AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three tr...AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.展开更多
AIM To understand the influence of frailty on postoperative outcomes for laparoscopic and open colectomy. METHODS Data were obtained from the National Surgical Quality Improvement Program(2005-2012) for patients under...AIM To understand the influence of frailty on postoperative outcomes for laparoscopic and open colectomy. METHODS Data were obtained from the National Surgical Quality Improvement Program(2005-2012) for patients undergoing colon resection [open colectomy(OC) and laparoscopic colectomy(LC)]. Patients were classified as non-frail(0 points), low frailty(1 point), moderate frailty(2 points), and severe frailty(≥ 3) using the Modified Frailty Index. 30-d mortality and complications were used as the primary end point and analyzed for the overall population. Complications were grouped into major and minor. Subset analysis was performed for patients undergoing colectomy(total colectomy, partial colectomy and sigmoid colectomy) and separately for patients undergoing rectal surgery(abdominoperineal resection, low anterior resection, and proctocolectomy). We analyzed the data using SAS Platform JMP Pro version 10.0.0(SAS Institute Inc., Cary, NC, United States). RESULTS A total of 94811 patients were identified; the majority underwent OC(58.7%), were white(76.9%), andnon-frail(44.8%). The median age was 61.3 years. Prolonged length of stay(LOS) occurred in 4.7%, and 30-d mortality was 2.28%. Patients undergoing OC were older(61.89 ± 15.31 vs 60.55 ± 14.93) and had a higher ASA score(48.3% ASA3 vs 57.7% ASA2 in the LC group)(P < 0.0001). Most patients were non-frail(42.5% OC vs 48% LC, P < 0.0001). Complications, prolonged LOS, and mortality were significantly more common in patients undergoing OC(P < 0.0001). OC had a higher risk of death and complications compared to LC for all frailty scores(non-frail: OR = 4.7, and OR = 4.67; mildly frail: OR = 2.51, and OR = 2.47; moderately frail: OR = 2.94, and OR = 2.02, severely frail: OR = 2.37, and OR = 2.34, P < 0.05) and an increase in absolute mortality with increasing frailty(non-frail 0.68% OC, mildly frail 1.39%, moderately frail 3.44%, and severely frail 5.83%, P < 0.0001). CONCLUSION LC is associated with improved outcomes. Although the odds of mortality are higher in non-frail, there is a progressive increase in mortality with increasing frailty.展开更多
BACKGROUND The management of gallbladder perforation(GBP)with fistulous communication(Neimeier type I)is controversial.AIM To recommend management options for GBP with fistulous communication.METHODS A systematic revi...BACKGROUND The management of gallbladder perforation(GBP)with fistulous communication(Neimeier type I)is controversial.AIM To recommend management options for GBP with fistulous communication.METHODS A systematic review of studies describing the management of Neimeier type I GBP was performed according to the PRISMA guidelines.The search strategy was conducted in Scopus,Web of Science,MEDLINE,and EMBASE(May 2022).Data extraction was obtained for patient characteristics,type of intervention,days of hospitalization(DoH),complications,and site of fistulous communication.RESULTS A total of 54 patients(61%female)from case reports,series,and cohorts were included.The most frequent fistulous communication occurred in the abdominal wall.Patients from case reports/series had a similar proportion of complications between open cholecystectomy(OC)and laparoscopic cholecystectomy(LC)(28.6 vs 12.5;P=0.569).Mortality was higher in OC(14.3 vs 0.0;P=0.467)but this proportion was given by only one patient.DoH were higher in OC(mean 26.3 d vs 6.6 d).There was no clear association between higher rates of complications of a given intervention in cohorts,and no mortality was observed.CONCLUSION Surgeons must evaluate the advantages and disadvantages of the therapeutic options.OC and LC are adequate options for the surgical management of GBP,with no significant differences.展开更多
AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90...AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.展开更多
AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecyst...AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecystectomy from January 2013 through December2014 were reviewed retrospectively for demographics,indication for surgery,operative course and outcome.In our institution the decision to perform postoperative blood analysis is left for the discretion of the surgeon,therefore we had the possibility to compare the results of those who had blood analyses results to those who did not.Analysis was performed to identify variables associated with the decision to perform postoperative blood tests.Subsequently a univariate and multivariate analyses was performed comparing the two cohorts.Secondary subgroup analysis was performed to identify factors associated with procedure related complications.RESULTS Five hundred and thirty-two elective laparoscopic cholecystectomies for symptomatic gallstones were performed during the study period.Sixty-four percent of the patients(n=340)had blood tests taken post operatively.Patients that had laboratory tests taken were older(P=0.006,OR=1.01),had longer surgery(P<0.001,OR=3.22)had more drains placed(P<0.001,OR=3.2)and stayed longer in the hospital(P<0.001,OR=1.2).A subgroup analysis of the patients who experienced complications revealed longer stay in the hospital(P<0.001),higher body mass index(BMI)(P=0.04,OR=1.08),increased rates of drain placement(P=0.006,OR=3.1)and higher conversion rates(P=0.01,OR=14.6).Postoperative blood tests withdrawals were not associated with complications(P=0.44).On Multivariate analysis BMI and drain placement were independently associated with complications.CONCLUSION The current study indicate that routine postoperative blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones does not predict complications and may have an added benefit in diagnosis and management of cases were the surgeon encountered true technical difficulty during surgery.展开更多
Acute appendicitis is the most common surgical emergency that we encounter. Adynamic Intestinal obstruction due to appendicitis or its complication may be seen time and often. Mechanical obstruction because of appendi...Acute appendicitis is the most common surgical emergency that we encounter. Adynamic Intestinal obstruction due to appendicitis or its complication may be seen time and often. Mechanical obstruction because of appendicitis is uncommon and even rarer for a closed loop obstruction to occur. Although it was described as early as 1901, very few cases have been reported. We report the case of a 20 years male who presented with generalized colicky pain abdomen, abdominal distension, vomiting and obstipation for three to four days. Vital signs were stable. His abdomen was distended and peritonitic, especially in the right iliac fossa. Rest of the physical examination was unremarkable. Blood tests were normal except for leucocytosis with neutrophilia. An abdominal X-ray finding was indicating a small bowel obstruction. A midline laparotomy was performed. On intraoperative examination, distended loops of small bowel from the jejunum to the distal ileum was observed, and a constricting ring around the terminal ileum created by a phlegmonous appendicitis with its tip adherent to the root of mesentery was found, obstructing an edematous loop of small bowel without signs of ischemia. As the bowel was viable simple appendectomy was done. Postoperatively, he had an uneventful recovery and was discharged after 3 d.展开更多
A standard hepaticojejunostomy technique might be difficult to perform, especially when the bile duct is small and located deep in the liver hilum. Herein we present a new procedure, the Hand-Fan technique, that was u...A standard hepaticojejunostomy technique might be difficult to perform, especially when the bile duct is small and located deep in the liver hilum. Herein we present a new procedure, the Hand-Fan technique, that was used to enhance the exposure and ease the performance of these challenging anastomoses. Thirty-one patients who had had hepaticojejunostomy with this technique for bile duct injury and other benign biliary pathologies from July 2004 to June 2011 were included into the study. Median postoperative hospital stay was 7 days (6-25 days) and median follow-up time was 33 months (2-84 months). Liver function tests revealed that the blood bilirubin levels of the patients were normalized after hepaticojejunostomy. Follow-up showed that there were no signs of clinical recurrence or impaired bile flow. The Hand-Fan technique considerably facilitates challenging hepaticojejunostomies. Surgeon’s comfort is exceptional and the clinical results are satisfactory.展开更多
BACKGROUND The hepatic artery(HA)is one of the most threatened vascular structures during hepatopancreatobiliary(HPB)surgeries and interventional procedures.It can be affected by many clinical pictures,especially tumo...BACKGROUND The hepatic artery(HA)is one of the most threatened vascular structures during hepatopancreatobiliary(HPB)surgeries and interventional procedures.It can be affected by many clinical pictures,especially tumors,due to its anatomical position and neighborhood.AIM To reveal the evolution and recent developments in the management of HA traumas in the light of the literature.METHODS In this article,100 years of MEDLINE(PubMed)literature and articles including cases and series of HA injuries were reviewed,and the types of injury occurrence,treatment,and related complications and their management were compiled.RESULTS The risk of HA injury increases during cholecystectomies and pancreatoduodenectomies,among the most common operations.HA anatomy shows anomalies in approximately 15%-25%of the cases,further increasing this risk.The incidence of HA injury is not precisely known.Approaches that have evolved in recent years in managing patients with HA injury(laceration,transection,ligation,resection)with severe morbidity and mortality risk are reviewed in light of the current literature.CONCLUSION In conclusion,complications and deaths due to HA injury are less common today.The risk of complications increases in patients with hemodynamic instability,jaundice,cholangitis,and sepsis.Revealing the variations in the preoperative radiological evaluation will reduce the risks.In cases where HA injury is detected,arterial flow continuity should be tried to maintain with primary anastomosis,arterial transpositions,or grafts.In cases where bile duct injury develops,patients should be directed to HPB surgery centers,considering the possibility of accompanying HA injury.Large-scale and multicentric studies are needed to understand better the early and long-term results of HA ligation and determine preventive procedures.展开更多
BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,inciden...BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,incidence 2%-2.6%)and early hepatic artery thrombosis(HAT,incidence 3%-5%)have a poor prognosis in transplant patients,having impacts on graft and patient survival.In the present study,we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.AIM To investigate whether intraoperative thromboelastography(TEG)is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation(LT).METHODS We retrospectively collected thromboelastographic traces,in addition to known risk factors(cold ischemic time,intraoperative requirement for red blood cells and fresh-frozen plasma transfusion,prolonged operating time),in 27 patients,selected among 530 patients(≥18 years old),who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT(case group).Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion.We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications(1:1 match)(control group).The chosen matching parameters were:Patient graft and donor characteristics[age,sex,body mass index(BMI)],indication for transplantation,procedure details,United Network for Organ Sharing classification,BMI,warm ischemia time(WIT),cold ischemia time(CIT),the volume of blood products transfused,and conventional laboratory coagulation analysis.Normally distributed continuous data are reported as the mean±SD and compared using one-way Analysis of Variance(ANOVA).Nonnormally distributed continuous data are reported as the median(interquartile range)and compared using the Mann-Whitney test.Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher’s exact test depending on best applicability.IBM SPSS Statistics version 24(SPSS Inc.,Chicago,IL,United States)was employed for statistical analysis.Statistical significance was set at P<0.05.RESULTS Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively.The incidence of early hepatic artery occlusion was 3.02%,whereas the incidence of PVT was 2.07%.A comparison between the case and control groups showed some differences in the duration of surgery,which was longer in the case group(P=0.032),whereas transfusion of blood products,red blood cells,fresh frozen plasma,and platelets,was similar between the two study groups.Thromboelastographic parameters did not show any statistically significant difference between the two groups,except for the G value measured at basal and 120’postreperfusion time.It was higher,although within the reference range,in the case group than in the control group(P=0.001 and P<0.001,respectively).In addition,clot lysis at 60 min(LY60)measured at 120’postreperfusion time was lower in the case group than in the control group(P=0.035).This parameter is representative of a fibrinolysis shutdown(LY60=0%-0.80%)in 85%of patients who experienced a thrombotic complication,resulting in a statistical correlation with HAT and PVT.CONCLUSION The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT,suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.展开更多
We are reporting the first documented case of an abdominal desmoid tumor presenting primarily after liver transplantation. This tumor, well described in the literature as occurring both in conjunction with familial ad...We are reporting the first documented case of an abdominal desmoid tumor presenting primarily after liver transplantation. This tumor, well described in the literature as occurring both in conjunction with familial adenomatous polyposis as well as in the postsurgical patient, has never been noted after solid organ transplantation and was therefore not included in our differential upon presentation. Definitive diagnosis required the patient to undergo surgical excision and immunochemical staining of the mass for confirmation. A review of the literature showed no primary tumors after transplantation. In a population of patients who received a small bowel transplant after they developedshort gut post radical resection of aggressive fibromatosis, only rare recurrences were seen. No connection of tumor development with immunosuppression or need to decrease immunosuppressant treatment has been demonstrated in these patients. Our case and the literature show the risk of this tumor presenting in the post-transplantation patient and the need for a high index of suspicion in patients who present with a complex mass after transplantation to prevent progression of the disease beyond a resectable lesion. Results of a thorough search of the literature are detailed and the medical and surgical management of both resectable and unresectable lesions is reviewed.展开更多
BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective....BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective.Poorly differentiated neuroendocrine carcinomas(NECs)represent only 5%-10%of digestive NETS.Due to aggressive growth and rapid metastatic diffusion,early diagnosis and a multidisciplinary approach are mandatory.The role of surgery and radiotherapy in this setting is still debated,and chemotherapy remains the treatment of choice.CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3(Ki67 index>90%)on May 2015 and initially treated with 3 cycles of first-line chemotherapy,but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection.In September 2015,the first post-surgery total-body computed tomography(CT)scan showed an early pelvic disease relapse.Therefore,systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response.This was followed by pelvic radiotherapy(50 Gy).On April 2016,a CT scan and 18F-fluorodeoxy-glucose positron emission tomography imaging showed a complete response(CR)of the pelvic lesion,but pathological abdominal inter-aortocaval lymph nodes were observed.Due to disease progression of abdominal malignant nodes,the patient received radiotherapy at 45 Gy,and finally obtained a CR.As of January 2021,the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.展开更多
To the Editor:We sincerely applaud the work done by Gupta et al.,in which they analyzed a single-center experience regarding gallbladder per-foration(GBP)management[1].Currently,there is a lack of cohort studies to ad...To the Editor:We sincerely applaud the work done by Gupta et al.,in which they analyzed a single-center experience regarding gallbladder per-foration(GBP)management[1].Currently,there is a lack of cohort studies to adequately describe the approach strategies and man-agement for this pathology,with international guidelines making ambiguous recommendations[2,3].Their study stratified GBP types and provided details regarding clinical presentation,comorbidities,preoperative diagnosis,etiology,imaging techniques,and surgical approach.The study reported a high conversion rate when a la-paroscopic approach was attempted for cholecystectomy.展开更多
AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ...AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.展开更多
Urethrocutaneous fistula may complicate hypospadias repair.We noticed that double-layered preputial dartos flaps added to tubularized incised plate urethroplasty can reduce the risk of urethrocutaneous fistula.The aim...Urethrocutaneous fistula may complicate hypospadias repair.We noticed that double-layered preputial dartos flaps added to tubularized incised plate urethroplasty can reduce the risk of urethrocutaneous fistula.The aim of this study was to compare the outcomes of tubularized incised plate urethroplasty with double-layered preputial dartos flaps to with single-layered local fascial flaps in preventing urethrocutaneous fistula.A retrospective cohort study was conducted between January 2017 and December 2020 at Jordan University Hospital(Amman,Jordan).Boys who were aged between 6 months and 5 years,diagnosed with distal hypospadias,and not circumcised were included.The primary outcome was the occurrence of urethrocutaneous fistula in patients who underwent tubularized incised plate urethroplasty with a double-layered fascial flap.The results showed a total of 163 boys with distal hypospadias;among them,116 patients underwent tubularized incised plate urethroplasty with a single-layered fascial flap,and 47 underwent tubularized incised plate urethroplasty with a double-layered fascial flap.The development of urethrocutaneous fistula was higher in the group receiving tubularized incised plate urethroplasty with a single-layered fascial flap than in the group receiving tubularized incised plate urethroplasty with a double-layered fascial flap after 1 month,6 months,and 12 months(6.9%vs 0,10.3%vs 0,and 5.2%vs 0,respectively),and the difference after 6 months was statistically significant(P=0.02).展开更多
Pancreatic cancer,notorious for its late diagnosis and aggressive progression,poses a substantial challenge owing to scarce treatment alternatives.This review endeavors to furnish a holistic insight into pancreatic ca...Pancreatic cancer,notorious for its late diagnosis and aggressive progression,poses a substantial challenge owing to scarce treatment alternatives.This review endeavors to furnish a holistic insight into pancreatic cancer,encompassing its epidemiology,genomic characterization,risk factors,diagnosis,therapeutic strategies,and treatment resistance mechanisms.We delve into identifying risk factors,including genetic predisposition and environmental exposures,and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer.Additionally,we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy.We also dissect the primary mechanisms underlying treatment resistance in this malignancy,illustrating the latest therapeutic options and advancements in the field.Conclusively,we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.展开更多
Background: Indocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making during surgical procedures, in particular to assess organs perfusion. Methods: We used the ICG fluorescen...Background: Indocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making during surgical procedures, in particular to assess organs perfusion. Methods: We used the ICG fluorescence during liver transplantations in six cirrhotic patients to help assessing the graft biliary duct perfusion in order to identify the appropriate level to perform the anastomosis. We also used ICG fluorescence also in five patients receiving kidney-pancreas transplantation to evaluate the perfusion levels of the duodenal stump of the pancreas graft. Results: Follow-up period for the patients was 12 months. The perioperative period was uneventful, no biliary complications such as leaks or stenosis were reported after liver transplantation, no complications of the entero-enteric anastomoses occurred after pancreatic transplantation. Conclusions: ICG fluorescence seems to safely provide important objectifiable perfusion information during organ transplantation procedures that can integrate surgeon's expertise. In fact, detecting intra-operatively perfusion defects, it allows real time modifications on technical strategies potentially useful to reduce the feared risk of anastomotic leakage and consequent severe complications.展开更多
Robotic approach is already a new technological system in surgery and its potential advantages such as ergonomics,reduced tremor,3D view and improved instruments movements have been well described(1,2).Concerning the ...Robotic approach is already a new technological system in surgery and its potential advantages such as ergonomics,reduced tremor,3D view and improved instruments movements have been well described(1,2).Concerning the current literature,the studies addressing the robotic benefits on left pancreatectomies are few.However,it has been showed that robotic distal pancreatectomy is both feasible and safe as well as the laparoscopic and the standard open approach.Although,there is a lack of high-level economic studies comparing these techniques(3-6).展开更多
基金Supported by CARIT Foundation(Fondazione Cassa di Risparmio di Terni e Narni),No.0024137
文摘AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy(RG), laparoscopic gastrectomy(LG), open gastrectomy(OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients(RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery(P = 0.42) and stage of the disease(P = 0.16). Intraoperative blood loss was significantly lower in the LG(95.93 ± 119.22) and RG(117.91 ± 68.11) groups compared to the OG(127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG(27.78 ± 11.45), LG(24.58 ± 13.56) and OG(25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay(P < 0.0001). A similar complications rate was found(P = 0.13). The leakage rate was not different(P = 0.78) between groups.CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.
文摘AIM To understand the influence of frailty on postoperative outcomes for laparoscopic and open colectomy. METHODS Data were obtained from the National Surgical Quality Improvement Program(2005-2012) for patients undergoing colon resection [open colectomy(OC) and laparoscopic colectomy(LC)]. Patients were classified as non-frail(0 points), low frailty(1 point), moderate frailty(2 points), and severe frailty(≥ 3) using the Modified Frailty Index. 30-d mortality and complications were used as the primary end point and analyzed for the overall population. Complications were grouped into major and minor. Subset analysis was performed for patients undergoing colectomy(total colectomy, partial colectomy and sigmoid colectomy) and separately for patients undergoing rectal surgery(abdominoperineal resection, low anterior resection, and proctocolectomy). We analyzed the data using SAS Platform JMP Pro version 10.0.0(SAS Institute Inc., Cary, NC, United States). RESULTS A total of 94811 patients were identified; the majority underwent OC(58.7%), were white(76.9%), andnon-frail(44.8%). The median age was 61.3 years. Prolonged length of stay(LOS) occurred in 4.7%, and 30-d mortality was 2.28%. Patients undergoing OC were older(61.89 ± 15.31 vs 60.55 ± 14.93) and had a higher ASA score(48.3% ASA3 vs 57.7% ASA2 in the LC group)(P < 0.0001). Most patients were non-frail(42.5% OC vs 48% LC, P < 0.0001). Complications, prolonged LOS, and mortality were significantly more common in patients undergoing OC(P < 0.0001). OC had a higher risk of death and complications compared to LC for all frailty scores(non-frail: OR = 4.7, and OR = 4.67; mildly frail: OR = 2.51, and OR = 2.47; moderately frail: OR = 2.94, and OR = 2.02, severely frail: OR = 2.37, and OR = 2.34, P < 0.05) and an increase in absolute mortality with increasing frailty(non-frail 0.68% OC, mildly frail 1.39%, moderately frail 3.44%, and severely frail 5.83%, P < 0.0001). CONCLUSION LC is associated with improved outcomes. Although the odds of mortality are higher in non-frail, there is a progressive increase in mortality with increasing frailty.
文摘BACKGROUND The management of gallbladder perforation(GBP)with fistulous communication(Neimeier type I)is controversial.AIM To recommend management options for GBP with fistulous communication.METHODS A systematic review of studies describing the management of Neimeier type I GBP was performed according to the PRISMA guidelines.The search strategy was conducted in Scopus,Web of Science,MEDLINE,and EMBASE(May 2022).Data extraction was obtained for patient characteristics,type of intervention,days of hospitalization(DoH),complications,and site of fistulous communication.RESULTS A total of 54 patients(61%female)from case reports,series,and cohorts were included.The most frequent fistulous communication occurred in the abdominal wall.Patients from case reports/series had a similar proportion of complications between open cholecystectomy(OC)and laparoscopic cholecystectomy(LC)(28.6 vs 12.5;P=0.569).Mortality was higher in OC(14.3 vs 0.0;P=0.467)but this proportion was given by only one patient.DoH were higher in OC(mean 26.3 d vs 6.6 d).There was no clear association between higher rates of complications of a given intervention in cohorts,and no mortality was observed.CONCLUSION Surgeons must evaluate the advantages and disadvantages of the therapeutic options.OC and LC are adequate options for the surgical management of GBP,with no significant differences.
文摘AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.
文摘AIM To evaluate the value of blood testing after elective laparoscopic cholecystectomy and its association with procedure related complications.METHODS Charts of all patients undergoing elective laparoscopic cholecystectomy from January 2013 through December2014 were reviewed retrospectively for demographics,indication for surgery,operative course and outcome.In our institution the decision to perform postoperative blood analysis is left for the discretion of the surgeon,therefore we had the possibility to compare the results of those who had blood analyses results to those who did not.Analysis was performed to identify variables associated with the decision to perform postoperative blood tests.Subsequently a univariate and multivariate analyses was performed comparing the two cohorts.Secondary subgroup analysis was performed to identify factors associated with procedure related complications.RESULTS Five hundred and thirty-two elective laparoscopic cholecystectomies for symptomatic gallstones were performed during the study period.Sixty-four percent of the patients(n=340)had blood tests taken post operatively.Patients that had laboratory tests taken were older(P=0.006,OR=1.01),had longer surgery(P<0.001,OR=3.22)had more drains placed(P<0.001,OR=3.2)and stayed longer in the hospital(P<0.001,OR=1.2).A subgroup analysis of the patients who experienced complications revealed longer stay in the hospital(P<0.001),higher body mass index(BMI)(P=0.04,OR=1.08),increased rates of drain placement(P=0.006,OR=3.1)and higher conversion rates(P=0.01,OR=14.6).Postoperative blood tests withdrawals were not associated with complications(P=0.44).On Multivariate analysis BMI and drain placement were independently associated with complications.CONCLUSION The current study indicate that routine postoperative blood tests after elective laparoscopic cholecystectomy for symptomatic gallstones does not predict complications and may have an added benefit in diagnosis and management of cases were the surgeon encountered true technical difficulty during surgery.
文摘Acute appendicitis is the most common surgical emergency that we encounter. Adynamic Intestinal obstruction due to appendicitis or its complication may be seen time and often. Mechanical obstruction because of appendicitis is uncommon and even rarer for a closed loop obstruction to occur. Although it was described as early as 1901, very few cases have been reported. We report the case of a 20 years male who presented with generalized colicky pain abdomen, abdominal distension, vomiting and obstipation for three to four days. Vital signs were stable. His abdomen was distended and peritonitic, especially in the right iliac fossa. Rest of the physical examination was unremarkable. Blood tests were normal except for leucocytosis with neutrophilia. An abdominal X-ray finding was indicating a small bowel obstruction. A midline laparotomy was performed. On intraoperative examination, distended loops of small bowel from the jejunum to the distal ileum was observed, and a constricting ring around the terminal ileum created by a phlegmonous appendicitis with its tip adherent to the root of mesentery was found, obstructing an edematous loop of small bowel without signs of ischemia. As the bowel was viable simple appendectomy was done. Postoperatively, he had an uneventful recovery and was discharged after 3 d.
文摘A standard hepaticojejunostomy technique might be difficult to perform, especially when the bile duct is small and located deep in the liver hilum. Herein we present a new procedure, the Hand-Fan technique, that was used to enhance the exposure and ease the performance of these challenging anastomoses. Thirty-one patients who had had hepaticojejunostomy with this technique for bile duct injury and other benign biliary pathologies from July 2004 to June 2011 were included into the study. Median postoperative hospital stay was 7 days (6-25 days) and median follow-up time was 33 months (2-84 months). Liver function tests revealed that the blood bilirubin levels of the patients were normalized after hepaticojejunostomy. Follow-up showed that there were no signs of clinical recurrence or impaired bile flow. The Hand-Fan technique considerably facilitates challenging hepaticojejunostomies. Surgeon’s comfort is exceptional and the clinical results are satisfactory.
文摘BACKGROUND The hepatic artery(HA)is one of the most threatened vascular structures during hepatopancreatobiliary(HPB)surgeries and interventional procedures.It can be affected by many clinical pictures,especially tumors,due to its anatomical position and neighborhood.AIM To reveal the evolution and recent developments in the management of HA traumas in the light of the literature.METHODS In this article,100 years of MEDLINE(PubMed)literature and articles including cases and series of HA injuries were reviewed,and the types of injury occurrence,treatment,and related complications and their management were compiled.RESULTS The risk of HA injury increases during cholecystectomies and pancreatoduodenectomies,among the most common operations.HA anatomy shows anomalies in approximately 15%-25%of the cases,further increasing this risk.The incidence of HA injury is not precisely known.Approaches that have evolved in recent years in managing patients with HA injury(laceration,transection,ligation,resection)with severe morbidity and mortality risk are reviewed in light of the current literature.CONCLUSION In conclusion,complications and deaths due to HA injury are less common today.The risk of complications increases in patients with hemodynamic instability,jaundice,cholangitis,and sepsis.Revealing the variations in the preoperative radiological evaluation will reduce the risks.In cases where HA injury is detected,arterial flow continuity should be tried to maintain with primary anastomosis,arterial transpositions,or grafts.In cases where bile duct injury develops,patients should be directed to HPB surgery centers,considering the possibility of accompanying HA injury.Large-scale and multicentric studies are needed to understand better the early and long-term results of HA ligation and determine preventive procedures.
文摘BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,incidence 2%-2.6%)and early hepatic artery thrombosis(HAT,incidence 3%-5%)have a poor prognosis in transplant patients,having impacts on graft and patient survival.In the present study,we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.AIM To investigate whether intraoperative thromboelastography(TEG)is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation(LT).METHODS We retrospectively collected thromboelastographic traces,in addition to known risk factors(cold ischemic time,intraoperative requirement for red blood cells and fresh-frozen plasma transfusion,prolonged operating time),in 27 patients,selected among 530 patients(≥18 years old),who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT(case group).Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion.We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications(1:1 match)(control group).The chosen matching parameters were:Patient graft and donor characteristics[age,sex,body mass index(BMI)],indication for transplantation,procedure details,United Network for Organ Sharing classification,BMI,warm ischemia time(WIT),cold ischemia time(CIT),the volume of blood products transfused,and conventional laboratory coagulation analysis.Normally distributed continuous data are reported as the mean±SD and compared using one-way Analysis of Variance(ANOVA).Nonnormally distributed continuous data are reported as the median(interquartile range)and compared using the Mann-Whitney test.Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher’s exact test depending on best applicability.IBM SPSS Statistics version 24(SPSS Inc.,Chicago,IL,United States)was employed for statistical analysis.Statistical significance was set at P<0.05.RESULTS Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively.The incidence of early hepatic artery occlusion was 3.02%,whereas the incidence of PVT was 2.07%.A comparison between the case and control groups showed some differences in the duration of surgery,which was longer in the case group(P=0.032),whereas transfusion of blood products,red blood cells,fresh frozen plasma,and platelets,was similar between the two study groups.Thromboelastographic parameters did not show any statistically significant difference between the two groups,except for the G value measured at basal and 120’postreperfusion time.It was higher,although within the reference range,in the case group than in the control group(P=0.001 and P<0.001,respectively).In addition,clot lysis at 60 min(LY60)measured at 120’postreperfusion time was lower in the case group than in the control group(P=0.035).This parameter is representative of a fibrinolysis shutdown(LY60=0%-0.80%)in 85%of patients who experienced a thrombotic complication,resulting in a statistical correlation with HAT and PVT.CONCLUSION The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT,suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.
文摘We are reporting the first documented case of an abdominal desmoid tumor presenting primarily after liver transplantation. This tumor, well described in the literature as occurring both in conjunction with familial adenomatous polyposis as well as in the postsurgical patient, has never been noted after solid organ transplantation and was therefore not included in our differential upon presentation. Definitive diagnosis required the patient to undergo surgical excision and immunochemical staining of the mass for confirmation. A review of the literature showed no primary tumors after transplantation. In a population of patients who received a small bowel transplant after they developedshort gut post radical resection of aggressive fibromatosis, only rare recurrences were seen. No connection of tumor development with immunosuppression or need to decrease immunosuppressant treatment has been demonstrated in these patients. Our case and the literature show the risk of this tumor presenting in the post-transplantation patient and the need for a high index of suspicion in patients who present with a complex mass after transplantation to prevent progression of the disease beyond a resectable lesion. Results of a thorough search of the literature are detailed and the medical and surgical management of both resectable and unresectable lesions is reviewed.
文摘BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective.Poorly differentiated neuroendocrine carcinomas(NECs)represent only 5%-10%of digestive NETS.Due to aggressive growth and rapid metastatic diffusion,early diagnosis and a multidisciplinary approach are mandatory.The role of surgery and radiotherapy in this setting is still debated,and chemotherapy remains the treatment of choice.CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3(Ki67 index>90%)on May 2015 and initially treated with 3 cycles of first-line chemotherapy,but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection.In September 2015,the first post-surgery total-body computed tomography(CT)scan showed an early pelvic disease relapse.Therefore,systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response.This was followed by pelvic radiotherapy(50 Gy).On April 2016,a CT scan and 18F-fluorodeoxy-glucose positron emission tomography imaging showed a complete response(CR)of the pelvic lesion,but pathological abdominal inter-aortocaval lymph nodes were observed.Due to disease progression of abdominal malignant nodes,the patient received radiotherapy at 45 Gy,and finally obtained a CR.As of January 2021,the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.
文摘To the Editor:We sincerely applaud the work done by Gupta et al.,in which they analyzed a single-center experience regarding gallbladder per-foration(GBP)management[1].Currently,there is a lack of cohort studies to adequately describe the approach strategies and man-agement for this pathology,with international guidelines making ambiguous recommendations[2,3].Their study stratified GBP types and provided details regarding clinical presentation,comorbidities,preoperative diagnosis,etiology,imaging techniques,and surgical approach.The study reported a high conversion rate when a la-paroscopic approach was attempted for cholecystectomy.
文摘AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.
文摘Urethrocutaneous fistula may complicate hypospadias repair.We noticed that double-layered preputial dartos flaps added to tubularized incised plate urethroplasty can reduce the risk of urethrocutaneous fistula.The aim of this study was to compare the outcomes of tubularized incised plate urethroplasty with double-layered preputial dartos flaps to with single-layered local fascial flaps in preventing urethrocutaneous fistula.A retrospective cohort study was conducted between January 2017 and December 2020 at Jordan University Hospital(Amman,Jordan).Boys who were aged between 6 months and 5 years,diagnosed with distal hypospadias,and not circumcised were included.The primary outcome was the occurrence of urethrocutaneous fistula in patients who underwent tubularized incised plate urethroplasty with a double-layered fascial flap.The results showed a total of 163 boys with distal hypospadias;among them,116 patients underwent tubularized incised plate urethroplasty with a single-layered fascial flap,and 47 underwent tubularized incised plate urethroplasty with a double-layered fascial flap.The development of urethrocutaneous fistula was higher in the group receiving tubularized incised plate urethroplasty with a single-layered fascial flap than in the group receiving tubularized incised plate urethroplasty with a double-layered fascial flap after 1 month,6 months,and 12 months(6.9%vs 0,10.3%vs 0,and 5.2%vs 0,respectively),and the difference after 6 months was statistically significant(P=0.02).
基金supported by the National Natural Science Foundation of China(No.82273452).
文摘Pancreatic cancer,notorious for its late diagnosis and aggressive progression,poses a substantial challenge owing to scarce treatment alternatives.This review endeavors to furnish a holistic insight into pancreatic cancer,encompassing its epidemiology,genomic characterization,risk factors,diagnosis,therapeutic strategies,and treatment resistance mechanisms.We delve into identifying risk factors,including genetic predisposition and environmental exposures,and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer.Additionally,we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy.We also dissect the primary mechanisms underlying treatment resistance in this malignancy,illustrating the latest therapeutic options and advancements in the field.Conclusively,we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.
文摘Background: Indocyanine green (ICG) fluorescence imaging is a promising tool for intraoperative decision-making during surgical procedures, in particular to assess organs perfusion. Methods: We used the ICG fluorescence during liver transplantations in six cirrhotic patients to help assessing the graft biliary duct perfusion in order to identify the appropriate level to perform the anastomosis. We also used ICG fluorescence also in five patients receiving kidney-pancreas transplantation to evaluate the perfusion levels of the duodenal stump of the pancreas graft. Results: Follow-up period for the patients was 12 months. The perioperative period was uneventful, no biliary complications such as leaks or stenosis were reported after liver transplantation, no complications of the entero-enteric anastomoses occurred after pancreatic transplantation. Conclusions: ICG fluorescence seems to safely provide important objectifiable perfusion information during organ transplantation procedures that can integrate surgeon's expertise. In fact, detecting intra-operatively perfusion defects, it allows real time modifications on technical strategies potentially useful to reduce the feared risk of anastomotic leakage and consequent severe complications.
文摘Robotic approach is already a new technological system in surgery and its potential advantages such as ergonomics,reduced tremor,3D view and improved instruments movements have been well described(1,2).Concerning the current literature,the studies addressing the robotic benefits on left pancreatectomies are few.However,it has been showed that robotic distal pancreatectomy is both feasible and safe as well as the laparoscopic and the standard open approach.Although,there is a lack of high-level economic studies comparing these techniques(3-6).