Pancreatic resection for metastasis from renal cell carcinoma: A single institution experience and meta-analysis of survival outcomes.

AIMS: To evaluate short-term clinical and long-term survival outcomes of pancreatic resection for pancreatic metastasis from renal cell carcinoma (RCC). METHODS: A retrospective evaluation of patients undergoing pancreatic resection for metastasis from RCC over a 12-years period was conducted. Furthermore, a systematic search of electronic data sources and bibliographic reference lists were conducted to identify studies investigating the same clinical question. Short-term clinical and long-term survival outcomes were evaluated. Kaplan-Meier survival plots were constructed for survival outcomes. Cox-proportional regression analysis was performed to determine factors associated with survival. Finally, meta-analysis of survival outcomes was conducted using random-effects modelling. RESULTS: Eighteen patients underwent pancreatic resections for RCC pancreatic metastasis within the study period. The mean age of the included patients was 63.8 ± 8.0 years. There were 10(55.6 %) male and 8(44.4 %) female patients. Pancreatectomy was associated with 4(25.0 %) Clavien-Dindo (C-D) I, 5(31.3 %) C-D II, and 7(43.7 %) C-D III complications, 7(38.8 %) pancreatic fistula, 3(16.7 %) post-pancreatectomy acute pancreatitis, 1(5.6 %) delayed gastric emptying, and 1(5.6 %) chyle leak. The mean length of hospital stay was 18 ± 16.3 days. The median survival was 64 months (95 % CI 60-78). The 3-and 5-year disease-free survival rates were 83.3 % and 55.5 %, respectively. The 3-and 5-year survival rates were 100 % and 55.6 %, respectively. The pooled analyses of 553 patients demonstrated 3-and 5-year survival rates of 77.6 % and 60.7 %, respectively. CONCLUSIONS: Pancreatectomy for RCC metastasis is associated with acceptable short-term clinical and promising long-term survival outcomes. Considering the rarity of the entity, escalation of level of evidence in this context is challenging.

Meta-analysis and trial sequential analysis of randomized controlled trials comparing aggressive versus non-aggressive intravenous fluid therapy in acute pancreatitis: an insight into the existence of type 2 error.

BACKGROUND AND AIM: We aimed to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with acute pancreatitis. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All randomized controlled trials (RCTs) reporting outcomes of aggressive versus non-aggressive IVF therapy in acute pancreatitis were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modeling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors. RESULTS: We included 10 RCTs reporting 993 patients with acute pancreatitis who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR: 2.68, P = 0.0005) and longer length of stay (MD: 0.94, P < 0.00001) compared with the non-aggressive approach. There was no statistically significant difference in mortality (RD: 0.02, P = 0.31), SIRS (OR: 0.93, P = 0.89), respiratory failure (OR: 2.81, P = 0.07), pancreatic necrosis (OR: 1.98, P = 0.06), severe pancreatitis (OR: 1.31, P = 0.38), clinical improvement (OR: 1.12, P = 0.83) or AKI (OR: 1.06, P = 0.91) between the two groups. Sub-group analysis demonstrated higher morbidity and mortality associated with the aggressive approach in more severe disease. Trial sequential analysis detected risk of type 2 error. CONCLUSIONS: Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.

Predicting obstructive sleep apnoea and perioperative respiratory adverse events in children: role of upper airway collapsibility measurements.

BACKGROUND: Obstructive sleep apnoea (OSA) and perioperative respiratory adverse events are significant risks for anaesthesia in children undergoing adenotonsillectomy. Upper airway collapse is a crucial feature of OSA that contributes to respiratory adverse events. A measure of upper airway collapsibility to identify undiagnosed OSA can help guide perioperative management. We investigated the utility of pharyngeal closing pressure (PCLOSE) for predicting OSA and respiratory adverse events. METHODS: Children scheduled for elective adenotonsillectomy underwent in-laboratory polysomnography 2-12 weeks before surgery. PCLOSE measurements were obtained while the child was anaesthetised and breathing spontaneously just before surgery. Logistic regression was used to assess the predictive performance of PCLOSE for detecting OSA and perioperative respiratory adverse events after adjusting for potential covariates. RESULTS: In 52 children (age, mean [standard deviation] 5.7 [1.8] yr; 20 [38%] females), airway collapse during PCLOSE was observed in 42 (81%). Of these, 19 of 42 (45%) patients did not have OSA, 15 (36%) had mild OSA, and eight (19%) had moderate-to-severe OSA. All 10 children with no evidence of airway collapse during the PCLOSE measurements did not have OSA. PCLOSE predicted moderate-to-severe OSA (odds ratio [OR] 1.71; 95% confidence interval [CI]: 1.2-2.8; P=0.011). All children with moderate-to-severe OSA could be identified at a PCLOSE threshold of -4.0 cm H2O (100% sensitivity), and most with no or mild OSA were ruled out (64.7% specificity; receiver operating characteristic/area under the curve=0.857). However, there was no significant association between respiratory adverse events and PCLOSE (OR 1.0; 95% CI: 0.8-1.1; P=0.641). CONCLUSIONS: Measurement of PCLOSE after induction of anaesthesia can reliably identify moderate or severe OSA but not perioperative respiratory adverse events in children before adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ANZCTR ACTRN 12617001503314.

How should we treat long-standing overt ventriculomegaly in adults (LOVA)? A retrospective cohort study.

Long-standing overt ventriculomegaly in adults (LOVA) is a heterogenous group of conditions with differing presentations. Few studies have evaluated success rates of available surgical treatments, or ascertained the natural history. There is a need to assess the efficacy of both endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) as first-line treatments. We conducted a retrospective, single-centre study of adults with LOVA at a tertiary neurosurgery centre in England, UK, aiming to identify presentation, management strategy, and outcome following treatment. A total of 127 patients were included (mean age 48.1 years, 61/127 male). Most patients were symptomatic (73.2%, n = 93/127, median symptom duration 10 months). The most common symptoms were gait ataxia, headache, and cognitive decline (52.8%, 50.4%, and 33.9%, respectively). Fourteen patients had papilloedema. Ninety-one patients (71.7%) underwent surgery (84 ETV, 7 VPS). Over a median follow-up of 33.0 months (interquartile range [IQR] 19.0-65.7), 82.4% had a clinical improvement after surgery, and 81.3% had radiological improvement. Clinical improvement rates were similar between ETV and VP shunt groups (82.1% vs 85.7%, p = 0.812). Surgical complication rates were significantly lower in the ETV group than the VP shunt group (4.8% vs 42.9%, p < 0.001). Of the patients treated surgically, 20 (22.0%) underwent further surgery, with 14 patients improving. This study demonstrates the efficacy of ETV as a first-line treatment for LOVA.

Meta-analysis of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy.

The role of surgical resection in patients with recurrent pancreatic cancer is unclear. We aimed to evaluate the survival outcomes of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy. A literature search was carried out in CENTRAL, EMBASE, MEDLINE, CINAHL, and Web of Science. Proportion meta-analysis model was constructed to quantify 1 to 5-year survival after pancreatic re-resection for locally recurrent pancreatic cancer. Random-effects modelling was applied to calculate pooled outcome data. Fifteen retrospective studies were included, reporting a total of 250 patients who underwent pancreatic re-resection for locally recurrent pancreatic cancer following their index pancreatectomy. Pancreatic re-resection was associated with 1-year survival 70.6% (95% confidence interval [CI], 65.0-76.2), 2-year survival 38.8% (95% CI, 28.6-49.0), 3-year survival 20.2% (95% CI, 13.8-26.7), and 5-year survival 9.2% (95% CI, 5.5-12.8). The between-study heterogeneity was insignificant in all outcome syntheses. Repeat pancreatectomy for local recurrence of pancreatic cancer in the remnant pancreas following the index pancreatectomy is associated with acceptable overall patient survival. We recommend selective re-resection of such recurrences in younger patients with favorable tumor size and location. Our findings may encourage more robust studies to be conducted in this context to provide stronger evidence.

Jelly snakes to reduce early postoperative vomiting in children after adenotonsillectomy: The randomized controlled snakes trial.

BACKGROUND: Despite the use of dual antiemetic agents, postoperative nausea and vomiting (PONV) occurs in an unacceptably large number of patients post-tonsillectomy. There has been increased interest in alternative and non-pharmacological treatments for PONV e.g., chewing gum. We investigated if chewing a large confectionary jelly snake had prophylactic antiemetic effects postoperatively in young children. METHODS: Prospective, open-label randomised controlled trial of 240 patients, 2-16 years. Patients administered a confectionary jelly snake to chew postoperatively were compared with a control group. The primary outcome was the number of episodes of vomiting within 6 h of the operation on an intention-to-treat basis. SECONDARY OUTCOMES: incidence of nausea, vomiting at 6 and 24 h, rescue antiemetic use, acceptability, delayed discharge. RESULTS: 233 patients were randomised to receive the confectionary snake (snake group, 118) or standard care (control group, 115). The number of vomiting episodes in 6 h was similar between groups on an intention-to-treat basis, with 39 episodes across 22 (19%) patients in the control group and 31 across 19 (16%) patients in the snake group (p = 0.666). From post anaesthetic care unit until 24 h there was no difference in doses of antiemetics or delayed discharge due to PONV. A secondary as per protocol analysis did not change this result. CONCLUSIONS: Chewing of confectionery jelly snakes within one hour of waking following adenotonsillectomy with vapour-maintained anaesthesia and two prophylactic antiemetics did not further reduce the incidence of early vomiting. REGISTRATION: prospective registration at the Australia and New Zealand Clinical Trials Registry (ACTRN12618000637246).

Meta-analysis of adjuvant chemotherapy versus no adjuvant chemotherapy for resected stage I pancreatic cancer.

BACKGROUND: To evaluate comparative outcomes of pancreatic cancer resection with or without adjuvant chemotherapy in patients with stage I pancreatic cancer. METHODS: A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without adjuvant chemotherapy were included, and their risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. Survival outcomes were analyzed using the hazard ratio and odds ratio for the time-to-event and dichotomous outcomes, respectively. RESULTS: We included 6 comparative studies reporting a total of 6,874 patients with resected stage 1 pancreatic cancer, of whom 3,951 patients had no adjuvant chemotherapy, and the remaining 2,923 patients received adjuvant chemotherapy. The use of adjuvant chemotherapy was associated with significantly higher overall survival (hazard ratio 0.71, 95% confidence interval 0.62-0.82, P < .00001) and 2-year survival (65.1% vs 57.4%, odds ratio 1.99; 95% confidence interval 1.01-1.41, P = .04) compared to no use of adjuvant chemotherapy. However, there was no statistically significant difference in 1-year (86.8% vs 78.4%, odds ratio 1.60; 95% confidence interval 0.72-3.57, P = .25), 3-year (46.0% vs 44.0%, odds ratio 1.07; 95% confidence interval 0.90-1.29, P = .43), or 5-year survival (24.8% vs 23.3%, odds ratio 1.03; 95% confidence interval 0.80-1.33, P = .81) between the 2 groups. CONCLUSION: Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that adjuvant chemotherapy may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.

Meta-analysis of Long-term De Novo Acid Reflux-Related Outcomes Following Sleeve Gastrectomy: Evidence Against the Need for Routine Postoperative Endoscopic Surveillance.

OBJECTIVES: To evaluate the incidence of long-term de novo acid reflux-related complications following sleeve gastrectomy (SG) to determine whether routine postoperative surveillance endoscopy is necessary. METHODS: A systematic search of Medline, Embase, CINAHL, CENTRAL, the Web of Science, and bibliographic reference lists was conducted. A proportion meta-analysis model was constructed to quantify the risk of the de novo gastro-oesophageal reflux disease (GORD), oesophagitis, and Barrett's oesophagus (BE) at least 4 years after SG. Random-effects modelling was applied to calculate pooled outcome data. RESULTS: Thirty-two observational studies were included reporting a total of 7904 patients who underwent primary SG and were followed up for at least 4 years. The median follow-up period was 60 months (48-132). Preoperative acid-reflux symptoms existed in 19.1% ± 15.1% of the patients. The risk of development of de novo GORD, oesophagitis, and BE after SG was 24.8% (95% CI 18.6-31.0%), 27.9% (95% CI 17.7-38.1%), and 6.7% (95% CI 3.7-9.7%), respectively. The between-study heterogeneity was significant in all outcome syntheses. It was suspected that several of the included studies have not reported BE and oesophagitis because such events might not have happened in their cohorts. CONCLUSIONS: Long-term risk of de novo GORD after SG seems to be comparable with those of the general population which questions the merit of surveillance endoscopy after SG in asymptomatic patients. De novo BE and oesophagitis after SG have not been reported by most of the available studies which may lead to overestimation of the rates of both outcomes in any evidence synthesis. We recommend endoscopic surveillance for symptomatic patients only.

Evaluating the Feasibility of Hydrogel-Based Neural Cell Sprays.

Neurological injuries have poor prognoses with serious clinical sequelae. Stem cell transplantation enhances neural repair but is hampered by low graft survival (ca. 80%) and marker expression/proliferative potential of hydrogel-sprayed astrocytes was retained. Combining a cell spray format with polymer encapsulation technologies could form the basis of a non-invasive graft delivery method, offering potential advantages over current cell delivery approaches.

Stem cell sprays for neurological injuries: a perspective.

Injuries to the brain and spinal cord have major clinical consequences with high costs for healthcare systems. Neural cell transplantation therapies have significant translational potential to promote regeneration post-injury with clinical trials commencing for various pathologies. However, there are challenges associated with current clinical approaches used for systemic or direct delivery of transplant cells to neural tissue in regenerative applications. These include risks associated with surgical microinjection into neural tissue (e.g. haemorrhage, cell clumping) and high cell loss due to systemic clearance or with cell passage through fine gauge needles into densely packed neural tissue. This article presents lines of evidence supporting the concept that cell spray delivery technology can offer significant translational benefits for neural transplantation therapy, versus current cell delivery methods. Potential benefits include rapid/homogenous cell delivery, release over large surface areas, minimal invasiveness, compatibility with neurosurgical procedures in acute injury, no predictable clinical complications and the capacity to combine cell therapies with drug/biomolecule delivery. Accordingly, we consider that the development of cell spray delivery technology represents a key goal to develop advanced cell therapies for regenerative neurology.