Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

Debulking hepatectomy for colorectal liver metastasis: Analysis of risk factors for progression free survival.

BACKGROUND: The study explores the role of liver debulking surgery in cases of unresectable colorectal liver metastases (CRLM), challenging the traditional notion that surgery is not a valid option in such scenarios. MATERIALS AND METHODS: Patients with advanced but resectable disease who underwent surgery with a curative intent (Group I) and those with advanced incompletely resectable disease who underwent a "debulking" hepatectomy (Group II) were compared. RESULTS: There was no difference in the intra-operative and post-operative results between the two groups. The 3-year and 5-year OS rates were 69% and 47% for group 1 vs 64% and 35% for group 2 respectively (p = 0.14). The 3-year and 5-year PFS rates were 32% and 21% for group 1 vs 12% and 8% for group 2 respectively (p = 0.009). Independent predictors of PFS in the debulking group were bilobar metastases (HR = 2.70; p = 0.02); the presence of extrahepatic metastasis (HR = 2.65, p = 0.03) and the presence of more than 9 metastases (HR = 2.37; p = 0.04). Iterative liver surgery for CRLM was a significant protective factor (HR = 0.34, p = 0.04). CONCLUSION: An aggressive palliative surgical approach may offer a survival benefit for selected patients with unresectable CRLM, without increasing the morbidity. The decision for surgery should be made on a case-by-case basis.

Short-term outcomes of laparoscopic extended hepatectomy versus major hepatectomy: a single-center experience.

INTRODUCTION: Laparoscopic major hepatectomy (LMH) remains restricted to a few specialized centers and poses a challenge to surgeons performing laparoscopic resections. Laparoscopic extended resections are even more complex and rarely conducted. METHODS: From a single-institution database, we compared the short-term outcomes of patients who underwent major and extended laparoscopic resections, stratifying the entire retrospective cohort into four groups: right hepatectomy, left hepatectomy, right extended hepatectomy, and left extended hepatectomy. Patient demographics, tumor characteristics, operative variables, and especially postoperative outcomes were evaluated. RESULTS: 250 patients underwent major and extended laparoscopic liver resections, including 160 right, 31 right extended, 36 left, and 23 left extended laparoscopic hepatectomies. The most common indication for resection was colorectal liver metastases (64%). Laparoscopic extended hepatectomy (LEH) showed significantly longer operative time, more blood loss, need for Pringle maneuver, conversion to open surgery, higher rates of liver failure, postoperative ascites, and intra-abdominal hemorrhage, R1 margins and length of stay when compared with the LMH group. Mortality rates were similar between groups. Multivariate analysis revealed intraoperative blood transfusion (OR = 5.1[CI-95%: 1.15-6.79]; p = 0.02) as an independent predictor for major complications. CONCLUSIONS: LEH showed to be feasible, however with higher blood loss and significantly associated to major complications.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Design and preliminary validation of a high-fidelity vascular simulator for robot-assisted manipulation.

The number of robot-assisted minimally invasive surgeries is increasing annually, together with the need for dedicated and effective training. Surgeons need to learn how to address the novel control modalities of surgical instruments and the loss of haptic feedback, which is a common feature of most surgical robots. High-fidelity physical simulation has proved to be a valid training tool, and it might help in fulfilling these learning needs. In this regard, a high-fidelity sensorized simulator of vascular structures was designed, fabricated and preliminarily validated. The main objective of the simulator is to train novices in robotic surgery to correctly perform vascular resection procedures without applying excessive strain to tissues. The vessel simulator was integrated with soft strain sensors to quantify and objectively assess manipulation skills and to provide real-time feedback to the trainee during a training session. Additionally, a portable and user-friendly training task board was produced to replicate anatomical constraints. The simulator was characterized in terms of its mechanical properties, demonstrating its realism with respect to human tissues. Its face, content and construct validity, together with its usability, were assessed by implementing a training scenario with 13 clinicians, and the results were generally positive.

Stapled Anastomosis Versus Hand-Sewn Anastomosis With Mucosectomy for Ileal Pouch-Anal Anastomosis: A Systematic Review and Meta-analysis of Postoperative Outcomes, Functional Outcomes, and Oncological Safety.

PURPOSE: This systematic review and meta-analysis aimed to compare outcomes between stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA with mucosectomy in cases of ulcerative colitis and familial adenomatous polyposis. METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines 2020 and AMSTAR 2 (Assessing the methodological quality of systematic reviews) guidelines. We included randomized clinical trials (RCTs) and controlled clinical trials (CCTs). Subgroup analysis was performed according to the indication for surgery. RESULTS: The bibliographic research yielded 31 trials: 3 RCTs, 5 prospective clinical trials, and 24 CCTs including 8872 patients: 4871 patients in the stapled group and 4038 in the hand-sewn group. Regarding postoperative outcomes, the stapled group had a lower rate of anastomotic stricture, small bowel obstruction, and ileal pouch failure. There were no differences between the 2 groups in terms of operative time, anastomotic leak, pelvic sepsis, pouchitis, or hospital stay. For functional outcomes, the stapled group was associated with greater outcomes in terms of seepage per day and by night, pad use, night incontinence, resting pressure, and squeeze pressure. There were no differences in stool Frequency per 24h, stool frequency at night, antidiarrheal medication, sexual impotence, or length of the high-pressure zone. There was no difference between the 2 groups in terms of dysplasia and neoplasia. CONCLUSIONS: Compared to hand-sewn anastomosis, stapled ileoanal anastomosis leads to a large reduction in anastomotic stricture, small bowel obstruction, ileal pouch failure, seepage by day and night, pad use, and night incontinence. This may ensure a higher resting pressure and squeeze pressure in manometry evaluation. PROTOCOL REGISTRATION: The protocol was registered at PROSPERO under CRD 42022379880.

Oncological Outcome After Laparoscopic 'No-touch' RAMPS Versus 'Touch' Left Pancreatectomy for Pancreatic Adenocarcinoma.

BACKGROUND/AIM: The validity of laparoscopic distal pancreatectomy in left-sided pancreatic adenocarcinoma (PDAC) is still unclear. However, a meticulous surgical dissection through a "no-touch" technique might allow a radical oncological resection with minimal risk of tumor dissemination and seeding. This study aimed to evaluate the oncological outcomes of the laparoscopic "no touch" technique versus the "touch" technique. PATIENTS AND METHODS: From 2001 to 2020, we retrospectively analyzed 45 patients undergoing laparoscopic distal pancreatectomy (LDP) for PDAC in two centers. Factors associated with overall (OS), disease-free survival (DFS) and time to recurrence (TTR) were identified. RESULTS: The OS rates in the 'no-touch' and 'touch' groups were 95% vs. 78% (1-year OS); 50% vs. 50% (3-year OS), respectively (p=0.60). The DFS rates in the 'no-touch' and 'touch' groups were 72 % vs. 57% (1-year DFS); 32% vs. 28% (3-year DFS), respectively (p=0.11). The TTR rates in the 'no-touch' and 'touch' groups were 77% vs. 61% (1-year TTR); 54% vs. 30% (3-year TTR); 46% vs. 11% (5-year TTR); respectively (p=0.02) In multivariate analysis the only factors were Touch technique [odds ratio (OR)=2.62, p=0.02] and lymphovascular emboli (OR=4.8; p=0.002). CONCLUSION: We advise the 'no-touch' technique in patients with resectable PDAC in the pancreatic body and tail. Although this study does not provide definitive proof of superiority, no apparent downsides are present for the 'no-touch' technique in this setting although there could be oncological benefits.

A systematic review and meta-analysis of hernia sac management in laparoscopic groin hernia mesh repair: reduction or transection?

BACKGROUND: There is no consensus regarding hernia sac management during laparoscopic hernia repair, and this systematic review and meta-analysis aimed to compare the postoperative outcomes of sac reduction (RS) and sac transection (TS) during laparoscopic mesh hernia repair. METHODS: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) guidelines. We used the RevMan 5.4 statistical package from the Cochrane collaboration for meta-analysis. A random effects model was used. RESULTS: The literature search yielded six eligible studies including 2941 patients: 821 patients in the TS group and 2120 patients in the RS group. In the pooled analysis, the TS group was associated with a lower incidence of seroma (OR = 1.71; 95% CI [1.22, 2.39], p = 0.002) and shorter hospital stay (MD = -0.07; 95% CI [-0.12, -0.02], p = 0.008). There was no significant difference between the two groups in terms of morbidity (OR = 0.87; 95% CI [0.34, 2.19], p = 0.76), operative time (MD = -4.39; 95% CI [-13.62, 4.84], p = 0.35), recurrence (OR = 2.70; 95% CI [0.50, 14.50], p = 0.25), and Postoperative pain. CONCLUSIONS: This meta-analysis showed that hernia sac transection is associated with a lower seroma rate and shorter hospital stay with similar morbidity, operative time, recurrence, and postoperative pain compared to the reduction of the hernia sac. PROTOCOL: The protocol was registered in PROSPERO with ID CRD42023391730.

Assessing textbook outcome after single large hepatocellular carcinoma resection.

BACKGROUND: This study aimed to investigate the impact and predictors of an ideal surgical care following SLHCC resection. METHODS: SLHCC patients who underwent LR in two tertiary hepatobiliary centers between 2000 and 2021 were retrieved from prospectively maintained databases. The quality of surgical care was measured by the textbook outcome (TO). Tumor burden was defined by the tumor burden score (TBS). Factors associated with TO were determined on multivariate analysis. The impact of TO on oncological outcomes was assessed using Cox regressions. RESULTS: Overall, 103 SLHCC patients were included. Laparoscopic approach was considered in 65 (63.1%) patients and 79 (76.7%) patients presented with moderate TBS. TO was achieved in 54 (52.4%) patients. Laparoscopic approach was independently associated with TO (OR 2.57; 95% CI 1.03-6.64; p = 0.045). Within 19 (6-38) months of median follow up, patients who achieved TO had better OS compared to non-TO patients (1-year OS: 91.7% vs. 66.9%; 5-year OS: 83.4% vs. 37.0%, p < 0.0001). On multivariate analysis, TO was independently associated with improved OS, especially in non-cirrhotic patients (HR 0.11; 95% CI 0.02-0.52, p = 0.005). CONCLUSIONS: TO achievement could be a relevant surrogate marker of improved oncological care following SLHCC resection in non-cirrhotic patients.

Towards AI-driven longevity research: An overview.

While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.

Robotic versus open total pancreatectomy: a systematic review and meta-analysis.

Limited data are available on postoperative outcomes in patients undergoing robotic total pancreatectomy (RTP). This systematic review and meta-analysis aimed to compare the postoperative outcomes of RTP and open total pancreatectomy (OTP). We performed a systematic review with meta-analysis according to the PRISMA 2020 and AMSTAR 2 guidelines. We included studies conducted through August 10, 2022, that systematically searched electronic databases and compared RTP with OTP. We retained four controlled clinical trials in the literature search, including 156 patients: 65 in the RTP group and 91 in the OTP group. There was no difference between the RTP group and OTP group in terms of mortality, severe complications, morbidity, bleeding, biliary leak, delayed gastric emptying, reoperation, operative time, length of stay, harvested lymph nodes, and positive resection margin. The RTP reduces the delay of the first liquid diet, first oral diet, and out of bed. RTP is feasible and safe in selected patients. Robotic surgery allows for a quicker recovery. In cases of major vessel invasion, conversion to laparotomy should be preoperatively considered.

Pure abdominal laparoscopic approach versus thoraco-abdominal laparoscopic approach: What is the best technique for liver resection in segment 7 and segment 8? An answer from the Institut Mutualiste Montsouris experience with short- and long-term outcome evaluation.

BACKGROUND: Lesions in segments 7 and 8 are a challenge during standard laparoscopic liver resection. The addition of transthoracic trocars could be useful in the standard abdominal approach for laparoscopic liver resection. We report our experience with a thoraco-abdominal laparoscopic combined approach for liver resection with the aim of comparing short- and long-term outcomes. METHODS: We reviewed 1,003 laparoscopic liver resections in a prospectively maintained, single-institution database. We compared patient outcomes intraoperatively and postoperatively. We analyzed the long-term outcomes of the colorectal liver metastasis subgroup. Propensity score matching 1:1 was performed based on the following variables: age, American Society of Anesthesiologists, body mass index, previous abdominal surgery, multiple or single liver resection, lesion >50 mm or <50 mm, presence of solitary or multiple lesions, T stage, and N stage. RESULTS: The standard abdominal approach was used in 110 laparoscopic liver resections, and the thoraco-abdominal laparoscopic combined approach was used in 62 laparoscopic liver resections. The thoraco-abdominal laparoscopic combined approach was associated with better intraoperative results (less blood loss and no need for conversion to open surgery). The R1s rate for segmentectomy 7 and 8 was lower in the thoraco-abdominal laparoscopic combined approach in the entire group and in the colorectal liver metastasis subgroup. In the colorectal liver metastasis subgroup, the 3- and 5-year overall survival was 90% and 80% in the thoraco-abdominal laparoscopic combined approach group and 76% and 52% in the standard abdominal approach group, respectively (P = .02). In univariate and multivariate analysis, the thoraco-abdominal laparoscopic combined approach was a significant factor that positively affected disease-free survival and overall survival. CONCLUSION: The thoraco-abdominal laparoscopic combined approach in laparoscopic liver resection in segments 7 and 8 is safe and feasible, and it has demonstrated better oncologic outcomes than the pure abdominal approach, especially in segmentectomy.

Conditional cumulative incidence of postoperative complications stratified by complexity classification for laparoscopic liver resection: Optimization of in-hospital observation.

BACKGROUND: The optimal in-hospital observation periods associated with minimal risks of complications and unplanned readmission after laparoscopic liver resection are unknown. The purpose of this study was to assess changes in the risks of postoperative complications over time. METHODS: Surgical complexity of laparoscopic liver resection was stratified into grades I (low complexity), II (intermediate), and III (high) using our 3-level complexity classification. The cumulative incidence rate and conditional probability of postoperative complication and risk factors for complication Clavien-Dindo grade ≥II (defined as treatment-requiring complications) were assessed. RESULTS: The cumulative incidence of treatment-requiring complications was higher in patients undergoing grade III resection than in patients undergoing grade I resection (32.3% vs 10.4%, P < .001) and grade II resection (32.3% vs 20.7%, P = .019). The conditional probability of postoperative complication stratified by our complexity classification decreased over time and was <10% for patients undergoing grade I resection on postoperative day 1, grade II resection on postoperative day 4, and grade III resection on postoperative day 10. CONCLUSION: The conditional cumulative incidence of treatment-requiring complications for patients undergoing laparoscopic liver resection is well stratified based on the 3-level complexity classification. Conditional complication risk analysis stratified by the 3 complexity grades may be useful for optimizing in-hospital observation after laparoscopic liver resection.

A systematic review and meta-analysis of liver venous deprivation versus portal vein embolization before hepatectomy: future liver volume, postoperative outcomes, and oncological safety.

Introduction: This systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and oncological safety before major hepatectomy. Methods: We conducted this systematic review and meta-analysis following the PRISMA guidelines 2020 and AMSTAR 2 guidelines. Comparative articles published before November 2022 were retained. Results: The literature search identified nine eligible comparative studies. They included 557 patients, 207 in the LVD group and 350 in the PVE group. This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, percentage of FLR hypertrophy, lower failure of resection due to low FLR, faster kinetic growth, higher day 5 prothrombin time, and higher 3 years' disease-free survival. This study did not find any difference between the LVD and PVE groups in terms of complications related to embolization, FLR percentage of hypertrophy after embolization, failure of resection, 3-month mortality, overall morbidity, major complications, operative time, blood loss, bile leak, ascites, post hepatectomy liver failure, day 5 bilirubin level, hospital stay, and three years' overall survival. Conclusion: LVD is as feasible and safe as PVE with encouraging results making some selected patients more suitable for surgery, even with a small FLR. Systematic review registration: The review protocol was registered in PROSPERO before conducting the study (CRD42021287628).

R1 Vascular or Parenchymal Margins: What Is the Impact after Resection of Intrahepatic Cholangiocarcinoma?

Background: to date, long-term outcomes of R1 vascular (R1vasc) and R1 parenchymal (R1par) resections in the setting of intrahepatic cholangiocarcinoma (iCCA) have been examined in only one study which did not find significant difference. Patients and Methods: we analyzed consecutive patients who underwent iCCA resection between 2000 and 2019 in two tertiary French medical centers. We report overall survival (OS) and disease-free-survival (DFS). Univariate and multivariate analyses were performed to determine associated factors. Results: 195 patients were analyzed. The number of R0, R1par and R1vasc patients was 128 (65.7%), 57 (29.2%) and 10 (5.1%), respectively. The 1- and 2-year OS rates in the R0, R1par and R1vasc groups were 83%, 87%, 57% and 69%, 75%, 45%, respectively (p = 0.30). The 1- and 2-year DFS rates in the R0, R1par and R1vasc groups were 58%, 50%, 30% and 43%, 28%, 10%, respectively (p = 0.019). Resection classification (HR 1.56; p = 0.003) was one of the independent predictors of DFS in multivariate analysis. Conclusions: the survival outcomes after R1par resection are intermediate to those after R0 or R1vasc resection. R1vasc resection should be avoided in patients with iCCA as it does not provide satisfactory oncological outcomes.

Umbilical Cord PRP vs. Autologous PRP for the Treatment of Hip Osteoarthritis.

Umbilical cord platelet-rich plasma (C-PRP) has more growth factors and anti-inflammatory molecules compared with autologous PRP (A-PRP) derived from peripheral blood. The aim of this study was to compare intra-articular C-PRP or A-PRP injections in terms of safety and clinical efficacy for the treatment of patients with hip osteoarthritis (OA). This study investigated the results of 100 patients with hip OA treated with three weekly ultrasound-guided injections of either C-PRP or A-PRP. Clinical evaluations were performed before the treatment and after two, six, and twelve months with the HHS, WOMAC, and VAS scores. No major adverse events were recorded. Overall, the improvement was limited with both treatments. Significant improvements in VAS (p = 0.031) and HHS (p = 0.011) were documented at two months for C-PRP. Patients with a low OA grade (Tonnis 1-2) showed a significantly higher HHS improvement with C-PRP than A-PRP at twelve months (p = 0.049). C-PRP injections are safe but offered only a short-term clinical improvement. The comparative analysis did not demonstrate benefits compared with A-PRP in the overall population, but the results are influenced by OA severity, with C-PRP showing more benefits when advanced OA cases were excluded. Further studies are needed to confirm the most suitable indications and potential of this biological injective approach.

Ultrasound-guided injection of platelet-rich plasma or cord blood platelet-rich plasma in nonunion: a randomized controlled trial.

Aim: To compare the ability of autologous platelet-rich plasma (PRP) and cord blood PRP (PRPc) to accelerate bone healing. Patients & methods: 71 patients with mechanically stable nonunion were treated weekly (3 consecutive weeks) with ultrasound-guided percutaneous injections of PRP or PRPc in a controlled randomized clinical trial. The primary outcome was healing (12 months) and secondary outcomes were radiological evolution (2 and 6 months) and changes in pain intensity (6 months). Results & conclusion: Bone consolidation was assessed over time without significant differences between PRP and PRPc treatment. In patients with persistent nonunion, pain perception decreased more after PRP treatment. PRPc appears to be a valid alternative when specific clinical conditions suggest avoiding the use of autologous blood products.

Although the regenerative capacity of bone tissue is well recognized, the fracture repair process may be impaired by unfavorable conditions resulting in delayed union or complete nonunion. In this scenario, the use of autologous blood derivates to accelerate bone healing has been proposed. The aim of this study was to compare the therapeutic efficacy of autologous platelet-rich plasma (PRP) and cord blood PRP (PRPc) in bone nonunion. PRPc contains high levels of cytokines and growth factors, has low immunogenicity and can be successfully stored until use. This study verified that bone consolidation was similar in PRP and PRPc treatments, thus supporting PRPc as a valid therapeutic option when clinical conditions discourage the use of autologous blood derivates.

Randomised, double-blind comparison of a fixed co-formulation of intra-articular polynucleotides and hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: two-year follow-up.

BACKGROUND: A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period. METHODS: Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. EVALUATIONS: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. STATISTICAL ANALYSIS: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons. RESULTS: KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group. CONCLUSIONS: The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease. TRIAL REGISTRATION: NCT02417610 . Registration, 15/04/2015. ClinicalTrials.gov database link.

Commercial Bone Grafts Claimed as an Alternative to Autografts: Current Trends for Clinical Applications in Orthopaedics.

In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use.