernias (both symptomatic and radiologic hernias) at 12 months after surgery. The secondary outcomes include operative outcomes, 30-day postoperative complications, pathological results, and patient-reported outcomes (short form-12 health survey questionnaire and body image questionnaire). Both primary (intention-to-treat) and secondary (as-treated principles) analyses will be performed for all outcomes. The statistical significance level was set at p < 0.05 (two-sided testing). DISCUSSION: This trial may show that the non-muscle-cutting periumbilical transverse incision will reduce the incidence of incisional hernias compared to the midline incision. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) of Republic of Korea, KCT0006082 . Registered on April 12, 2021.

Multidisciplinary Treatment Strategy for Early Colon Cancer: A Review-An English Version.

Treatment for early colon cancer has progressed rapidly, with endoscopic resection and minimally invasive surgery. It is important to select patients without risk of lymph node metastasis before deciding on endoscopic resection for early colon cancer treatment. Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. A multidisciplinary approach is emphasized to establish a treatment strategy for early colon cancer to minimize the risk of complications and obtain excellent oncologic outcomes by selecting an appropriate treatment optimized for the patient's stage and condition. Therefore, we aimed to review the optimal multidisciplinary treatment strategies, including endoscopy and surgery, for early colon cancer.

Anastomotic leak after minimally invasive anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery: a study protocol for a multicentre randomized clinical trial.

BACKGROUND: Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer. METHODS/DESIGN: Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate. DISCUSSION: Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial. TRIAL REGISTRATION: Clinical Research Information Service KCT0003523. Registered on February 18, 2019.

Role of C-Reactive Protein, White Blood Cell Counts, and Serum Glucose Levels as Early Predictors of Infectious Complications After Laparoscopic Colorectal Surgery for Colorectal Cancer.

BACKGROUND: The early detection of infectious complications of colorectal surgery leads to better patient outcomes. This study aimed to assess the role of C-reactive protein (CRP), white blood cell count (WBC), and serum glucose in the early prediction of infectious complications of laparoscopic colorectal surgery. METHODS: Patients who underwent laparoscopic colorectal surgery were included and stratified into two groups: infectious complication (IC) or no infectious complication (non-IC). Serum levels were measured on postoperative days (PODs) 2 and 4. RESULTS: Analysis of 224 patients (IC group: 27, Non-IC group: 197) revealed higher CRP levels in IC group on POD 2 (P = .001). On POD 4, CRP levels and WBC counts were higher in IC group (P<.001, P = .011, respectively). The area under the curve (AUC) of the receiver operating characteristic (ROC) for CRP on PODs 2 and 4 were .743 and .907, respectively, and for WBC on POD 4 was .687. The cut-offs of CRP on PODs 2 and 4 were 156.2 mg/L and 91.3 mg/L, respectively; the cut-off of WBC was 7,220 cells/mm3. Sensitivity of CRP level ≥91.3 mg/L or WBC count ≥7,220 cells/mm3 was 96.3%; (cf. 88.9% for CRP alone), and specificity of CRP level ≥91.3 mg/L and WBC count ≥7,220 cells/mm3 was 93.4% (cf. 82.2% for CRP alone). DISCUSSION: The CRP level on postoperative day (POD) 2 and the combined CRP and WBC on POD 4 were meaningful in predicting infectious complications after laparoscopic colorectal surgery. However, serum glucose levels had a low predictive value for infectious complications.

Capacitive coupling leading to electrical skin burn injury during laparoscopic surgery.

Purpose: Trocar-site burns occurring during laparoscopic surgery have been reported in various cases, and several efforts to reduce them are underway. This study aimed to analyze the effect of capacitive coupling on trocar site by observing electrical and histological changes for electrical skin burn injury. Methods: To measure the electrical changes relating to capacitive coupling, the temperature, current, voltage, and impedance around the trocar were measured when an open circuit and a closed circuit were formed using insulation intact instruments and repeated after insulation failure. After the experiment, the tissue around the trocar was collected, and microscopic examination was performed. Results: When open circuits were formed with the intact insulation, the impedance was significantly reduced compared to the cases of closed circuits (142.0 Ω vs. 109.3 Ω, p = 0.040). When the power was 30 W and there was insulation failure, no significant difference was measured between the open circuit and the closed circuit (147.7 Ω vs. 130.7 Ω, p = 0.103). Collagen hyalinization, nuclear fragmentation, and coagulation necrosis suggesting burns were observed in the skin biopsy at the trocar insertion site. Conclusion: This study demonstrated that even with a plastic trocar and electrosurgical instruments that have intact insulation, if an open circuit is formed, capacitive coupling increases, and trocar-site burn can occur. When using electrocautery, careful manipulation must be taken to avoid creating an open circuit to prevent capacitive coupling related to electrical skin burn.

Ileal long-segment ischemia after the unintended ligation of variant ileal branch during laparoscopic right hemicolectomy.

The variant terminal trunk of the superior mesenteric artery (SMA) could be confused with the ileocolic artery (ICA) as it runs on the right side of the superior mesenteric vein. If the variant ileal branch of SMA is mistaken for the ICA, unintentional ligation could cause long-segment ischemia in the ileum. We encountered a rare case of ileal ischemia caused by unintentional ligation of the variant ileal branch of the SMA during laparoscopic right hemicolectomy, which was confirmed by indocyanine green (ICG) angiography and hyperspectral imaging (HSI). Intraoperative real-time perfusion monitoring using ICG angiography and tissue oxygen saturation monitoring using HSI could help detect segments of hypoperfusion and prevent hypoperfusion-related anastomotic complications.

Is the oncological impact of vascular invasion more important in right colon cancer?

Vascular invasion is an unfavorable prognostic factor for the recurrence and systemic metastasis of colon cancer. An interesting study in this issue evaluate the difference in the oncological impact of vascular invasion according to tumor side in colon cancer. The authors suggest that the oncological impact of vascular invasion could be worse in nonmetastatic right colon cancer than in nonmetastatic left colon cancer. Herein, hematoxylin-eosin staining was used to detect vascular invasion. In a recent study, elastin staining could detect more venous invasion. It is expected that the molecular pathologic characteristics of colon cancer can be identified precisely and the oncological outcomes of colon cancer can be improved in the future.

Differences in Factors Predicting Lymph Node Metastasis Between pT1 Rectal Cancer and pT1 Colon Cancer: A Retrospective Study.

BACKGROUND: Studies have demonstrated conflicting results regarding factors that predict lymph node metastasis (LNM) in pT1 colorectal cancers. We hypothesized that these discrepancies could be related to different factors predicting LNM between rectal and colon cancer. This study aimed to compare predicting factors for LNM between pT1 rectal and colon cancer. METHODS: This retrospective study evaluated a prospectively maintained database that included 380 patients with pT1 colorectal cancer from January 2010 to December 2020. Patients were grouped according to whether they had rectal or colon cancer, with or without LNM, and factors predicting LNM were analyzed. RESULTS: In pT1 rectal cancer, LNM was associated with deeper submucosal (SM) invasion (P = .024) and a higher proportion of poorly differentiated tumors (P = .006). In pT1 colon cancer, LNM was associated with a higher proportion of moderately/poorly differentiated tumors (P = .002) and lymphatic invasion (P = .004). In the multivariate analysis for rectal cancer, depth of SM invasion (≥3000 µm) was an independent predictive factor for LNM (95% confidence interval [CI], 1.48-27.94; P = .013), whereas for colon cancer, moderately/poorly differentiated tumors (95% CI, 1.38-8.13; P = .008) and lymphatic invasion (95% CI, 1.44-11.78; P = .008) were independent predictive factors for LNM. DISCUSSION: There were distinct differences in the factors predicting LNM between pT1 rectal cancer and colon cancer. These results suggest the necessity in differentiating between rectal and colon cancer when performing studies on LNM in pT1 colorectal cancer.

Risk factors of incisional hernia after laparoscopic colorectal surgery with periumbilical minilaparotomy incision: a propensity score matching analysis.

Purpose: Incisional hernia is one of the most common complications after abdominal surgery conducted through a midline incision. Considerable debate remains regarding the design, comorbidity, suture material, and method. We investigated the risk factors for incisional hernia after laparoscopic colorectal surgery in the presence of limited surgery-related factors. Methods: A retrospective study was designed with 541 patients who underwent laparoscopic colorectal surgery performed by a single operator from January 2015 to December 2017. Due to open conversions, other abdominal operations, or follow-up loss, only 445 patients were included in the study. After propensity score matching, 266 patients were included. The study was based on diagnosis of incisional hernia on computed tomography at 6 and 12 months postoperatively. Results: Of the 266 total patients, 133 underwent abdominal closure using PDS (Ethicon), while the remaining 133 underwent closure with Vicryl (Ethicon). Of these patients, nine were diagnosed with incisional hernia at the 12-month follow-up six (4.5%) in the Vicryl group and three (2.3%) in the PDS group (p = 0.309). The incidence of incisional hernia was significantly increased in females (odds ratio [OR], 15.233; 95% confidence interval [CI], 1.905-121.799; p = 0.010), in patients with body mass index (BMI) of >25 kg/m2 (OR, 4.740; 95% CI, 1.424-15.546; p = 0.011), and in patients with liver disease (OR, 19.899; 95% CI, 1.614-245.376; p = 0.020). Conclusion: BMI of >25 kg/m2, female, and liver disease were significant risk factors for incisional hernia after elective laparoscopic colorectal surgery performed through a transumbilical minilaparotomy incision.

Compression automation of circular stapler for preventing compression injury on gastrointestinal anastomosis.

BACKGROUND: Conventional manual compression relies on the surgeon's subjective sensations, so excessive compression can cause tissue injury to the stapling line of the intestinal anastomosis. METHODS: Automatic compression monitoring and compression control system was developed for circular stapler. The tissue injury related compression variables were evaluated and accommodated by compression control device. The compression injury-reducing performance was verified on collagen sheets of in vitro experiments. RESULTS: Excessive pressure and tissue deformation were associated with compression-induced tissue damages. The safe pressure range was very narrow in weaker tissue than normal collagen. The automatic system performed proper compression within a safe pressure range without tissue injury. CONCLUSIONS: Manual compression of circular stapler could cause tissue injuries by excessive pressure and tissue deformation. Our automatic compression system is designed to control peak pressure to prevent the compressive tissue injury.

FSP-1 expression in cancer cells is relevant to long-term oncological outcomes in nonmetastatic colorectal cancer.

Purpose: Recent studies have revealed that the expression of cancer-associated fibroblast (CAF) activation biomarkers in cancer cells is associated with clinical outcomes in patients with certain types of malignant tumors. However, whether the expression of CAF activation biomarkers affects the prognosis of colorectal cancer (CRC) has not been fully elucidated. This study aimed to evaluate the association between the expression of CAF activation biomarkers in cancer cells with cancer invasion and long-term oncological outcomes in patients with CRC. Methods: Cancer specimens obtained from 135 patients with stage I-III CRC were examined using immunohistochemical staining to evaluate the expression of fibroblast specific protein-1 (FSP-1), fibroblast activation protein α (FAPα), α-smooth muscle actin (α-SMA), and vimentin in cancer cells. Results: FSP-1 expression in cancer cells was significantly associated with lymphatic invasion, perineural invasion, tumor (T) status, and lymph node (N) status. FAPα expression in cancer cells was significantly associated with lymphatic invasion. On univariate and multivariate analyses, FSP-1 and α-SMA expression in cancer cells were associated with a short 10-year overall survival (OS) and high 10-year systemic recurrence (SR), respectively. Tumor budding was associated with a short 10-year OS. However, FAPα and vimentin did not contribute to the prognosis in this study. Conclusion: In this study, we found that FSP-1 expression in cancer cells was related to cancer invasion. Additionally, FSP-1 and α-SMA expression in cancer cells was associated with 10-year OS and SR, respectively. Therefore, these markers may be used as predictors of long-term oncological outcomes in patients with CRC.

Optimal ICG dosage of preoperative colonoscopic tattooing for fluorescence-guided laparoscopic colorectal surgery.

BACKGROUND: Indocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery. PURPOSE: This study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery. METHODS: Colorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient's age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM. RESULTS: In the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5-1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859). CONCLUSIONS: Preoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.

Laparoscopic versus open surgery for left flexure colon cancer: A propensity score matched analysis from an international cohort.

AIM: Surgical treatment of splenic flexure cancer (SFC) still presents some debated issues, including the role of laparoscopic surgery. The literature is based on small single-centre series, while randomized controlled studies comparing open and laparoscopic treatment for colon cancer exclude SFC. This study aimed to determine the role of laparoscopic surgery in the treatment of SFC, comparing short- and long-term outcomes with open surgery. METHOD: This was an international multicentre retrospective cohort study that analysed patients from 10 tertiary referral centres. From a cohort of 641 cases, 484 patients with Stage I-III SFC submitted to elective surgery with curative intent were selected. After 1:1 propensity score matching, 130 patients in the laparoscopic group (LapGroup) were compared with 130 patients in the open surgery group (OpenGroup). RESULTS: After propensity score matching, the two groups were comparable for demographic and clinical parameters. OpenGroup presented a higher incidence of overall (P = 0.02) and surgery-related complications (P = 0.05) but a similar rate of severe complications (P = 0.75). Length of stay was notably shorter in the LapGroup (P = 0.001). Overall (P = 0.793) as well as cancer-specific survival (P = 0.63) did not differ between the two groups. CONCLUSIONS: Elective laparoscopic surgery for Stage I-III SFC is feasible and associated with improved short-term postoperative outcomes compared to open surgery. Moreover, laparoscopic surgery appears to provide excellent long-term cancer outcomes.