Radioembolization for Treatment of Hepatocellular Carcinoma: Current Evidence and Patterns of Utilization.

Primary liver malignancy, of which hepatocellular carcinoma (HCC) is the most common type, is the second most common cause of death due to cancer worldwide. Given the historically poor prognosis of liver cancer, there has been major research on its treatment options, with significant advancements over the last decade. Transarterial radioembolization (TARE) is a locoregional treatment option for HCC that involves transarterial delivery of the ß-emitter yttrium-90 via resin or glass microspheres to arterialized tumor vasculature, delivering a tumoricidal dose to the tumor. The recent 2022 update of the Barcelona Clinic Liver Cancer (BCLC) treatment algorithm features a more prominent role for locoregional treatment, including the incorporation of radioembolization for very-early-stage (BCLC-0) and early-stage (BCLC-A) diseases. This review provides a contemporary summary of the evolving role of TARE in treatment of HCC in light of recent and upcoming trials.

Recurrent common bile duct stones as a late complication of endoscopic sphincterotomy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) has become well established as a modality for the management of common bile duct stones (CBDS), especially in the setting of associated cholangitis. Our study aims to determine the rate of long term morbidity of recurrent CBDS post ES. METHODS: A retrospective analysis of patients who underwent ERCP and ES (ERCP+ES) was undertaken on a prospectively maintained database from 1998 to 2012 at the Northern Hospital, Melbourne. Primary CBDS were defined as those detected at least 6 months after complete clearance of the CBD. Prior cholecystectomy was a requirement for inclusion and patients with primary CBD stones in the setting of an intact sphincter were excluded. RESULTS: A total of 1148 patients underwent ERCP, of which 573 had an ES. Fifty-one patients underwent an ES prior to developing primary CBDS (8.9%). The time to recurrence ranged from 6 months to 15 years (mean 3.3 years). The number of procedures per patient ranged from 2 to 11, with 51% requiring 3 or more ERCPs. Factors associated with primary CBDS recurrence included a dilated CBD > 12 mm, stricture of the major papilla post ES to 2 - 5 mm and presence of the ampulla within or on the edge of a duodenal diverticulum. CONCLUSION: The results demonstrate that ERCP + ES has an inherent long-term complication of recurrent primary CBDS formation. While this can be managed with repeat ERCP, the advent of laparoscopic bile duct exploration should lead us to re-examine the role of ERCP + ES in younger patients.

Atypical femoral fracture in a patient treated with denosumab.

Atypical fractures of the femur (AFF) have been reported in the literature at an increasing rate over the past decade, especially in patients who have been on prolonged courses of bisphosphonates. However, there have only been a few reported cases of AFF in those treated with other antiresorptive medications. In this case report, a 72-year-old woman with chronic obstructive pulmonary disease and osteoporosis presented with an atraumatic right femoral fracture in the setting of denosumab use. In contrast with other reports, this patient had received bisphosphonate therapy for a short duration before the switch to denosumab. While causality between the fracture and denosumab use cannot be established in this case, there is a growing number of reports of a similar association. Ongoing vigilance is required to determine whether denosumab is associated with or potentially a cause of AFF.

Non-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescens.

Serratia marcescens is a common nosocomial infection but a rare cause of osteomyelitis and more so of vertebral osteomyelitis. Vertebral osteomyelitis caused by this organism has been reported in few studies. We report a case of S. marcescens vertebral discitis and osteomyelitis affecting multiple non-contiguous vertebras. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes, such as S. marcescens, need to be considered, especially when risk factors such as intravenous heroin use, post-spinal surgery and immunosuppression are present. Therefore, blood culture and where necessary biopsy of the infected region should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility. Prompt diagnosis of S. marcescens vertebral osteomyelitis followed by the appropriate treatment can achieve successful outcomes.

Identifying risk factors and patterns for unplanned readmission to a general medical service.

OBJECTIVE: To identify factors and patterns associated with 7- and 28-day readmission for general medicine patients at a tertiary public hospital. METHODS: A retrospective observational study was conducted using an administrative database at a general medicine service in a tertiary public hospital between 1 January 2007 and 31 December 2011. Demographic and clinical factors, as well as readmission patterns, were evaluated for the association with 7- and 28-day readmission. RESULTS: The study cohort included 13 802 patients and the 28-day readmission rate was 10.9%. In multivariate analysis, longer hospital stay of the index admission (adjusted relative risk (ARR) 1.34), Charlson index ≥ 3 (ARR 1.28), discharge against medical advice (ARR 1.87), active malignancy (ARR 1.83), cardiac failure (ARR 1.48) and incomplete discharge summaries (ARR 1.61) were independently associated with increased risk of 28-day readmission. Patients with diseases of the respiratory system, neurological or genitourinary disease, injury and unclassifiable conditions were likely to be readmitted within 7 days. Patients with circulatory and respiratory disease were likely to be readmitted with the same system diagnosis. CONCLUSION: Readmission of general medicine patients within 28 days is relatively common and is associated with clinical factors and patterns. Identification of these risk factors and patterns will enable the interventions to reduce potentially preventable readmissions.

Asymptomatic elevation of creatine kinase in patients with hyponatremia.

Elevated creatine kinase (hyper-CKemia) has been observed in small number of patients with hyponatremia. This study evaluated the features and outcomes of patients admitted with hyponatremia complicated by hyper-CKemia. Patients admitted with hyponatremia and concurrently found to have elevated creatine kinase (CK) of above 375 IU/L (male) or 225 IU/L (female), over a 5-year period were retrospectively reviewed. Those with myocardial injury (elevated CK-MB isoenzyme [CK-MB/CK percentage of >2.5%] or Troponin T [>0.02 µg/L]), traumatic or ischemic muscle damage, primary myopathic disorder, seizures prior to CK measurement or those taking medications which can cause myopathy, were excluded. Thirty-two patients with hyponatremia and hyper-CKemia were identified. All patients had no muscular symptoms or weakness. The commonest cause of hyponatremia in this cohort was related to diuretics (50%). The mean sodium level on presentation was 116.0 ± 6.9 mmol/L and the median peak CK was 895.5 (interquartile range: 610.8-1691.8) IU/L. Six (18%) patients developed acute kidney injury (AKI). The length of hospital admission of the entire cohort was 8.0 ± 5.8 days. Patients with hyper-CKemia in the setting of diuretic-associated hyponatremia were older and had longer hospital length of stay compared with primary-polydipsia-associated. Asymptomatic hyper-CKemia is an uncommon association with hyponatremia of various etiologies. Hyponatremia-associated hyper-CKemia can be complicated by AKI.

Minimal change disease associated with newly diagnosed mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare but aggressive form of non-Hodgkin's lymphoma. Involvement of the kidney is an infrequent occurrence in patients with MCL and can be the result of direct infiltration or paraneoplastic glomerulopathy. Proliferative glomerulonephritis, membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis have previously been reported in association with MCL. We report a 55-year-old woman who developed nephrotic syndrome due to biopsy proven minimal change disease (MCD) in association with MCL. Proteinuria decreased with prednisolone treatment and MCD remains in remission without any immunosuppressant after the treatment of the underlying MCL.

Addressing disparities in health outcomes for patients with advanced pancreatic cancer and limited English proficiency.

INTRODUCTION: There are significant challenges and a lack of data related to culturally and linguistically diverse (CALD) cancer patients. We compared patient characteristics, treatment patterns, and outcomes of patients with advanced pancreatic cancer that required an interpreter. METHODS: Registry data was extracted for advanced pancreatic cancer patients from a single health institution with a comprehensive Transcultural and Language Service (TALS). Demographic and clinicopathologic characteristics were compared. Kaplan-Meier survival estimates with log-rank testing, and univariate and multivariable regression analysis were performed to compare the group with limited English proficiency (LEP) to the English proficient (EP) group. RESULTS: Of 155 patients, 32.9% (n = 51) required the TALS. The LEP group had a higher mean age (71.2 vs. 76.8 years; p = 0.005) and received less chemotherapy (42.3% vs. 31.4%, p = 0.220). Univariate analysis revealed a shorter median overall survival (OS) in the LEP group (3.6 vs. 5.0 months), with a hazard ratio [HR] of 1.51 (95% confidence interval [CI]: 1.03-2.21, p = 0.033). Upon multivariable analysis, adjusting for Eastern Cooperative Oncology Group (ECOG) performance scale, the number of sites of metastatic disease and chemotherapy use, the strength of association between LEP and OS reduced marginally (HR 1.42, 95% CI: 0.93-2.16), and was no longer statistically significant (p = 0.103). CONCLUSIONS: In patients with advanced pancreatic cancer utilizing a comprehensive TALS, there was a trend to poorer survival with limited English proficiency, although this association was not statistically significant. An ongoing research commitment to the CALD experience is necessary to build a granular understanding of this population and ensure equitable outcomes.

How to do a laparoscopic pancreaticoduodenectomy.

This paper describes our technique of laparoscopic pancreaticoduodenectomy and our experience in performing this procedure.

Haemoglobin drift in patients following Whipple's procedure.

BACKGROUNDS: This study aims to identify the objective findings of haemoglobin (Hb) drift in patients that had a Whipple's procedure in the last 10 years, their transfusion status intraoperatively and post-operatively, the potential factors affecting Hb drift, and the outcomes following Hb drift. METHODS: A retrospective study was conducted at Northern Health, Melbourne. All adult patients who were admitted for a Whipple's procedure from 2010 to 2020 were included and information collected retrospectively for demographics, pre-operative, operative and post-operative details. RESULTS: A total of 103 patients were identified. The median Hb drift calculated from a Hb level at the end of operation was 27.0 g/L (IQR 18.0-34.0), and 21.4% of patients received a packed red blood cell (PRBC) transfusion during the post-operative period. Patients received a large amount of intraoperative fluid with a median of 4500 mL (IQR 3400-5600). Hb drift was statistically associated with intraoperative and post-operative fluid infusion leading to concurrent issues with electrolyte imbalance and diuresis. CONCLUSION: Hb drift is a phenomenon that does happen in major operations such as a Whipple's procedure, likely secondary to fluid over-resuscitation. Considering the risk of fluid overload and blood transfusion, Hb drift in the setting of fluid over-resuscitation needs to be kept in mind prior to blood transfusion to avoid unnecessary complications and wasting of other precious resources.

Comparing Stone Recurrence Following Surgical Common Bile Duct Exploration or Endoscopic Stone Extraction for Patients with Common Bile Duct Stones.

Background: Laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) are two methods of retrieving common bile duct (CBD) stones. Aspects of CBD stone management, such as sphincterotomy, have been implicated as risks for CBD stone recurrence although evidence is weak. The aim of this study was to compare stone recurrence following LCBDE and/or ERCP. Methods: Data were collected retrospectively for patients undergoing LCBDE and/or ERCP for CBD stones at a single center from 2008 to 2018. Primary outcome was stone recurrence (>6 months after duct clearance). Risk factors for recurrence were assessed using univariate and multivariate analyses. Results: A total of 445 patients underwent LCBDE-only, 79 patients underwent ERCP-only and 80 patients underwent LCBDE-ERCP. LCBDE-only patients were younger and preoperatively less morbid than ERCP-only patients. Although there was no significant difference for recurrence, there was a trend toward higher recurrence with ERCP-only compared with LCBDE-only and LCBDE-ERCP (5.1% versus 2.0% and 2.5%, P = .280). On univariate comparison, patients with a recurrence were significantly older, had a higher admission white cell count, higher number of ERCPs, increased transampullary stent use, and higher maximum CBD diameter. Total number of ERCP was the only independent predictor of stone recurrence (odds ratio 6.85 [2.55-18.42], P < .001) following multivariate regression. Conclusion: Management plan was not associated with stone recurrence. The total number of ERCP was the only independent predictor of recurrence. Within the limitations of case selection and bias toward LCBDE, this study suggests that limiting repeated ERCP may reduce CBD stone recurrence.

Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in a renal transplant recipient.

Abstract Calcific uremic arteriolopathy (CUA) is a rare but life-threatening disorder of arteriolar calcification. It frequently leads to severe ischemia, intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually occurs in patients with chronic kidney disease (CKD), especially those on dialysis, and its occurrence is rare in kidney transplant recipients. The treatment of this disorder is not clearly defined, and no randomized prospective trials are available. Treatment has focused on optimizing dialysis treatment, control of bone mineral parameters, wound care, experimental anticalcification therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric oxygen. Such treatments are based on the pathophysiological considerations and evidences from case reports or series. Recently, several cases have reported about the emerging benefits of intravenous sodium thiosulfate (STS) in the treatment of CUA. STS has resulted in rapid pain relief, wound healing, and prevention of death. We report a case of CUA in a 63-year-old Caucasian man with a functioning renal allograft. In this patient, intravenous STS was administered for 8 months, which was the principal therapy, which resulted in complete resolution of the CUA and skin healing.

Does sodium bicarbonate reduce painful voiding after flexible cystoscopy? A prospective, randomized, double-blind, controlled trial.

OBJECTIVE: • To determine if sodium bicarbonate (Ural) reduces painful voiding after flexible cystoscopy. PATIENTS AND METHODS: • 300 patients over 18 years old undergoing elective flexible cystoscopy were enrolled in a randomized, double-blinded, placebo-controlled trial. Patients with active urinary tract infections, indwelling urinary catheters and/or requiring additional procedures such as biopsy and dilatation were excluded. • Painful voiding was quantified using a pain analogue scale from 0 to 10. Pre-existing painful voiding, previous experience with Ural and flexible cystoscopy were recorded. • Flexible cystoscopy was performed to a standard protocol. Patients were randomised after recruitment to receive Ural or placebo (glucose) powder four times a day for two days after the procedure. Trial outcome was assessed by estimating the change in pain incidence and severity from before to two days after by post-procedural questionnaire. RESULTS: • Painful voiding was present in 84 of the 300 patients post flexible cystoscopy (45 of 160 patients receiving Ural; 39 of 140 receiving placebo), but overall mean pain scores were low (1.25; standard deviation 2.4; on a 0-10 scale). • Treatment with Ural compared to placebo was associated with a non-significant reduction in frequency of pain (28.9% vs 31.3%; incidence rate ratio 0.66; 95% CI 0.29-1.46; P = 0.30) and severity of pain (odds ratio 0.72; 95% CI 0.30-1.74; P = 0.47). CONCLUSION: •In the replicable context of low post-cystoscopy pain levels, we believe Ural does not reduce painful voiding after flexible cystoscopy.

Circulating microRNA expression is reduced in chronic kidney disease.

BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, which have roles in renal development and disease. They exist in biological fluids including blood and urine and may have signalling roles and potential as disease biomarkers. METHODS: We measured the levels of miRNAs in patients with different stages of chronic kidney failure including those receiving maintenance haemodialysis treatment. RESULTS: In patients with severe chronic renal failure, circulating levels of total and specific miRNAs are reduced in comparison to patients with mild renal impairment or normal renal function. A strong correlation exists between detected circulating miRNAs and estimated glomerular filtration rate, and less strong correlations with other features of chronic kidney disease, such as anaemia and hyperparathyroidism. CONCLUSION: These findings have important implications for the use of circulating miRNAs as biomarkers in individuals with renal impairment and for the pathogenesis of uraemia.

Should Common Bile Duct Exploration for Choledocholithiasis Be a Specialist-Only Procedure?

Background: Common bile duct exploration (CBDE) is performed uncommonly. Issues surrounding its uptake in the laparoscopic era include perceived difficulty and lack of training. We aim to determine the success of CBDE performed by "specialist" and "nonspecialist" common bile duct (CBD) surgeons to determine whether there is a substantial difference in success and safety. Methods: A 10-year retrospective audit was performed of patients undergoing CBD exploration for choledocholithiasis. Northern Health maintains an on-call available "specialist" CBD surgeon roster to aid with CBDE. Results: Five hundred fifty-one patients were identified, of which 489/551 (88.7%) patients had stones successfully cleared. Specialists had a higher success rate (90.8% versus 82.6%, P = .008), associated with a longer surgical time. Method (transcystic or transductal), approach (laparoscopic or open), and indication for operation were similar between groups. There was no significant difference in complications. To be confident of a surgeon having an 80% success rate, 70 procedures over 10 years were required, however, an "in-control" 50% success rate may only require 1 procedure per year. Conclusion: While specialist CBDE surgeons have improved success rates, nonspecialist general surgeons also have a good and comparable success rate with an equivalent complication rate. With realistic annual targets, nonspecialist CBD surgeons should be encouraged to perform CBDE in centers without specialist support.

Factors That Predict the Success of Laparoscopic Common Bile Duct Exploration for Choledocholithiasis: A 10-Year Study.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) can be performed to treat choledocholithiasis at the time of laparoscopic cholecystectomy. The aim of this study was to identify factors that predict the success of LCBDE. MATERIALS AND METHODS: A retrospective audit was performed on patients who underwent LCBDE for the management of choledocholithiasis at Northern Health between 2008 and 2018. RESULTS: A total of 513 patients were identified with an overall success rate of 90.8%. Most LCBDE were done through a transcystic approach with the remainder through a choledochotomy. When comparing patients with a successful operation to those that were unsuccessful, univariate analysis demonstrated significant differences in preoperative white cell count and number of duct stones found. Age and elevated nonbilirubin liver function tests were found to be significant factors associated with the failure of LCBDE on multivariate analysis. The likelihood of a failed operation in those with multiple stones was observed to be almost halved compared with patients with single stone although this did not reach significance [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.28-1.01, P=0.055]. Multivariate analysis indicated that unsuccessful procedures (OR: 10.13, 95% CI: 4.34-23.65, P<0.001) and multiple duct stones (OR: 3.79, 95% CI: 1.66-8.67, P=0.002) were associated with an increased risk of severe complications. CONCLUSIONS: A single impacted stone may be more difficult to remove, however complications were more likely to be associated with multiple duct stones. With no other clinically relevant predictive factors, and because of the high success of the procedure and the low morbidity, LCBDE remains an option for all patients with choledocholithiasis.

Mediastinal parathyroid carcinoma presenting with severe skeletal manifestations.

Parathyroid carcinoma is a rare malignancy, accounting for about 1% of primary hyperparathyroidism. We report the case of a 23-year-old man who presented with poorly united mid-shaft fracture of the left femur with severe hypercalcaemia in the setting of 99 mTc sestamibi-avid lesions in the mediastinal and thoracic vertebrae. The patient underwent surgery, and histopathology revealed a low-grade parathyroid carcinoma. After surgery, the patient developed severe hungry bone syndrome requiring intensive calcium, magnesium and active vitamin D supplementation. A review of the literature was undertaken with regards to mediastinal parathyroid carcinoma, management of refractory hypercalcaemia in this setting and hungry bone syndrome.

Bilateral renal inflammatory pseudotumour effectively treated with corticosteroid.

Inflammatory pseudotumour (IPT) is a rare disease of unknown cause that most commonly involves the lung but can occur in almost any site in the body. Occurrence in the kidneys is very rare and bilateral renal involvement even rarer. There are 34 previously reported cases in the English-language medical literature between 1966 and 2008. Herein we report a case of IPT infiltrating both kidneys. We have also reviewed the clinical features, radiological findings, treatment and outcome of renal IPT. Clinical features at presentation are commonly non-specific. Features on imaging are inadequate to make a diagnosis of IPT or to clearly distinguish it from malignancy. Consequently diagnosis has frequently been made after nephrectomy and on a few occasions with the aid of percutaneous or open biopsies. The majority of renal IPT (83%) have been treated with nephrectomy and those cases with bilateral IPT have received corticosteroids.

Review: The role of microRNAs in kidney disease.

MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-ß activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.

Malignant pleural mesothelioma with associated minimal change disease and acute renal failure.

Paraneoplastic manifestations in malignant pleural mesothelioma are rare. We report a case of malignant pleural mesothelioma associated with minimal change disease (MCD). A 58-year-old man with occupational exposure to asbestos presented with severe peripheral edema, heavy proteinuria, and acute renal failure shortly after the diagnosis of mesothelioma had been confirmed. The renal biopsy demonstrated MCD. The underlying pathogenesis of this association remains unknown.