High neutrophil‐to‐lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer

Objectives

To study the role of the neutrophil‐to‐lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer.

Methods

We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil‐to‐lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil‐to‐lymphocyte ratio cut‐off of 3.0 was determined, with a concordance index of 0.89. Kaplan–Meier curves, log–rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil‐to‐lymphocyte ratio with survival outcomes.

Results

Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil‐to‐lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P = <0.01; hazard ratio 2.02, P = <0.01; hazard ratio 5.06, P = <0.01), whereas chemotherapy conferred better overall survival (hazard ratio 0.546, P = 0.01). Furthermore, the role of chemotherapy prolonged survival longer in patients with a neutrophil‐to‐lymphocyte ratio <3.0 (median overall survival 13.0 vs 22.0 months, hazard ratio 0.273, P = 0.008) compared with a neutrophil‐to‐lymphocyte ratio ≥3.0 (median overall survival 4.0 vs 7.0 months, hazard ratio 0.452, P = 0.020). More importantly, when dichotomized to the four different pre‐ and post‐chemotherapy groups, patients with a pre‐ and post‐chemotherapy neutrophil‐to‐lymphocyte ratio <3.0 had the best additional median overall survival of 19.0 months compared with patients with a pre‐ and post‐chemotherapy neutrophil‐to‐lymphocyte ratio ≥3.0 (3.0 months).

Conclusions

Elevated neutrophil‐to‐lymphocyte ratio is independently associated with poorer chemotherapeutic response and overall survival in patients with advanced or metastatic bladder cancer. The neutrophil‐to‐lymphocyte ratio can be an inexpensive novel factor in prognosticating disease progression and providing better patient counseling.     

Model for end‐stage liver disease‐sodium and survival benefit in liver transplantation

There are currently no studies calculating the survival benefit of liver transplantation (LT) according to model for end‐stage liver disease‐sodium (MELD‐Na) and based on the competing risk (CR) method. We enrolled consecutive adult patients with chronic end‐stage liver disease entering the waiting list (WL) for primary LT (WL group = 337) and undergoing LT (LT group = 220) in the period 2006–2009. Two independent multivariable regressions (WL and LT models) were created to measure the prognostic power of MELD‐Na with respect to MELD. For the WL model, both Cox and CR multivariable analyses were performed. Estimates were finally included in a Markov model to calculate 3‐year survival benefit. WL Cox model: MELD‐Na (P < 0.0001) and MELD (P < 0.0001) significantly predicted survival. WL CR model: MELD‐Na (P = 0.0045) and MELD (P = 0.0109) significantly predicted survival. LT Cox model: MELD‐Na (P = 0.7608) and MELD score (P = 0.9413) had not correlation with survival. Benefit model: MELD and MELD‐Na had an overlapping significant impact on 3‐year survival benefit; CR method determined a significant decrease in 3‐year life expectancy (LE) estimations. MELD‐Na and MELD scores similarly predicted 3‐year LT survival benefit, but the gain in LE is significantly lower when a CR method is adopted.     

Infiltrative lamina propria invasion pattern as an independent predictor for cancer‐specific and overall survival of instillation treatment‐naïve stage T1 high‐grade urothelial bladder cancer

Objectives

To investigate established prognostic factors and relatively new histopathological tumor characteristics including metric substage and lamina propria invasion patterns in a large series of T1 high‐grade non‐muscle‐invasive bladder cancer.

Methods

Between 1989 and 2012, 322 patients with initial stage T1 high‐grade bladder cancer underwent transurethral resection, followed by re‐transurethral resection and a conservative approach with follow‐up regime alone or instillation treatment. Transurethral resection specimens were reassessed by two experienced urological pathologists for tumor grade according to the World Health Organization 1973 classification, metric T1 substage, lamina propria invasion pattern and associated carcinoma in situ. The median follow‐up period was 42 months (interquartile range 25–72 months). In addition to Kaplan–Meier analyses, uni‐ and multivariable Cox regression analyses were used to compare progression‐free survival, cancer‐specific survival and overall survival for the studied parameters comparing two subcohorts.

Results

While in patients after instillation treatment no examined feature was shown as an independent predictor for prognosis, there were predictive histopathological features in multivariable Cox regression analyses in instillation treatment‐naïve patients: associated carcinoma in situ (hazard ratio 2.278, 95% confidence interval 1.119–4.634, P = 0.023) and World Health Organization 1973 grade 3 (hazard ratio 2.950, 95% confidence interval 1.021–8.536, P = 0.046) for worse progression‐free survival, infiltrative lamina propria tumor pattern for worse cancer‐specific survival (hazard ratio 2.369, 95% confidence interval 1.034–5.429, P = 0.042) and overall survival (hazard ratio 1.049, 95% confidence interval 1.024–1.075, P = 0.001).

Conclusions

The results of the present T1 high‐grade bladder cancer series suggest that lamina propria invasion pattern is a promising parameter to predict the prognosis of T1 high‐grade bladder cancer in an instillation treatment‐naïve subcohort. Prospective multicenter evaluations are warranted. The need for instillation treatment in T1 high‐grade bladder cancer is clearly demanded.     

Long‐term survival in visceral transplant recipients in the new era: A single‐center experience

There is a paucity of data on long‐term outcomes following visceral transplantation in the contemporary era. This is a single‐center retrospective analysis of all visceral allograft recipients who underwent transplant between November 2003 and December 2013 with at least 3‐year follow‐up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver‐intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three‐, 5‐, and 10‐year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3‐, 5‐, and 10‐year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end‐stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long‐term survival.     

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor‐positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor‐positive, human epidermal receptor 2‐negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real‐world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression‐free survival (PFS) and overall survival (OS). Patients were classified as ET‐naïve or by relapse status following adjuvant ET (“early” recurrence during or ≤12 months of completing adjuvant ET, or “late” >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan‐Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8‐12.3) for early relapse, 15.4 months (10.2‐21.2) for late relapse, and 18.7 months (10.1‐20.8) among ET‐naïve patients (P = .018). Median OS was 39.8 months (25.0‐55.1) for early relapse and 61.4 months (47.1‐61.4) for late relapse, but was not reached (NR; 55.6–NR) for ET‐naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor‐positive MBC.     

Lymph node ratio as best prognostic factor in triple‐negative breast cancer patients with residual disease after neoadjuvant chemotherapy

Although lymph node status (ypN) is one of the most important prognostic factors of survival, the lymph node ratio (LNR) has emerged as an equitable factor. We aimed to compare the prognostic value of both ypN and LNR in patients with residual triple‐negative breast cancer (TNBC) after neo‐adjuvant chemotherapy (NAC). This was a retrospective cohort study of patients treated in a tertiary care center during the period 2000‐2014. We stratified the population based on LNR (≤0.20, 0.20‐0.65, and >0.65) and ypN (N1, N2, and N3) status. The overall survival (OS) and progression‐free survival (PFS) were estimated with Kaplan‐Meier curves and the log‐rank + test. We further compared patient mortality and disease recurrence using multivariate Cox regression analysis. We evaluated 169 patients with a median follow‐up of 87 months. At 2 years of follow‐up, patients with low‐risk LNR compared to those with moderate and high risk had a higher PFS (54% vs 31% vs 18%, respectively; P < .001) and OS (74% vs 64% vs 45%, respectively; P < .001). Moreover, ypN1 patients compared to ypN2 and ypN3 showed similar results in PFS (53% vs 35% vs 19%, respectively; P = .001) and OS (73% vs 69% vs 43%, respectively; P < .001). Compared to the low‐risk population, patients with moderate (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.41‐8.71) and high risk (HR: 6.90; 95% CI: 2.29‐20.77) had a worse PFS. Regarding OS, moderate‐risk (HR: 2.85; 95% CI: 1.10‐7.38) and high‐risk patients (HR: 6.48; 95% CI: 2.13‐19.76) showed considerably worse outcomes. On the other hand, ypN staging was not associated with PFS or OS in the multivariate analysis. The LNR is a better prognostic factor of survival than ypN. The LNR should be considered in the stratification of risk after NAC in patients with TNBC.     

Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV‐associated posttransplant lymphoproliferative disorder and worse survival

Epstein‐Barr virus (EBV)–associated posttransplant lymphoproliferative disorder (EBV‐PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single‐center retrospective study to evaluate the risks for PTLD in LTRs over a 7‐year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan‐Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)‐LTRs (P < .02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33‐8.21, P = .01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10‐6.74, P = .03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57‐76.09, P < .0001). Early PTLD (first year) was associated with alemtuzumab use (P = .04), whereas IPF was a predictor for late PTLD (after first year) (P = .002), after controlling for age and sex. Kaplan‐Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P = .04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.     

Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p < 0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55–1.19, p = 0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45–1.02, p = 0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57–6.91, p = 0.28 and HR 4.59, 95%CI 0.91–23.25, p = 0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR = 1.16; OS: HR = 1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.     

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)‐positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy‐proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow‐up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2? disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR‐HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African‐American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.     

Solid‐type RCC originating from native kidneys in renal transplant recipients should be monitored cautiously

Incidental hemodialysis‐related renal cell carcinoma (id‐RCC) has been reported to have a good prognosis. However, we have observed rapid progression of id‐RCC in some renal transplant patients. Operative indications for id‐RCC detected via computed tomography (CT) immediately before renal transplantation (RTx) remain unclear. The purpose of this study was to examine the effects of immunosuppression on the progression of solid‐type RCC (s‐RCC) and cystic‐type RCC (c‐RCC). We divided 202 patients with id‐RCC into four groups as follows: Group 1, s‐RCC with RTx (n = 17); Group 2, c‐RCC with RTx (n = 27); Group 3, s‐RCC without RTx (n = 53); and Group 4, c‐RCC without RTx (n = 105). Five‐year cancer specific survival (CSS) rates were significantly worse in Group 1 than Group 3 (79.6% and 100%, respectively, P = 0.012), as were non‐recurrence rates (NRRs) (59.2 and 100%, respectively, P < 0.001). In contrast, 5‐year CSS rates were similar in Group 2 and Group 4 (100% and 95.7%, respectively, P = 0.295) as were NRR (100% and 98.7%, respectively, P = 0.230). Solid‐type RCC should be removed immediately after RTx, and more carefully monitored for recurrence during follow‐up.     

Donor‐specific anti‐HLA antibodies are not associated with nonanastomotic biliary strictures but both are independent risk factors for graft loss after liver transplantation

Donor‐specific alloantibodies (DSA) have been associated with rejection and shorter graft survival after orthotopic liver transplantation (OLT). We examined the role of DSA in nonanastomotic biliary strictures (NAS) after OLT. Patients receiving first OLT who developed NAS (n = 68) and a control group without NAS (n = 83), with pre‐OLT and 12 months post‐OLT serum samples, were included. DSA were specified using the Luminex single antigen test. Risk factors for NAS and graft survival were analyzed. The presence of preformed DSA was not significantly different between patients with NAS and controls (P = .89). After 12 months, 26.5% of NAS patients and 16.9% of controls had generated de novo DSA (P = .15). Neither de novo class I DSA nor de novo class II DSA were associated with NAS. De novo DSA generally developed after the diagnosis of NAS. Time‐dependent regression analysis identified both NAS (aHR 8.05, CI 3.28 – 19.77, P < .01) and de novo class II DSA (aHR 2.84, CI 1.38 – 5.82, P < .01) as independent risk factors for graft loss. Preformed or de novo DSA were not associated with the development of NAS. However, NAS as well as de novo class II DSA were independent risk factors for graft loss after OLT.     

Decreasing frequency and improved outcomes of hepatitis C‐related liver transplantation in the era of direct‐acting antivirals – a retrospective cohort study

Benefit of direct‐acting antivirals (DAA) for hepatitis C virus (HCV) on clinical outcomes is unclear. We examined temporal trends in liver transplant (LT) listings, receipt of LT, re‐LT, and survival between pre‐DAA (2009–2012) and DAA era (2013–2016) using UNOS database. Of 32 319 first adult LT, 15 049 (47%) were performed for HCV. Trends on listing, first LT, and of re‐LT for HCV showed 23%, 20%, and 21% decrease in DAA compared to pre‐DAA era (P < 0.0001). One‐year liver graft and patient survival among HCV LT improved in DAA era (90% vs. 86% and 92% vs. 88%, respectively, P < 0.0001). Non‐HCV LT showed no improvement in survival (89% vs. 89% and 92% vs. 92.4%, P = NS). On cox regression, compared to non‐HCV LTs in DAA era, LT for HCV in pre‐DAA era had worse patient survival (HR 1.56 [1.04–2.35]). The outcome was similar when compared to LTs for HCV in DAA era and for non‐HCV in pre‐DAA era. Burden of HCV‐related LT waitlist and LT is declining in DAA era, with improved post‐transplant outcomes, more so in later than earlier DAA era. Our findings negate recent Cochrane meta‐analysis on DAA therapy and encourage studies to examine HCV clinical outcomes outside LT setting.     

Double‐lung versus heart‐lung transplantation for precapillary pulmonary arterial hypertension: a 24‐year single‐center retrospective study

Transplant type for end‐stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart‐lung (HLT) versus double‐lung (DLT) transplantation. Single‐center analysis (38 HLT–30 DLT; 1991–2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug‐induced (nine); hepato‐portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six). HLT decreased from 91.7% [1991–1995] to 21.4% [2010–2014]. Re‐intervention for bleeding was higher after HLT; (P = 0.06) while primary graft dysfunction grades 2 and 3 occurred more after DLT; (P < 0.0001). Graft survival at 90 days, 1, 5, 10, and 15 years was 93%, 83%, 70%, 47%, and 35% for DLT vs. 82%, 74%, 61%, 48%, and 30% for HLT, respectively (log‐rank P = 0.89). Graft survival improved over time: 100%, 93%, 87%, 72%, and 72% in [2010–2014] vs. 75%, 58%, 42%, 33%, and 33% in [1991–1995], respectively; P = 0.03. No difference in chronic lung allograft dysfunction (CLAD)‐free survival was observed: 80% & 28% for DLT vs. 75% & 28% for HLT after 5 and 10 years, respectively; P = 0.49. Primary graft dysfunction in PH patients was lower after HLT compared to DLT. Nonetheless, overall graft and CLAD‐free survival were comparable and improved over time with growing experience. DLT remains our preferred procedure for all forms of precapillary PH, except in patients with complex CHD.     

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.     

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer

Palbociclib is a cyclin‐dependent kinase 4/6 inhibitor indicated for treatment of hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer in combination with endocrine therapy. We investigated the efficacy and safety of palbociclib in patients enrolled in North America during two‐phase 3 trials: PALOMA‐2 (n = 267, data cutoff: May 31, 2017) and PALOMA‐3 (n = 240, data cutoffs: April 13, 2018, for overall survival, October 23, 2015, for all other outcomes). In PALOMA‐2, treatment‐naïve postmenopausal patients with advanced breast cancer were randomized 2:1 to palbociclib (125 mg/d; 3 weeks on/1 week off [3/1]) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. In PALOMA‐3, patients who progressed on prior endocrine therapy were randomized 2:1 to palbociclib (125 mg/d; 3/1) plus fulvestrant (500 mg, per standard of care) or placebo plus fulvestrant; pre/perimenopausal patients received ovarian suppression with goserelin. Palbociclib plus endocrine therapy prolonged median progression‐free survival vs placebo plus endocrine therapy in North American patients (PALOMA‐2: 25.4 vs 13.7 months, hazard ratio, 0.54 [95% CI, 0.40–0.74], P < .0001; PALOMA‐3: 9.9 vs 3.5 months, hazard ratio, 0.52 [95% CI, 0.38–0.72], P < .0001). Objective response and clinical benefit response rates were greater with palbociclib vs placebo in North American patients in both trials. While overall survival data are not yet mature for PALOMA‐2, median overall survival was increased in PALOMA‐3 (32.0 vs 24.7 months, hazard ratio, 0.75 [95% CI, 0.53–1.04]), though this did not reach statistical significance (P = .0869). Safety profiles in North American patients were similar to those of the overall populations; neutropenia was the most common treatment‐emergent adverse event. No new safety signals were observed. In summary, palbociclib plus endocrine therapy is an effective treatment option for North American women with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.     

Nighttime procedures are not associated with adverse outcomes in kidney transplantation

Surgeries performed during the night are associated with higher complication rates. The aim of this study was to determine the impact of nighttime surgery on the outcome after kidney transplantation. In all, 873 deceased donor kidney transplants were retrospectively analyzed and grouped according to the time of surgery: daytime (8 am to 8 pm , n = 610) versus nighttime (8 pm to 8 am , n = 263). Statistical analysis compared patient/graft survival, rate of delayed graft function (DGF), acute rejection rate, and surgical complications. One and 5‐year patient and graft survival did not differ between daytime and nighttime transplants. DGF occurred in 31.1% of daytime compared to 37.6% of nighttime procedures (P = 0.06). Acute allograft rejection was observed in 22.6% of daytime compared to 18.3% in nighttime graft recipients (P = 0.15). Nighttime procedures were associated with 22.4% complications compared to 22.1% in daytime procedures (P = 0.92). Most importantly, if transplantations were postponed until the next morning, cold ischemia time (CIT) would have increased from 16.6 h to 24.6 h (P < 0.0001) which would have resulted in decreased long‐term survival (P < 0.02). Nighttime kidney transplants are neither associated with a higher surgical complication rate nor worse 5‐year outcomes than daytime procedures, thus are justified to keep CIT short.     

Modified donor lymphocyte infusion‐associated acute graft‐versus‐host disease after haploidentical T‐cell‐replete hematopoietic stem cell transplantation: incidence and risk factors

We performed a study to investigate the profile of donor lymphocyte infusion (DLI)‐associated acute graft‐versus‐host disease (GVHD) in haploidentical T‐cell‐replete hematopoietic stem cell transplantation (HSCT). A total of 124 patients receiving modified DLI after haploidentical T‐cell‐replete HSCT were enrolled. The cumulative incidence of DLI‐associated acute GVHD was 53.2% for grades II–IV and 28.4% for grades III–IV. The duration of GVHD prophylaxis after DLI was the only risk factor for DLI‐associated grades III–IV acute GVHD (p < 0.05). The cumulative incidence of grades III–IV acute GVHD in patients with prophylaxis more than six, four to six, two to four, and <2 wk were 9.3%, 14.4%, 31.6%, and 49.5%, respectively (p = 0.018). Furthermore, DLI‐associated grades III–IV acute GVHD was the only risk factor for overall survival (p = 0.038, OR   = 2.869) and transplant‐related mortality (p = 0.018, OR = 3.296) but not a risk factor for relapse after DLI (p = 0.840). This study confirms for the first time that the duration of GVHD prophylaxis after DLI is the only risk factor for the development of grades III–IV acute GVHD. Donor lymphocyte infusion with prophylaxis more than six wk was associated with a lower incidence of grades III–IV acute GVHD.     

Association between diverticular disease requiring surgical intervention and mortality in the postlung transplant population ‐ a retrospective cohort study

Lung Transplant recipients are at increased risk of complicated diverticular disease. We aim to assess the rate of diverticular surgery in a postlung transplantation population and identify risk factors for surgery. We performed a retrospective cohort study of lung transplant recipients from 2007 to 2011. Demographic variables were evaluated with the Mann–Whitney U and chi‐squared tests. Cox regression was performed to evaluate 1‐ and 2‐year landmark survival, assess predictor variables of diverticular surgery and evaluate impact of surgery on CLAD development. Of 17 of 158 patients (10.7%) underwent diverticular‐related surgery. Surgical patients had significantly worse survival than nonsurgical patients at 1 year [aHR 2.93 (1.05–8.21), P = 0.041] and 2 year [aHR 4.17 (1.26–13.84), P = 0.020] landmark analyses. Transplant indication of alpha‐1 antitrypsin disease and cystic fibrosis were significantly associated with the need for diverticular surgery. Emergent surgery was associated with poorer survival [aHR 5.12(1.00–26.27), P = 0.050]. Lung transplant patients requiring surgery for complicated diverticular disease have significantly poorer survival than those who do not require surgery. Surgery was more common in patients transplanted for A1AT and CF. Optimal assessment and risk stratification of diverticular disease is necessary to prevent excessive morbidity and mortality following transplantation.     

Optimizing anti‐T‐lymphocyte globulin dosing to improve long‐term outcome after unrelated hematopoietic cell transplantation for hematologic malignancies

Prophylaxis of graft‐versus‐host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT) remains challenging. Because prospective randomized trials of in‐vivo T cell depletion using anti‐T‐lymphocyte globulin (ATLG) in addition to a calcineurin inhibitor and methotrexate (MTX) led to conflicting outcome results, we evaluated the impact of ATLG on clinical outcome, lymphocyte‐ and immune reconstitution survival models. In total, 1500 consecutive patients with hematologic malignancies received matched unrelated donor (MUD) HCT with cyclosporin and MTX (N = 723, 48%) or with additional ATLG (N = 777, 52%). In the ATLG cohort, grades III‐IV acute (12% vs 23%) and extensive chronic GVHD (18% vs 34%) incidences were significantly reduced (P < .0001). Nonrelapse mortality (27% vs 45%) and relapse (30% vs 22%) differed also significantly. Event‐free and overall survival estimates at 10 years were 44% and 51% with ATLG and 33% and 35% without ATLG (P < .002 and <.0001). A dose‐dependent ATLG effect on lymphocyte‐ and neutrophil reconstitution was observed. At ATLG exposure, lymphocyte counts and survival associated through a logarithmically increasing function. In this survival model, the lymphocyte count optimum range at exposure was between 0.4 and 1.45/nL (P = .001). This study supports additional ATLG immune prophylaxis and is the first study to associate optimal lymphocyte counts with survival after MUD‐HCT.     

Neo‐adjuvant chemotherapy and axillary de‐escalation management for patients with clinically node‐negative breast cancer

This study aimed to explore the optimal time of sentinel lymph node biopsy (SLNB) and neo‐adjuvant chemotherapy (NAC) and to assess the feasibility of selective elimination of axillary surgery after NAC in clinically node‐negative (cN0) patients. From April 2010 to August 2018, 845 patients undergoing surgery after NAC were included in this retrospective study to analyze the correlation between different clinicopathological characteristics of cN0 patients and negative axillary lymph node after NAC (ypN0). Among the 148 cN0 patients, 83.1% (123/148) were ypN0. The rates of ypN0 in patients with hormone receptor positive (HR+)/HER2?, HR+/HER2+, HR?/HER2+, and triple‐negative (TN) breast cancer were 75.4% (46/61), 82.6% (19/23), 85.2% (23/27), and 94.6% (35/37), respectively (P < 0.001). The rates of ypN0 in TN and HER2+ patients were 94.6% and 95.5%, which were significantly higher than that in HR+/HER2? patients (P < 0.05). Molecular subtypes, clinical stage, radiologic complete response, and pathologic complete response (bpCR) of the breast tumor correlated with ypN0 after full‐course NAC (P < 0.05). Molecular subtypes (OR = 2.374, P = 0.033), clinical stage (OR = 0.320, P = 0.029), and bpCR (OR = 0.454, P = 0.012) were independent predictors for ypN0. The optimal time of SLNB and NAC in cN0 patients might be different among different molecular subtypes: it would be preferable to perform SLNB prior to NAC for HR+/HER2? patients, and SLNB after NAC for TN and HER2+ patients to reduce the risk of axillary lymph node dissection. In view of the high ypN0 rate in cN0 patients, axillary surgical staging might be selectively eliminated, especially for HER2+ and TN patients.