Pregabalin for decreasing pancreatic pain in chronic pancreatitis

BACKGROUND: Chronic abdominal pain is one of the major symptoms in people with chronic pancreatitis. The role of pregabalin in people with chronic pancreatic pain due to chronic pancreatitis is uncertain. OBJECTIVES: To assess the benefits and harms of pregabalin in people with chronic abdominal pain due to chronic pancreatitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, issue 6, and MEDLINE, EMBASE, Science Citation Index Expanded, trials registers until June 2015. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCT) performed in people with chronic pancreatic pain due to chronic pancreatitis, irrespective of language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on intention-to-treat analysis. MAIN RESULTS: Only one study, funded by Pfizer, met the inclusion criteria for the review. A total of 64 participants (with chronic pain due to chronic pancreatitis) were randomly assigned to receive escalating doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (30 participants). Participants received pregabalin or placebo for three weeks on an outpatient basis; the outcomes were measured at the end of the treatment (i.e. three weeks from commencement of treatment). Potential participants taking concomitant analgesic medication and expected to stay on a stable regime during the trial were allowed to enter the study. This trial was at low risk of bias. The overall quality of evidence was low or moderate.Only the short-term outcomes were available in this trial. The medium and long-term outcomes, number of work days lost, and length of hospital stay due to admissions for pain control were not available. This trial found that the changes in opiate use (MD -26.00 mg; 95% CI -47.36 to -4.64; participants = 64; moderate-quality evidence), and pain score percentage changes from baseline (MD -12.00; 95% CI -21.82 to -2.18; participants = 64; moderate-quality evidence) were better in participants taking pregabalin compared to those taking placebo. This trial also found that there were more adverse events in participants taking pregabalin compared to those taking placebo (RR 1.71; 95% CI 1.20 to 2.43; participants = 64). The differences between pregabalin and placebo were imprecise for short-term health-related quality of life measured with the EORTC CLQ-30 questionnaire (MD 11.40; 95% CI -3.28 to 26.08; participants = 64; moderate-quality evidence), proportion of people with serious adverse events (RR 1.76; 95% CI 0.35 to 8.96; participants = 64; low-quality evidence), and proportion of people requiring hospital admissions (RR 0.44; 95% CI 0.04 to 4.62; participants = 64; low quality evidence). AUTHORS' CONCLUSIONS: Based on low- to moderate-quality evidence, short-term use of pregabalin decreases short-term opiate use, and short-term pain scores, but increases the adverse events compared to placebo, in people with chronic pain due to chronic pancreatitis. The clinical implication of the decreases in short-term opiate use and short-term pain scores is not known.Future trials assessing the role of pregabalin in decreasing chronic pain in chronic pancreatitis should assess the medium- or long-term effects of pregabalin and should include outcomes such as, quality of life, treatment-related adverse events, number of work days lost, number of hospital admissions, and the length of hospital stay, in addition to pain scores, to assess the clinical and socioeconomic impact

Duodenum-preserving pancreatic resection versus pancreaticoduodenectomy for chronic pancreatitis

BACKGROUND: Surgical excision by removal of the head of the pancreas to decompress the obstructed ducts is one of the treatment options for people with symptomatic chronic pancreatitis. Surgical excision of the head of the pancreas can be performed by excision of the duodenum along with the head of the pancreas (pancreaticoduodenectomy (PD)) or without excision of the duodenum (duodenum-preserving pancreatic head resection (DPPHR)). There is currently no consensus on the method of pancreatic head resection in people with chronic pancreatitis. OBJECTIVES: To assess the benefits and harms of duodenum-preserving pancreatic head resection versus pancreaticoduodenectomy in people with chronic pancreatitis for whom pancreatic resection is considered the main treatment option. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers to June 2015 to identify randomised trials. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCT) performed in people with chronic pancreatitis undergoing pancreatic head resection, irrespective of language, blinding, or publication status, for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR), mean difference (MD), rate ratio (RaR), or hazard ratio (HR) with 95% confidence intervals (CI) based on an available-case analysis. MAIN RESULTS: Five trials including 292 participants met the inclusion criteria for the review. After exclusion of 23 participants mainly due to pancreatic cancer or because participants did not receive the planned treatment, a total of 269 participants (with symptomatic chronic pancreatitis involving the head of pancreas and requiring surgery) were randomly assigned to receive DPPHR (135 participants) or PD (134 participants). The trials did not report the American Society of Anesthesiologists (ASA) status of the participants. All the trials were single-centre trials and included people with and without obstructive jaundice and people with and without duodenal stenosis but did not report data separately for those with and without jaundice or those with and without duodenal stenosis. The surgical procedures compared in the five trials included DPPHR (Beger or Frey procedures, or wide local excision of the head of the pancreas) and PD (pylorus-preserving pancreaticoduodenectomy or Whipple procedure). The participants were followed up for various periods of time ranging from one to 15 years. The trials were at unclear or high risk of bias. The overall quality of evidence was low or very low.The differences in short-term mortality (up to 90 days after surgery) (RR 2.89, 95% CI 0.31 to 26.87; 369 participants; 5 studies; DPPHR: 2/135 (1.5%) versus PD: 0/134 (0%); very low quality evidence) or long-term mortality (maximal follow-up) (HR 0.65, 95% CI 0.31 to 1.34; 229 participants; 4 studies; very low quality evidence), medium-term (three months to five years) (only a narrative summary was possible; 229 participants; 4 studies; very low quality evidence), or long-term quality of life (more than five years) (MD 8.45, 95% CI -0.27 to 17.18; 101 participants; 2 studies; low quality evidence), proportion of people with adverse events (RR 0.55, 95% CI 0.22 to 1.35; 226 participants; 4 studies; DPPHR: 23/113 (adjusted proportion 20%) versus PD: 41/113 (36.3%); very low quality evidence), number of people with adverse events (RaR 0.95, 95% CI 0.43 to 2.12; 43 participants; 1 study; DPPHR: 12/22 (54.3 events per 100 participants) versus PD: 12/21 (57.1 events per 100 participants); very low quality evidence), proportion of people employed (maximal follow-up) (RR 1.54, 95% CI 1.00 to 2.37; 189 participants; 4 studies; DPPHR: 65/98 (adjusted proportion 69.4%) versus PD: 41/91 (45.1%); low quality evidence), incidence proportion of diabetes mellitus (maximum follow-up) (RR 0.78, 95% CI 0.50 to 1.22; 269 participants; 5 studies; DPPHR: 25/135 (adjusted proportion 18.6%) versus PD: 32/134 (23.9%); very low quality evidence), and prevalence proportion of pancreatic exocrine insufficiency (maximum follow-up) (RR 0.83, 95% CI 0.68 to 1.02; 189 participants; 4 studies; DPPHR: 62/98 (adjusted proportion 62.0%) versus PD: 68/91 (74.7%); very low quality evidence) were imprecise. The length of hospital stay appeared to be lower with DPPHR compared to PD and ranged between a reduction of one day and five days in the trials (208 participants; 4 studies; low quality evidence). None of the trials reported short-term quality of life (four weeks to three months), clinically significant pancreatic fistulas, serious adverse events, time to return to normal activity, time to return to work, and pain scores using a visual analogue scale. AUTHORS' CONCLUSIONS: Low quality evidence suggested that DPPHR may result in shorter hospital stay than PD. Based on low or very low quality evidence, there is currently no evidence of any difference in the mortality, adverse events, or quality of life between DPPHR and PD. However, the results were imprecise and further RCTs are required on this topic. Future RCTs comparing DPPHR with PD should report the severity as well as the incidence of postoperative complications and their impact on patient recovery. In such trials, participant and observer blinding should be performed and the analysis should be performed on an intention-to-treat basis to decrease the bias. In addition to the short-term benefits and harms such as mortality, surgery-related complications, quality of life, length of hospital stay, return to normal activity, and return to work, future trials should consider linkage of trial participants to health databases, social databases, and mortality registers to obtain the long-term benefits and harms of the different treatments

Mesenchymal Stem Cells: A Future Option for Intervening Disease Management

Regeneration, revitalizing and reversal (RRR) are the primordial functions of the stem cells in the field of regenerative medicine. Though there are several cases of successful stem cell transplantation the reversal of metabolic diseases and the acquired secondary complications like chronic renal failure, neuropathy, stroke or vascular diseases are not well studied. The transplanted cells in many cases failed to home or graft in the host with no reason to attribute for such failures. Therefore, it becomes necessary to address these secondary complications with cellular therapy. The oxidative stress of the cells and tissues are attributed to the hostile microenvironment, not suitable for the survival of newly recruited cells. From our few animal studies and published literatures sources elsewhere, we foresee a huge potential for using mesenchymal stem cells (MSCs) to initially combat the secondary cardiovascular and neuronal complications in the management of the metabolic diseases. However, not all the stem cells have been tested in these lines, and further we do not know, whether all the progenitor cells from various sources and origin will behave like MSCs, which needs to be studied extensively

A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection

OBJECTIVE: This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia-reperfusion (IR) injury during elective liver resection. METHOD: A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network metaanalysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. RESULTS: Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. CONCLUSION: Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits

Feasibility of Comparing the Results of Pancreatic Resections between Surgeons: A Systematic Review and Meta-Analysis of Pancreatic Resections

Background. Indicators of operative outcomes could be used to identify underperforming surgeons for support and training. The feasibility of identifying HPB surgeons with poor operative performance ("outliers") based on the results of pancreatic resections is not known. Methods. A systematic review of Medline, Embase, and the Cochrane library was performed to identify studies on pancreatic resection including at least 100 patients and published between 2004 and 2014. Proportions that lay outside the upper 95% and 99.8% confidence intervals based on results of the systematic reviews were considered as "outliers." Results. In total, 30 studies reporting on 10712 patients were eligible for inclusion in this review. The average short-term mortality after pancreatic resections was 3.1% and proportion of patients with procedure-related complications was 47.0%. None of the classification systems assessed the long-term impact of the complications on patients. The surgeon-specific mortality should be 5 times the average mortality before he or she can be identified as an outlier with 0.1% false positive rate if he or she performs 50 surgeries a year. Conclusions. A valid risk prognostic model and a classification system of surgical complications are necessary before meaningful comparisons of the operative performance between pancreatic surgeons can be made

Development, Validation, and Modelling of Image Guidance Systems for Surgery

Image guidance systems for surgery enable the surgeon to make use of information from various sources during surgery. Such systems have the potential to improve outcomes for patients by allowing the surgeon to easily assimilate prior knowledge from pre-operative clinical scans as well as novel intra-operative imaging techniques. A key challenge is how to filter and process this information to allow it to be presented in an accurate, timely, and intuitive manner. Badly designed or poorly understood image guidance systems risk distracting the surgeon with irrelevant or incorrect information, leading to patient harm. The aim of my research is to develop tools to better quantify the performance of surgical image guidance systems, and measure how the system performance affects patient outcomes. I will present the results of my work developing the “SmartLiver”[1] image guidance system for minimally invasive liver surgery. I will follow this with a proposal for a generalised model of image guidance systems as multi input control systems

Performance of image guided navigation in laparoscopic liver surgery – A systematic review

Background: Compared to open surgery, minimally invasive liver resection has improved short term outcomes. It is however technically more challenging. Navigated image guidance systems (IGS) are being developed to overcome these challenges. The aim of this systematic review is to provide an overview of their current capabilities and limitations. Methods: Medline, Embase and Cochrane databases were searched using free text terms and corresponding controlled vocabulary. Titles and abstracts of retrieved articles were screened for inclusion criteria. Due to the heterogeneity of the retrieved data it was not possible to conduct a meta-analysis. Therefore results are presented in tabulated and narrative format. Results: Out of 2015 articles, 17 pre-clinical and 33 clinical papers met inclusion criteria. Data from 24 articles that reported on accuracy indicates that in recent years navigation accuracy has been in the range of 8–15 mm. Due to discrepancies in evaluation methods it is difficult to compare accuracy metrics between different systems. Surgeon feedback suggests that current state of the art IGS may be useful as a supplementary navigation tool, especially in small liver lesions that are difficult to locate. They are however not able to reliably localise all relevant anatomical structures. Only one article investigated IGS impact on clinical outcomes. Conclusions: Further improvements in navigation accuracy are needed to enable reliable visualisation of tumour margins with the precision required for oncological resections. To enhance comparability between different IGS it is crucial to find a consensus on the assessment of navigation accuracy as a minimum reporting standard

Multispectral tissue mapping: developing a concept for the optical evaluation of liver disease

Purpose: Alterations in the optical absorption behavior of liver tissue secondary to pathological processes can be evaluated by multispectral analysis, which is increasingly being explored as an imaging adjunct for use in liver surgery. Current methods are either invasive or have a limited wavelength spectrum, which restricts utility. This proof of concept study describes the development of a multispectral imaging (MSI) method called multispectral tissue mapping (MTM) that addresses these issues. Approach: The imaging system consists of a tunable excitation light source and a near-infrared camera. Following the development stage, proof of concept experiments are carried out where absorption spectra from colorectal cancer liver metastasis (CRLM), hepatocellular carcinoma (HCC), and liver steatosis specimen are acquired and compared to controls. Absorption spectra are compared to histopathology examination as the current gold standard for tissue assessment. Generalized linear mixed modeling is employed to compare absorption characteristics of individual pixels and to select wavelengths for false color image processing with the aim of visually enhancing cancer tissue. Results: Analysis of individual pixels revealed distinct absorption spectra therefore suggesting that MTM is possible. A prominent absorption peak at 1210 nm was found in lipid-rich animal tissues and steatotic liver specimen. Liver cancer tissue had a heterogeneous appearance on MSI. Subsequent statistical analysis suggests that measuring changes in absorption behavior may be a feasible method to estimate the pixel-based probability of cancer being present. In CRLM, this was observed throughout 1100 to 1700 nm, whereas in HCC it was concentrated around 1140 and 1430 nm. False color image processing visibly enhances contrast between cancer and normal liver tissues. Conclusions: The system’s ability to enable no-touch MSI at 1100 to 1700 nm was demonstrated. Preliminary data suggest that MTM warrants further exploration as a potential imaging tool for the detection of liver cancer during surger