Efficacy of local anaesthetic infiltration via wound catheters after open hepatic surgery: a systematic review and meta-analysis.

BACKGROUND: This study analysed whether local anaesthetic wound catheter infiltration (LA-WCI) as an adjunct to intravenous patient-controlled analgesia (IV-PCA) provides superior outcomes compared to IV-PCA alone following liver resection. METHODS: A systematic review and meta-analysis was conducted for randomised control trials (RCTs) comparing LA-WCI with IV-PCA(LA-WCI group) versus IV-PCA alone (IV-PCA group). PubMed and the Cochrane Library were searched for relevant articles. RESULTS: Six RCTs with a total of 440 patients were included. Opioid use in the initial 48 h was less in the LA-WCI group [MD -21.27 mg (-39.39,-3.15), p = 0.02]. Pain scores were lower in the LA-WCI group at rest at POD0 (post-operative day 0)6-8 h (p = 0.0009), POD1AM(p = 0.01), POD1PM(p = 0.02) and POD2 (p = 0.0006), and exertion at POD0 0-2 h (p = 0.05), POD1AM(p = 0.03), POD1PM(p = 0.03), POD2 (p = 0.03) and POD3 (p = 0.01). LA-WCI group had reduced length of hospital stay [MD -1.32 days (-2.23,-0.40),p = 0.005], time to ambulation [MD -5.94 h (-8.47,-3.42),p = 0.00001] and incidence of nausea and vomiting (PONV) [OR 0.17 (0.07,0.43),p = 0.0002]. No differences were observed in length of intensive care unit (ICU) stay or incidence of surgical site infections. DISCUSSION: LA-WCI as an adjunct to opiate IV-PCA post-hepatectomy reduces opioid use, pain scores at multiple time points at rest and exertion, length of hospital stay, time to ambulation and PONV. However, LA-WCI use does not alter length of ICU stay or incidence of wound infection.

Clinical outcomes of non-operative management and clinical observation in non-angioembolised hepatic trauma: A systematic review of the literature.

PURPOSE: Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE. METHODS: A systematic literature review searched "liver trauma", "hepatic trauma", "conservative management", "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test. RESULTS: A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%. CONCLUSION: NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.

COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis.

Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60-65 years) (OR 4.26; 95% CI, 2.14-8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms. In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%). Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities.

Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. METHODS: A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. RESULTS: Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001). CONCLUSIONS: We identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.

Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo.

The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBPα expression were linked onto PDAC-specific 2'-Fluropyrimidine RNA aptamers (2'F-RNA) - P19 and P1 for construction of a cell type-specific delivery vehicle. Both P19- and P1-C/EBPα-saRNA conjugates increased expression of C/EBPα and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail.

Follicular thyroid carcinoma: differences in clinical relevance between minimally invasive and widely invasive tumors.

BACKGROUND: Evidence on the biological behavior and clinical courses of minimally invasive and widely invasive follicular thyroid carcinoma (MI-FTC, WI-FTC) is still debatable. The current study was conducted to identify differences between MI and WI tumors and those prognostic parameters influencing late outcome such as local recurrence and survival. METHODS: From January 1998 to October 2013, 71 patients were operated on in our department because of a FTC. A retrospective cohort study was carried out to compare 42 MI-FTC and 29 WI-FTC. The comparison involved evaluation of patient characteristics, tumor characteristics, tumor staging, and risk assessment. RESULTS: A diameter greater than 4.0 cm, the presence of vascular invasion, the TNM stage III-IVA, and the high risk at AMES system risk stratification were independent factors significantly related to the presence of a WI-FTC. The only independent predictor of recurrence and disease-free survival at 10-year follow-up was a tumor size greater than 4.0 cm. CONCLUSIONS: More attention must be paid in the postoperative tumor re-staging of those patients with tumor size larger than 4.0 cm, which was the only parameter predicting recurrence and influencing disease-free survival. Nevertheless, definitive recommendations cannot be made without a longer follow-up.

Piperacillin/tazobactam for surgical prophylaxis during pancreatoduodenectomy: meta-analysis.

BACKGROUND: Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics. METHODS: Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000-2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4. RESULTS: A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien-Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group. CONCLUSION: Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien-Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice.

Meta-analysis of studies comparing single-incision laparoscopic appendectomy and conventional multiport laparoscopic appendectomy.

BACKGROUND: There is no consensus that single-incision laparoscopic appendectomy (SILS-A) is on a par with conventional multiport laparoscopic appendectomy (CMLA). The aim of this meta-analysis was to assess feasibility, safety, and potential benefits of SILS-A when compared with CMLA. METHODS: A literature search for studies comparing SILS-A and CMLA was performed. Studies were reviewed for the outcome of interest: patient characteristics, operative outcome, postoperative recovery, postoperative morbidity, patient satisfaction, and cosmetic results. RESULTS: Thirteen studies comparing SILS-A and CMLA were reviewed: two prospective randomized trials, four prospective studies, and seven retrospective studies. Overall, 893 patients were operated on: by SILS-A in 402 cases (45.0%) versus 491 cases (55.0%) by CMLA. Patients in the SILS-A group were significantly younger than those in the CMLA group (31.2 versus 33.5 y). No other differences were found. Patient satisfaction score was impossible to meta-analyze. CONCLUSIONS: Appendectomy via SILS-A may be considered as an alternative to CMLA. However, these results must be approached with caution as they are based on data from nonrandomized observational studies. The feasibility and safety of SILS-A must be mainly assessed for difficult clinical situations such as severe obesity, localized abscess, or diffuse peritonitis from a ruptured appendix in the setting of new prospective randomized trials.

Systematic review with meta-analysis of prospective randomized trials comparing minimally invasive video-assisted thyroidectomy (MIVAT) and conventional thyroidectomy (CT).

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) has gained acceptance among surgeons as its feasibility has been well documented. The aim of this systematic review with meta-analysis has been to assess and validate the safety and feasibility of MIVAT when compared to conventional thyroidectomy (CT) and to verify other potential benefits and drawbacks. METHODS: A literature search for prospective randomized trials comparing MIVAT and CT was performed. Trials were reviewed for the primary outcome measures: overall morbidity, recurrent laryngeal nerve palsy, postoperative hypocalcemia, and postoperative hematoma; and for the secondary outcome measures: operative time, conversion to standard procedure, intraoperative blood loss, intraoperative drain insertion, nodule size and thyroid weight, postoperative pain evaluation, length of hospital stay, patient satisfactory score, and cosmetics results. Standardized mean difference (SMD) was calculated for continuous variables and odds ratio for qualitative variables. RESULTS: Nine prospective randomized studies comparing MIVAT and CT were analyzed. Overall, 581 patients were randomized to either MIVAT (289, 49.7 %) or CT (292, 50.3 %). The primary outcome measures of MIVAT were comparable with those of CT without statistically significant difference. Patients who underwent MIVAT experienced significantly less pain than those operated on conventionally during the whole postoperative period. Patient satisfactory score significantly favored MIVAT (9.0 vs. 6.8, SMD = -3.388, 95 % CI = -5.720 to -1.057). Operative time was significantly longer in MIVAT (75.2 vs. 59.2 min, SMD = 1.246, 95 % CI = 0.227-2.266). CONCLUSIONS: MIVAT is a safe and feasible alternative for the removal of small-volume benign thyroid disease and low-risk papillary thyroid carcinomas showing better cosmetics results and less postoperative pain but significantly longer operative time when compared to CT. New multicenter randomized studies are needed to evaluate the technique in more complex circumstances such as intermediate-risk thyroid cancer, lymph node removal, thyroiditis, and Graves' disease.

Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms.

Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Factors predicting in-hospital mortality of patients with diffuse peritonitis from perforated colonic diverticulitis.

AIM: Diverticulitis free perforation still remains a major life-threatening condition. Herein we evaluate factors influencing prognosis of patients with perforated colonic diverticulitis and the current validity of Mannheim Peritonitis Index (MPI) in predicting mortality. MATERIAL OF STUDY: From January 2000 to October 2010, 39 patients were operated on for generalized peritonitis from perforated diverticulitis RESULTS: Five postoperative deaths (12.8%) related to septic shock occurred. A cross-sectional study between deceased and non-deceased patients was carried out. Deceased patients were significantly older than non-deceased (76.4 vs. 59.1 years,p=0.019); duration of symptoms was longer in deceased patients (102 vs. 26.9 hours, p=0.000); MPI was higher in deceased patients (31.4 vs. 21.2, p=0.000). Age, duration of symptoms and MPI were independent risk factors predicting poor prognosis. The highest sensitivity and specificity of MPI in predicting mortality was shown for a score higher than 27. CONCLUSIONS: MPI is still effective in predicting postoperative mortality. People who nurse older persons must pay higher attention to complaints in order to reduce the delay in hospitalization.

Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon.

This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.

Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review.

BACKGROUND: The T-cell costimulation blocking agent belatacept has been identified as a possible substitute for calcineurin inhibitors, however, no consensus has been established against its use over the standard care agent Tacrolimus. AIM: To evaluate the effectiveness of belatacept based maintenance immuno-suppressive regimens in comparison to tacrolimus in renal transplantion. METHODS: We did extensive search of all the available literature comparing the role of belatacept to tacrolimus in renal transplant recipients by searching the PubMed, Embase, Cochrane, Crossref, Scopus, clinical trials registry on October 5, 2020. RESULTS: The literature search identified four randomized controlled trials (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). However, incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05). CONCLUSION: The evidence reviewed in this meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus; however, observed significantly reduced new onset diabetes mellitus after transplantation incidence and lower serum low density lipid profile levels in belatacept group. In addition, the adaptation of belatacept in renal transplantation has been forestalled by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity.

The Impact of COVID-19 on Kidney Transplant Recipients in Pre-Vaccination and Delta Strain Era: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

Oncocytic cell tumors of the thyroid: factors predicting malignancy and influencing prognosis, treatment decisions, and outcomes.

BACKGROUND: The distinction between malignant and benign thyroid oncocytic cell tumors (OCTs) before and during surgery still represents a diagnostic challenge. We focused on the search for specific factors that predict malignancy and influence the prognosis of OCTs, and for their most appropriate management. METHODS: From January 1998 to May 2007, 57 patients underwent thyroidectomy in our surgical department because of OCT. A cross-sectional study of 28 patients with carcinoma and 29 patients with adenoma was performed: demographic data, tumor characteristics, diagnostic results, patient management, postoperative, and follow-up results were evaluated. RESULTS: The prevalence of malignancy was 49.1%. The mean tumor size was significantly greater for carcinomas than for adenomas (3.0 cm vs. 1.8 cm; p = 0.003). Threshold sizes of more than 3.0 cm and 4.0 cm were significant for predicting malignancy (p = 0.020 and p = 0.010, respectively). Tumor multifocality, microfollicular features, and severe cytological atypia also were significantly related to malignancy (p = 0.012 and p = 0.025, respectively). Recurrent OCT was observed in three patients with carcinoma. One patient with distant metastases died from the disease. Older age, tumor size, thyroid capsular invasion, higher TNM stage, and AMES high risk were factors significantly related to tumor recurrence. Multivariate analysis showed that larger tumor size was the only factor predictive of malignancy and influencing recurrence. CONCLUSIONS: All OCTs should be referred to surgery because of the high prevalence of malignancy. In the case of OCTs with larger tumor size and microfollicular features with severe cytological atypia, total thyroidectomy is strongly recommended as initial treatment also in relation with the more likely aggressive biological behavior of greater tumors.

Prophylactic intra-abdominal drainage following colorectal anastomoses. A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinically evident Anastomotic Leakage (AL) remains one of the most feared complications after colorectal resections with primary anastomosis. The primary aim of this systematic review and meta-analysis was to determine whether Prophylactic Drainage (PD) after colorectal anastomoses confers any advantage in the prevention and management of AL. METHODS: Systematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized studies comparing clinical outcomes of patients with Drained (D) or Undrained (UD) colorectal anastomoses performed for any cause. RESULTS: Four randomized controlled trials comparing D and UD patients undergoing colorectal resections with primary anastomosis were included for quantitative synthesis. In total, 1120 patients were allocated to group D (n = 566) or group UD (n = 554). The clinical AL rate was 8.5% in the D group and 7.6% in the UD group, with no statistically significant difference (P = 0.57). Rates of radiological AL (D: 4.2% versus UD: 5.6%; P = 0.42), mortality (D: 3.6% versus UD: 4.4%; P = 0.63), overall morbidity (D: 16.6% versus UD: 18.6%, P = 0.38), wound infection (D: 5.4% versus UD: 5.3%, P = 0.95), pelvic sepsis (D: 9.7% versus UD: 10.5%, P = 0.75), postoperative bowel obstruction (D: 9.9% versus UD: 6.9%, P = 0.07), and reintervention for abdominal complication (D: 9.1% versus UD: 7.9%, P = 0.48) were equivalent between the two groups. CONCLUSIONS: The present meta-analysis of randomized controlled trials investigating the value of PD following colorectal anastomoses does not support the routine use of prophylactic drains.

Liver Activation of Hepatocellular Nuclear Factor-4α by Small Activating RNA Rescues Dyslipidemia and Improves Metabolic Profile.

Non-alcoholic fatty liver disease (NAFLD) culminates in insulin resistance and metabolic syndrome. Because there are no approved pharmacological treatment agents for non-alcoholic steatohepatitis (NASH) and NAFLD, different signaling pathways are under investigation for drug development with the focus on metabolic pathways. Hepatocyte nuclear factor 4-alpha (HNF4A) is at the center of a complex transcriptional network where its disruption is directly linked to glucose and lipid metabolism. Resetting HNF4A expression in NAFLD is therefore crucial for re-establishing normal liver function. Here, small activating RNA (saRNA) specific for upregulating HNF4A was injected into rats fed a high-fat diet for 16 weeks. Intravenous delivery was carried out using 5-(G5)-triethanolamine-core polyamidoamine (PAMAM) dendrimers. We observed a significant reduction in liver triglyceride, increased high-density lipoprotein/low-density lipoprotein (HDL/LDL) ratio, and decreased white adipose tissue/body weight ratio, all parameters to suggest that HNF4A-saRNA treatment induced a favorable metabolic profile. Proteomic analysis showed significant regulation of genes involved in sphingolipid metabolism, fatty acid ß-oxidation, ketogenesis, detoxification of reactive oxygen species, and lipid transport. We demonstrate that HNF4A activation by oligonucleotide therapy may represent a novel single agent for the treatment of NAFLD and insulin resistance.

The use of radiofrequency ablation in pancreatic cancer in the midst of the dawn of immuno-oncology.

Despite significant improvement in treatment, the prognosis of pancreatic ductal adenocarcinoma remains poor as the biology of the tumour affects survival even when a radical resection has been performed. Pancreatic cancer remains resistant to currently available chemotherapeutic options. Recently, immunotherapy has achieved significant results in certain types of cancer. However, for pancreatic cancer, results were not initially encouraging as pancreatic cancer microenvironment is highly immunosuppressive. Radiofrequency ablation is currently used as treatment option especially for liver cancer with significant results. However, in pancreatic cancer, the use of radiofrequency ablation is relatively new. Radiofrequency ablation has been identified as a promising mechanism to induce antigen-presenting cell infiltration and enhance systemic antitumour T-cell immune response and tumour regression. In this short communication, we briefly review the role of radiofrequency ablation in pancreatic cancer and explore the idea that the combination of radiofrequency ablation with immunotherapy could represent a novel and promising treatment.

Normothermic ex-vivo liver perfusion: where do we stand and where to reach?

INTRODUCTION: Nowadays liver transplantation is considered as the treatment of choice, however, the scarcity of suitable donor organs limits the delivery of care to the end-stage liver disease patients leading to the death while on the waiting list. The advent of ex-situ normothermic machine perfusion (NMP) has emerged as an alternative to the standard organ preservation technique, static cold storage (SCS). The newer technique promises to not only restore the normal metabolic activity but also attempt to recondition the marginal livers back to the pristine state, which are otherwise more susceptible to ischemic injury and foster the poor post-transplant outcomes. Areas covered: An extensive search of all the published literature describing the role of NMP based device in liver transplantation as an alternative to SCS was made on MEDLINE, EMBASE, Cochrane, BIOSIS, Crossref, Scopus databases and clinical trial registry on 10 May 2018. Expert commentary: The main tenet of NMP is the establishment of the physiological milieu, which permits aerobic metabolism to continue through out the period of preservation and limits the effects of ischemia-reperfusion (I/R) injury. In addition, by assessing the various metabolic and synthetic parameters the viability and suitability of donor livers for transplantation can be determined. This important technological advancement has scored satisfactorily on the safety and efficacy parameters in preliminary clinical studies. The present review suggests that NMP can offer the opportunity to assess and safely utilize the marginal donor livers if deemed appropriate for the transplantation. However, ongoing trials will determine its full potential and further adoption.