IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.

BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.

Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.

BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.

Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01).

BACKGROUND: Primary analysis of the multicenter, open-label, single-arm, phase II DESTINY-Breast01 trial (median follow-up 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with a median follow-up of 26.5 months (data cut-off 26 March 2021). PATIENTS AND METHODS: Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety. RESULTS: The ORR by ICR was 62.0% [95% confidence interval (CI) 54.5% to 69.0%] in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) and 18.2 months (95% CI 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had one or more grade ≥3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n = 29), of which 2.7% (n = 5) were grade 5. CONCLUSIONS: These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Midkine Promotes Odontoblast-like Differentiation and Tertiary Dentin Formation.

Autophagy is an intracellular self-degradation process that is essential for tissue development, cell differentiation, and survival. Nevertheless, the role of autophagy in tooth development has not been definitively identified. The goal of this study was to investigate how autophagy is involved in midkine (MK)-mediated odontoblast-like differentiation, mineralization, and tertiary dentin formation in a mouse tooth pulp exposure model. In vitro studies show that MK and LC3 have similar expression patterns during odontoblast-like cell differentiation. Odontoblast-like cell differentiation is promoted through MK-mediated autophagy, which leads to increased mineralized nodule formation. Subcutaneous transplantation of hydroxyapatite/tricalcium phosphate with rMK-treated human dental pulp cells led to dentin pulp-like tissue formation through MK-mediated autophagy. Furthermore, MK-mediated autophagy induces differentiation of dental pulp cells into odontoblast-like cells that form DSP-positive tertiary dentin in vivo. Our findings may provide 1) novel insight into the role of MK in regulating odontoblast-like differentiation and dentin formation in particular via autophagy and 2) potential application of MK in vital pulp therapy.

Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study.

BACKGROUND: The phase Ib KEYNOTE-173 study was conducted to assess the safety and preliminary antitumor activity of neoadjuvant chemotherapy plus pembrolizumab in high-risk, early-stage, non-metastatic triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Six pembrolizumab plus chemotherapy regimens were evaluated (cohorts A-F). All cohorts received a pembrolizumab 200-mg run-in dose (cycle 1), then eight cycles of pembrolizumab in combination with a taxane with or without carboplatin for 12 weeks, and then doxorubicin and cyclophosphamide for an additional 12 weeks before surgery. Primary end points were safety and recommended phase II dose (RP2D); secondary end points were pathological complete response (pCR) rate, objective response rate, and event-free and overall survival. Exploratory end points were the relationship between outcome and potential biomarkers, such as tumor programmed death ligand 1 (PD-L1) expression (combined positive score) and stromal tumor-infiltrating lymphocyte levels (sTILs). RESULTS: Sixty patients were enrolled between 18 February 2016, and 28 February 2017. Dose-limiting toxicities occurred in 22 patients, most commonly febrile neutropenia (n = 10 across cohorts). Four cohorts (B, C, D, F) did not meet the RP2D threshold; two cohorts did (A, E). The most common grade ≥3 treatment-related adverse event was neutropenia (73%). Immune-mediated adverse events and infusion reactions occurred in 18 patients (30%) and were grade ≥3 in six patients (10%). The pCR rate (ypT0/Tis ypN0) across all cohorts was 60% (range 49%-71%). Twelve-month event-free and overall survival rates ranged from 80% to 100% across cohorts (100% for four cohorts). Higher pre-treatment PD-L1 combined positive score, and pre- and on-treatment sTILs were significantly associated with higher pCR rates (P = 0.0127, 0.0059, and 0.0085, respectively). CONCLUSION: Combination neoadjuvant chemotherapy and pembrolizumab for high-risk, early-stage TNBC showed manageable toxicity and promising antitumor activity. In an exploratory analysis, the pCR rate showed a positive correlation with tumor PD-L1 expression and sTIL levels. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02622074.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with early breast cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

In view of the planned new edition of the most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of primary breast cancer published in 2015, it was decided at the ESMO Asia Meeting in November 2018, by both the ESMO and the Korean Society of Medical Oncology (KSMO), to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the latest ESMO 2019 guidelines to take into account the ethnic and geographical differences associated with the treatment of early breast cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with early breast cancer representing the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO) Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices, and the drug availability and reimbursement situations, in the individual participating Asian countries.

Lactobacillus probiotics improved the gut microbiota profile of a Drosophila melanogaster Alzheimer's disease model and alleviated neurodegeneration in the eye.

Alzheimer's disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects of Lactobacillus probiotics through feeding to our Drosophila melanogaster AD model. The administration of Lactobacillus strains was able to rescue the rough eye phenotype (REP) seen in AD-induced Drosophila, with a more prominent effect observed upon the administration of Lactobacillus plantarum DR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-induced Drosophila and found elevated levels of Wolbachia. The administration of DR7 restored the gut microbiota diversity of AD-induced Drosophila with a significant reduction in Wolbachia's relative abundance, accompanied by an increase of Stenotrophomonas and Acetobacter. Through functional predictive analyses, Wolbachia was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's diseases, while Stenotrophomonas was negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7's ability to ameliorate the AD effects in our AD-induced Drosophila. Thus, we propose that Wolbachia be used as a potential biomarker for AD.

Lactobacillus plantarum DR7 alleviates stress and anxiety in adults: a randomised, double-blind, placebo-controlled study.

Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomised, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×109 cfu/day) for 12 weeks reduced symptoms of stress (P=0.024), anxiety (P=0.001), and total psychological scores (P=0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 (P<0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning (P<0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine ß-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo (P<0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.

Effectiveness and core components of infection prevention and control programmes in long-term care facilities: a systematic review.

BACKGROUND: Infection prevention and control (IPC) is a measure to prevent healthcare-associated infections in healthcare settings. There is limited evidence of the effectiveness of IPC programmes in long-term care facilities (LTCFs). AIM: To review and analyse the effectiveness and the components of IPC programmes in LTCFs for older adults. METHODS: Electronic databases (PubMed, EMBASE, CINAHL and Cochrane CENTRAL) were searched systematically for English-language articles assessing IPC interventions in LTCFs, published over the last decade (2007-2016). The components of IPC programmes were analysed based on the World Health Organization (WHO) manuals for improving IPC activities. Two reviewers independently assessed the quality of studies using the Cochrane risk-of-bias tool and the risk-of-bias assessment tool for non-randomized studies. FINDINGS: Seventeen studies met the eligibility criteria; 10 studies were randomized trials (58.8%) and the others were non-randomized trials to examine the impact of IPC programmes on infection and/or performance outcomes of healthcare workers. None of the included studies implemented all of the WHO core components. Behavioural change strategies using education, monitoring and feedback were reported to be successful interventions for reducing the threat of healthcare-associated infections. Generally, studies using four or more elements of the WHO multi-modal strategy reported significant reductions in infection rates. CONCLUSIONS: There is some evidence for the effectiveness of IPC interventions using education, monitoring, feedback and four or more elements of the WHO multi-modal strategy to control healthcare-associated infections in LTCFs.

Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial.

BACKGROUND: Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. OBJECTIVES: To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. METHODS: In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. RESULTS: A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC-14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC-14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported. CONCLUSIONS: PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.

Clinical relevance of amnestic versus non-amnestic mild cognitive impairment subtyping in Parkinson's disease.

BACKGROUND AND PURPOSE: To clarify whether subtyping of amnestic and non-amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes. METHODS: We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting-state functional connectivity between the patients with de-novo PD with amnestic MCI (PD-aMCI) (n = 50) and non-amnestic MCI (PD-naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de-novo PD-aMCI (n = 125) and PD-naMCI (n = 61). RESULTS: The demographic data showed that scores in memory domains were lower in the PD-aMCI group compared with the PD-naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD-aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD-aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD-naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD-aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD-naMCI (P = 0.022). In addition, the PD-aMCI group had a higher risk of dementia conversion than the PD-naMCI group. CONCLUSIONS: This study suggests that the designation of PD-MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.

Changes in Bone Mineral Density After Kidney Transplantation.

BACKGROUND: Numerous studies have shown that osteoporosis is common in kidney transplant recipients. However, the change in bone mineral density after kidney transplantation (KT) is not fully understood. METHODS: Thirty-nine kidney transplant recipients with bone densitometry at pretransplant and 24 months after KT were reviewed. RESULTS: The recipients' median age (44.5 ± 10.7 years) and dialysis duration before KT (4.2 ± 3.4 years) were recorded. The T-scores of the lumbar spine and femur neck at 24 months after KT were positively associated with the respective pretransplant T-score (P < .001 in the lumbar spine and P < .001 in the femur neck). However, the T-score after KT did not show significant change (P = .680 in lumbar spine, P = .093 in femur neck). Changes in the T-scores of the lumbar spine and femur neck over 24 months (delta T-score) were negatively associated with the respective pretransplant T-scores (P = .001 in lumbar spine, P = .026 in femur neck). Changes in the T-scores of the lumbar spine and femur neck over 24 months (delta T-score) were also associated with the pretransplant T-scores after the adjustment of other variables. CONCLUSION: The change of bone mineral density was related with pretransplant bone mineral density. Careful follow-up of bone densitometry for KT recipients was needed.

Suspected Frequent Relapsing IgG4-related Lung Disease in Kidney Transplant Patient: A Case Report.

Besides the initial description of IgG4-related pancreatic disease, other sites are now commonly involved. However, occurrence of IgG4-related disease is rare in organ transplanted patients. A 57-year-old man who received a kidney transplantation presented with recurrent dyspnea on exertion. A computed tomography scan of the chest revealed bilateral interlobular septal thickening and multiple tubular and branching small nodular lesions in the right upper lobe, and mass-like consolidation of the left middle lobe. Despite no elevation of serum IgG4 level, a percutaneous core needle biopsy on consolidative mass showed interstitial fibrosis and infiltration of IgG4-positive plasma cells to be more than > 20 per high power field. After treatment with glucocorticoids and rituximab, the consolidative mass of the left middle lobe disappeared.

Predictors of compartment syndrome of the foot after fracture of the calcaneus.

Aims: Identifying predictors of compartment syndrome in the foot after a fracture of the calcaneus may lead to earlier diagnosis and treatment. The aim of our study was to identify any such predictors. Patients and Methods: We retrospectively reviewed 303 patients (313 fractures) with a fracture of the calcaneus who presented to us between October 2008 and September 2016. The presence of compartment syndrome and potential predictors were identified by reviewing their medical records. Potential predictors included age, gender, concomitant foot injury, mechanism of injury, fracture classification, time from injury to admission, underlying illness, use of anticoagulant/antiplatelet agents, smoking status and occupation. Associations with predictors were analyzed using logistic regression analysis. Results: Of the 313 fractures of the calcaneus, 12 (3.8%) developed a compartment syndrome. A Sanders type IV fracture was the only strongly associated factor (odds ratio 21.67, p = 0.007). Other variables did not reach statistical significance. Conclusion: A Sanders type IV fracture is the best predictor of compartment syndrome after a fracture of the calcaneus. Cite this article: Bone Joint J 2018;100-B:303-8.

Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience.

PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

Lateral neck dissection affects the voice in thyroid cancer patients.

OBJECTIVE: This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients. METHODS: Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups. RESULTS: Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery. CONCLUSION: In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.