Current standards and future perspectives in adjuvant treatment for biliary tract cancers

Biliary tract cancer, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are rare tumours with a rising incidence. Prognosis is poor, since most patients are diagnosed with advanced disease. Only ~20% of patients are diagnosed with early-stage disease, suitable for curative surgery. Despite surgery performed with potentially-curative intent, relapse rates are high, with around 60–70% of patients expected to have disease recurrence. Most relapses occur in the form of distant metastases, with a predominance of liver spread. In view of high tumour recurrence, adjuvant strategies have been explored for many years, in the form of radiotherapy, chemo-radiotherapy and chemotherapy. Historically, few randomised trials were available, which included a variety of additional tumours (e.g. pancreatic and ampullary tumours); most evidence relied on phase II and retrospective studies, with no high-quality evidence available to define the real benefit derived from adjuvant strategies.Since 2017, three randomised phase III clinical trials have been reported; all recruited patients with resected biliary tract cancer (CCA and GBC) who were randomised to observation alone, or chemotherapy in the form of gemcitabine (BCAT study; included patients diagnosed with extrahepatic CCA only), gemcitabine and oxaliplatin (PRODIGE-12/ACCORD-18; included patients diagnosed with CCA and GBC) or capecitabine (BILCAP; included patients diagnosed with CCA and GBC). While gemcitabine-based chemotherapy failed to show an impact on patient outcome (relapse-free survival (RFS) or overall survival (OS)), the BILCAP study showed a benefit from adjuvant capecitabine in terms of OS (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis), with confirmed benefit in terms of RFS. Based on the BILCAP trial, international guidelines recommend adjuvant capecitabine for a period of six months following potentially curative resection of CCA as the current standard of care for resected CCA and GBC. However, BILCAP failed to show OS benefit in the intention-to-treat (non-sensitivity analysis) population (primary end-point), and this finding, as well as some inconsistencies between studies has been criticised and has led to confusion in the biliary tract cancer medical community.This review summarises the adjuvant field in biliary tract cancer, with evidence before and after 2017, and comparison between the latest randomised phase III studies. Potential explanations are presented for differential findings, and future steps are explored.     

Emodin attenuates acute lung injury in Cecal-ligation and puncture rats

Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.     

A systematic review of combined pelvic and acetabular injuries

PurposeInjuries of both pelvic ring and acetabulum as rare very few articles are available in literature. There are no set protocols in defining the injury let alone defining early and definitive management strategies. This article is an attempt to encompass all available data to give us guidelines in managing these injuries.MethodsAn extensive literature review was carried out on PubMed/Medline, google scholar and Embase databases was done with the eligibility criteria of 1) Case series with a minimum of 20 cases. 2) The patient’s outcome reported. 3) Full article available. 4) Article in English. 5) Minimum Jadad score of 3. As per PRISMA guidelines the search was done and gradually filtered down to relevant articles which were 8 in number.ResultsThe incidence of these injuries range from 5 to 16%. The transverse acetabular fracture pattern is the commonest followed by associated both column fractures. There is equal propensity of Anteroposterior compression and lateral compression injuries. The injury mechanism appears to transmitted lateral force from the greater trochanter inwards with an implosion injury causing acetabular and pelvic injury as a continuum. The initial management is similar to managing pelvic ring injuries with focus on patient resuscitation, hemodynamic stabilization and temporary stabilization. The injury severity score and the mortality rates are comparable to isolated unstable pelvic ring injuries. Definitive management focuses on fixing the posterior pelvic ring first followed by the acetabular fracture and then the anterior pelvic ring. The displacement rates and outcome is worse than isolated acetabular injuries or pelvic injuries.ConclusionCombined Pelvic and acetabular injuries are complex injuries which need to be managed initially as we manage pelvic injury and later as we fix as an acetabular fracture meticulously.     

Stage 1 acute kidney injury is independently associated with infection following cardiac surgery

ObjectivesSevere acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality.MethodsIn this retrospective propensity score–matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsStage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71–3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45).ConclusionsStage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.     

A 4‐year follow‐up case of extrusive luxation in a patient with cerebral palsy

Cerebral palsy (CP) is a condition caused by brain damage before, during, or shortly after birth. Communication can be a challenge when treating patients with CP. Some patients can communicate verbally, while others use augmentative alternative communication tools or have individualized means of communication. Therefore, professional dental treatment in individuals with CP is challenging, especially if the patient is affected by dental trauma and requires emergency treatment. This report shows how individualized communication skills assessment allowed us to successfully manage a 9‐year‐old patient with CP, who suffered extrusive luxation of the permanent lower incisor. In the present case, the teeth were repositioned briefly after the trauma had occurred and then stabilized with a flexible splint according to international guidelines. The teeth remained vital and periodontal repair was observed during the 4‐year follow‐up.     

Utility of INR For Prediction of Delayed Intracranial Hemorrhage Among Warfarin Users with Head Injury

BackgroundIncidence of delayed intracranial hemorrhage (DICH) in patients on warfarin has been controversial. No previous literature has reported the utility of international normalized ratio (INR) in predicting traumatic DICH.ObjectivesUtilizing INR to risk stratify head trauma patients who may be managed without repeat imaging.MethodsThis was a retrospective study at a Level II trauma center. All patients on warfarin with head injuries from March 2014 to December 31, 2017 were included. Each patient underwent an initial head computed tomography scan (HCT) and subsequent repeat HCT 12 h after. Patients presenting > 12 h after head injury received only one HCT. Two blinded neuroradiologists reviewed each case of DICH. Statistical analysis evaluated Glasgow Coma Scale (GCS), Injury Severity Score (ISS), heart rate, systolic blood pressure (SBP), age, and platelet count.ResultsThere were 395 patients who qualified for the protocol; 238 were female. Average age was 79 years. Seventy-seven percent of patients underwent repeat HCT. Five resulted in DICH (INR 2.6–3.0), three of which might have been present on initial HCT; incidence rate of 0.51–1.27%. One patient required neurosurgical intervention. Among 80 patients with INR < 2, no DICH was identified, resulting in high sensitivity, but with a wide confidence interval; sensitivity of 100% (95% confidence interval [CI] 47.8–100), specificity 21% (95% CI 16.6–28.9). Correlation of factors: ISS (p = 0.039), GCS (p = 0.978), HR (p = 0.601), SBP (p = 0.198), age (p = 0.014), and platelets (p = 0.281).ConclusionNo patient with INR < 2 suffered DICH, suggesting that warfarin users presenting with INR < 2 may be managed without repeat HCT. For INR > 2, patients age and injury severity can be used for shared decision-making to discharge home with standard head injury precautions and no repeat HCT.