OBJECTIVETo investigate the causes and affecting factors of unplanned reoperations in cancer patients.

METHODSAll patients, who underwent surgery and unplanned surgical reoperations in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between November 1, 2012 and October 1, 2013, were included in this study. The causes and affecting factors of unplanned reoperations were retrospectively analyzed with logistic regression model.

RESULTSA total of 16, 362 operations were performed in that period, in which 126 cases underwent unplanned reoperation. The incidence rate of unplanned reoperation was 0.77%. The top three causes for unplanned reoperation were bleeding or hematoma in 44 cases (34.92%), wound infection or split in 37 cases (29.37%), and anastomotic leak in 14 cases (11.11%). Logistic regression analysis showed that tumor classification, surgery grade and gender were independent factors for the unplanned reoperations.

CONCLUSIONSThe main causes of unplanned reoperation are bleeding or hematoma, wound infection or split and anastomotic leak. Tumor classification, surgery grade and gender are the independent factors for unplanned reoperations.

Anastomotic Leak ; Hemorrhage ; Humans ; Logistic Models ; Neoplasms ; Postoperative Complications ; epidemiology ; Reoperation ; statistics & numerical data ; Retrospective Studies

OBJECTIVETo investigate the risk factors of intra-abdominal infection(IAI) after colorectal cancer surgery.

METHODSClinical and follow-up data of 773 colorectal cancer patients undergoing operation in our hospital from October 2011 to December 2014 were retrospectively analyzed. Patients were divided into intra-abdominal cavity infection group (110 cases, IAI group) and non intra-abdominal infection group(663 cases, non-IAI group). All the patients administered prophylactic antibiotics 30 minutes to 2 hours before operation. Univariate and multivariate analysis were performed to evaluate the risk factors of IAI.

RESULTSPreoperative factors associated with postoperative IAI included hepatic cirrhosis, kidney diseases, diabetes or other basic diseases, prophylactic use of drugs, hypoalbuminemia, anemia, intestinal obstruction, and American Society of Anesthesiologists (ASA) anesthetic grading score (all P<0.05). Postoperative factors associated with postoperative IAI included use of laparoscopy or stapler, united exenteration, existence of anastomotic fistula, time of drainage tube placement, operation time and tumor staging (all P<0.05). Multivariate logistic regression analysis showed that preoperative diabetes(OR=2.36, 95% CI:1.45 to 4.76, P<0.01), combined exenteration (OR=2.02, 95% CI:1.02 to 4.00, P<0.01), anastomotic leak (OR=4.41, 95% CI:1.77 to 10.99, P=0.001), operation time≥140 minutes (OR=2.88, 95% CI:1.78 to 4.67, P<0.01) and period of postoperative drainage≥10 days(OR=4.57, 95% CI:2.78 to 7.52, P<0.01) were independent risk factors of postoperative IAI, while the use of stapler was protective factor (OR=0.37, 95% CI: 0.23 to 0.60, P<0.01). Compared with prophylactic use of cephamycins plus metronidazole, cefuroxime plus metronidazole had a higher rate of IAI(OR=2.10, 95% CI:1.23 to 3.58, P=0.007).

CONCLUSIONSPrevention of postoperative IAI is required for colorectal cancer patients, particularly in those with preoperative diabetes, combined exenteration, anastomotic leak, operation time longer than 140 minutes and postoperative drainage period longer than 10 days. Preoperative use of cephamycins plus metronidazole has better efficacy in prevention of postoperative IAI.

Anastomotic Leak ; Colorectal Neoplasms ; surgery ; Digestive System Surgical Procedures ; adverse effects ; Drainage ; Humans ; Intestinal Obstruction ; Intraabdominal Infections ; epidemiology ; Laparoscopy ; Neoplasm Staging ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Risk Factors

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.
Anastomotic Leak/etiology* ; Humans ; Laparoscopy/methods* ; Postoperative Complications/epidemiology* ; Prognosis ; Prospective Studies ; Rectal Neoplasms/pathology* ; Rectum/surgery* ; Retrospective Studies ; Transanal Endoscopic Surgery/methods* ; Treatment Outcome

Objective: To explore the advantages and safety of a modified mattress inversion suturing using double barbed sutures compared with the traditional overlap method in totally laparoscopic esophagojejunostomy overlap anastomosis. Methods: A retrospective cohort study was conducted. The inclusion criteria were as follows: (1) patients were aged 18 - 80 years old; (2) adenocarcinoma was preoperatively confirmed by pathological analysis; (3) patients had undergone a complete laparoscopic radical total gastrectomy; (4) patients had undergone esophagojejunostomy using the overlap method; (5) patients received a grade of I-III on the American Society of Anesthesiologists physical status classification system; (6) patients' complete follow-up data had been collected. Patients with a history of other malignant tumors, multi-origin tumors, emergency surgery, non-R0 radical resection or distant metastasis were excluded. The clinical data of 89 gastric cancer patients who underwent total laparoscopic radical total gastrectomy in the Department of Gastrointestinal Surgery in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were collected. These patients were grouped according to the esophagojejunostomy method used. Of 89 patients, 32 received modified mattress inversion suturing with double barbed sutures to close the common opening of esophagojejunostomy (the modified anastomosis group), while 57 received traditional overlap anastomosis in which the common opening was closed by barbed suture (the traditional anastomosis group). The operation conditions (incision length, conversion to laparotomy, duration of esophagojejunostomy) and postoperative recovery (time to commencement of a liquid diet, duration of postoperative hospital stay, anastomotic leakage, anastomotic stenosis, and anastomotic bleeding) were compared between the two groups. Results: There was no significant difference in the baseline data of the two groups for any parameter (all P>0.05). All patients received complete laparoscopic radical gastrectomy without conversion to laparotomy. There were no significant differences in the length of the median incision, the proportion of food intake on the first day after surgery, or in the incidence of anastomotic complications such as anastomotic leakage, anastomotic stenosis, and anastomotic bleeding between the two groups (P>0.05). Compared with the traditional anastomosis group, patients in the modified anastomosis group had shorter anastomosis time [26 (19-62) minutes vs. 36 (20-50) minutes, Z=-2.546, P=0.011] and postoperative hospital stay [7 (6-12) days vs. 9 (7-42) days, Z=-4.202, P<0.001]. The differences were statistically significant (all P<0.05). In a subgroup analysis of tumor TNM stage III, Siewert type II and neoadjuvant chemotherapy patients, there was no significant difference in the incidence of anastomotic complications between the modified group and the traditional group. However, the postoperative hospital stay duration in the modified anastomosis group was less than in the traditional anastomosis group. The duration of anastomosis in Siewert type II patients was also shorter in the modified anastomosis group than in the traditional anastomosis group [26 (19-62) minutes vs. 38 (21-50) minutes, Z=-2.105, P=0.035], and the difference was statistically significant (all P<0.05). Conclusion: Complete laparoscopic esophagojejunostomy using modified mattress inversion suturing with double barbed sutures is a safe and feasible anastomosis method to close the common opening of esophagojejunostomy, with shorter operation time, faster postoperative recovery and shorter hospital stay than the traditional method.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anastomosis, Surgical/methods* ; Anastomotic Leak/epidemiology* ; Constriction, Pathologic ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Middle Aged ; Retrospective Studies ; Sutures ; Young Adult

Objective: To compare and analyze the perioperative clinical effects of minimally invasive Ivor-Lewis esophagectomy (MIE-Ivor-Lewis) and minimally invasive McKeown esophagectomy (MIE-McKeown). Methods: A total of 147 patients who underwent endoscopic esophageal cancer surgery from April 2018 to August 2019 were selected, including 85 patients undergoing MIE-McKeown surgery and 62 patients undergoing MIE-Ivor-Lewis surgery. The measurement data were expressed as (x±s), the comparison of normally distributed measurement data was performed by independent sample t-test, and the comparison of count data was performed by χ(2) test or Fisher's exact test. Results: The operation time of McKeown (M) group and Ivor-Lewis (IL) group were (219.2±72.4) minutes and (225.8±65.3) minutes. The mediastinal lymph node dissection number of M and IL groups were 13.3±4.8 and 11.6±6.5, respectively. The number of left recurrent laryngeal nerve lymph node dissection were 3.5±1.2 and 3.1±1.4, respectively. The intraoperative blood loss were (178.3±41.3) ml and (163.2±64.1) ml, respectively. The number of patients reoperated for postoperative bleeding were 1 and 0, respectively. The number of patients with postoperative gastric bleeding were 0 and 1, respectively. The postoperative chest tube retention time were (2.8±1.3) days and (3.1±1.2) days, respectively. The number of patients with anastomotic leakage were 7 and 1, respectively. The number of patients with lung infection were 13 and 5, respectively, and with chylothorax were 2 and 1, respectively, without statistically significant difference (P>0.05). The number of patients with hoarseness were 11 and 3, respectively. The total incidence of complication were 41.2% (35/85) and 17.7% (11/62), and the postoperative hospital stay were (14.7±6.5) days and (12.3±2.3) days, with statistical difference (P<0.05). Conclusion: MIE-Ivor-Lewis and MIE-McKeown are safe and effective in treating esophageal cancer, but the complication of MIE-Ivor-Lewis is less than that of MIE-Mckeown, and the perioperative clinical effect of MIE-Ivor-Lewis is better than that of MIE-McKeown.
Anastomotic Leak/etiology* ; Esophageal Neoplasms/surgery* ; Esophagectomy/adverse effects* ; Humans ; Minimally Invasive Surgical Procedures/adverse effects* ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

OBJECTIVETo explore the related factors of anastomotic leakfollowing anterior resection for the rectal cancer and the association of the preoperative nutritional risk screening 2002(NRS2002) score.

METHODSClinical data of 396 rectal cancer patients who underwent elective anterior resection from January 2010 to July 2015 at Affiliated Lu'an Hospital of Anhui Medical University were collected. Patient's nutritional risk score on admission was calculated by NRS2002 scoring system according to original medical records. NRS2002 score less than 3 was defined as nutritious risk. Chi-squared test, or Fisher exact test and multivariate logistic regression wereused to analyze the association of the clinical pathological factors and NRS2002 risk factor with anastomotic leak.

RESULTSOf the 396 patients, NRS2002 score≥3, and anastomotic leak occurred in 157(39.6%) and 13(3.3%), respectively. In univariate analysis, different ages, NRS2002 score, preoperative intestinal obstruction, distance from anastomosis to anal vergeand tumor TNM stage were significantly associated with postoperative anastomotic leak(all P<0.05). The incidence of postoperative anastomotic leak among patients with NRS2002 score≥3 was significantly higher than those with NRS2002 score<3[6.4%(10/157) vs. 1.3%(3/239), χ(2)=7.806, P=0.005]. Multivariate analysis showed that NRS2002 score≥3(OR=3.988, 95% CI:1.004-15.837, P=0.049), existence of preoperative intestinal obstruction(OR=5.780, 95% CI:1.320 ~ 25.311, P=0.020),distance from anastomosis to anal verge≤5 cm(OR=0.236, 95% CI: 0.071 ~ 0.785, P=0.019) were the independent risk factors of anastomotic leak following anterior resection for the rectal cancer.

CONCLUSIONRectal cancer patients undergoing anterior resection with preoperative NRS2002 score≥3 should receive reasonable perioperative nutritional support to prevent anastomotic leak.

Anastomotic Leak ; epidemiology ; prevention & control ; Chi-Square Distribution ; Humans ; Logistic Models ; Multivariate Analysis ; Nutritional Support ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Risk Factors

Laparoscopic mini-gastric bypass surgery is a safe and simple surgical intervention for treating morbid obesity and diabetes mellitus and is now being performed more frequently. Radiologists must be critical in their postoperative evaluation of these patients. In this pictorial review, we explain and illustrate the surgical technique, normal postoperative anatomy, and associated complications as seen on imaging examinations, including fluoroscopy and computed tomography.
Adult ; Anastomotic Leak/epidemiology ; Cholelithiasis/epidemiology ; Constriction, Pathologic/epidemiology ; Diabetes Mellitus/*therapy ; Female ; Fluoroscopy ; Gastric Bypass/*methods ; Hemorrhage/epidemiology ; Humans ; Laparoscopy ; Male ; Middle Aged ; Obesity, Morbid/*surgery ; Stomach/radiography/surgery ; Tomography, X-Ray Computed

Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.
Adult ; Aged ; Anastomotic Leak/etiology* ; Case-Control Studies ; China/epidemiology* ; Female ; Humans ; Incidence ; Laparoscopy ; Male ; Middle Aged ; Postoperative Complications/epidemiology* ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Retrospective Studies ; Risk Factors

OBJECTIVETo explore the clinical efficacy and safety of gastroepiploic tunnel esophagogastrostomy applied in minimally invasive esophagectomy and gastroesophageal cervical anastomosis.

METHODSClinical data of 137 esophageal cancer patients who received minimally invasive esophagectomy from December 2013 to June 2015 in Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University were analyzed retrospectively, including 84 patients receiving anastomosis with tubular anastomat (circular staple group), and 53 patients receiving gastroepiploic tunnel anastomosis(tunnel group, position of tunnel anastomosis located in the side of gastrocolic omentum, about 2-3 cm apart from fundus). Incidence of postoperative anastomotic leakage and stricture was compared between two groups.

RESULTSAll the 137 patients completed minimally invasive esophageal surgeries successfully without conversion to open thoracic or abdominal operation. The time for anastomosis was(20.2±3.1) minutes in circular stapler group and (38.9±2.9) minutes in tunnel group respectively, and the difference was statistically significant (t=75.22, P=0.000 0). The incidence of postoperative anastomotic leakage was 21.4%(18/84) in circular stapler group and 0(0/53) in tunnel group respectively, and the difference was statistically significant (P=0.000 3). All the patients were followed up for more than 6 months. During follow-up period, the incidence of postoperative anastomotic stricture was 14.3%(12/84) in circular stapler group and 3.8%(2/53) in tunnel group respectively, and the difference was statistically significant(P=0.047 9).

CONCLUSIONThe gastroepiploic cervical tunnel anastomosis is safe and effective and can reduce the incidence of postoperative anastomotic leakage as well as anastomotic stricture.

Anastomosis, Surgical ; adverse effects ; methods ; Anastomotic Leak ; epidemiology ; prevention & control ; Comparative Effectiveness Research ; Constriction, Pathologic ; epidemiology ; prevention & control ; Esophageal Neoplasms ; complications ; surgery ; Esophagectomy ; adverse effects ; methods ; Esophagoplasty ; adverse effects ; methods ; Humans ; Minimally Invasive Surgical Procedures ; adverse effects ; methods ; Neck ; surgery ; Omentum ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Surgical Stapling ; adverse effects ; methods