Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies

BackgroundDuctal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC).ObjectiveTo assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC.Design, setting, and participantsA single-center retrospective review of all patients with cT1–4/N0–1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients.Outcome measurements and statistical analysisMetastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models.Results and limitationsA total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation.ConclusionsMen undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed.Patient summaryThis study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.     

Elevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation

PurposeWe aimed to assess the prognostic value of Neutrophil to Lymphocyte Ratio (NLR) on long-term outcomes and graft dysfunction after lung transplantation.MethodsWe retrospectively reviewed all patients receiving a lung transplant at our institution from 2011 to 2014. The primary exposure was elevated NLR at the time of transplant, defined by NLR>4. The primary outcomes were graft failure and three-year all-cause mortality. Multivariate logistic regression and Kaplan-Meier survival analysis were used to analyze outcomes.Results95 patients were included. 40 patients (42%) had an elevated NLR. Elevated NLR was associated with graft failure (OR: 4.7 [1.2–18.8], p = 0.02), and three-year mortality (OR: 5.4 [1.3–23.2], p = 0.03) on multivariate logistic regression. Patients with elevated NLR demonstrated significantly lower survival on Kaplan-Meier analysis (50% versus 74%, p = 0.02). The c-statistic for our multivariate model was 0.91.ConclusionElevated neutrophil to lymphocyte ratio is associated with poor long-term survival and graft failure after lung transplantation.     

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance)

Annals of Surgical Oncology - De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete...     

Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.     

Low Bone Mineral Density at Initial Diagnosis in Children and Adolescents with Graves’ Disease

Previous studies have reported reduced bone mineral density (BMD) in patients with hyperthyroidism. We assessed the association of BMD in children and adolescents with Graves’ disease (GD) after correcting for potential confounders affecting BMD such as age, sex, and pubertal status. Forty-four children and adolescents with GD and 172 age- and sex-matched healthy controls were enrolled in this study. We analyzed auxological features, BMD, and levels of thyroid hormone, thyroid-stimulating hormone, and thyroid autoantibodies. We measured BMD by dual-energy X-ray absorptiometry at the time of diagnosis in all patients. The mean age of all patients with GD (9 boys and 32 girls) was 12.1 ± 2.2 years (range, 7.0–16.0). Their initial mean free T4 and thyroid-stimulating hormone levels were 3.51 ± 1.56 ng/dL and 0.04 ± 0.03 IU/L, respectively. The mean BMD Z-scores of the lumbar spine (LS), femoral neck, and total body less head of patients with GD were significantly lower than those of control subjects. Eleven patients (26.8%) had low bone density (LS BMD Z-scores < ?2.0). To identify correlations of patient characteristics with BMD Z-scores at each site, alkaline phosphatase had a significant negative correlation with BMD Z-scores at LS and femoral neck, but not total body less head (r = ?0.441; p = 0.004 and r = ?0.351; p = 0.025, respectively). Children and adolescents with newly diagnosed GD had lower bone mass than their healthy peers. These results suggest that BMD measurement at initial evaluation may be necessary in this population.     

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience

Hernia - Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective...     

Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates

Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell–mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.     

Transurethral Foley catheter misplacement into the upper urinary tract in a patient with a history of lung cancer and chemotherapy: a case report and considerations to keep in mind

Indwelling urethral catheter placement is a common and comparatively safe procedure. Misplacement of a urethral catheter into the upper urinary tract is unusual, and only a few cases have been reported. We describe the case of a 43-year-old man who presented with oliguria and had a history of chemotherapy for known metastatic lung cancer. As he had no history of urological disease, urethral catheterization was expected to be uneventful. The catheter was unable to be pulled back to the bladder neck once the balloon was inflated, and the patient expressed discomfort. Subsequent computed tomography revealed that the tip of the catheter was placed in the middle of the right ureter. Unbeknownst to the physicians before urethral catheterization, the patient had severe lower urinary tract symptoms and urinary bladder dysfunction with hydronephrosis, likely due to chemotherapy. Based on the patient’s symptoms and imaging results, we judged the possibility of severe ureteral injury to be low. The malpositioned catheter was removed uneventfully after complete balloon deflation and then reinserted properly. He was admitted to the medical department but died as a result of an exacerbation of the underlying disease unrelated to the incident. If urethral catheter placement seems abnormal, physicians should aspirate and irrigate to confirm correct positioning before balloon inflation; then, they should carefully pull the inflated balloon near the neck of the bladder while monitoring the patient’s symptoms. Although urethral catheter placement is comparatively safe, physicians must keep in mind that patients who have undergone chemotherapy might be at a risk for this rare complication.     

The impact of a Housing First intervention and health-related risk factors on incarceration among people with experiences of homelessness and mental illness in Canada

ObjectiveTo examine the effect of a Housing First (HF) intervention and health-related risk factors on incarceration among adults with experiences of homelessness and mental illness.MethodsParticipants (N = 508) were recruited at the Toronto site of the At Home/Chez Soi study. The outcome was incarceration in Ontario from 2009 to 2014. Exposures were intervention group (HF vs. treatment as usual), Axis I mental health diagnoses, emergency department (ED) visit, and history of traumatic brain injury (TBI). Logistic regression was used to examine the association between exposures and incarceration.ResultsOf 508 participants, 220 (43.3%) were incarcerated at least once during the study period. Among those incarcerated, 81.9% were male, 52.7% had been diagnosed with alcohol dependence/abuse, 60.9% had been diagnosed with substance dependence/abuse, 65.1% reported having visited an ED within the last 6 months, and 66.4% had a history of TBI. After adjusting for demographic covariates, substance dependence/abuse (aOR: 2.06; 95% CI: 1.40, 3.03), alcohol dependence/abuse (aOR: 1.52, 95% CI: 1.04, 2.22), ED visit (aOR: 1.54; 95% CI: 1.02, 2.32), and history of TBI (aOR: 2.60; 95% CI: 1.75, 3.85) were associated with incarceration. We found no significant effect of the HF intervention on incarceration outcome (aOR: 1.08; 95% CI: 0.76, 1.55).ConclusionsAmong adults with experiences of homelessness and severe mental illness, those with substance and alcohol dependence/abuse disorders, history of TBI, and recent ED visits were at increased odds of incarceration. Strategies are needed to prevent and reduce incarceration for this population, including treatment of mental illness in the community.Supplementary InformationThe online version of this article (10.17269/s41997-020-00433-z) contains supplementary material, which is available to authorized users.