EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Laparoscopic and robotic surgery for colorectal cancer in older patients: a systematic review and meta-analysis.

INTRODUCTION: As life expectancy has been increasing, older patients are becoming more central to the healthcare system, leading to more intensive care use and longer hospital stays. Nevertheless, advancements in minimally invasive surgical techniques offer safe and effective options for older patients with colorectal diseases. This study aims to provide comprehensive evidence on the role of minimally invasive surgery in treating colorectal diseases in older patients. MATERIAL AND METHODS: All articles directly compared the minimally invasive approach with open surgery in patients aged ≥65 years. The present metanalysis took 30-day complications as primary outcomes. Length of hospital stay, readmission, and 30-day mortality were also assessed, as secondary outcomes. Further subgroup analyses were carried out based on surgery setting, lesion features, and location. RESULTS: After searching the main databases, 84 articles were included. Evaluation of 30-day complications rate, length of hospital stay, and 30-day mortality significantly favored minimally invasive approaches. The outcome readmission did not show any significant difference. CONCLUSIONS: The current metanalysis demonstrates clear advantages of minimally invasive techniques over open surgery in colorectal procedures for older patients, particularly in reducing complications, mortality, and hospitalization. This suggests that prioritizing these techniques, based on available expertise and facilities, could improve outcomes and quality of care for older patients undergoing colorectal surgery.

Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival.

PURPOSE: The optimal treatment strategy of patients affected by colorectal cancer (CRC) with synchronous unresectable liver metastases (SULM) is at present undefined. It is not known if a palliative primary tumor resection followed by chemotherapy could have a survival benefit compared to upfront chemotherapy (CT). The aim of the study is to analyze the safety and effectiveness of both therapeutic strategies in a group of patients treated at one institution. METHODS: A prospectively collected database was queried for patients affected by colorectal cancer with synchronous unresectable liver metastases between January 2004 and December 2018, defining and comparing 2 groups: patients treated by chemotherapy alone (group 1) vs patients who underwent primary tumor resection with or without a first line chemotherapy (group 2). The primary end point was Overall Survival (OS), estimated by the Kaplan-Meier method. RESULTS: One hundred sixty-seven patients were included: 52 in group 1 and 115 in group 2, median follow-up 48 months (range 25-126). A difference of 14 months in overall survival was observed between group 2 compared to group 1 (28 vs 14 months respectively; p < 0.001). Furthermore, overall survival increased in patients who underwent liver metastases resection (p < 0.001) or percutaneous radiofrequency ablation after surgery (p < 0.001). CONCLUSION: With the limits of a retrospective analysis, the study shows that surgical resection of the primary tumor has a significant impact on survival compared to chemotherapy alone. Randomized controlled trials are needed to confirm these data.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Impact of radioguided occult lesion localization in the management of cervical recurrences from differentiated thyroid cancer.

BACKGROUND: Surgery is the elective treatment for cervical relapse from differentiated thyroid cancer (DTC) but it is technically challenging, with risk of failure and morbidity. We explored the feasibility and the efficacy of radioguided occult lesion localization (ROLL) with intratumoral 99mTc radiolabeled human albumin macroaggregates ([99mTc]MAA) injection in this setting. METHODS: Fifteen patients who underwent ROLL by ultrasonography (US)-guided intratumoral injection of [99mTc]MAA between December 2013 and October 2016 for DTC recurrence were considered for this study. A hand-held gamma-probe was employed for intrasurgical lesion detection. Mini-invasive ROLL-guided excision for soft tissue recurrence and ROLL-assisted modified radical neck dissection for lymph-node metastases were performed respectively. RESULTS: DTC recurrence was located in loco-regional lymph-nodes (N.=8 patients) and in thyroid bed (N.=7 patients). A total of 27 lesions was identified and injected before surgery. On a total of 124 lesions resected, histology showed 38 DTC metastases. In particular, 26 out of 27 lesions injected with [99mTc]MAA were correctly detected intra-operatively and resected without surgical complications. Ten patients received subsequent radioactive iodine (RAI) treatment to verify the complete recurrence resection. At a median follow-up of 16 months patients were classified in complete response (N.=4), biochemical incomplete response (N.=3), indeterminate response (N.=1) with no evidence of structural disease. The remaining 7 patients were classified as structural incomplete response for cervical persistent disease (N.=2), for cervical recurrence (N.=2) and for both cervical and lung metastases progression (N.=3). CONCLUSIONS: ROLL is a simple and safe procedure in the surgical management of DTC loco-regional relapse.

Risk factors for Low Anterior Resection Syndrome (LARS) in patients undergoing laparoscopic surgery for rectal cancer.

BACKGROUND: Total mesorectal excision (TME) represents the "gold standard" of rectal cancer surgery. In locally advanced lesions neoadjuvant treatments (e.g. radiotherapy-nRT, radio chemotherapy-cnRT) have been shown to improve TME oncological results, reducing local recurrences rate. Nevertheless, these treatments have significant functional consequences impacting patients' quality of life (QoL). The resulting syndrome is known as Low Anterior Resection Syndrome (LARS). The purpose of this work was to evaluate the association between risk factors and the development of LARS in a prospective series of laparoscopic sphincter-saving TME. METHODS: The study was conducted as a retrospective observational epidemiological study of a prospective database, including all patients undergoing laparoscopic anterior resection surgery for rectal cancer at our Unit from 1st January 2013 to 31st May 2018. The diagnosis of LARS was performed using the LARS Score. We classified risk factors in patient-related, pre-, intra- and post-operative factors. RESULTS: The sample included 153 consecutive patients. Forty-one were affected by "low" rectal cancer, 74 by "middle" rectal cancer, 38 by "high" rectal cancer. The prevalence of overall LARS (major LARS + minor LARS) in our series was 35.9% (55/153 cases). Association between nRT and overall/major LARS was significant (respectively p = 0.03 and 0.02). Distal localization of tumor was also significantly associated with LARS [overall LARS (p = 0.03), major LARS (p = 0.014)]. CONCLUSIONS: In our study, neoadjuvant radiotherapy and tumor localization resulted independent risk factors for LARS after laparoscopic sphincter-saving TME. Tumor localization in the "middle" and "high" rectum resulted a protective factor compared to the localization in "low" rectum.

A systematic review and meta-analysis of endoscopic mucosal resection vs endoscopic submucosal dissection for colorectal sessile/non-polypoid lesions.

BACKGROUND: Current international guidelines strongly advise endoscopic submucosal dissection (ESD) instead of endoscopic mucosal resection (EMR) for the endoscopic resection of sessile colorectal tumours >20 mm. AIMS: To compare the safety and efficacy of EMR and ESD for treating large non-invasive colorectal lesions. MATERIAL AND METHODS: We performed a systematic review using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library) on February 21st, 2021 and a meta-analysis to assess en-bloc and R0 rates, and related adverse events. RESULTS: Twenty-four studies were included, comparing 3,424 ESD and 5,122 EMR procedures. The en-bloc resection rate was 90.8% in the ESD and 33.0% in the EMR group (p < .001). The R0 resection rate was 85.0% in the ESD and 64.6% in the EMR group (p = .005). The rate of perforation was 5.1% in the ESD and 1.67% in the EMR group (p < .001). The bleeding rate was 4.3% in the ESD and 3.6% in the EMR group (p = .008). The overall need for surgery, including oncologic reasons and complications, was 5.9% in the ESD and 3.1% in the EMR group (p < .001). CONCLUSIONS: ESD for large non-pedunculated colorectal lesions allows a higher rate of R0 resections than EMR, at the cost of a higher perforation rate and the need for additional surgery.

Long-term Oncologic Results After Stenting as a Bridge to Surgery Versus Emergency Surgery for Malignant Left-sided Colonic Obstruction: A Multicenter Randomized Controlled Trial (ESCO Trial).

OBJECTIVE: To assess overall (OS), time to progression (TTP), and disease-free survival (DFS) at 3 years after treatment, comparing stenting as bridge-to-surgery (SBTS) versus emergency surgery (ES) in neoplastic left colon obstruction, secondary endpoints of the previously published randomized controlled trial. BACKGROUND: While SBTS in neoplastic colon obstruction may reduce morbidity and need for a stoma compared with ES, concern has been raised, about long-term survival. METHODS: Individuals affected by left-sided malignant large-bowel obstruction were enrolled from 5 European hospitals and randomly assigned (1:1 ratio) to receive SBTS or ES. The computer-generated randomization sequence was stratified by center on cT and concealed by the use of a web-based application. Investigators and participants were unmasked to treatment assignment. The secondary outcomes analyzed here were OS, TTP, and DFS. Analysis was by intention to treat. This study is registered, ID-code NCT00591695. RESULTS: Between March 2008 and November 2015, 144 patients were randomly assigned to undergo either SBTS or ES; 115 (SBTS n = 56, ES n = 59) were eligible for analysis, while 20 participants were excluded for a benign disease, 1 for unavailability of the endoscopist while 8 withdrew from the trial. With a median follow-up of 37 months (range 1-62), no difference was observed in the SBTS group compared with ES in terms of OS (HR 0.93 (95% CI 0.49-1.76), P = 0.822), TTP (HR 0.81 (95% CI 0.42-1.54), P = 0.512), and DFS (HR 1.01 (95% CI 0.56-1.81), P = 0.972). Planned subgroup analysis showed no difference in respect to age, sex, American Society for Anesthesiology score, body mass index, and pT between SBTS and ES groups. Those participants randomized for the SBTS group whose obstruction was located in the descending colon had a better TTP compared with ES group (HR 0.44 (95% CI 0.20-0.97), P = 0.042), but no difference was observed in terms of OS (HR 0.73 (95% CI 0.33-1.63), P = 0.442) and DFS (HR 0.68 (95% CI 0.34-1.34), P = 0.261) in the same individuals. CONCLUSIONS: This randomized controlled trial shows that, although not powered for these seconday outcomes, OS, TTP, and DFS did not differ between groups at a minimum follow-up of 36 months.

68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

OBJECTIVES: The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. MATERIALS AND METHODS: Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6 months; (6) PSA < 1.5 ng/mL or any PSA in case of negative choline-PET/CT (n = 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n = 25); first-time BCR (group-2, n = 121); BCR after salvage therapy (group-3, n = 77). RESULTS: Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65 ng/mL (0.2-8.9) and median PSAdt = 9.3 months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p < 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. CONCLUSION: This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

Intraoperative use of fluorescence with indocyanine green reduces anastomotic leak rates in rectal cancer surgery: an individual participant data analysis.

BACKGROUND: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. METHODS: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. RESULTS: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220-0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. CONCLUSIONS: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.

Intracorporeal or Extracorporeal Ileocolic Anastomosis After Laparoscopic Right Colectomy: A Double-blinded Randomized Controlled Trial.

OBJECTIVES: The aim of the study was to determine whether there are clinically relevant differences in outcomes between laparoscopic right colectomy (LRC) with intracorporeal ileocolic anastomosis (IIA) and LRC with extracorporeal IA (EIA). BACKGROUND: IIA and EIA are 2 well-established techniques for restoration of bowel continuity after LRC. There are no high-quality studies demonstrating the superiority of one anastomotic technique over the other. METHODS: This is a double-blinded randomized controlled trial comparing the outcomes of LRC with IIA and LRC with EIA in patients with a benign or malignant right-sided colon neoplasm. Primary endpoint was length of hospital stay (LOS). This trial was registered with ClinicalTrials.gov, number NCT03045107. RESULTS: A total of 140 patients were randomized and analyzed. Median operative time was comparable in IIA versus EIA group {130 [interquartile range (IQR) 105-195] vs 130 (IQR 110-180) min; P = 0.770} and no intraoperative complications occurred. The quicker recovery of bowel function after IIA than EIA [gas: 2 (IQR 2-3) vs 3 (IQR 2-3) days, P = 0.003; stool: 4 (IQR 3-5) vs 4.5 (IQR 3-5) days, P = 0.032] was not reflected in any advantage in the primary endpoint: median LOS was similar in the 2 groups [6 (IQR 5-7) vs 6 (IQR 5-8) days; P = 0.839]. No significant differences were observed in the number of lymph nodes harvested, length of skin incision, 30-day morbidity (17.1% vs 15.7%, P = 0.823), reoperation rate, and readmission rate between the 2 groups. CONCLUSIONS: LRC with IIA is associated with earlier recovery of postoperative bowel function than LRC with EIA; however, it does not reflect into a shorter LOS.

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial.

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13-year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P<0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma. (Registered at clinicaltrials.gov identifier: 00435955).

How bothersome double-J ureteral stents are after semirigid and flexible ureteroscopy: a prospective single-institution observational study.

PURPOSE: To evaluate in details the actual extent of double-J stent-related symptoms after semirigid (URS) and flexible (RIRS) ureteroscopy using a validated questionnaire. METHODS: We asked to complete the Ureteric Stent Symptoms Questionnaire (USSQ) to all stone patients undergoing URS or RIRS with stent placement from 2010 to 2015. Stent-related symptoms' prevalence, severity, and impact on daily life were analyzed using descriptive statistics and five-order Likert scales. Subgroups analyses were performed. RESULTS: 232 patients completed the USSQ. Stents had a deep impact on urinary symptoms (daily frequency ≥ 1 per hour 59.1%, ≥ 1 nocturnal micturition 90.1%, urgency 86.6%, burning 82.3%) that represented a problem for 88.4% of patients. 83.2% complained of pain, mostly in the kidney (67.9%) or in the bladder area (31.3%), particularly during physical activity (72.9%) and micturition (77.0%). Pain interfered with everyday life in 92.2%. General health, working, and sexual activity were also affected. 62.0% of patients would be dissatisfied (51.6% unhappy or terrible) if further ureteral stenting was proposed in future. Younger patients and females were more affected. Limitations include observational design and lack of baseline evaluation. CONCLUSIONS: Ureteral stents are responsible for significant urinary symptoms and pain after semirigid and flexible ureteroscopy. They also considerably affect general health, working and sexual activity. Urologists should consider it carefully before stenting, inform patients about stent-related symptoms, and minimize stent indwelling time.

Intraoperative air leak test reduces the rate of postoperative anastomotic leak: analysis of 777 laparoscopic left-sided colon resections.

BACKGROUND: The evidence supporting the use of the air leak test (ALT) after laparoscopic left-sided colon resection (LLCR) to test the colorectal anastomosis (CA) integrity aiming at reducing the rate of postoperative CA leakage (CAL) is not conclusive. The aim of this study was to challenge the use of ALT after elective LLCR. METHODS: It is a retrospective analysis of a prospectively collected database including all patients undergoing elective LLCR with primary CA and no proximal bowel diversion between January 1996 and June 2017. The decision to perform the ALT was based on the individual surgeon routine practice. A multivariate analysis was performed to identify independent risk factors for CAL. RESULTS: A total of 777 LLCR without proximal diversion were included in the analysis: the CA was tested in 398 patients (ALT group), while intraoperative ALT was not performed in 379 patients (No-ALT group). The two groups were similar in demographic characteristics, indication, and type of procedure. Intraoperative ALT was positive in 20 (5%) patients: a stoma was created in 14 (70%) patients, while 6 (30%) patients had a suture repair alone. Overall, postoperative CAL occurred in 32 patients (4.1%): the postoperative CAL rate was lower in ALT patients (2.5% vs. 5.8%, p = 0.025). A reoperation was needed in 87.5% of cases. No CAL occurred in the 20 patients with intraoperative positive ALT. Multivariate analysis showed that ASA score 3-4 (OR 5.39, 95% CI 2.53-11.51, p < 0.001) and male sex (OR 3.96, 95% CI 1.66-9.43, p = 0.002) were independent risk factors for postoperative CAL, while intraoperative ALT independently reduced the postoperative CAL rate (OR 0.40, 95% CI 0.18-0.88, p = 0.022). CONCLUSION: Intraoperative ALT allows to detect AL defects after LLCR that can be effectively managed intraoperatively, leading to a significant lower risk of postoperative CAL.

The use of 3D laparoscopic imaging systems in surgery: EAES consensus development conference 2018.

BACKGROUND: The use of 3D laparoscopic systems is expanding. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: Systematic reviews of the PubMed and Embase libraries were performed to identify evidence on potential benefits of 3D on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by an international surgical and engineering expert panel which were presented and voted at the EAES annual congress, London, May 2018. RESULTS: 9967 abstracts were screened with 138 articles included. 18 statements and two recommendations were generated and approved. 3D significantly shortened operative time (mean difference 11 min (8% [95% CI 20.29-1.72], I2 96%)). A significant reduction in complications was observed when 3D systems were used (RR 0.75, [95 CI% 0.60-0.94], I2 0%) particularly for cases involving laparoscopic suturing (RR 0.57 [95% CI 0.35-0.90], I2 0%). In 69 box trainer or simulator studies, 64% concluded trainees were significant faster and 62% performed fewer errors when using 3D. CONCLUSION: We recommend the use of 3D vision in laparoscopy to reduce the operative time (grade of recommendation: low). Future robust clinical research is required to specifically investigate the potential benefit of 3D laparoscopy system on complication rates (grade of recommendation: high).

Highly sensitive MYD88L265P mutation detection by droplet digital polymerase chain reaction in Waldenström macroglobulinemia.

We here describe a novel method for MYD88L265P mutation detection and minimal residual disease monitoring in Waldenström macroglobulinemia, by droplet digital polymerase chain reaction, in bone marrow and peripheral blood cells, as well as in circulating cell-free DNA. Our method shows a sensitivity of 5.00×10-5, which is far superior to the widely used allele-specific polymerase chain reaction (1.00×10-3). Overall, 291 unsorted samples from 148 patients (133 with Waldenström macroglobulinemia, 11 with IgG lymphoplasmacytic lymphoma and 4 with IgM monoclonal gammopathy of undetermined significance) were analyzed: 194 were baseline samples and 97 were followup samples. One hundred and twenty-two of 128 (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored positive for MYD88L265P To investigate whether MYD88L265P detection by droplet digital polymerase chain reaction could be used for minimal residual disease monitoring, mutation levels were compared with IGH-based minimal residual disease analysis in 10 patients, and was found to be as informative as the classical, standardized, but not yet validated in Waldenström macroglobulinemia, IGH-based minimal residual disease assay (r2=0.64). Finally, MYD88L265P detection by droplet digital polymerase chain reaction on plasma circulating tumor DNA from 60 patients showed a good correlation with bone marrow findings (bone marrow median mutational value 1.92×10-2, plasma circulating tumor DNA value: 1.4×10-2, peripheral blood value: 1.03×10-3). This study indicates that droplet digital polymerase chain reaction assay of MYD88L265P is a feasible and sensitive tool for mutation screening and minimal residual disease monitoring in Waldenström macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be reliably tested, as can circulating tumor DNA, which represents an attractive, less invasive alternative to bone marrow for MYD88L265P detection.

Haplo-identical allografting with post-transplant cyclophosphamide in high-risk patients.

Haplo-identical transplants (Haplo-Tx) are an important alternative for patients with hematological malignancies who lack a HLA-identical donor. Seventy-one T-replete Haplo-Tx were performed in 70 high-risk patients at our center; 22/70 (31%) patients with refractory/relapsed leukemia received sequential salvage therapy (SeqTh) with high-dose chemotherapy followed by Haplo-Tx during the chemotherapy-induced neutropenia. Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (days + 3 and + 4) with tacrolimus and mycophenolic acid. After a median follow-up of 29.2 months, 3-year overall survival (OS) and event-free survival (EFS) were 43.8 and 40.2%, while 3-year cumulative incidences (CIs) of non-relapse mortality (NRM) and relapse (RI) were 27 and 33%. Day 100 and day 400 CI of grade III-IV acute and moderate-severe chronic GVHD were 11 and 15%. Three-year RI was significantly lower in patients in complete remission (CR) versus those not in CR at the time of transplant (21.5 vs. 48%, p = 0.009) and in patients who received PBSC as compared to BM (22 vs. 45%, p = 0.009). In patients treated with SeqTh, 3-year OS was 19%, while 3-year RI and NRM were 52 and 28% at a median follow-up of 50 months. Overall, Haplo-Tx was feasible in heavily pretreated high-risk patients without a suitable HLA-identical donor.

Yttrium-90 ibritumomab tiuxetan (Zevalin) followed by BEAM (Z-BEAM) conditioning regimen and autologous stem cell transplantation (ASCT) in relapsed or refractory high-risk B-cell non-Hodgkin lymphoma (NHL): a single institution Italian experience.

Chemo-refractory NHL has a very poor outcome; the addiction of RIT to salvage regiment pre ASCT had recently demonstrated promising results.We performed a retrospective sequential study to determine the feasibility of standard Zevalin with BEAM in high-risk relapse/refractory NHL. A matched cohort analysis with a group treated with standard BEAM without Zevalin was performed as secondary endpoint. Between October 2006 and January 2013, 37 NHL patients at high risk for progression or early (< 1 year) or multiple relapses were treated with Z-BEAM and ASCT after R-DHAP or R-ICE as salvage therapy. Clinical characteristics were 19 refractory and 18 early or multiple relapse; 16 patients received 1, and 21 had 2 or more previous rituximab-containing chemotherapy. At the end of treatment, response was CR 22 (59%), PR 10 (27%), PD 4 (11%), and toxic death (TD) 1 (3%). With a median follow up of 61 months, 3-year PFS was 61% and OS 61%. Fifteen patients died, 12 of lymphoma. Comparison with 21 treated with BEAM alone showed a numerical higher 3-yr PFS rate in favor of Z-BEAM but not statistically significant (57 vs 48%). With the limitation of the small sample subgroup analysis, a significant benefit was observed in relapsed patients for PFS (78% Z-BEAM vs 22% BEAM p = 0.016) and OS (83% Z-BEAM vs 22% BEAM p = 0.001). In relapsed/refractory high-risk NHL, Z-BEAM+ASCT is able to achieve a good ORR. Three-year PFS is promising for early relapsed patients but is not satisfactory for those with refractory disease.

Safety of single-incision robotic cholecystectomy for benign gallbladder disease: a systematic review.

BACKGROUND: Multiport laparoscopic cholecystectomy (MLC) is the gold standard technique for cholecystectomy. In order to reduce postoperative pain and improve cosmetic results, the application of the single-incision laparoscopic cholecystectomy (SILC) technique was introduced, leading surgeons to face important challenges. Robotic technology has been proposed to overcome some of these limitations. The purpose of this review is to assess the safety of single-incision robotic cholecystectomy (SIRC) for benign disease. METHODS: An Embase and Pubmed literature search was performed in February 2017. Randomized controlled trial and prospective observational studies were selected and assessed using PRISMA recommendations. Primary outcome was overall postoperative complication rate. Secondary outcomes were postoperative bile leak rate, total conversion rate, operative time, wound complication rate, postoperative hospital stay, and port site hernia rate. The outcomes were analyzed in Forest plots based on fixed and random effects model. Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 13 studies provided data about 1010 patients who underwent to SIRC for benign disease of gallbladder. Overall postoperative complications rate was 11.6% but only 4/1010 (0.4%) patients required further surgery. A postoperative bile leak was reported in 3/950 patients (0.3%). Conversion occurred in 4.2% of patients. Mean operative time was 86.7 min including an average of 42 min should be added as for robotic console time. Wound complications occurred in 3.7% of patients. Median postoperative hospital stay was 1 day. Port site hernia at the latest follow-up available was reported in 5.2% of patients. CONCLUSIONS: The use of the Da Vinci robot in single-port cholecystectomy seems to have similar results in terms of incidence and grade of complications compared to standard laparoscopy. In addition, it seems affected by the same limitations of single-port surgery, consisting of an increased operative time and incidence of port site hernia.

Multiparametric Magnetic Resonance/Ultrasound Fusion Prostate Biopsy: Number and Spatial Distribution of Cores for Better Index Tumor Detection and Characterization.

PURPOSE: We evaluated the minimum core number for better index tumor detection to determine the best core site as well as biopsy Gleason score heterogeneity in the same index lesion. The aim was to optimize the highest Gleason score detection. MATERIALS AND METHODS: A total of 327 patients with negative digital rectal examination underwent magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy for elevated/rising prostate specific antigen and/or 1 or more detectable lesions on multiparametric magnetic resonance imaging after a previous negative standard biopsy. Depending on the diameter of each index lesion (8 or less, or greater than 8 mm) 4 or 6 cores, respectively, were taken according to a well determined sequence. RESULTS: Of the patients 166 (50.7%) had prostate cancer, including 79 (47.6%) with an 8 mm or less index lesion and 87 (52.4%) with a greater than 8 mm index lesion. Of patients with an index tumor 8 mm or less 7 (8.9%) had 1, 31 (39.2%) had 2, 27 (34.2%) had 3 and 14 (17.7%) had 4 positive cores. Similarly, of patients with a lesion greater than 8 mm 8 (9.2%) had 1, 30 (34.5%) had 2, 13 (14.9%) had 3, 14 (16.1%) had 4, 12 (13.8%) had 5 and 10 (11.5%) had 6 positive cores. The major prevalence of positive cores was observed in the center of the target. Gleason score heterogeneity was found in 12.6% of those with an 8 mm or less target vs 26.4% with a target greater than 8 mm. In the center of the target there was a slight prevalence of Gleason pattern 4 or greater, or a lesser pattern. CONCLUSIONS: Approaching magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy with a single core might be inadequate. Rather, taking 2 cores in the center of the index lesion may provide more accurate cancer detection and optimize the chances of finding the highest Gleason pattern.