The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal ...abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM).
Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival.
ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA del(17p) and/or t(4;14) and/or t(14;16), and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively.
The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Background
Although definitive long-term results are not yet available, the global safety of laparoscopic surgery for rectal cancer treatment remains controversial. We evaluated differences in the ...safety of laparoscopic rectal resection versus open surgery for cancer.
Methods
A systematic review from 2000 to 2011 was performed searching the Medline and Embase databases (prospero registration CRD42012002406). We included randomized and prospective controlled clinical studies comparing laparoscopic and open resection for rectal cancer. Primary end points were 30-day mortality and overall morbidity. Then a meta-analysis was conducted by a fixed-effect model, performing a sensitivity analysis by a random-effect model. Relative risk (RR) was used as an indicator of treatment effect; a RR of less than 1.0 was in favor of laparoscopy. Publication bias was assessed by funnel plot and heterogeneity by the
I
2
test and subgroup analysis on surgical and medical complications.
Results
Twenty-three studies, representing 4,539 patients, met the inclusion criteria; eight were randomized for a total of 1,746 patients. Mortality was observed in 1.0 % of patients in the laparoscopic group and in 2.4 % of patients in the open group. The overall RR was 0.46 (95 % confidence interval 0.21–0.99,
p
= 0.048). The raw incidence of overall complications was lower in the laparoscopic group (31.8 %) compared to the open group (35.4 %). The overall RR was 0.83 (95 % confidence interval 0.76–0.91,
p
< 0.001).
Conclusions
On the basis of evidence of both randomized and prospective controlled series, mortality and morbidity RR, including subgroup analysis, were significantly lower after laparoscopic compared to open surgery.
Background and Aims Twenty years after the first description of the technique, the debate is still open on the role of self-expandable metallic stent (SEMS) placement as a bridge to elective surgery ...for symptomatic left-sided malignant colonic obstruction. The aim was to compare morbidity rates after colonic stenting bridge to surgery (SBTS) versus emergency surgery (ES) for left-sided malignant obstruction. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) on SBTS or ES for acute symptomatic malignant left-sided large bowel obstruction. The primary outcome was overall morbidity within 60 days after surgery. Results The meta-analysis included 8 RCTs and 497 patients. Overall mortality within 60 days after surgery was 9.6% in SBTS-treated patients and 9.9% in ES-treated patients (relative risk RR, 0.99; P = .97). Overall morbidity within 60 days after surgery was 33.9% in SBTS-treated patients and 51.2% in ES-treated patients (RR, 0.59; P = .023). The temporary stoma rate was 33.9% after SBTS and 51.4% after ES (RR, 0.67; P < .001). The permanent stoma rate was 22.2% after SBTS and 35.2% after ES (RR, 0.66; P = .003). Primary anastomosis was successful in 70.0% of SBTS-treated patients and 54.1% of ES-treated patients (RR, 1.29; P = .043). Conclusions SBTS was associated with lower short-term overall morbidity and lower rates of temporary and permanent stoma. Depending on multiple factors such as local expertise, clinical status including level of obstruction, and level of certainty of diagnosis, SBTS does offer some advantages with less risk than ES for left-sided malignant colonic obstruction in the short term.
Abstract Background The introduction of robotics revolutionized prostate cancer surgery because the magnified three-dimensional vision system and wristed instruments allow microsurgery to be ...performed. The advantages of robotic surgery could lead to improved continence outcomes in terms of early recovery compared with the traditional surgical methods. Objective To describe the total anatomical reconstruction (TAR) technique during robot-assisted radical prostatectomy (RARP). Primary endpoint: evaluation of the continence rate at different time points. Secondary endpoint: evaluation of urine leakage and anastomosis stenosis rates related to the technique. Design, setting, and participants June, 2013 to November, 2014; prospective consecutive series of patients with localized prostate cancer (cT1-3, cN0, cM0). Surgical procedure RARP with TAR was performed in all cases. Lymph node dissection was performed if the risk of lymph nodal metastasis was over 5%, according to the Briganti updated nomogram. Measurements Preoperative, intraoperative, postoperative, and pathological variables were analyzed. Enrolled patients were arbitrarily divided into three groups according to a time criterion. The relationships between the learning curve and the trend of the above-mentioned variables were analyzed using LOESS analysis. Continence was rigorously analyzed preoperatively and at 24 h, 1 wk, 4 wk, 12 wk, and 24 wk after catheter removal. Results and limitations In total, 252 patients were analyzed. The continence rates immediately after catheter removal and at 1 wk, 4 wk, 12 wk, and 24 wk after RARP were 71.8%, 77.8%, 89.3%, 94.4%, and 98.0%, respectively. Multivariate analysis revealed that the nerve sparing technique, D’Amico risk groups, lymph node dissection, and prostate volume were involved in the early recovery of urinary continence. One ileal perforation requiring reoperation was recorded. The transfusion rate was 0.8%. Thirty-one (12.3%) postoperative complications were recorded up to 6 mo after surgery. Among these, eight acute urinary retentions (3.2%) and three urine leakages (1.2%) were recorded. There was a lack of randomization and comparison with other techniques. Both anatomical dissection of the prostatic apex and TAR were used. The results may not be generalized to low-volume centers. Conclusions The TAR technique showed promising results in the early recovery of urinary continence, as well as watertight anastomosis and a low rate of urine leakage. The oncologic results were not affected. Comparative studies are needed to support the quality of reported results. Patient summary On the basis of our findings, it seems that the risk of urinary incontinence following radical prostatectomy can be lowered via meticulous anatomical reconstruction using a robotic system. Comparative studies are required to support the reported results.
Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide ...maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma.
We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance).
In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio HR, 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients.
Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.
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.
Background and aims
This systematic review and meta-analysis compares the safety and effectiveness of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) in the treatment of ...flat and sessile colorectal lesions >20 mm preoperatively assessed as noninvasive.
Methods
We reviewed the literature published between January 2000 and March 2014. Pooled estimates of the proportion of patients with en bloc, R0 resection, complications, recurrence, and need for further treatment were compared in a meta-analysis using fixed and random effects.
Results
A total of 11 studies and 4678 patients were included. The en bloc resection rate was 89.9% for ESD vs 34.9% for EMR patients (RR 1.93 p < 0.001). The R0 resection rate was 79.6% for ESD vs 36.2% for EMR patients (RR 2.01 p < 0.001). The rate of perforation was 4.9% for the ESD group and 0.9% for EMR (RR 3.19, p < 0.001), while the rate of bleeding was 1.9% for ESD and 2.9% for EMR (RR 0.68, p = 0.070). Therefore, the overall need for further surgery, including surgery for oncologic reasons and surgery for complications, was 7.8% for ESD and 3.0% for EMR (RR 2.40, p < 0.001).
Conclusions
ESD achieves a higher rate of en bloc and R0 resection compared to EMR, at the cost of a higher risk of complications. This, added to an increased need for surgery for oncologic reasons for a plausible tendency to extend indication for endoscopic excision, increases the risk of further surgery after ESD.
In a retrospective analysis, 21 acute myeloid leukemia patients receiving single-agent sorafenib maintenance therapy in complete remission (CR) after hematopoietic stem cell transplantation (HSCT) ...were compared with a control group of 22 patients without maintenance. Sorafenib was initiated a median of 3 months (IQR: 2.3–3.5) after allogeneic HSCT with a median daily dosage of 400 mg (range: 200–800) orally, and lasted a median of 11.3 months (IQR: 3.3–24.4). No significant increase in graft versus host disease or toxicity was observed. Adverse events were reversible with dose adjustment or temporary discontinuation in 19/19 cases. With a median follow-up of 34.7 months (IQR: 16.9–79.5), sorafenib maintenance significantly improved cumulative incidence of relapse (
p
= 0.028) as well as overall survival (OS) (
p
= 0.016), especially in patients undergoing allogeneic HSCT in CR1 (
p
< 0.001). In conclusion, sorafenib maintenance after allogeneic HSCT is safe and may improve cumulative incidence of relapse and OS in FLT3–ITD-mutated AML.
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.
Artificial intelligence is gaining interest among clinicians, but its results are difficult to be interpreted, especially when dealing with survival outcomes and censored observations. Explainable ...machine learning (XAI) has been recently extended to this context to improve explainability, interpretability and transparency for modeling results. A cohort of 231 patients undergoing an allogeneic bone marrow transplantation was analyzed by XAI for survival by two different uni- and multi-variate survival models, proportional hazard regression and random survival forest, having as the main outcome the overall survival (OS) and its main determinants, using the survex package for R. Both models’ performances were investigated using the integrated Brier score, the integrated Cumulative/Dynamic AUC and the concordance C-index. Global explanation for the whole cohort was performed using the time-dependent variable importance and the partial dependence survival plot. The local explanation for each single patient was obtained via the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile. The survex package common interface ensured a good feasibility of XAI for survival, and the advanced graphical options allowed us to easily explore, explain and compare OS results coming from the two survival models. Before the modeling results to be suitable for clinical use, understandability, clinical relevance and computational efficiency were the most important criteria ensured by this XAI for survival approach, in adherence to clinical XAI guidelines.
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